Sexually transmitted diseases in the tropics

Transcription

INTRODUCTION
G. Carosi, E. Nunzi, A. Matteelli and P. Fiallo
The term venereal diseases was initially used to identify, mainly for classification, five infections,
which were classically known to be transmitted from person to person through sexual intercourse:
syphilis, gonorrhoea, chancroid, lymphogranuloma venereum and granuloma inguinale. The
recognition of the increasing number of infections and conditions that are sexually transmitted has
led to the introduction of new terminologies. The term Sexually Transmitted Diseases (STD) was
first introduced and widely accepted. More recently the term Sexually Transmitted Infections (STI)
has been introduced to underline the fact that many of the agents responsible for STD are of public
health concern even when the disease does not manifest. In fact, HPV, HSV and the HIV pathogen
may persist silently in the host before overt disease or complications occur. The term Reproductive
Tract Infection (RTI) is preferred by those working in reproductive health to include conditions like
bacterial vaginosis or candidiasis, for which sexual transmission is not recognised as an important
route of diffusion. Moreover, this last term has the important advantage of being destigmatising as it
avoids any reference to sexuality.
There are presently more than 25 agents responsible for STI (Table 1), which can be grouped as
follows: those for which a sexual contact is the predominant route of transmission, those for which
sexual transmission is debated or of little importance, and pathogens transmitted by oral-faecal
exposure, frequently reported in homosexuals.
Table 1: Transmitted in adults predominantly by sexual intercourse
Bacteria
Viruses
Neisseria gonorrhoea
Human
ImmunoChlamydia trachomatis
deficiency Virus 1 and 2
Calymmatobacterium
Human T lymphotropic
granulomatis
virus
Ureaplasma urcalyticum
Herpes Simplex virus 2
Human papillomavirus
Other
Trichomonas Vaginitis
Phtirius pubis
Hepatitis B virus
Cytomegalovirus
Molluscum contagiosum
virus
Sexual transmission described but not well defined or not the predominant mode
Bacteria
Viruses
Other
• Mycoplasma hominis
• Human T lymphotropic
• Candida albicans
Virus 2
• Gardnerella vaginalis
• Sarcoptes scabiei
and other vaginal
• Hepatitis C virus
bacteria
• Herpes Simplex virus 1
• Group B streptococcus
• Human Herpes virus
type 8
Transmitted by sexual contact involving oral-faecal exposure
• Shigella spp
• Hepatitis C virus
• Entamoeba histolytica
• Campylobacter spp
• Giardia lamblia
STD agents can produce a variety of clinical symptoms, which can be grouped in to STD
syndromes (Table 2). The recognition of these STD syndromes is extensively described in specific
chapters of this book, is of practical importance for management of individual cases.
Table 2: Commond STD syndromes and etiologic agents
Syndrome
STD Agent (s)
Urethritis (male)
N. gonorrhoea, C. trachomatis, U. urenlyticum,
T. vaginalis, HIV
Epididymitis
N. gonorrhoea, C. trachomatis, T. vaginalis
Mucopurulent cervicitis
N. gonorrhoea, C. trachomatis
Vulvovaginitis/vaginosis
C. albicans, T. vaginalis, Anaerobes
Pelvic Inflammatory Diseases
HSV 1-2, T. palidum, H. duereyi, C. trachomatis
(LGV strain), C. granulomatis
Genital and anal warts
Human Papillomavirus
Having recognised that the list of STD pathogens and syndromes is continuously expanding, an
important issue remains to be cleared. What is the importance, and what are the practical
implications, of recognising that an agent is a STD (or STI – RTI) pathogen? The importance is
two-folds as all STD pathogens share two common features: the mechanisms of transmission and
the method of control. The number of secondary cases originating from one patient affected with
STD is determined by the product of three factors: the number of sexual partners, the probability of
transmission during a single sexual contact, and the period of fectiousness. As a consequence, any
intervention for control will have to consider actions to reduce the chances of exposure (ex: fewer
sex partners), to reduce the efficiency of transmission (ex. Condom use) and to shorten the duration
of infectivity (ex: early diagnosis and treatment). These actions will be effective on all STDs at the
same time. Actions will also have to be targeted at the same time, both at individual and population
levels.
Without doubt, STD control does represent a health priority in most developing countries. Each
year, the incidence of new bacterial STDs in the world exceeds 300 millions, while the prevalence
of active or latent infection with the common chronic viral STDs as genital Herpes Simplex, Human
Papillomavirus, Hepatitis B. Virus, and increasingly, the Human Immunodeficiency Virus is
estimated in billions of cases. STDs may be associated with a significant morbidity and mortality,
as a result of complications and sequelae following infection. A disproportionate burden is carried
by female gender. Complications in women include cervical cancer, pelvic inflammatory disease
with resulting infertility, chronic pain and ectopic pregnancy and childbirth. As both the incidence
of STD and the number of pregnancies are increasing worldwide, an increasing burden of neonatal
infectious morbidity is expected. Finally a causal link between HIV transmission and STDs has
been demonstrated. The explosive spread of HIV in areas where STD are highly endemic is due to
the amplifying effect that the later exert on both the infectiousness of the index HIV infected case,
and the susceptibility of the partner. Based on this understanding, STD control is considered a
cornerstone of HIV prevention programmes worldwide.
This book is intended to provide a practical and updated bench tool for both health managers and
service providers at peripheral level. It is part of those initiatives mounted to face the every day
increasing challenge of STDs, particularly in the Southern and Eastern part of the world.
ECONOMIC ASPECTS AND COST PROJECTIONS
Susan Foster
Introduction
Economic considerations can be critically important in guiding the selection of appropriate target
groups, in determining the optimal intensity of effort and the effect of interventions at various
points in the process of treatment seeking and care and, as a result, in the optimal choice of a
strategy in terms of both impact and cost-effectiveness.
In this chapter the economic benefits of STI treatment are outlined, available evidence of the costs
of STI detection and treatment examined and general considerations for costings identified.
The Benefits of STI Treatment
Treating STIs in the population will have a number of benefits for both public health and
individuals.
The public health benefits include a reduction in the burden of STI and HIV infection in a
population and thus a reduction in the likelihood of transmission and attendant treatment costs,
together with income losses to the household, community and economy.
The personal gains are those of preventing infertility or Pelvic Inflammatory Disease, (PID), pain,
suffering and possibly death. Chlamydia, gonorrhoea and syphilis in particular can have severe
consequences. The costs of the effects of untreated STIs are substantial, and are disproportionately
borne by women with the most common being PID which can lead to ectopic pregnancy and/or
infertility.
Few data exist on the costs of the consequences of STIs in the developing world where infertility in
a woman can be a catastrophe, leading to divorce and destitution. Many women become infertile
without even realising that they have had PID (Population Reports, 1993) and overall 55-85 per cent
of women with untreated PID become infertile. Couples spend considerable amounts of time and
money in search of a cure. In Zambia a hospital which offered repairs to eliminate tubal blockages
to cure infertility attracted women from as far as away Namibia and Botswana, a high percentage of
whom were HIV seropositive (O'Brien, personal communication) .
The benefits of averting a case of HIV are much greater because it is incurable and leads to death
usually within six to ten years, often after a prolonged illness. For the purposes of this chapter,
therefore, benefits in terms of numbers of both STI and HIV infections averted will be taken into
account.
The benefits of STI treatment would be those of STI infections averted and of HIV infections
averted and can be estimated as follows:
STIs averted = per cent of the population infected with STI x STI transmission rate x (number of
partners while infected - number of partners already infected) = new STI infections.
HIV infections averted = per cent of the population infected with HIV x HIV transmission rate (in
the absence of STI) x STI co-factor x (number of partners while infected - number of partners
already infected) = new HIV infections.
The STI co-factor is that by which the presence of an STI increases the likelihood of transmission
of HIV. The likelihood of risk per exposure to HIV in any sexual contact is normally in the order of
0.1 percent. However, with an STI present the risk per exposure increases. Epidemiological data
suggest that this co-factor is in the order of 3-5 overall, but estimates of the co-factor effect, when
calculated per exposure, are much higher (Hayes et al, 1995).
Although in theory the benefits in terms of HIV infections averted can be estimated, the actual
number of HIV infections averted through the treatment of STIs is very difficult to calculate in
practice for a number of reasons. STIs comprise a wide range of illnesses with variable propensities
for enhancing HIV transmission. The evidence for GUD is relatively convincing but for other STIs
it is less so - what, for example, is the contribution of bacterial vaginosis or candidiasis, or of
gonorrhoea? The prevalence of the different diseases vary both by sex and by area. The
transmissibility of STIs themselves in a developing country context is not yet well specified. Nor is
it clear whether people with asymptomatic infections are as likely to transmit disease as those with
symptomatic infections.
The Importance of the Core Group Concept
Many researchers have stressed the importance of the core group concept: an acknowledgement that
not everyone in a population incurs the same level of risk. Treatment of an STI in a person with
many partners, who is at high risk, will prevent more STIs and HIV infections than the treatment of
a person with few partners who is at comparatively low risk. An example is the wife of a man with
several partners compared with a female SW with 4-5 partners per day. The wife is probably at the
end of the chain of transmission and unlikely to infect anyone other than her husband presumably
the source of her infection - whereas the SW, if left untreated, may transmit infection to a large
number of clients who will then in turn infect their wives.
Anderson and May describe the likelihood of any given person contracting a disease as a function
of the average rates of exposure to infection, of transmission per exposure and of the average
duration of infection. Rates and patterns of sexual mixing are very important risk determinants for
STIs (Anderson and May, cited in Aral et al, 1996). The spread of STIs in a population will be
“driven by spread among highly vulnerable groups of individuals that are characterised by high
rates of partner change (often with each other), longer duration of infection often related to poor
access to acceptable health care, and highly efficient transmission of infection per exposure, all
contributing to high rates of STDs.” (Aral et al, 1996).
The term core group is often assumed to be almost synonymous with SW. However its working
deflnition bears closer scrutiny. Over and Piot (1996) characterise the core as constituting
approximately 2 per cent of the population, being 10 times as sexually active as the non_core and
having a new sex partner every five days as opposed to a new partner every 50 days for the noncore. Using this definition the group would clearly include SWs but it might also include male truck
drivers, miners who are living away from their families, military men and others who might have
approximately one new partner a week. While imprecise, the concept of the core group is
nonetheless useful in considering the cost effectiveness of specific interventions.
Over and Piot modelled the impact of interventions in both core and non-core groups, finding that
interventions in the core were approximately 10 times more effective. Table 1 summarises their
findings with regard to the number of disability adjusted life years (DALYs) saved per case
prevented or cured in the core and noncore groups for the main STIs.
Table 1: Disability Adjusted Life Years
Disease or infection
DALYs saved: Core
Chancroid
55.6
Chlamydia
113.5
Gonorrhoea
120.2
HIV without ulcers
359.6
HIV with ulcers
430.2
Syphilis
396.3
Source: Over and Piot, 1996
DALYs saved: Non-core
3.8
11.4
11.6
54.6
58.7
41.1
Over and Piot (1996) also modelled the number of DALYs saved for alternative STI interventions
using both “favourable” and “unfavourable” assumptions.
“Favourable” assumptions included that the target group was the non-core group. They estimated
that the cost per DALY of condom subsidies and IEC would be US$41 in the non-core, and
US$0.13 in the core. The cost per DALY saved by treating the classic STIs was estimated to be
over US$50 in the non-core, and less than US$0.56 in the core.
Over and Piot (1996) observe that a policy of targeting the core 'averts 10 times as many cases (of
STIs) as would have been averted by a policy directed at the non-core group'. They also note that
interventions in the core group will be approximately 10 times more expensive than interventions in
the non-core groups. Targeting the core group may result in stigmatising the people in the selected
group which may, in turn, exacerbate STI transmission in many settings. They recommend that core
group interventions include deliberate measures to reduce stigmatisation - even if this increases
expense. For example, one way to reduce stigma might be be to include a broader group than those
in the core group. However such a policy of 'dilution of the access group' with non-core groups 'will
dramatically reduce the cost-effectiveness of the intervention'. The authors observe that policy
makers must take account of the tradeoff between stigmatisation of the core group and reducing the
cost effectiveness of the programme (Over and Piot, 1996).
Modelling STI transmission and its impact on HIV incidence involves many uncertainties regarding
key parameters. Modelling their different possible values is complex and beyond the scope of this
book. The interested reader is referred to Robinson et al (1995), Morris and Kretzschmar (1995),
Thomas and Tucker (1996) and Garnett and Anderson (1996) for further discussion of models of
sexual behaviour and HIV transmission.
Cost of STI Detection and Treatment: Available Evidence
In assessing the possible cost of reaching people at risk of STIs, it useful to estimate the numbers of
people at risk through factors such as age and occupation.
It is now recognised that high rates of STIs and of partner change are found among both men and
women and in a number of different groups. Groups may be at higher risk because of their
occupation, gender, age, or geographical location. Currently, adolescents account for a high
percentage of all infections. At the same time some of the highest risk groups, such as female and
male SWs, MSM and IDUs, may be socially marginalised and therefore lack access for financial,
cultural, or social reasons, to existing services including treatment. Other groups, such as the
military, police, students and out-of-school youth are also at high risk but are relatively easily
reached. Figure 10 locates most of the major groups in terms of HIV and STI prevention with
regard to two characteristics: degree of risk and degree of accessibility through existing channels.
Costs of Interventions to Prevent STI and HlV Transmission
STI treatment is one of a number of strategies, employed singly or in combination, to slow
transmission of HIV. It may be useful therefore, to review costs of those other broader strategies
prior to focusing on the costs of STI treatments in particular.
Soderlund et al (1993) and Mills et al (1992) collected data on the costs of slowing HIV
transmission through various strategies, including:
• promoting safer sexual behaviour through mass media strategies
• promoting safer sexual behaviour through person-to-person education
• condom social marketing
• provision of STI treatment and prevention services.
A sample of case studies was chosen to reflect these different strategies, where possible from low,
low-middle, and uppermiddle income countries. Somé of their findings are reported below
(Soderlund et al, 1993). Costs were reported in US dollars and do not take account of client costs.
Costs of Promoting Safer Sexual Behaviour through Mass Media Strategies
Costs of mass media campaigns in the Dominican Republic, Gabon and Hungary were collected.
The Dominican Republic and Gabon cases involved mass media campaigns while the Hungary case
involved school based education programmes and its costs are therefore closer to those of personto-person strategies mentioned below. The total cost of mass media programmes aimed at the entire
population in the Dominican Republic and Gabon were US$438,677 and US$357,347 respectively,
of which US$160,244 and US$210,384 represented costs of radio and television and US$150,300
and US$117,922 were print and other costs. When divided by the entire populations of 7.44 million
and 1.1 million respectively the cost per person was US$0.06 and US$0.32. If, for example, the
strategies had been targeted primarily at adults and the strategies reached 75 per cent of the target
adult population, the costs per person would have been US$0.16, and US$0.87 per person served.
The cost of the Hungary programme was US$1.33 per pupil year of education - one hour per month
- and the cost consisted mostIy of teachers' salaries.
Costs of Promoting Safer Sexual Behaviour through Person-to-Person Education
Case studies for person-to-person education were chosen from Uganda, Cameroon (Yaounde),
Zimbabwe (Bulawayo) and Brazil (Rio de Janeiro). The Uganda project was a workplace education
programme aimed at 400,000 employees of 400 companies, whereas the other three projects were
aimed at SWs and their partners. The Brazilian project focused specifically on male adolescent
SWs. The costs per contact ranged from US$0.47 in Zimbabwe to US$1.89 in Uganda and US$3.73
in Brazil.
Condom Distribution
Two types of condom distribution programmes were costed. The above four projects also
distributed condoms in the context of person-to-person education. The costs, per condom
distributed, ranged from US$0.10 in Zimbabwe to US$0.70 in Brazil, reflecting the intensity of the
strategy needed to reach these marginalised adolescent boys in Rio.
In addition, data were obtained on ten condom social marketing projects, many of which focused on
FP rather than being HlVspecific. The total cost in Zaire was US$2 million and in Côte d'lvoire
US$268,000. The Zaire project sold 18 million condoms and the Cote d'lvoire project 1.8 million
for the cost per condom sold of US$0.11 and US$0.15 respectively. The range of costs per condom
sold by the other projects reviewed was US$0.02-US$0.30. As projects progressed, condom sales
usually increased while unit costs decreased.
Diagnosis and Screening
Screening for Specific Infections
The fact that many women and men are infected with STIs but have no symptoms has led to a
variety of approaches using existing health services, in particular FPCs, ANCs, and/or MCHCs.
Piot and Rowley (1992) estimated the costs of screening for four STIs in women: chlamydia,
gonorrhoea, chancroid, and syphilis. The costs ranged from US$0.17 per diagnosis for the clinical
diagnosis of chlamydia, gonorrhoea, and chancroid, with sensitivities of 40 per cent, 40 per cent and
80 per cent respectively, to US$1.58 for serological diagnosis of syphilis, and to US$5.08 for
antigen detection of chlamydia, or culture of gonorrhoea or chancroid. Culture of chlamydia was the
most costIy at US$12.08. The treatment cost per case calculated ranged from US$0.32 for
chancroid to US$1.20 for gonorrhoea. However, the authors note that development of drug
resistance will change drug costs, costs per case and treatment effectiveness. Indeed, these costs do
appear very low.
Another possibility is the presumptive treatment of all women who attend specific health services.
Piot and Rowley estimated the costs of presumptive treatment of every woman without diagnosis.
At 5 per cent prevalence of the four infections, the cost of presumptive treatment is lower than any
other method for syphilis, chlamydia, and chancroid. For gonorrhoea, the cost is lowest for
treatment based on clinical diagnosis, but the estimate of effectiveness for those women treated is
only 18 per cent compared with 95 per cent for presumptive treatment of all women (Piot and
Rowley, 1992).The drugs used have ceased to be effective in many countries because of drug
resistance, and these calculations would need to be verified on a local basis.
One possibility would be to add STI screening, diagnosis and treatment to the services of FPCs.
Only one study was found which addressed the costs of this, a clinic serving a poor inner-city
population in Texas, US. The incremental costs of adding STI services to the clinic were found to
represent approximately 16 per cent of the clinic budget, of which testing costs were 65 per cent and
treatment costs 35 per cent. The average costs of testing were US$10.77, and of treatment
US$65.82. Staff and laboratory costs each accounted for 43 per cent of the total, drugs 6 per cent,
and supplies 8 per cent (Begley et al, 1989). A number of other studies are being conducted to
investigate the feasibility of adding STI services to FPCs and results should be available within the
next few years.
Diagnosis
One key question concerns how much should be spent upon improved diagnostics? What is it worth
to improve the syndromic approach for STIs? This depends largely on the extent of both over and
under diagnosis.
The extent to which this is a problem for STIs has only begun to be explored. In high prevalence
areas there is probably little cause for concern. However in areas where STI prevalence is low, such
as rural Bangladesh, the syndromic approach may be very wasteful. Hawkes et al (unpublished)
found that approximately 90 per cent of the expenditure on syndromic management of STIs for
women reporting vaginal discharge was wasted - virtually none had STIs.
The cost of treatment for STIs is significant: the cost of drugs, health services, and patient and
family costs, which may include significant stigma, even divorce and domestic violence. The case
can easily be made for looking into improved STI diagnostics. But how much additional
expenditure is economically justified and how can this be calculated? Phillips and Phillips-Howard
(1996) have proposed a simple formula: it is worth paying up to the cost of treatment minus the
percentage of suspected cases confirmed, divided by 100 per diagnosis.
Treatment
Provision of STI Treatment and Prevention Services
The report by Soderlund et al (1993) also compared the costs of STI treatment in three different
settings, with two projects targeted at non-core groups, and one at a core group. One project, in
Maputo, Mozambique, was integrated within health services, another was a free-standing referral
service in Johannesburg, South Africa and the core group project served high-risk female SWs in
Nairobi, Kenya. In all three, capital costs were low. A more detailed breakdown of costs is
presented in Table 2.
Table 2: Cost of Provision of STI Treatment and Prevention Services
Disease or infection
DALYs saved: NonDALYs saved: NonCore: Nairobi
Location
core: Maputo
core: Johannesburg
Capital costs
0
6,654
3,346
Recurrent costs
367,600
272,830
67,293
of which Salaries
23,960 (a)
165,624 (59%)
17,194 (24%)
Other costs
343,640 (93%)
10,726 (39%)
50,009 (71%)
Total costs
367,600
279,484
70,684
Number of visits
38,867
27,506
1,276
Cost per visit
9.46
10.16
55.39
(a) Only the salaries of support and administrative staff are included in this figure; clinic staff were
included within the ‘other’ category.
Source: Soderlund et al, 1993.
Costs per visit were similar in the two projects targeting non-core groups, US$9.46 and US$10.16.
As predicted by Over and Piot (1996), the core group project involved a wider range of services
including free condoms as well as other measures to improve access and takeup, and is thus not
directly comparable. Its costs were significantly higher but so were the benefits.
Costs of Passive Case Detection and Treatment
In many countries current practice is to wait for clients with STI symptoms to present for treatment:
passive case treatment. The baseline cost for this, according to Mills et al (1992), was US$9.46 per
case treated in Maputo and US$10.16 in Johannesburg. A report on STI treatment in Tanzania notes
that 'it is never cost effective to seek laboratory conflrmation prior to treatment and in almost all
cases where STI prevalence is higher than 25 per cent, which might reasonably be expected among
those seeking treatment for STIs, presumptive treatment is called for' (World Bank, 1992).
However, costs of STI treatment are rising. High and rising incidence of drug resistance means that
the older and cheaper antibiotics are no longer effe_ctive against the majority of STIs. Given the
lack of cheap and reliable diagnostic methods, syndromic treatment is currently the best and most
cost-effective option in areas with high STI prevalence. However as the price of the necessary drugs
rises, the economic trade-off between the cost of better diagnosis and syndromic management needs
to be kept under review. The decisions to be made regarding when to step up to a more expensive
but more effective antibiotic can also be estimated with some accuracy.
Table 3 presents the estimated costs per syndromic treatment using various types of antibiotics and
shows the significant differences in cost: approximately a factor of 10 between older, cheaper
antibiotics and newer options. The range of costs to treat urethral discharge is US$0.83-US$10.45;
to treat vaginal discharge, US$1.61-US$14.28; and to treat genital ulcer, US$0.77-US$7.22. These
drugs need to be chosen on the basis of local sensitivity, ie by establishing which organisms are
resistant to particular drugs.
Table 3: Treatment Costs for Syndromic Diagnosis
Syndrome
Drug Choices
Course of Treatment
Urethral Discharge
For gonorrhoea
Cefixime
400mg by mouth as a
single dose
Ceftriaxone
250mg IM as a single dose
Ciprofloxacin
500 mg by mouth as a
single dose
Spectinomycin
2g IM as a single dose
Kanamycin
2 g IM as a single dose
Cotrimoxazole
10 tablets once daily for 3
days
For chlamydia
Doxycycline
100mg by mouth 2 times
daily for 7 days
Tetracycline
daily for 7 days
Erythromycin
daily for 7 days
Range of total cost to treat syndrome
Vaginal Discharge
For gonorrhoea and (see above)
chlamydia
For trichomoniasis and Metronidazole
2g by mouth as a single
bacterial vaginosis
dose
For candidiasis
Micronazole
200mg vaginally once
daily for 3 days
Clotrimoxazole (a)
200mg vaginally once
daily for 3 days
Nystatin
100,000 U vaginally once
daily for 14 days
For vaginitis and cervicitis (c)
For vaginitis only (d)
Cost (US$)
3.00
4.00
2.25
5.00 – 8.00
0.50
0.40
0.43
0.88
2.45
0.83-10.45
0.05
3.78 (b)
0.73
1.09 (b)
1.61 – 14.28
0.78 – 3.83
Genital Ulcer
For syphilis
Benzathine penicillin
2.3 million U IM during
one visit
Procaine penicillin
1.2 million U IM daily for
10 days
For chancroid
Eythromycin
daily for 7 days
Ciprofloxacin
500mg by mouth as a
single dose
Ceftriaxone
250mg by IM as a single
dose
Co-trimoxazole (a)
2 tablets two times daily
for 7 days
For herpes (first
Acyclovir
episode)
daily for 7 days
Range of total cost to treat syndrome (excluding herpes)
Lower Abdominal Pain
For gonorrhoea and
(see above)
chlarnydia
For anaerobic bacteria
Metronidazole 400mg by
mouth 2 times daily for 10
days
0.40
3.22 (e)
1.84
2.25
4.00
0.37
38.87 (b)
0.77-7.22
0.20
1.03-10.65
Note: Costs are drawn from several listings and are approximate.
IM = Intramuscularly; U = Units
(a) Trimethoprim, 80mglsulphamethoxazole, 400mg
(b) Average cost calculated from International Drug Prlce Indlcator (175)
(c) Treatment for gonorrhoea. chlamydia, trichomoniasis, bacterial vaghosis,
(d) Treatrnent for trlchomonlasi& bacterlal vaglnosis, and candldlasls
(e) Cost of 12 one-milllon-unit vials of powder supplled by UNICEF (175)
Source: WHOlGPA, cited in Population Reports, 1993.
Recently a number of studies have been published which compare the cost effectiveness of
syndromic management with clinical management. Gilson et al (1997) in Mwanza, Tanzania
estimated the treatment cost using syndromic management at approximately US$7. This involved
working at the rural health centre level, and syndromic management was administered by PHC
workers.
LaRuche et al (1995), using more advanced antibiotics in Côte d'lvoire found that the effectiveness
of treatment using clinical algorithms in peripheral health centres in Abidjan was approximately 90
per cent. They reported that the average cost of drugs, intramuscular ceftriaxone and oral
ciprofloxacin, was US$5.60 per cure, with a maximum of US$10.70. This was at PHC level and
diagnosis was without the use of laboratory tests. Adding other associated costs would probably
bring the total to about US$8. In Pikine, a low-income suburb of Dakar, Senegal, treatment costs
were estimated at US$4.80 for men and US$15.30 for women (van der Veen et al, 1994).
In Malawi, Costello et al (1998) compared the costs and effectiveness of syndromic treatment with
those incurred by the national policy of clinical management. They found that the cost of using
effective drugs for syndromic management was approximately the same as less effective drugs
based on clinical practice. More than half the drugs were wasted, in that 23 per cent were
ineffe_ctive for the condition; 7 per cent were given in ineffective doses or for the wrong duration
and 24 per cent were given in overdosage. Thirty per cent of drug costs were wasted through
ineffective prescribing, and nearly one third of patients did not receive an effective treatment for
their condition. They concluded that more effective syndromic management could be introduced at
no extra drug cost.
Another study, by WHO, found that syndromic management would be two to three times less costIy
than clinical diagnosis and three to four times less expensive than laboratory based aetiological
diagnosis when all direct costs were taken into account.
Costs of a Large-Scale STI Project: An Example from Mozambique
In Mozambique an effort was made to cost an entire integrated STI/HIV control programme for
Maputo province, with a population of 1 million people. The estimated total cost of treatment was
US$426,558, excluding capital and staff costs, for an estimated 38,867 patients who would be seen
in STI consulting rooms as well as 50,000 pregnant women who would be screened for syphilis
(Bastos et al, 1992). The cost was US$10.80 per treatment. The programme also required 20 fulltime paramedics, the cost of which is not included in the above total. Estimating their salaries at
US$3,000 per year each would bring the overall total to US$486,558 per year, or US$12.52 per
person per treatment. The recurrent costs summary are presented in Table 4.
Table 4: Recurrent Costs of EC Funded Maputo Integrated STI Project (a)
Essential supplies (patient & partners)
Administrative and secretarial
24,000
Diagnostics
103,622
Therapeutic
88,936
Condom/education
78,000
Needles/syringes
24,000
Laboratory, slides, tubes
24,000
Transport, taxes, distribution (supplies)
38,400
Subtotal
380.958
Services
Telephone
Fuel
Subtotal
8,400
15,600
24,000
Maintenance
Transport
Buildings
Subtotal
6,000
15,600
21,600
Grand Total
(a) Excludes staff costs
Source: Bastos dos Santos et al, 1992
426,558
It must be noted that these costs reflect a low level of use by the population of only 3.9 per cent per
year, or about 8 per cent of the adult population, 15 years or older. Approximately 27 per cent of
these costs are fixed or semifixed (salaries, buildings, telephone, fuel), and approximately 15 per
cent are related to syphilis screening of pregnant women. Assuming that the facilities could cope
with additional demand for STI treatments, the cost of treatment would rise by approximately
US$8.50 for each additional person seen and treated. Assuming that the underlying level of STI
prevalence was 25 per cent and that each person infected with an STI came for treatment once in the
year, the overall expenditure would have to rise significantly. If all cases were to be treated -17 per
cent of the adult population - the cost would be 170,000 new cases x US$8.50 or about US$1.5
million. This is a low estimate of the actual costs; coping with the new demand would clearly
require additional staff and buildings, but changes might be made in the use of diagnostics or in the
drugs used. This estimate also does not include the cost of generating the additional demand
through peer education and mass media or of reinfections in those already treated.
Private SectorTreatment
Another set of studies has focused on the situation with regard to STI treatment in the private sector.
Trebucq et al (1994) found that men in Yaounde and Douala, the two largest towns of Cameroon,
who sought care for urethritis in the private sector paid very high prices for prescriptions and
treatment, ranging from US$3.50 to US$110 in one case. The median costs were US$21 in Douala
and US$18 in Yaounde, with costs highest when the men had sought care from medical doctors. In
all cases, the costs of drugs prescribed were higher than those recommended by WHO for the
syndromic management of gonorrhoea and chlamydia infections. Less than three quarters of
prescriptions were filled in full.
Crabbé et al (1996) followed up this work in Cameroon and found that men with urethritis who had
consulted in the formal sector had paid a median of US$24 and those who had consulted in the
informal sector had paid a median of US$10. The sample of men was of a relatively high
socioeconomic level and educated, 83 per cent having had secondary school education. The authors
point out that in Cameroon during the time of these studies drugs were unavailable in public health
centres, so people were obliged to take prescriptions to pharmacies where prices were very high.
These flndings of the high cost of private sector treatment were echoed in another francophone
country, Côte d'lvoire, where LaRuche et al (1995) reported that the cost of an effective STI
treatment at a pharmacy was US$25-US$36. No similar data were found for anglophone African
countries where drug costs are generally lower.
A project in Masaka District, Uganda, is working with private sector practitioners to improve
prescribing habits and to encourage the use of syndromic management. A study found that the level
of knowledge amongst private practitioners in intervention areas was better than that in control
areas and that effective drugs as recommended by the syndromic management guidelines were
available. One shortcoming is that in a number of drug outlets, the principal practitioner had been
trained in syndromic management but had not shared this information with other staff who might
see clients in their absence.
The Issue of Drug Resistance: When to Step up
Another important consideration is resistance of STIs to cheap first-line antibiotics. When is it
appropriate to step up to a more expensive but more effective drug? Phillips and Phillips-Howard
(1996), drawing on the example of antimalarials, propose the following formula. The switch should
be made from old drug 1 to new drug 2 when Cf (Fl-F2) > Ct2-Ctl where Cf = the cost of failure, Fl
and F2 are the failure rates of drugs 1 and 2, and Ctl and Ct2 are the costs of treatment of drugs 1
and 2 respectively.
For example: urethral discharge can be treated with cotrimoxazole at US$0.40, or with
ciprofloxacin at US$2.25. Suppose the failure rate with cotrimoxazole has reached 30 per cent, and
each failure gives rise to a cost estimated at US$10 in lost wages, revisits and additional treatments,
infections of partners, increased risk of HIV transmission, and so on. The alternative is
ciprofloxacin at US$2.25, with only a 3 per cent failure rate. In this case it would be worth adopting
the new drug since the cost of failure, calculated as Cf (Fl-F2) [10 x 0.27 = 2.70] is greater than the
cost of the switch, calculated as Ct2 - Ctl [US$2.25 US$0.40 = US$1.85]. If the percentage of
failures rises still further with cotrimoxazole, or the people being treated have a cost of failure
higher than US$10, for example, highly sexually active core group members who are more likely to
transmit STIs or HIV, it would be even more economically advantageous to make the switch. This
result is highly dependent on the cóst of failure and establishing this figure precisely is difficult as it
will vary according to the STI being treated, the prevalence of HIV, whether the person being
treated is a core group member and so on.
This type of calculation can be used in decisions about other drug combinations for STIs and other
infectious diseases. With few exceptions the costs of drugs tend to fall over time and it is important
for policy makers and health authorities to remain aware of changing prices and to ensure that fair
prices are being paid.
Partner Notification
While there are obvious advantages in persuading partners to present for treatment, there are
reasons to question whether, with a limited budget for STI treatment, significant resources should
be expended on partner notification.
There are a number of possible methods for partner notification, each with different cost
implications. First is counselling of the infected patient on the need to refer the partner for treatment
partner referral. This may be accompanied by a card or other reminder to facilitate the process assisted referral. Experience has shown in some cases that it is preferable for the card not to
mention the STI but rather to stress the health protective aspects, especially for syphilis, where the
life of an unborn infant may be affected if the partner remains untreated (Jenniskens et al, 1995).
A second form of referral is termed conditional or negotiated referral. In this instance, the patient is
given time to notify partners. If they do not present within a given time span, the health services
staff take further steps, which may involve a reminder system, to encourage attendance. In areas
with wellfunctioning and extensive postal or telephone systems this may be a relatively low cost
method.
The third, and most costIy method is provider referral, or active contact tracing which involves field
follow-up of patient contacts. This can be done without disclosing the identity of the index patient.
It relies on the patient providing the names of partners, and of partners who are most likely to be
infected. As noted by Steen et al (1996) the majority of those who are referred are longterm partners
of index patients rather than those who are most likely to have infected them. This method involves
substantial costs in terms of staff time, vehicle costs and often results in a low yield of high-risk
partners.
Experience with these different approaches has been mixed at best. A study in Nigeria found that
nearly half of 156 patient referred partners (47 per cent) attended for treatment, whereas home visits
to 56 patients yielded only four attendances (7 per cent) (Asuzu et al, 1984). In Zimbabwe
experience with partner referral was less good, with 22 per cent of patient referred partners
attending, while experience with field visits was better with a further 17 per cent presenting for
treatment (Winfield and Latif, 1985). In Kenya, nearly half of all partners given a referral card by
their pregnant partner attended for treatment with many mentioning that they had come from
concern for their unborn baby. The card did not mention syphilis (Jenniskens et al, 1995).
Various types of coercion have been attempted. For example, staff in a Kenyan clinic withheld AN
cards, without which women cannot give birth in public facilities, from women identified as having
syphilis until they brought their partners for treatment. Other clinics similarly refused to treat these
women and the numbers of infected women who were treated declined (Jenniskens et al, 1995). It is
likely that many sought treatment in the private sector where requirements for partner notiflcation
were considerably more relaxed. Denial of care to an infected, symptomatic person, and in
particular to a pregnant women who has attended a facility for treatment, probably drives them to
seek less effective, more expensive care in the informal or private sector. Coercion and denial of
treatment raise serious ethical issues and should be discouraged.
Partner referral can be costIy and ineffective. Experience has shown that partner referral can cost
four to eight times as much per case as treating the index case. The trade-off is stark. Should
available resources be spent on pursuing reluctant partners who fail to attend when encouraged to
do so, or on attempting to identify and treat infected core group members? It seems likely that the
marginal or incremental cost per case of finding reluctant partners is much higher than those of
either treating existing symptomatic patients, or of providing services for core group members.
Costs of Intensified Strategies for Hard- and Easy-to-Reach Groups
Working with hard-to-reach groups may involve additional expenditure, for example on the
mobilisation and outreach required to gain acceptability and credibility for a programme.
Additional expenditure will also arise when making STI interventions more effective in attracting
risk-group members through the provision of more services or by making existing services more
appropriate or accessible. As Over and Piot (1996) point out, these additional expenditures are still
likely to be more cost effective than a similar level of expenditure on interventions for the general
population, given the high rates of STIs and likelihood of transmission amongst the target groups
which they address.
Holmes et al (1996) observe that among female SWs near the US naval station in Subic Bav. the
Philippines, there was a group which was termed 'the core of the core' - the one third of the SWs
who had experienced at least one episode of gonorrhoea in the previous five months. Treating this
group would have treated 87 per cent of those actually infected and thus demonstrates how selective
screening, perhaps including the partners of clients as well as clients of infected SWs, could be
made more cost-effective.
A number of STI interventions have been targeted at SWs, mostIy female. An intervention in the
Pumwani area in Nairobi, Kenya, which provided condoms and STI treatment cost approximately
US$70,000 per year for 1,000 SWs. Given that this represents one entire year's care, which could
easily include seven treatments, plus condom provision, the cost per person is less than it appears3.
The selective mass treatment programme for gonorrhoea in SWs in Subic Bay (conducted in 1967)
found that although gonorrhoea prevalence fell among SWs, it quickly returned to higher levels as
prevalence rates did not fall among their US servicemen partners. Thus, a selective mass treatment
programme contributed nothing further to gonorrhoea control (Holmes et al, 1996).
A DFID funded project in India supports the establishment of roadside clinics to provide
information and education, condom promotion and appropriate STI treatment to truck drivers and
their assistants. The clinics provide syndromic treatment to a mostIy male clientele. The cost of
treatment is estimated at Rs74, approximately £1.50, of which drugs cost RsS0. The cost per case
treated is estimated at Rs87-Rs93 with 80-85 per cent of patients cured after one visit. This cost
includes both fixed and recurrent costs estimated at Rs7,000 per year: of which Rs3,000 is for the
doctor's salary, Rs1,500 for an assistant, and Rsl,000 for other running costs including the
amortisation of capital costs. The total cost of building and equipping each clinic is estimated at
Rs6,000 (£120). These costs compare with the costs of conventional medical treatment of Rs100Rs300 per case using clinical diagnosis plus laboratory tests (ODA, 1995).
Condom promotion was undertaken among the military in Ghana with a lively poster campaign.
This programme, called 'Combat readiness: condom readiness' managed to raise awareness of
condoms through a campaign which was supported by high ranking military personnel and which
included articles in military publications, posters and T-shirts made available through the armed
forces own outlets, messes, canteens and bars. Condoms were sold at a very low price, about 2.7 per
cent of the price of a bottle of beer. Condom sales rose by a factor of about seven. Contributing
factors to success included appropriate language and style for the military audience, and ease of
access. No cost data were available on this project (Apeagyei et al, undated).
Cost of Intensified Intervention through Existing Health Services
The Mwanza Intervention Trial is a good example of the potential beneflts that can be achieved
through the intensification and improvement of existing health services. STI control was integrated
into both the urban and rural PHC system and the intervention was designed to be both sustainable
and replicable. Using locally adapted syndromic management guidelines, medical assistants and
rural medical aides now carry out initial examinations and prescribe treatment. Drugs are dispensed
immediately, health education provided, including the offer of condoms and the encouragement of
partner notification through the use of contact tracing cards. Health workers have received three
week training courses in which they were taught to diagnose and treat the most common STIs. The
course included a week of classroom teaching followed by two weeks of supervised practical work
in a clinic. Key features of the programme included the control of drugs and monthly supervision to
ensure that they were not being sold to patients; repeated training on the use of flowcharts and
public education programmes to promote prompt treatment (AIDS Action, 1994). Factors Affecting
the Cost of Interventions
Because the costs of health promotion and other types of intervention vary greatly from one place to
another, and from one intervention to another, it is not possible to make useful generalisations about
the costs of interventions and health promotion costs in particular. It is especially dangerous to
attempt to generalise about the costs of any particular intervention on the basis of one or two
examples.
Costs vary because of two types of factor: those related to characteristics of the country and those
related to the intervention itself. For example, economies of scale will be possible in certain
countries with high population density, high urbanisation or only one main language. They will also
be possible for certain types of intervention such as mass media, but not for others such as those
involving faceto-face interaction.
Cost-effectiveness of syndromic treatment: the example of the Mwanza intervention Trial
An intensified programme of strengthening STI treatment at PHC facilities demonstrated HIV
incidence over two years of 1.2 per cent in the intervention community compared with 1.9 per cent
in comparison communities - a 40 per cent reduction. In the catchment population of about 75,000
sexually-active adults, an estimated 254 HIV infections were thus averted. The cost of the
intervention was US$ 10.15 per person treated, of which USS2.11 was for drugs; the cost per HIV
infection averted was us $217.62. Given that the average age of persons in whom HIV infection was
averted was 28, the cost per DALY was approximately US$ 10 - this compares favourably with
such interventions as tuberculosis (TB) treatment, measles immunisation and vitamin A
supplementation. The Mwanza Intervention Trial has thus proved to be cost effective in comparison
with other health interventions (Gilson et al, 1997).
Economy of Scale
Since the end of the tríal, the intervention has been extended, without the necessity of new capital
investments, from the 25 original health units to all comparison communities and to many other
health facilities in the general region. A total of 150 health facilities are now covered.
Considerations for Costing under All Strategies
A number of additional points regarding the cost of interventions should be considered. First, given
the low level of take-up of existing services, and the high level of STI prevalence in most
developing countries, almost any intervention will involve additional costs. There are probably
some economies to be made and some wasteful practices taking place, but generally such savings
will be minimal. Additional investment will clearly be required in order to make any impact on the
current situation.
Second, earlier'upstream' intervention in the treatment seeking process will bring in additional
patients for treatment and make an impact on overall prevalence levels but this early intervention
will also give rise to greater demand and thus to higher treatment costs as well as additional
benefits. It is essential that this additional demand is provided for before it is generated - so that
rising expectations can be met.
Third is the importance of setting achievable coverage targets together with the marginal cost
implications of these targets. As more and more hard-to-reach groups are targeted, the costs per
person reached will rise, because they live in more remote areas, are reluctant to come for
treatment, or are more vulnerable and fearful of identification or stigmatisation. Similarly, the
marginal additional - cost per person of reaching 70 per cent of FP or AN attenders will be much
lower than reaching 90 per cent. A mass treatment programme which reached 70 per cent of the
population would be much more feasible than one which attempted to achieve 95 per cent coverage.
The money used to reach the additional 25 per cent of the population could probably best be used
elsewhere - unless it is known that the 25 per cent engage in high-risk behaviour or have partners
who do.
A fourth consideration is the balance which will exist between fixed and variable costs. Fixed costs
include the costs of staffing, equipping and maintaining a building. Variable costs, consisting
mostIy of recurrent costs such as drugs and other consumables, change with the volume of service
provided. The costs of some types of intervention, such as a radio or television campaign, would
remain the same whether they were addressing 1 million or 10 million people. Expanding the
provision of existing services to meet demand or to improve the provision of STI care through such
services will mainly be a question of providing additional funds for variable costs, up to the point at
which existing staff and facilities need to be augmented to cope with demand. New clinics or other
initiatives will require an investment in fixed costs as well, although some of these costs might be
borne by the private sector. It is difficult to generalise about the percentage of costs which are fixed
and which variable. In two similar hospitals in neighbouring districts of Zambia, the percentage of
fixed costs was 33 per cent in one hospital, and 57 per cent in the other, largely because of very
different patterns of drug use, nearly five times higher in one hospital than in the other. At three
rural health centres where provision of drugs was limited to low cost essential ones, fixed costs,
mostIy salaries, accounted for 75 per cent of the total cost of a treatment. The actual percentage of
fixed and variable costs needs to be adjusted to local circumstances and in accordance with actual
cost data.
Who Should Pay?
A critical issue in relation to STI treatment is that of who should bear the cost of detecting and
treating STIs. Over and Piot (1966) point out that since STIs are transmissible, preventing or
treating a single case of STI brings benefits which go well beyond the treatment of that individual in
terms of the benefits to those who would otherwise have been infected. They refer to these as
'dynamic benefits', which are 'externalities' in economic terms and thus constitute a failure of the
market mechanism, which in turn justifies government intervention to subsidise STI control.
In support of the argument that government should be involved in subsidising STI treatment, Aral et
al (1996) make an interesting comment on the distribution of costs and responsibilities for
preventing and treating STIs, as follows. “Whether the emphasis is on the acquisition of infection
by all susceptible individuals in the community or on the transmission of infection from a relatively
small number of infected individuals has important implications for the distribution of costs and
beneflts of prevention across the population.... If the emphasis is on prevention of acquisition, the
whole population incurs the financial costs of interventions and the intangible costs of undergoing
preventive behaviour change; they also receive the benefits of avoiding acquisition of infection. If
the emphasis is on prevention of transmission, the members of the highest risk groups of susceptible
and infected persons incur the major cost of behaviour change, while the members of the general
population still receive the benefit of avoiding acquisition and avoiding future public health costs.
Thus everyone should still incur the financial cost of implementing interventions.”
Over and Piot (1996) point out that it is politically unpopular to deliver services to socially marginal
populations and that 'it is ironic that decision-makers who avoid these populations because they are
concerned only about the health of their mainstream constituency could better protect that
constituency from STIs by spending ... on programs targeted at socially marginalised populations
who are especially vulnerable to infection'.
Fees for Service
Finally, even if governments do subsidise the provision of STI treatment, it is likely, in many
settings, that patients will be asked to bear some of the cost. If this is the case, careful thought must
be given to the implications of charging for STI treatment or preventive measures.
It is often said that a charge should be “nominal” but what does this really mean? In Britain a
charge of approximately US$8.40 is made for a prescription on the National Health Service,
although many people are exempt- including those on income support, children, the elderly and the
chronically ill. It is a level of fee which is considered to be fair but to discourage frivolous use, and
when it is raised every so often there is much consternation and comment in the press. Nevertheless
this 'nominal' charge represents approximately 0.04 per cent of the mean GNP per person of the UK
of about US$19,000, where income distribution is relatively equal. In the UK, the top 20 per cent of
the population by income has 44 per cent of the wealth, and the lowest 20 per cent has 4.6 per cent.
In Kenya, with a per person mean GNP of US$280, the top 20 per cent has 62 per cent of the wealth
and the lowest 20 per cent, 3.4 per cent - a mean per person income of only US$48. Much of the
income of the lowest part of the population is in the form of goods and services which are produced
and consumed on the farm, and thus not traded for cash so the poor's cash income is considerably
lower, perhaps as little as US$12. Out of this they must pay for essentials such as school fees,
consumables including soap, cooking oil, candles, transportation, clothing, agricultural inputs - in
addition to medical fees.
If the same principle of a nominal fee of 0.04 per cent of mean GNP per person were applied in
Kenya, the corresponding fee level would be US$0.12. This would be nominal for the middle
classes, but for the lowest 20 per cent income group, whose mean income per person is only US$48,
and of which as little as or US$12 is in cash, even this nominal fee could represent nearly 1 per cent
of their cash income - the equivalent of a fee of US$190 in Britain. So in setting the level of even
nominal fees it is extremely important to keep in mind the unequal distribution of income and the
needs and ability to pay of the lowest income groups.
If the price of the most appropriate provider is set too high, the incentive to use sub-standard
providers will increase.
The municipal referral STI clinic in Nairobi began to charge a substantial fee for services in 1990.
This was added to an existing charge already paid at a first consultation prior to referral to a clinic.
These fees amounted to as much as US$2 over and above the costs incurred throúgh transport, lost
wages, etc and led to a massive decline in use of STI services. Among men, the mean monthly
attendance decreased by 40 per cent after fees were introduced. In women the reduction was 65 per
cent (Moses et al, 1992).
Clearly the introduction of user charges and the possible resultant decline in attendance - similar
experiences have been reported in Ghana, Mozambique, Zaire and Zimbabwe - may result in
increasing numbers of untreated STIs and HIV.
If fees are to be introduced, they should be initiated carefully and only once people have begun to
appreciate and use services. In any case, consideration must be given to the ability to pay of lowerincome groups, including women and adolescents, so as maintain their use of essential services.
The cost of care is one of the most important factors determining health seeking behaviour of
patients with STIs. If large numbers of patients with STIs are unable to access adequate treatment
because of high user fees, a significant adverse impact on HIV transmission can be envisaged. Thus
there are strong public health grounds for advocating the treatment of STIs without charge as is
often done for TB.
Examples of screening: syphilis, gonorrhoea and chlamydia
Syphilis
Syphilis is particularly common and dangerous for both mother and infant. In Kenya approximately
5 per cent of pregnant women have syphilis; in rural Tanzania, 10 per cent of AN attenders
(Mayaud et al, 1995). Syphilis can lead to complications of pregnancy and pose dangers for the
unborn child. In Zambia, 19 per cent of miscarriages and 42 per cent of stillbirths may be
attributable to syphilis, while congenital syphilis contributes as much as 30 per cent to perinatal
mortality (Temmerman et al, unpublished). In a population based study in Malawi, 26 per cent of
stillbirths, 11 per cent of neonatal deaths, 5 per cent of postnatal deaths and 8 per cent of infant
deaths were attributable to active maternal syphilis infection (McDermott et al, 1993, cited in
Jenniskens et al, 1995).
In Kenya, syphilis seroprevalence among AN attenders was approximately 5.3 per cent in 1991. In a
project involving testing for syphilis and referral of positive results to an STI clinic, the cost per
person tested and treated was estimated as US$2.50 per client. Eleven out of 291 - 3.8 per cent were found to be infected, making the cost of detecting one case US$66. Unfortunately, the authors
report that only about half of the women were screened, and of those screened and found positive
only one out of 11 women received treatment. The actual cost per case of congenital syphilis
prevented was US$730. Reasons for failure to receive adequate treatment included failure to return
to the clinic or to attend the referral clinic. Some women were denied treatment at the referral clinic
because they had been re-tested with expired tests which gave false negative results (Temmerman et
al, unpublished). Following this unsuccessful programme, a new initiative was undertaken to
provide 'one-stop' detection and treatment of syphilis. In this second programme, nearly all the
women were treated successfully along with about half of their partners who presented for treatment
(AIDS Action, 1994).
Another project in Kenya involved the decentralisation of syphilis prevention to nurses in ANCs. In
this sample, 6.5 per cent of women, a total of 860, were seroreactive of whom 751 - 87 per cent
were treated appropriately, including half their partners. Total recurrent costs of the programme in
nine clinics serving approximately 13,000 women were about US$20,000: approximately US$1.50
per woman screened, US$26 per treated case, and US$48 per case of congenital syphilis averted.
The authors also estimated costs at different syphilis seroprevalence levels. At 15 per cent, the cost
per averted case of congenital syphilis would be US$10, and at 1 per cent, US$70. The
decentralised method, compared with the former system in Nairobi, reduced the cost per averted
case more than tenfold (Jenniskens et al, 1995).
In Zambia, an attempt was made to cost a syphilis screening programme. An estimated US$600 in
materials costs per 1,000 women was expected. If staff-time costs were added and assuming that the
two tests per attender, plus the treatment of seroreactive women and the two thirds of their spouses
who would agree to attend, would require the equivalent of one nurse or similar staff, the cost
would rise by approximately US$ 1,500 to around US$2,100. The treatment cost was estimated at
US$1, and the cost per adverse outcome - likely to be 7 spontaneous abortions, 19 perinatal deaths,
and 14 syphilitic infants per 1,000 births was US$12. Including staff costs this would rise to US$42
(Hira et al, 1990). If the actual cost of the rapid plasma reagin was closer to the US$0.60 estimated
by a project in Mozambique, then the overall cost of screening in Zambia would rise significantly to
US$1,600, excluding staff costs, and US$3,100 including staff costs. If all of the 327,000 women
who had a child in Zambia in 1990, the date of the last census, had been screened, the cost would
have been in the order of US$2.76 million.
Gonorrhoea and Chlamydia
Chlamydia and gonorrhoea cause considerable morbidity and mortality in both developing and
industrialised countries. A study in Canada on the cost of finding chlamydial infections estimated
the probability of occurrence of different complications of chlamydia. The probability of PID was
estimated as 14 per cent, symptomatic cervicitis 20 per cent and asymptomatic cervicitis 66 per
cent. Of those with PID, the likelihood of infertility was estimated as 15 per cent and ectopic
pregnancy 5.5 per cent. Treatment costs of these conditions were estimated as Can$4,196 for a
hospitalised case of PID, Can$572 for an ambulatory case (average Can$1,478), ectopic pregnancy
as Can$3,879, and infertility as Can$3,916 (Estany et al, 1989).
Several projects have addressed the issues of screening for gonorrhoea and chlamydia. Mayaud et al
(1995), working in Tanzania, found that risk assessment and other screening options for chlamydia
and gonorrhoea did not work well. Of the 964 AN attenders in the study, 39 per cent had an STI, 10
per cent had syphilis and 8 per cent had either gonorrhoea or chlamydia. The authors found that the
costs of laboratory screening for gonorrhoea and chlamydia were high and only mass treatment of
all pregnant women achieved high levels of sensitivity. However, as only 8.4 per cent of the women
were infected with chlamydia or gonorrhoea, the cost per true case treated was high, at US$2 1.40.
In Martinique, chlamydia prevalence was estimated at 27 per cent of AN attenders. The authors
estimated the costs of diagnosis and therapy for the complications of chlamydia - diagnosis and
therapy for chlamydia-related conjunctivitis and pneumonia in children, and salpingitis in women at US$1.2 million, which included US$110 for neonatal conjunctivitis, US$300 for pneumonia on
an out-patient basis or US$2,600 for inpatients, and US$5,000 for salpingitis. The cost of cell
culture for chlamydia was estimated at US$32. The cost of treatment of a pregnant woman and of
her partner with erythromycin was estimated at US$20 per person. The cost of screening all
pregnant women, approximately 6,000 annually, with culture and treating both the women and their
partners was estimated to be US$250,000. This gives a benefit:cost ratio of 4.8:1, a cost per woman
screened of US$42 and a cost per case detected in the women of US$153. The authors concluded
that screening for chlamydia in this population was cost effective (Chout et al, 1995). They also cite
a previous study which reported that taking cultures from pregnant women was cost effective if the
prevalence of infection was greater than 14.8 per cent (Nettleman and Bell, 1991, cited in Chout et
al, 1995).
Factors affecting cost of interventions
Characteristics of Countries or Intervention Areas
• Overall size and distribution of the population: population size will reflect the possibility of
economies of scale. A mass media intervention aimed at a population of 3 million will cost
more per person, other things being equal, than one aimed at 30 million. Population
distribution is also a key parameter: if the population is primarily urban or grouped in other
ways - for example in refugee camps or agricultural areas - they will be reached more easily
than if they are scattered throughout the country.
• Population density: the density of the population throughout the county has major
implications for interventions. A country such as Bangladesh with very high population
density has approximately 8,000 people living within a 1 kilometre radius of any given fixed
point in a fertile area and many more in a city, whereas in rural Zambia or Mali, the flgure is
in the region of 200 people within the same radius. If the fixed costs of driving a lorry to a
speciflc point in rural Zambia to distribute condoms were distributed over 200 people, the
cost per person would be in the order of 40 times higher than a similar intervention in
Bangladesh. Additionally, people would be expected to walk further and therefore would
have to value the intervention more to make use of it, whereas in Bangladesh effective
distribution can be done on foot or on bicycle. The Bangladesh Rural Advancement
Committee (BRAC) project made use of workers on foot to distribute contraceptives but this
would not be possible in most of Africa (Foster, 1990).
• Degree of urbanisation: this will determine the costs of reaching people with any given
intervention, since it is usually the case that health and education services, newspapers, radio
and television are more accessible, even to poor people, in urban areas. Urban areas are also
more densely populated and have better infrastructure making distribution and transport
costs lower.
• Infrastructure development: costs will be higher where basic infrastructure such as roads,
telephones and public transportation is poor. Time spent travelling or waiting for a telephone
line is increased and productivity reduced as a result. In some developed urban areas, such
as Bangkok, traffic congestion consumes large amounts of time as people travel to and from
work and on work-related business.
• Number of languages spoken in the country: costs of mass media and other types of
campaign will be higher if posters, educational materials, radio broadcasts and television
spots have to be prepared in several languages. A country such as Tanzania, where Swahili
is spoken throughout, will have a major advantage over Zambia where at least three or four
main languages are spoken.
• General education and literacy levels: another factor affecting costs will be literacy levels
especially among women and adolescents. If low literacy makes print material unfeasible
and face-to-face interventions essential, costs will be correspondingly higher. Also,
expenditure on printed media will have limited benefits.
• Access to mass media such as radio, television, and newspapers: in many countries access to
modern means of communication is limited either by low levels of ownership of radios or
inability to purchase the batteries required to keep radios working. Furthermore, women's
access to radio is often limited by men's control over this resource. Television and
newspapers reach only a small fraction of the population in most African countries but are
nonetheless very influential and help to form opinion among policy makers and elites.
• Degree of development of health services, and density of provision: in some countries,
largely as a result of other factors listed here, health service provision is thin, requiring
people to travel long distances to receive even basic health care. In such countries, rural
Zambia is an example, providing even a basic health centre which serves a small, scattered
population is a major problem for the government, and the costs per person served are very
•
high. In this situation, the trade-off is between providing a more extensive service but at a
greater distance from the population, or providing a very basic service at a number of points
nearer the population. People in such areas must therefore value any given service much
more highly in order to make the effort to use it. Unfortunately the difficulties of supplying
such remote points with essential consumables and equipment often result in wasted
journeys and undermine client confidence in the service.
Salary levels: in some countries medics and paramedics are paid relatively well and in others
they are paid extremely poorly. Thus an intervention which relies heavily on health workers
will be cheaper in a country with low wage levels. However it must be remembered that low
wage levels do not reflect their true scarcity value. In fact, since migration and the 'brain
drain' are likely to be problematic in such situations, remaining staff are likely to be severely
overworked. The low financial cost of their time may be a very poor reflection of the
economic value of the time they have to spend on a given intervention. Paradoxically the
true value of their time is probably higher than that of better paid colleagues in richer
countries. It is important therefore not to overload staff further with unimportant or
unproductive tasks.
Characteristics of the Intervention
Costs of interventions vary for a number of other reasons, mostly unrelated or indirectly reláted to
the country context. These include the following:
•
•
•
•
•
Development costs: costs of producing and developing health promotion materials vary
depending on whether adequate expertise, for example artists, script writers, health
promotion specialists, graphic artists and printers, is available locally or whether expertise
has to be imported. Factors such as the number of languages in which materials have to be
produced and literacy levels will also affect development costs significantly.
Costs of training: salary, transport and materials costs, hotel accommodation and per diem
rates will affect the costs of training. In some countries competition for the attention of
scarce trained health staff by different projects has meant that it has become customary to
have training seminars in luxury hotels and to offer attractive incentives to encourage
participation. Higher-level health staff can usually choose which workshops and seminars to
attend with those which pay the highest per diem being the most popular. More affordable
models involve training local staff nearer to their duty posts, with reimbursement of travel
costs and provision of basic food and drink.
Costs of local staff: peer educators and trainers for face-to-face work. In some countries
local people have been selected and trained as peer educators at low cost. Remuneration is in
the form of an incentive of the equivalent of approximately U$5 monthly. While this is a
small amount of money, and ensures a better level of cooperation, it can add up to a
considerable amount when the number of peer educators required is taken into account. In a
district with 1,000 villages this would require US$5,000 per month, a total of US$60,000
per year.
Costs of radio or television broadcast time: these are often related to ownership of the
media, either public or private, with some, but not all, broadcast authorities willing to offer
subsidised or free prime-time slots for health promotion messages. Free slots may also be
offered at times when few people will be listening or watching and may therefore have
limited impact.
Costs of printing: these very depending on the demand for, and size of, the local printing
industry. There may be little or no competition, with government printers having a
monopoly with long turnaround time and poor quality.
•
Costs of expansion from pilot interventions or small scale projects: the example of peer
educators demonstrates the difficulties of scaling up from smallscale pilot or trial
intervention to a larger area in order to achieve higher rates of coverage. The cost of
producing an impact through face-to-face interventions is significant and there are virtually
no economies of scale to be achieved. It is important therefore that efforts are targeted
appropriately.
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Moses S, Manji F, Bradley JE, Nagelkerke NJD Malisa MA and Plummer FA (1992) Impact
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Notes:
1 “This information was previously published in Adler M., Foster S., Grosskurth H., Richens J., and
Slavin H. (1998) Sexually Transmitted Infections: Guidelines for Prevention and Treatment. UK
Department for International Development, Health and Population Occasional Paper”.
2 In this book costs provided in various references are quoted in their original currencies,
unadjusted either for inflation or for exchange rate fluctuations, in view of the fact that costs in
general are highly variable from one setting to another, for example the US and Zambia. and that
exchange rates have been extremely variable, especially those which were originally costed in local
African currencies. However, current costs and projections are made in 1996 UK Sterling whith
conversion from the US dollar at US$1.50 = UK£1 where appropriate.
3 In general seven treatments per year would be higher than average. Interventions of this nature
would need to obtain information about how other people are reinfected. Depending on this
information, it could have major implications for the cost effectiveness of mass treatment.
DISEASES PRESENTING
AS URETHRITIS/VAGINITIS: GONORRHOEA, CHLAMYDIA, TRICHOMONIASIS,
CANDIDIASIS, BACTERIAL VAGINOSIS
S.Talhari, Adele Benzaquen, Ana Tereza Orsi
According to WHO (1) gonococcal and non-gonococcal urethritis are a very important public health
problems. Bacterial vaginosis is also a quite frequent problem and will be dicussed as a special topic;
trichomoniasis and candidiasis are studied together with nongonococcal urethritis.
Gonorrhoea
Aetiology and pathology
Neisseria gonorhoeae is the cause of gonorrohoea, one of the commonest sexually transmitted diseases.
An estimated 62 million cases of gonorrhoea were diagnosed in the world in 1 995 (1) .
The incubation period is 2-5 days (1-14 days).
The urethra in both sexes, the anorectal and oropharyngeal areas are primarily affected. Para-urethral
glands, cervix, endometrium, fallopian tubes and peritoneum may also be affected in gonorhoea.
Clinical features
The classical clinical aspects of the gonococcal urethritis are: dysuria, urethral itching, and abundant
purulent urethral discharge figure 1 see page 207. Mucous discharge may also be the clinical
manifestation, and it is important to remember that in some male patients the gonococcal utethritis may
be assymptomatic (2).
Approximately 70% of female patients are asymptomatic.
The conjuntivae may be infected by autoinoculation. Cutaneous lesions and disseminated gonococcal
infection occur in about 1-3% of cases (3).
Prostatitis, epididimitis, and arthritis are rare complications in patients under adequate treatment.
Gonococcal balanoposthitis may occur, and is characterized by tender ulcers, pustules, or furuncles on
the prepuce or shaft of the penis and may occur in association with gonococcal urethritis or more
frequentely, without utethral infection (4). Abscesses of the prepuce and progressive ulceration of the
glans with Iymphadenopathy may be seen (4).
Septicaemic may rarely occur: the patient is severely ill with high fever, and meningitis or endocarditis
(3).
N. gonorrhoeae can be transmitted at birth. Neonatal gonorrhoea can cause ophtalmia neonatorum,
scalp abscesses, vaginal, rectal, oral, joint and disseminated infections (5). Acquired beyond 1 month of
age, gonorrhoea is virtually diagnostic of sexual abuse (5).
In the prepubertal girl, gonorrhoea is usually present with severe vulvitis, edema, dysuria, and copious
malodorous vaginal discharge (5).
Prepubertal boys are symptomatic with urethritis and discharge.
Diagnosis
Whenever is possible, the diagnosis of gonorrhoea should be confirmed by demostration of N.
gonorrhoeae.
Gram stain of the pus demonstrating intracellular Gram negative diplococci and culture on selective
media such as Thayer-Martin of exudate or secretion remain the essential methods.
For the detection of gonococci in phatyngeal and rectal specimens, the sue of selective medium is
essential.
Unfortunately the confirmation of gonorrhoea is not always possible. The syndromic treatment is a new
strategy that seems to be useful in rural areas or health centers without the laboratory facilities for the
correct diagnosis (Table 1).
Treatment
400mg cefixime seems to be the preferable single-dose oral treatment for umcomplicated gonorrhoea
(6, 7). 1,0g Azithromycin or 400 mg Ofloxacin are also alternatives for single-dose oral treatment.
A single dose of intra-muscular application of 250 mg of ceftriaxone or 500 mg of oral ciprofloxacin or
200 mg of oral sparfloxacin (8) are also highly effective against N. gonorrohoeae.
A single dose of intra-muscular application of 2 400 000U of procaine penicillin, or 3,5g of ampicillin,
all with oral 1,0g probenecid are alternative treatments for gonorrhoea. It is important to remember that
gonococci resistant to penicillin is very high in many countries (9, 10, 11, 12).
Strains of gonococci with decreased susceptibility to ciprofloxacin have been described in the USA
(13), and quinolone-resistant strains have been reported from Hong-Kong (14) and Australia (15).
According to Knapp et al. (16) fluoroquinolone-resistant strains of N. gonorrhoeae account for
approximately 10% of all gonococcal strains isolated in Hong Kong and the Republic of Philippines.
50% of N. gonorrhoeae from some Far Eastern countries present with decreased susceptibility
(intermediate resistance) to fluoroquinolones.
Tetracyclines and quinolones are contra-indicated for pregnant women and children.
All the patients with gonococcal urethritis should be encouraged for HIV testing.
Treatment of sex partners is an essential part of sexually transmitted diseases control. The syndromic
treatment is summarized in Tables 1 and 2.
Non-gonococcal urethritis
Non-gonococcal urethritis (NGU) is among the most common sexually trasmitted diseases. There were
an estimated 89 million patients with Clamydia, and 170 million with Thrichomonas infection in 1995
according to WHO anoding to who (1).
NGU can be caused by bacteria, viruses, parasites and yeasts (17). The most important NGUs are:
1. Clamydial urethritis
1.1. Aetiology and pathlogy
Clamydia trachomatis has a life cycle with both extracellular and intracellular components. Women
with untreated C. trachomatis may harbor the infection for up to 15 years (18). The prevalence of C.
trachomatis in women is 5-30% depending on the population studied (19).
The incubation period is 7 to 21 days.
There are 18 distinct serotypes of Clamydia trachomatis and serotypes D to K cause sexually trasmitted
genital infections and neonatal infections. It accounts for 35% to 50% of all cases of NGU, but also
causes deeper infections such as cevicitis, endometritis and salphingitis. Eye infection may result from
contact with infected genital secretions (3).
C. trachomatis types L1, L2 and L3 cause the Iymphogranuloma venereum.
1.2. Clinical features
C. trachomatis is the major cause of mucopurulent cervicitis and pelvic inflamatory disease (PID).
Mucopurulent cervicitis is the ignored counterpart in women of urethritis in men (20). Mucopurulent
cervicitis may be caused also by N. gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis,
Ureaplasma urealiticum and Herpes simplex virus.
Other manifestations of clamydial lower tract infection include: acute urethral syndrome, acute
bartholinitis and proctitis (21).
The clinical spectrum of PID ranges from subclinical endometritis to frank salpingitis, pelvic
peritonitis, periappendicitis and perihepatitis (22, 23).
In men the urethritis caused by Clamydia is often minimally symptomatic and characterized by mucous
discharge (figure 2, see page 208) and slight dysuria. Purulent discharge may occur and simulate
gonorrhoea.
In half of female and 1/3 of male patients the clamydial infection may occur without clinical symptoms
(24, 2).
C. trachomatis, like gonorrhoea, can infect a newborn during birth. Unlike gonorrhoea, Clamydia can
be carried asymptomatically in the rectum for up to 29 months (5). Infection detected in a child
younger than 2,5 years is not necessarily indicative of sexual abuse (4).
In prepubertal girls, the infection is typically vaginal, rather than cervical. It may present as a vaginal
dishcarge or be asymptomatic (4).
The main long-term sequelae of PID are infertility and adverse pegnancy (ectopic pregnance) aoutcome
(21).
Ocasionally balanitis may be associated with Clamydial urethritis (25).
1.3. Diagnosis
The isolation of C. trachomatis (McCoy cells culture) from the oral pharynx, vagina, or rectum and the
rapid assays using monoclonal antibodies with direct immunofluorescence or enzyme-linked
immunoassays are the current laboratorial methods utilized for the diagnosis of C. trachomatis.
Patients with clinical symptoms, and 4 or more pus cells per high power field on urethral smear, or 20
and more pus cells per field in the urine are indications for treatmente as NGU (26).
1.4. Treatment
For NGU caused by Clamydia the therapy of choice are the tetracyclines. The recommended treatment
is 500mg tetracycline hidrochloride four times a day for 7 days, or 100mg Doxycycline twice a day for
7 days or minocicline 100mg daily for 7 days. Doxycycline is largerly utilized and like the other
tetracyclines it is very effective. C. trachomatis resistant to tetracyclines is not frequent.
Tetracyclines are contra-indicated for pregnant and nursing women, and for children less than 8 years
old.
Erythromycin, 50mg/kg/day, 4 times daily for 7 to 14 days or 1 gr. Azythromycin as single dose are the
treatments of choice for children or pregnant women and for adult patients that for any reason cannot
take tetracycline.
A single-dose 1 gr. oral Azytromycin is an alternative for the uncomplicated chlamydial cervicitis and
urethritis. This treatment is equivalent to standard therapy with doxycycline (27, 28). Azytromycin can
be given where the causative pathogen of urethritis/cervicitis is uncertain, and it is often, therefore,
most useful in acute therapy where there is no immediate microbiological back-up (29).
Ofloxacin 200mg twice daily for 7 days is also very effective. As with the tetracyclines, it is contraindicated for pregnant women and for children.
In many places the confirmation of the diagnosis is impossible. The syndromic treatment tables 1 and 2
and the adeguate follow up is the option in this situation.
2. Other causes of NGU
C. trachomatis is the responsible of 30 to 40% of NGU, and Ureaplasma urealyticum is detected in up
to 40%.
Mycoplsmas, mainly U. urealyticum and Mycoplasma hominis, are normal commensal organisms of
the genital tract, which sometimes makes it difficult to determine their pathogenicity. However they are
responsible for urogenital infections, and U. urealyticum is a pathogen in male urethritis (30). The
treatment is the same for both.
Trichomonas vaginalis, herpes simplex virus, and Candida spp. are the single causative organism of the
NGU in approximately 1-2%.
Stahphylococcus, Streptococcus and E. coli may cause NGU.
In most of the patients the signs and symptoms of NGU are similar for the different pathogens. In as
many as 20-30% of patients no known pathogen can be isolated (17).
Whenever possible, the treatment should be oriented in accordance with the isolated agent.
As already mentioned, the tetracyclines are the treatment of choice for NGU caused by C. trachomatis
and U. urealyticum.
If the microbiological diagnosis is not available, the syndromic treatment is recommended tables 1 and
2.
Bacterial vaginosis
Aetiology and pathogenesis
In women with a normal vaginal flora the wet mount shows: normal epithelial cells, a dominant
Lactobacillus flora and no or only a few leukocytes (31)._Clinical aspects
According to Martius (31) the diagnosis of BV is based on the following aspects:
a) Increase in vaginal discharge - characterized by a thin, homogenous, and whitish-yellow or gray
colour, and sometimes frothy discharge;
b) The discharge has a fish odor specially after alkalization (coitus, menstrual period) or alkalization
with 10% potassium hydroxide (KOH);
c) Usually there is no erythema.
Diagnosis
a) Presence of clue cells on wet mount. The clue cells are epithelial cells heavily coated with bacteria
that have been identified as Gardnerela vaginalis;
b) G. vaginalis is found in high concentrations in the vaginal fluid of over 90% of women with BV
(32);
c) Patients with BV tipically have no or only a few Lactobacilli, sometimes Bacteroides sp, Mobilincus
sp, Mycoplasma and Peptostreptococcus may be envolved in BV;
d) Virtually all women with BV have a pH of more than 4.5 due to the lack of lactic-acid-producing
Lactobacilli (33).
Treatment
2g Tinidazol or 2mg Metronidazol single-dose oral treatment or Clindamycine 300 mg twice daily for 7
days.
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22. McCormack WM: Pelvic inflamatory disease. N. Engl. J. Med. 1994; 330: 115-119.
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24. Braum-Falco O, Plewing G, Wolf HH. Nichtgonorrhoische Urethritis. In: Dermatologie und
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de DST/AIDS, 2° edição, Brasilia, 1997.
27. Thorpe EM Jr, Stamm WE, Hook EW, GAII SA, Jones RB, Henry K, Whitworth G, Johnson RB.
Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for senven days
in community based practises. Gernitourin Med. 1996; 72: 93-97.
28. Carlin EM, Barton SE. Azitrhomycin as the firstline treatment of non-gonococcal urethritis (NGU):
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7: 185-9.
29. Waugh MA. Azitrhomycin in gonorrhoea. Int J STD AIDS 1996;1: 2-4.
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1997; 7: 1 32-6.
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Treatment, basel, Karger, 1996, vol. 24, pp. 34-39.
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GENITAL ULCERS
R. Bastos
It is difficult to give an accurate clinically based diagnosis in cases of genital ulcers disease, due
mainly to abnormal appearance of the ulcerations, and the frequent occurrence of mixed infections.
Etiology diagnosis required the availability of laboratory facilities, which are absolutely inexistent
in most health care centers and hospitals in developing countries. This syndrome thus theaters to be
one of the most complex clinical problems for those who deal with Sexsually Transmitted Diseases
(STD).
Genital Ulcer (GU) is best defined as a lesion characterized by the loss of tissue - epidermis and
dermis or genital mucous membrane. A lymphandenopathy around the genital area generally
accompanies the ulceration, but may occur in its absence, as in the case of Veneral
Lymphangranulom (VLG).
The importance of this syndrome has increased extraordinarily since it became evident that are also
indicated higher risks for the transmission of the human immunodeficiency virus (HIV).
Epidemiology
In general GU’s often go unregistered and unreported, which limits the exact domains of its
incidence and prevalence in the world, particularly in developing countries. With the exception of
syphilis, the communication of the various causes of GU is all but incomplete, because etiologic
diagnostic tests of the genital ulcer syndrome and adenopathy are not largely available, or are of
difficult execution. Even when available, the specific microbiological agent remains unidentified in
15-50% of cases.
GU’s are relativly more frequent in developing countries than in the industrialized world. Whereas
in Europe and North America 1-5% of the patients observed in STD clinics show GU, in Africa and
Asia these figures range from 20 to 70% of patients with STD. Some studies have shown
geographical variations in GU etiology. Syhilis, chancroid and herpes seem to have ubiquitous
geographical distribution, but Veneral Lymphangranuloma (VLG) and donovanosis apparently
occur predominantly in the tropics. VLG and donovanosis are rarely found in big industrial areas.
High prevalences of syphilis among pregnant women in countries of Southern Africa such as
Mozambique with 15% in a rural area, Swaziland with 13% in 1988 and 12% in South Africa in
1989. These high rates are contrasted with the low prevalences found in countries in West and
Central Africa such as the Ivory Coast and the Republic of Congo with 1% in 1992 and 1990
respectively.
The high prevalence of antibodies anti H. ducreyi observed in a rural population in Mozambique,
suggests that chancroid was responsible for a large proportion of observed GU’s. In this very same
region of Southern Africa, the diagnosis of chancroid was obtained in 42% of GU examined in
Swaziland, and in 22% and 14% respectively in men and women, in South Africa. The rate of STD
patients who suffer from a GU, may be determined by multiple factors, such as the prevalence of
other STD’s, the preferences and sexual habits including intercourse with prostitutes, who are an
usual source of infections, as well as the cultural tradition of circumcision. The organization of
programs against STD’s completely integrated with the struggle against AIDS has been
recommended, consequently, a better knowledge of this syndrome is expected in the near future.
The risks factors vary equally according to population and etiology. Chancroid is more frequently
observed in non-circumcised men, who belonging to the lower classes and whose infectious source
was a prostitute. In several countries syphilis affects a large proportion of homosexual men. The use
of condoms as a means of prevention is still very low, particularly in rural areas where the STD
rates are high; generally, women are less familiar with condoms than men rates of womens who
have never seen one in their lives reaching 43%.
As well as condom acceptability there is also the question of avaibility and accesibility in rural
areas.
Clinical manifestations of GU’s
Although the classical description of GU’s in textboobks is not always found in clinical pratice,
there are, however, certain guidelines that can help in the clinical diagnosis of these infections.
Syphilis
Agent: A spirochete, Treponema pallidum.
Incubation period: Usually between 2 and 6 weeks, but could be relatively long - up to 90 days.
Signs and Symptoms: The first manifestation of Syphilis, a small papule which soon develops into
an ulcer, the primary chancre, is classically a single lesion, round or oval, with very regular
contours, and diamters varying from 0,5 to 2 cm, presenting a relatively clean surface, clear serous
liquid, or little purulent exsudation; its base which is typically
hardened, can be appreciated by tactile examination and it is this
characteristic that gives it its name, indurated chancre (fig. 3,
left). They are usually painless or slightly so without an
inflammatory reaction. Nevertheless, a large variability in the
clinical manifestation and evolution can be observed, and
atypical cases are common.
As for location, the gland-preputial groove in man, and the labia
majora and labia minora in woman are the most frequent; when located in the uterine reck, the
papulous erosive aspect may be mistaken for exo or endocervicitis. Given the fact that it is often
painless, in woman, the ulceration goes frequently unnoticed. Depending on type of sexual
intercourse practiced, oral-pharyngeal, anal-rectal lesions and other (fingers, nipples, pubic region,
etc.) may also exist.
This primary chancre is usually associated with a moderate increase in the inguinal lymphatic
ganglia, hard, without periadenitis and little or not painful at all, however, the classical description
of the lymphatic nodes in syphilis is a relatively constant feature in these patients, which lessens its
value clinical diagnostic. No general symptom accompanies primary chancre.
If untreated, the chancre scars in between 1 and 8 weeks, leaving in most cases no trace, or a subtle
variation in the pigmentation. Under these circumstances, after a few weeks or months the
secondary manifestation of syphilis may arise.
Chancroid (Soft sore, Ulcus molle, Soft chancre)
Agent: A negative Gram bacillus - Haemophilus ducreyi.
Incubation period: It is usually shorter than a week, but 1 or 2 day-incubation periods are not rare.
This aspect may clinically, help, to distinguish chancre from symphilis and other ulcers. Howerver,
it can also occur with a prolonged incubation period of several weeks.
Signs and symptoms: The primary lesion is an erythematuous papula or a painful pustule in the
inoculation area (fig. 4, below). A patient in this phase of the evoltuion is hardly ever observed, and
most victims describe the exordium as a “painful sore”. In a large number of cases multiple
ulcerous lesion are already show, which are painful with non-harsed bases, some may be
superficial, but in most cases are deep and purulent and furrowed edges. Atypical shapes are
frequent: single lesions may be mistaken for syphilis chancre, nains herpes-like chancres, giant
chancres similar to thrush and swift chancres of spontaneous healing; despite less frequency,
phagedenic forms with vast tissue destruction cal also be observed. Not rarely does mixed chancre
occurs, which is substantially a simultaneous infection by Treponema pallidum and Haemophilus
ducreyi. Concomitant infection by HIV can produce changes in the usual clinical picture, making it
more atypical.
Associated lymphatic adenopathy could be a lead to diagnosis, since it is present in more than 50%
of confirmed case, usually unilateral, painful, voluminous and with inflamatory evidence, which can
evolve into fistulization or even ulceration.
Bacilli have a particular tropism for the skin, so cutaneous lesions are more frequent than lesions on
mucous membranes. In men, particularly un circumcised, the lesion is frequently located in the
renum, which can lead to its destruction, in the foreskin, where at times kissing ulcers are noticed,
and in the anuses of the homosexuals. In women it is located in the labia majora and in the pubic
region, and, in this case, may be accompanied by anal lesions due self-inoculation of neighboring
areas.
Figure 4: Chancroid
Veneral lymphogranuloma
Agent: A minute bacterium adapted to compultosy intracellular parasitims: Chlamydia trachomatis
corresponding to the serotypes L1, L2, L3.
Incubation period: on average from 2 to 3 weeks, but may have a longer incubation period.
Sings and symptoms: The primary lesion is a micro chancre (fig. 5, next page). Located in any part
of the external genitals, in the gland, or foreskin, rarely recognized in women. They are painless, of
rapid manifestation and in most cases go unnoticed. However, this lesion may present with a
purulent base, making it resulting in a hard very slightly parless lesion with no periadenitis
indistinguishable from a chancroid minor lesion; in these cases, the relatively longer incubation
period of LGV, can help establish a clinical diagnosis.
The classical clinical appearance consists in adenopathy (climatic bubo) which is characteristic (fig.
6, below). It usually occurs after the healing of the primary lesion and is unilateral or bilateral.
There are several inflammatory ganglia, matted together, with periadenitis, affecting both the
superficial and deep surfaces of the inguine-crural which gives it a characteristic appearance know
as the groove sign considered to be pathognomonic of LGV, but occuring in only 10 to 15% of
cases. They are painful, evolve with central softening, with fluctation, giving place to the formation
of multiple fistulae.
Fig. 5
Fig. 6
Posterior complications can appear as a result of lymphatic verous blockage caused by the infection,
distal edema develops in the genital organs in the first two years after an acute infection, and results
in genital elephantiasis, which, in women, is know as esthiomène, and in men as saxophone penis.
Later on it may lead to a complication, the annu-rectal syndrome, characterized by hemorrhages,
multiple abscesses and vegetant, lesions, evolving into rectal stenosis, the Jersild syndrome.
Genital herpes
Agent: A DNA virus belonging to the Herpesviridae family. Classically the Herpes simplex virus
type 2 is observed in genital lesions, but an increasing contamination by the Herpes simplex virus
type 1 in genital herpes has also been observed. Increased frequency of oral-genital relations may
explain this phenomen.
Three types of clinical manifestations caused by the HSV exist herpetic primary infection, the first
episode post primary herpes and recurrent infection.
Incubation period: primary herpes (or herpetic prime-infection) appears early, 3 to 7 days after
infection but can go up to 3 weeks.
Signs and symptoms: In primary herpes, the clinical status shows general and genital symptoms.
General signs: fever, headache, general indisposition, myalgia may appear and are more frequent in
women than in men. Its appearance may precede local symptoms and persist for 8 to 10 days.
Genital signs, begin mostly with paresthesia, pruritus and a burning feeling of the genital area
affected. In women the lesions are located in the vulval and perineal regions, whereas in men they
are more frequent in the foreskin and in the glands. The inicial lesion are the classical grouped small
blisters over and erythematuous surface. The extension to the neighboring regions is quick. The
blisters burat more rapidly in the damp zones of the genitals, leaving confluent superficial furrows
or ulcerations; the evolution into scarring occurs in 1, 2 or event 3 weeks, is the absence of
secondary-infection; this case, resembling recent chancroid lesions which hinders the healing
process. Pain accompanies the infectious process, particularly of the beginning, and is more intense
in the damper areas than in the dry zones of the genitals; dysuria and vaginal or urethral discharge
flow may occur if lesions of the mucous sembrane are present (cervical or urethral). Painful
inguinal adenophaty accompanies the process. Neuropathic symptoms due to sacral nerves root
involvement are common (lower urinal obstruction, obstipation, pareshesia, for instance).
First episode of post primary-infection: fewer lesions than in the primary-infection; they may be
located laterally, bilaterally or medically the painful adenopathy is variable; usually there are no
symptoms or general or neuropathic sign; if untreated, it evolves into scarring in 1 to 2 weeks.
Recurrent herpes: Approximately 2/3 of those who have a primary infection develop recurrence
later on. There are a large number of factors which cause recurrence: stress, fatigue, intercurrent
infection, fever, menstruation a local cutaneous trauma (frequent intercourse), prolonged exposition
to sun and heat.
It appears with few blister lesions, usually in clusters, with a diameter of 2 to 5 mm over a small
erythematuous surface, located in a lateral zone to the medium line; repeated outbreaks appear
usually in the same area of the penis, vulva or buttocks, some patients (ca. 50%) refer to prodromic
symptoms (parastesias, cutaneous hyperesthesia, pruritus, burning generally located over or close to
the lesion area) 1 to 2 days before the appearance of the lesions; lymphadenopathy general
neuropathic signs are rare; if untreated, it lasts for 5 to 7 days.
Certain patients who suffer from HSV have episodes in which they eliminate the virus from genital
areas in the absence of symptoms. Some of these individuals do not realize that they have genital
herpes. It is a non-symptomatic form of genital herpes.
Genital herpes and HIV: in the course of an HIV infection, sever forms are observed, where the
classic clinical presentations alters greatly, with confluent lesions, expanded, deep and without the
usual tendency for spontaneous cure; pain may be present on touch or manipulation during the
evolution. May be easily mistaken for chancroid: only a history of previous recurrences can be with
a clinical diagnosis.
Donovanosis or inguinal granuloma
Agent: A negative Gram bacillus coccus, presently classified in a temporary genus associated to the
Enterobacteriaceae family, named Calymmatobacterum granulomais found on the core of the
cytoplasm of big mononuclear, and known, as Danovan corpuscles.
Incubation period: Usually from 2 to 3 months.
Signs and symptoms: it stars with a nodule which softens and then ulcerates. It is a genital ulcer that
has a lengthy development, and does not have a tendencey to spontaneous healing; it is normally
with little or no pain at all.
There may be multiple lesions (fig. 7, left); chronic cases can be
very extensive with considerable tissue destruction up to the
genitals or public region; the lesion progresses by extending
itself over the neighboring skin and frquently spreads through
self-inoculation or lymphatic systemic dissemination; the lesions
are similar in men and women, but massive oedema in the labia
majora is common in women. Although usually there are no
systemic symptoms, generalized extra genital forms with bone,
joints and even lung affection have been reported.
The lesion or lesions have a beefy-red base, hypertrophic at times, normally without purulent
exudate; it is believed that the subcutaneous extension to the inguinal region can result in a mass
similar to a lymphatic adenopathy - a pseudobubo - but there is no involvement of lymphatic
ganglia. The vegetant forms, in oval protruberant or salient plaques, may simulate a carcinoma.
There are also chancreform ulcerations, which simulate chancroid. The diagnosis is based on
clinical data and on demonstration of intracellular Donovam corpuscles in the histocytes, and on
exams carried out by biopsy or cytology rubbing.
The lesions regress and disappear with adequate tratment, but in cases of long lasting lesions there
may be genital deformities, such as cutaneous hypo-pigmentation, and urethral, vaginal and anal
estenosis.
Diagnosis of GU’s
As it was stated above, the clinical dignosis of the genital ulcer syndrome and associated lymphatic
adenopathy is often inaccurate; however, a good clinical history and careful observation provides
useful indications as to the etiology of the lesions, and can lead to a presumptive diagnosis. In order
to reach an accurate etiologic diagnosis of GU’s it is necessary to make use of laboratory tests
currently available (Table 1).
There are new tests today for the diagnosis of GU’s. They are tests for the amplification of the
DNA, which have high sensitivity and specificity and have the advantage of not being invasive.
There are three tests on the market: PCR multiplex - polymerase chain reaction assay (M-PCR),
LCX - ligase chain reation assay, and AMP CT - transcription mediated amplification assay. With
these tests the presence of T. pallidum, H. ducreyl, HSV and C. trachomatis can be detected. These
tests are not yet available in developing countries. The M-PCR can simultaneously detect the
presence of T. pallidum, H. ducreyi and HSV from a single sample of UG secretion.
In developing countries, where genital ulcers and lymphatic associated adenopathy are more
frequent and their etiology more complex, the availability of laboratory means is very limited or
absolutely inexistent. An effort should be made in these countries to introduced syphilis serlogic
test (RPR or VDRL), at least for tracking the syphilitic infection in pregnant women. In the face of
the limited availability or the inexistence of laboratory means, other solutions may be applied,
namely the Syndromic menegement, with the use of algorithms adapted to each country or region.
Differential diagnosis
We previously stated that the clinical ulcers are atypical and any microorganism can produce a
socalled typical status of another microbial agent. Thus, each genital ulcer produced by an agent
usually transmitted via sex, is included in the differencial diagnosis of other ulcers. Other agents
may produce genital ulcers, some of which are occasionally transmitted also through sexual
intercourse, such as the parasite Sarcoptei scabiei, the scabies agent. A serologic test of syphilis will
always be useful in these cases.
Systemic illnesses also cause genital ulcerations. For instance, Berçet’s disease, herpetiform
Dermatitis, gangrenous Pyodermatitis, multiform Erythema and steady Erythema. A story of similar
recurrent lesions, in the same anatomic location - usually gland and foreskin, and associated with
recent assumption of medicine is very likely to cause fixed drug eruption. Cyclines, cotrimoxazol,
and, less frequently, barbiturics, are frquently responsible for such eruptions.
Treatment
Antibiotics that are active against all the agents that cause GU’s has not yet been found. In the
countries where etiological diagnosis is not available, the syndromatic approach is advisable. Under
these circumstances a therapeutic attitude towards a GU will be viewed covering, simultaneously,
the agents responsible for the more frequet ulcerous diseases, e.g. syphilis and chancroid. The cost
of medicaments is a major factor to be considered in the choice of the therapeutic schemes,
especially in developing countries.
T. pallidum is sensitive to benzatinic penicillin, in a single 2,4 MU IM dose. In HIV-seropositive
individuals, it is convenient to repeat the dose weekly with up to 3 injections. In case of allergy to
betalactamics, a few a cycline can also be used, namely Doxicyclin 100mg or Minocyclin 100mg
twice a day for 15 days, or Tetracyclin HCL 500mg 4 times a day for 15 days, or Erythromycine
500mg 4 times a day, for 15 days, particularly in women who are pregnant or breast-feeding, when
they are allergic to penicillin.
H. ducreyi responds to various antimicrobials, some of which in a single dose. However, in the past
few decades the bacterium has developed resistance to sulfanamid, penicillin and tetracycline
through the acquisition of plasmids that code for resistance to these drugs. Various treatment can be
currently recommended. Single dose treatment is advantageous because it prevents addictive
problems. The cost, however, is an important consideration in developing countries, where
chancroid prevails. Any of the following therapeutic schemes can be used:
1. Erythromycine (base or estearate), 500mg 3 times a day for 7 days.
2. Azithromycine, 1g in a single oral dose.
3. Cyprofloxacin, 500 mg in a single daily oral dose, 3 days. Cyproflaxin is contraindicated for
women who are breast-feeding, children and adolescents below 17 years of age.
4. Cefriaxone, 250 mg IM in a single dose.
5. Espectionomycine, 2g IM in a single dose.
6. Cotrimoxazol, 80/460mg, 2 pills twice a day, for 10 days.
Concomitant infection with HIV increaes the probability of therapeutic failure in a single dose
treatment, a more prolonged treatment being preferable.
C. trachomatis, responsible for LGV, responds well to the cyclines, which continue to be the drug at
choice. Thus, one can use Doxicycline 100mg or Minocycline 100mg twice a day, for 14 days, or
Tetracycline 500mg 4 times a day for 14 days. Alternatively, Erythremycine (base or estearate)
500mg 4 times a day, for 14 days.
Fluctuaring buboes in the case of LGV and Chancroid (when present) must be aspired with a large
diameter nedle. Repeated aspirations may be necessary, the produce must be carried out through the
normal adjoining skin, to avoid the formation of fistulas. A persisting bubo with fluctuation after
therapy has begun, does not mean unsuccessful treatment.
In cases of Donovanosis, Calymmatobacterium granulomatis is sensitive to Erythromycine
(estearate) 500mg or Tetracycline 500mg 4 time a day, or Doxicycline 100mg twice a day, for 2-3
weeks, until the lesions have regressed completely. In serious cases any of the scheme above can be
supplemented with Estreptomycine 1g IM twice a day, for 10 days. Penicillin is inefficient and
Ampiciline shows inconsistent results.
Genital herpes, caused by the Herpes Simplex Virus type 2 or type 1, does not have a definitive
treatment; that is, there is no viruscide that eliminates the virus from the body. Therefore the most
important aspect in the treatment of genital herpes may be giving correct information and guidance,
about the condition, to the patient. That means they need to know how the virus is transmitted, the
behavior of the virus in the body and its relationship with the host, as well as the signs and
symptoms of the disease, particularly learning to recognieze the prodomic signals. Another
objective of counseling is to calm the patient, seeing as stress is one of the factors that incur
relapses. Another aspect to be considered in counseling, has to do with the sexual partner (s).
Currently, there are medicines on the market which, in spite of their inability to eliminate the virus,
and thus preventing relapses, have a powerful inhibiting effect on the DNA polimerase (an
enzyme), thus stopping replication and viral multiplication. When administered early, it has the
following results: reduction of the sickness period, reduction of symptoms such as pain, reduction
of the duration of viral shedding, and less new lesions.
Aciclovir was the first generation of antiviral drugs of this class, and is recommended under certain
conditions: in the primary infection (particularly in the acute form), in the frequent recurrences, and
most of all in the cases associated with HIV infections. The administration doses are as follows:
Primary infection:
• Acute: 5mg/kg IV in 60 min. 3 times a day, for 10 days;
• Not acute: 200mg oral 5 times a day for 10 days;
Recurrences:
• Non-frequent and moderately acute: 200mg oral 5 times a day for 5 days.
• Frequent: 400mg oral twice a day;
• HIV infection associated: 200mg 5 times a day, for 10 days.
A second generation of anti-herpetic drugs is available on the market: Valaciclovir and Famciclovir,
both with identical effectiveness to Aciclovir, although they have the advantage of greates
bioavailability, therefore being able to be administered a lot less frequently than Aciclovir.
Valaciclovir is used in the 1000mg dose twice a day for 10 days for the herpetic primary infection,
and 500mg twice a day for 5 days in the treatment of relapses; in suppressive treatment, a 500mg
daily dose of Valaciclovir must be administered.
To achieve higher effectiveness with any of these drugs, the treatment must begin as soon as
possible, preferably in the first 12 hours the symptoms have begun.
Many individuals with genital herpes do not need Aciclovir because:
• The lesions regress espontaneously
• These drugs are excessively expensive.
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ANOGENITAL WARTS AND MOLLUSCUM CONTAGIOSUM
P. FIALLO, R. BASTOS
Anogenital warts (condylomata acuminata, or venereal warts) represent the clinical expression of
epidermal infection with the human papillomavirus (HPV) occurring on skin and mucosal surfaces
of external genitalia and perianal areas. These lesions vary from harmless but disturbing papules to
precursors of both benign and malignant neoplasias.
Etiology
The HPV, member of the family Papovaviridae, is a nondeveloped virus with an icosahedral capsid
containing a double-stranded, circular DNA genome. More than 60 different types of HPV have
been recognized using DNA hybridization techniques under stringent condition. HPV 6 and, to a
lesser degree, 11 are the most commonly isolated agents in genital warts; approximately 90% of
condylomata acuminata contain one of these types. Less frequently isolated viral types from genital
warts include 16, 18, 31, 33, and 35. Infection with more than one viral type has been estimated to
occur in at least 8 to 14% cases.
The risk of malignant transformation in infections with HPV-6 and HPV-11, fortunately, appears to
be low. By contrast, HPV types 16, 18, and 31, rarely identified in anogenital warts, are frequently
associated with both carcinoma in situ and invasive carcinoma. Buschke-Lowenstein giant
condylomata have been found to contain DNA of HPV 6, 11 and 16.
Epidemiology
The incidence of anogenital warts has risen dramatically in the last 15 to 20 years. Both sexes are
susceptible to infection. Although overt disease appears to be more common in men, the prevalence
of infection may be higher in women. Prevalence is greatest between the ages of 17 and 33 years,
with a peak incidence from ages 20 to 24 years. Venereal warts appear to be more common and
widespread in patients with immunodeficiencies.
Transmission
Genital warts are highly infective. They are commonly transmitted by sexual intercourse with
infected partners. Two-thirds of persons who have sexual contact with partners who have
condylomata acuminata will themselves develop lesions, but this may be an underestimate as the
tiny warts on the penis and cervix may be overlooked or misdiagnosed.
The incubation period is 3-8 months, but is occasionally shorter (three weeks). Condyloma
acuminatum in children is a potential indicator for sexual abuse. In new born, the suspected mode of
transmission is passage through an infected birth canal. Older children may rarely become infected
nonvenereally from caregivers either directly by manual contact or indirectly via fomites.
Clinical features
Condyloma acuminatum typically presents as multiple or solitary penile, vulvar, vaginal, cervical,
perineal, or perianal papules or plaques. The lesions may be skin-coloured, erythematous, or
hyperpigmented. They often have a verrucous surface and may be lobulated. Lesions on the glans
penis and penile shaft may be filiform, and often pedunculated. Occasionally, papules may appear
smooth, especially on the penile shaft. Some lesions, particularly in the perianal region, may assume
large sizes and have a decidedly cauliflower-like appearance. On the vulva, genital warts are
hyperplastic and may form large malodorous masses particularly in pregnancy, when they may be
sufficiently massive to interfere with partnutrition.
In uncircumcised men, lesions commonly occur on the inner aspect of the foreskin, the fraenum and
corona, whereas on the circumscribed penis lesions are found on the shaft and occasionally on the
glans penis and at the urethral meatus. In the female venereal warts are found most frequently on
posterior part of introitus, labia minora and clitoris, labia majora, perineum, anus, vagina, urethra,
and cervix.
Macular and, to lesser extent, papular penile lesions have been associated with HPV types 16, 18,
31, 33, and 35, whereas acuminate morphology suggests infection with more innocuous types
(HPV-6, HPV-11); however, the clinical appearance of anogenital lesions should not be taken to
infer the type of HPV infection. External condylomata acuminata suggest the possibility of cervical
or urethral infection.
Thus, evidence of HPV infection indicates the need for careful gynaecologic and urologic followup.
Genital warts may be widespread. In these cases they are often associated with an underlying
immune defect as seen, for example, in AIDS.
The duration of genital warts varies from a few weeks to many years. Spontaneous regression may
occur, more likely as a result of enhancement of cell-mediated immunity. During pregnancy warts
grow at an accelerated pace and occasionally may obstruct the vagina necessitating surgical
excision of the warts before term or even Caesarean section. After delivery warts usually involute.
Complications of genital warts include itching and occasionally bleeding.
Secondary infection seems to be uncommon but may produce crusting or erythema, as may trauma.
One particular rare type of wart is the giant condyloma of Buschke-Loewenstein which may
develop in either sex. The giant condyloma develops in podophyllinresistant warts of long duration,
often in the phimotic preputial sac; it is progressively destructive and looks malignant; however,
histologically it is benign and there are no metastasis.
Pathology
In the nuclei of the superficial cells of genital warts virus particles are found. The cytological
changes are characteristic, as seen in Papanicolau-stained smears, and include enlargement of the
squamous cells, multinucleation, hyperchromatosis, perinuclear clearing (koilocytosis) and
dyskeratosis.
Histologically, genital warts present papillomatosis and considerable acanthosis. The most
characteristic feature is the presence of areas in which large epithelial cells show hyperchromatic,
round nucleus and perinuclear vacuolization. Because vacuolization is a normal occurrence in the
upper portion of all mucosal surfaces, viral genesis is highly suspected only if cytoplasmic
vacuolization extends into the deeper portions of the stratum malpighii. The dermis is usually
edematous and moderately infiltrated with chronic inflammatory cells.
Malignant transformation
HPV infection has been implicated in the development of carcinoma. Both squamous carcinoma
and carcinoma in situ have been reported.
Clinically, the recent enlargement, aberration or induration of warts of relatively short duration, and
the occurrence of pain and serosanguinous discharge, should arouse suspicion of malignant change.
In any case in which neoplastic change is suspected, a biopsy is to be taken for histopathological
examination.
Diagnosis and differential diagnosis
The diagnosis of condyloma acuminatum is not always straightforward. Subclinical lesions can be
revealed by whitening them with application of 2 to 5% acetic acid for 3-5 minutes on the genital
skin. The sensitivity of this technique increases in proportion to the amount of time the acetic acid
remains on the skin. However, because hyperplastic epithelium secondary to various factors other
than HPV infection is identified by the acetic acid, the procedure is best employed by practitioners
experienced in its performance and interpretation. Colposcopy may be invaluable in assessing
vaginal and cervical lesions.
Condylomata lata of secondary syphilis are flat, disc-like, macerated lesions developing in the moist
areas of the vulva and around the anus. Dark-field microscopy of scrapings taken from these lesions
will invariably show the presence of numerous Treponema pallidum and the serology for syphilis is
always strongly positive. Molluscum contagiosum should be differentiated clinically as it presents
as small rounded papules with smooth surface, and an umbilicated centre. Other cutaneous
proliferations to be differentiated from genital warts include pearly penile papules,
fibroepitheliomas, seborrheic keratosis, neurofibromas and nevi. Hailey-Hailey disease and Darier's
disease may also be misdiagnosed as condyloma acuminatum.
Bowenoid papulosis is a HPV-associated papular condition of the anogenital region that clinically
resembles condyloma acuminatum, but histologically is consistent with carcinoma in situ; the
lesions may progress to invasive carcinoma or regress spontaneously.
Treatment
No treatment is really satisfactory. Accepted methods of treatment involve chemical and physical
destruction or removal.
Cytotoxic substances
Podophyllin resin 5 to 10% in propilene glycol is effective in the treatment of genital warts unless
they have formed vegetating masses or the so-called giant condyloma. Podophyllin is commonly
painted onto lesions once or twice a week, with carefully avoidance of the surrounding clinically
normal skin that has to be protected with soft paraffin. Patients should be instructed to wash the
treated area a few hours after the application, otherwise, a florid irritant dermatitis with erosion and
ulceration may result. A solution 0.5% purified podophyllin is available for home application by the
patient twice daily for 3 consecutive days of the week for up to 4 weeks. Podophyllin should not be
used on the cervix and must not be used during pregnancy as it has mutagenic properties. After
podophyllin application, there may be a severe local reaction, generally when the preparation is
allowed to remain in contact too long. In such an event treatment is stopped and 1 per cent
hydrocortisone ointment is applied twice daily until the reaction has cleared; podophyllin can then
be reapplied with caution. Podophyllin, if used in excess, may give rise to systemic side effects, in
particular peripheral neuropathy.
Trichloroacetic acid at various concentrations up to 80% is an alternative to podophyllin that pose
fewer risks of local irritation and systemic toxicity. As with podophyllin, the acid is painted
carefully onto the lesions, avoiding uninvolved skin; treatment may be repeated every 1 or 2 weeks
until an adequate response is obtained. An advantage is that, unlike pophyllin, the treated area does
not need to be cleansed after several hours, reducing concerns about patients for whom compliance
is an issue. Unfortunately, the response is often incomplete and recurrences frequent. Five per cent
fluorouracil cream or solution can be used for intrameatal warts.
Physical destructive methods
Electrocautery is useful for all types of warts including common flat warts but has to be done under
local anaesthesia. Cryotherapy, which is used without anaesthesia, is an excellent first-line therapy
for condyloma acuminatum. When employed carefully, response rates are high and adverse
sequelae are few.
Cryotherapy is also an acceptable treatment during pregnancy. It consists of a 10 to 15-second
freeze with an open spray or a cotton-tipped applicator, perhaps repeated once after thawing.
Because warts are to treated separately this treatment can be time consuming; furthermore it is not
practical for large warts. The most frequent adverse reactions include pain at the time of treatment,
erosion and even ulceration. Patients with darkly pigmented skin may experience post-inflammatory
hypopigmentation that may take months to improve.
The carbon dioxide laser has been employed for the destruction of recurrent or extensive
condylomata acuminata. Laser therapy necessitate the use of local anesthesia and require expensive
equipments. For extensive warts, especially at the perianal site, excision may be the only practical
method.
Prognosis
Many cases of condyloma acuminatum either fail to resolve with treatment or recur after apparent
resolution. The refractory nature of condylomata acuminata may often be attributed to subclinical
infection in the adjacent skin, failure to treat the involved skin adequately, or reinfection with the
virus.
Possible reservoirs for reinfection or the existence of an immunosuppressive state should be sought.
Prevention
The ideal management of condyloma acuminatum should involve primary prevention by identifying
and educating those at risk. Sexual abstinence and monogamy are protective, whereas condoms may
prevent transmission.
Molluscum contagiosum
Molluscum contagiosum is a common, benign, viral disease of the skin and mucous membranes
caused by a poxvirus (Molluscum contagiosum virus, MCV).
Etiology
MCV is a poxvirus that is distinct morphologically, serologically and pathogenetically from other
poxviruses. The virus is brick-shaped and measures 200 x 300 um. It has not been possible to grow
the virus and attempts at demonstrating antibodies in the serum have been disappointing. Two
different MCV strains (I and II) have been identified. No clinical differences have been found
between the two strains.
Epidemiology
Although the disease may develop at any age, the vast majority of cases are found in children. MCV
infection is believed to be transmitted by person-to-person spread by close bodily contacts and
possibly by fomites. Genital lesions in adults are likely transmitted sexually. Patients with AIDS are
at particular risk of MCV infection, with prevalence rates of 9 to 18 percent having been reported.
Clinical manifestations
The incubation period is variously estimated at 14-50 days. The individual lesion is a smooth,
pearly to flesh-coloured, dome-shaped papule. The lesion is often umbilicated, with a central pore
through which a curd like core may be easily expressed (fig. 8,
left). The lesions enlarge slowly reaching a diameter 5-10 mm
in 6-12 weeks. Rarely, and usually when one or very few are
present, a lesion may become as large as 3 or more cm in
diameter.
Lesions may be located on any area of the skin and mucous
membranes. They are usually grouped in one or two areas but
may be widely disseminated, particularly in patients with AIDS.
Although lesions are usually asymptomatic, pruritus may be present, and an eczematous reaction
may develop around some lesions. Patients with atopic dermititis or with impaired immune function
may develop secondary bacterial infections. The duration of the lesions is very variable and
although most cases are self-limiting within 6-9 months, some persist for years.
Pathology
The histologic appearance is characteristics. The epidermis grows down into the dermis as multiple,
often closely packed lobules. Many of the epithelial cells in the lower epidermis contain large,
intracytoplasmic inclusion bodies, the so-called “molluscum bodies”. These inclusion bodies
contain the viral particles and grow in size as they move toward the surface. In the centre of the
lesion, the stratum corneum ultimately disintegrates, releasing the molluscum bodies and producing
central crater forms.
Diagnosis and Differential Diagnosis
The diagnosis of molluscum contagiosum is usually obvious by the distinctive clinical appearance
of the lesions, stained smears of the expressed core and biopsy.
The solitary molluscum may resemble pyogenic granuloma, keratoacanthoma or an epithelioma and
in some cases may be difficult to identify without histological examination. Multiple molluscum
contagiosum must be differentiated from warts, varicella, pyoderma, papillomas, epitheliomas, and
lichen planus. In patients with AIDS cutaneous cryptococcal infection may mimic the appearance of
MCV infection.
Treatment
Removal of lesions with a Volkaman's spoon and touching the base with silver nitrate usually gives
satisfactory results. Cryoterapy with liquid nitrogen may be an alternative effective treatment.
More than one treatment is often necessary, because of recurrence or the development of new
lesions. Thus, the patient should be re-examined at fortnightly intervals for 2-3 months after starting
treatment. In patients with impaired immune function, molluscum contagiosum may be refractory to
treatment.
REFEFENCES
Fazel N., Wilczynski S., Lowe L. Su LD. Clinical, histopathologic, and molecular aspects of
cutaneous human papillomavirus infections. Dermatol Clin. 1999 Jul.; 17 (3): 521-36.
Beutner KR, Wiley DJ, Douglas JM, Tyring SK, Fife K., Stone KM. Genital warts and their
treatment. Clin. Infect Dis. 1999 Jan.; 28 Suppl. 1:S37-56.
Handsfield HH. Clinical presentation and natural course of anogenital warts. Am J Med.
1997 May 5; 102 (5A): 16-20.
Stone KM. Human papillomavirus infection and genital warts: update on epidemiology and
treatment. Clin. Infect Dis. 1995 Apr.; 20 Suppl. 1:S91-7.
Beutner KR., Wiley DJ., Douglas JM., Tyring SK, Fife K., Trofatter K., Stone KM. Genital
warts and their treatment. Clin. Infect Dis. 1999 Jan.; 28 Suppl. 1:S37-56.
Thompson CH. Identification and typing of molluscum contagiosum virus in clincal
specimens by polymerase chain reaction. J. Med. Virol 1997 Nov.; 53 (3):205-11.
Ordoukhanian E., Lane AT. Warts and molluscum contagiosum: beware of treatments worse
than the disease. Postgrad Med 1997 Feb.; 101(2):226-6, 229-32, 235.
Brown TJ, Yen Moore A., Tyring SK. An overview of sexually transmitted diseases. Part II.
J Am Acad. Dermatol 1999 Nov.; 41(5):661-680.
Bugert JJ., Darai G. Recent advances in molluscum contagiosum virus research. Arch Virol
Suppl. 1997; 13:35-47.
Lewis EJ., Lam M. Crutchfield CE 3rd. An update on molluscum contagiosum. Cutis 1997
Jul.; 60(1):29-34.
SCABIES AND PEDICULOSIS PUBIS
Zoung-Kanyi Bissek
Introduction
Scabies and pediculosis pubis are common ectoparasites that have been known since the dawn of
time. At first sight, it may seem unusual to classify scabies as a sexually transmitted disease, but the
fact that it is transmitted through intimate contact shows that sexual relation plays an important role
is its transmission.
It is true that scabies and pediculosis pubis do not lead to any genital complications that could cause
an alteration in fertility, but all the same, the fact that these diseases can be transmitted through
sexual contact presupposes that the subject is also vulnerable to other insidious STDs such as
gonorrhoea and chlamydiae infection whose consequences are far more disastrous.
Scabies
Epidemiology
Scabies in its endemic form exists in several areas of the world sometimes it assume epidemic
proportions.
The spread of scabies is facilitated by promiscuity and poor-hygiene living conditions, though the
disease is not limited to poor communities.
It is caused by Sarcoptes scabiei hominis which is a variety of skin parasite strictly adapted to
humans. It is transmitted essentially through inter-human contact though, infection may also result
from contact with contaminated linen. For the disease to be contracted from an infected person,
there must be intimate and prolonged contact.
When contact with an infected person occurs, the fertilized female mite is transmitted. This mite
penetrates the epidermis, making a burrow through the stratum corneum. The parasite remains
buried here throughout the duration of its life which may last about 30 days. Everyday, it lays eggs,
prolonging the length of the burrow 0.5 to 5mm per day. The eggs hatch in 3 to 4 days producing
larvae which regain the surface of the skin. These larvae develop into nymphae and then adult
mites. Copulation occurs on the surface of the skin and female mites thus fertilized are once again
ready to infest either the host himself or any other subject with whom he comes into contact.
Clinical features
The key symptom of scabies is pruritus. It is most felt at night. In the beginning, it is localized on
the inter digital spaces of the fingers (fig. 9, next page) and the buttocks, then it spreads to other
parts of the body (fig. 10, next page) sparing the head, the neck and the back. The disease is
contracted by the patient's sexual partner, bed mate or family members.
Close examination reveals a sinuous lesion measuring a few millimetres long. It is this lesion,
known as the scabetic burrow, which characterizes the disease. The scabetic burrow is the path
travelled by the mite in the stratum corneum. The mite lodges in the swollen end of the burrow,
while its eggs occupy the rest of the lesion.
Apart from these specific signs of scabies, there are other telltale signs such as pearl shaped
vesicles, linear striae, excoriations resulting from scratching and, super-infected lesions (fig. 11,
below).
Fig. 9
Fig. 10
Fig. 11
Fig. 12
The localization of the lesions is very telling. They appear on the spaces between the fingers, the
inner side of the wrists, the posterior and internal sides of the elbows, the anterior axillary folds, the
belt region and the buttocks. A few peculiarities may be noted, namely that in women the lesions
appear on the nipples and the areola of the breasts.
When scabies is contracted through sexual intercourse, it only differs from the ordinary scabies in
that the lesions appear predominantly on the genital organs. The infection of the genitals is
sometimes isolated, and in men, in particular, pruritic erythematous papules occur on the scrotum
and the penis. This type is referred to as nodular scabies (fig. 12, above). The lesions here are due to
hypersensitive reaction to the parasite or its excretions. In women, sexually contracted scabies is
rarely characterized by inguinal lesions. Rather, the papules most often appear on the buttocks and
in the peri-umbilical region.
Course and complications
Excoriations and striae resulting from intense scratching are covered by crusts and may become
super-infected. The germs most often encountered in the super-infected lesions are aerobic bacteria,
with a preponderance of Staphylococcus aureus followed by group A streptococci and
Pseudomonas aeruginosa (1).
Sometimes, when treatment is not begun soon enough, the scabies may be overlaid by impetigo,
ecthyma, cellulitis, lymphangitis and furunculosis, thereby complicating the original infection.
In long standing infections or when occurring in immuno-compromized individuals the scabies may
take the form of highly contagious crusted lesions (2). This crusted scabies is still referred to as
Norwegian scabies.
Diagnosis
Diagnosis is essentially based on history of contacts with infected people and physical examination.
However, some clinical forms may require biological confirmation, especially when the subjects are
clean people with very discrete lesions.
Diagnosis is made by examining under the microscope specimens shaved of the stratum corneum
bathed in an isotonic solution. These specimens are taken from the scabetic burrows or from recent
scabious nodulars. The clinical diagnosis is confirmed when the examination reveals sarcoptes or
their eggs.
Treatment
A few principles have to be followed:
treatment should involve both the infected person and his/her sexual partner. Treatment may
also concern other members of the family, especially infant in close contact with its infected
mother.
all parts of the body excluding the face should be treated.
the bed and clothing used within the 48 hours preceding to the treatment should be
disinfected.
when scabies is sexually contracted, remember to look for associated asymptomatic STD.
Therapeutic procedures
Lindane 1%: The drug is applied for a 12-hour period for adults and for a 6-hour period for
children. It is not recommended for pregnant or breast-feeding women and for children
under two. Lindane is known to have a high toxic potential. Its toxicity is mainly
neurological. Cases of resistance have been reported.
Pyrethrine 5%: This drug is less toxic. It is applicable for 12 hour period during three
consecutive days.
Benzyl benzoate 10%: It is applied twice with an interval of 10 minutes. The drug should be
left on the skin for 24 hours. This duration is reduced to 12 hours for pregnant women and
infants.
Crotamiton 10%: It is applied during two consecutive nights. The bath should be taken 24
hours after the last application.
DDT or Clofenotane is not recommended because of its limited effectiveness.
Ivermectin: If taken at a single dose of 200' Micro'g per kg. It appears to be very efficacious
against scabies (4). Taken at a dose of 100' Micro'g per kg, the drug does not seem to differ
in any significant way from benzyl benzoate 10% (5).
Pediculosis pubis
Pediculosis pubis is due to Phthirius inguinalis. It is transmitted when there is intimate contact. The
adult louse is very sedentary and remains glued to the base the hair, sinking its head into the follicle.
It is transmitted during sexual intercourse. According to Feldman, there is a 95 % chance of
contracting pediculosis pubis during a single sexual intercourse (6). However, the louse can also be
transmitted through contaminated linen.
Besides infesting the pubic area, the parasite may stick to the eyelash the eyebrow, the hairs of the
chest, ears and nose.
Clinical features
Pediculosis pubis is characterized by an intense pruritus. The lesions found in the pubic region are
essentially linear streaks and excoriations. These lesions are susceptible to super infection and
eczematization. At the abdomen, macular lesions may appear, having a diameter of less than 1 cm
and bluish-grey pigmentation. Such lesions are exceptional nowadays and can be seen on lightskinned people.
Diagnosis
Diagnosis is often difficult, especially as the lice are not easily visible. Upon close examination, the
nits may be found glued to the hair and the phthirius.
Treatment
A few principles should be borne in mind:
- the treatment involves the infested person and his/her sexual partner;
- the infested person should be tested for associated asymptomatic STD;
- the clothing and linen used 48 hours prior to the treatment should be disinfected;
- treatment is focused on the infested regions and the surrounding hairy areas.
Therapeutic procedures
-
Lindane 1% lotion or cream: when applied, it is left on for 8 to 12 hours. The treatment is
renewable on the 8th day. The shampoo version of the drug alone is inadequate. Lindane is
not recommended for pregnant or breast-feeding women.
Pyrethrine plus piperonyl butoxide: When applied, the drug is left on for a period ranging
from 30 minutes to one night, depending on the galenical form of the product. The treatment
is renewable on the 8th day.
DDT or Clofenotane: This drug has been abandoned on account of the numerous cases of
resistance.
Malathion: It is active against parasites and nits. The drug is applied once and left on for 12
hours.
REFERENCES
1. Brook I: Microbiology of secondary bacterial infection in scabies lesions. Journal of clinical
microbiology 1995: vol 33; 8; 2139 - 2140
2. Suarez Fernandez R; Martin Rodriguez F; Lopez Bran E; Nunez Alonso C; Sanchez De Paz F;
Sanchez Yus E. Norwegian scabies in a patient with AIDS: report of a case CUTIS: 1995; vol 56;
n¡ 1; pp 57 - 60.
3. WHO/GPA/TEM/94. 1 - Management of sexually transmitted diseases
4. Meinking Tl: Taplin D: Hermida Jl: Pardo R: Kerdel Fa. The treatment of scabies with
ivermectin. The new England journal of medicine; 1995; vol. 333; N¡ l; pp. 26- 30.
5. Glaziou P: Cartel Jl: Alzieu P: Broit C: Moulia-Pelat Jp: Martin Pmv, Comparison of ivermectin
and benzyl benzoate for a treatment of scabies. Tropical medicine and parasitology: 1993: vol. 44;
n¡ 4: pp. 331 - 332.
6. Feldman Y M, Phil M, Nikitas J A: Pediculosis pubis. Cutis 25: 482 - 489, 1980.
7. Brown S; Becher J; Bradly W, Treatment of ectoparasitic infection: review of the english language literature, 1982 - 1992. Clin infect dis, 1995 april, 20 suppl 1: S 104-9.
POST-PRIMARY SYPHILIS
P. Fiallo, R. Bastos
Post-primary syphilis may be distinguished according to clinical presentation and epidemiological
features in: secondary, latent and late syphilis.
Secondary syphilis is the stage when generalized manifestations occur, prevalently on the skin and
mucous membrane, after the chancre period. The clinical presentation results from propagation of
spirochetes from a primary chancre.
The interval between the primary lesion and the secondary eruptions varies considerably. Secondary
syphilis usually appears clinically 6 to 8 weeks after healing of the chancre, although in 15 percent
of patients the primary lesion will still be present when the secondary symptoms begin. The
secondary lesions subside within 2 to 6 weeks. In the pre-antibiotic era, up to 25 percent of
untreated patients experienced one or more subsequent generalized or localized mucocutaneous
relapses, particularly during the first year of infection, before entering the latent stage.
Constitutional symptoms
The patients with secondary syphilis may present with a flu like prodrome, although the majority of
patients present only mucocutaneous manifestations. Constitutional symptoms include malaise,
low-grade fever, appetite loss, headache and myalgia.
The headache, which is characteristically worst at night, may be the symptom which brings the
patient to the doctor. It is often caused by early syphilitic meningitis with increased intracranial
pressure and pleocytosis. Almost all secondary eruptions are accompanied by universal
micropolyadenitis.
Cutaneous manifestations, termed syphilids, are seen in over 80 percent of secondary syphilis cases.
They recur during the first 2 years of the disease unless adequate treatment is given. In the early
stages of the disease the eruptions have a symmetric pattern; those occurring later infection) are
pleomorphic, and more frequently asymmetrically distributed.
Over 95 percent of secondary syphilis eruptions have one of these four clinical presentations:
macular, maculopapular, papular, and annular. Other less frequently encountered clinical
presentations include nodular and pustular eruptions, nails changes and hair loss.
Macular syphilid
Macular syphilid represents the earliest cutaneous manifestation of the secondary stage. The lesions
usually begin 7 to 10 weeks following infection and 3 to 6 weeks after the chancre.
The eruption, also known as "roseola syphilitica", consists of bilaterally symmetric, pink in light
skin, coppery-red in black skin, round macules, about 1 to 2 cm in diameter, with indistinct edges.
The first spots are nearly always on the sides of the chest and the abdomen and may easily
overlooked, especially if the examination takes place under artificial light. As the rash develops, the
trunk and proximal extremities are progressively involved. The face is usually spared, but any area,
including the palms and soles, can be involved. The macules do not scale or itch and, being in some
patients sparse and evanescent, may pass unnoticed, particularly in subjects with deeply pigmented
skin. In untreated cases macular eruptions may recur; these later eruptions often consist of a few
larger lesions distributed irregularly and often confined to the limbs.
Papular syphilid
If this appears to be the first eruption, it usually means that the macular rash has passed
undiagnosed. More usually, early papular rashes arise in an existing macular syphilide maculopapular syphilide (fig. 13, below). As the secondary stage progresses, the lesions become
frankly papular.
The papule is the basic lesion of secondary syphilis. Its particular form of presentation can vary
widely depending on the nature and colour of the patient's skin, the site affected and the climate,
hygiene and clothing.
The typical papule is rather firm and round or, in large papules, sometimes oval. The colour varies
from reddish-brown in new lesions to brown in the older lesions. Early papules tend to be shiny, but
gradually they become covered with a thin layer of scale (papulosquamous syphilides). A thin,
white scaling ring on the surface of the lesion, known as Biette's collarette, is a helpful diagnostic
sign, although it is not pathognomonic. Papular syphilides are widely distributed, frequently involve
the palms (fig. 14, below) and soles, and may occur on the face and scalp.
Fig. 13
Fig. 14
On macerated skin surfaces eroded weeping papules with a tendency to hypertrophy often appear.
On the genitals, they take the form of large exudating papules known as "condylomata lata" (fig. 15,
below).
In men condylomata lata may occupy large parts of the glans, the coronal sulcus and the inner side
of the prepuce. In women hypertrophy may be very pronounced and the lesions are commonly
located around the vulva. Condylomata lata occur also around the anus.
In the later phases of secondary syphilis, papular eruptions are more frequently pleomorphic.
Nummular lesions, 1-3 cm in diameter, covered by massive layers of scales resembling psoriasis,
may appear. Papules can be arranged in annular or circinate configurations or appear as small
conical or spinular elements. These micropapular and miliary eruptions tend to be arranged in larger
or smaller groups over the body. The term "corymbose syphilide" is used when there is a large
central papule surrounded by small satellite papules.
Pustular ulcerative syphilid
Purulent breakdown of lesions of a papular syphilide may create small pustules which rapidly dry
up into crusts. Such a pustular rush occurs chiefly in debilitated or immunocompromized patients.
The widespread outbreak of these papulopustules evolving into ulcers characterizes the so called
"malignant syphilis", also known as "lue maligna". With some exceptions, such as HIV-infected
individuals, most of patients experiencing malignant syphilis probably have a selective, undefined
impairment in the immunologic response to T. pallidum.
Pigmentary changes
When a roseola is fading, it sometimes leaves a pattern of depigmented spots superimposed on
linear pigmented reticulated patches. Such a "leukoderma syphiliticum" is mostly located on the
sides of the neck and was formerly known as the "necklace of Venus". In dark-skinned individuals
intense loss of pigment within the affected areas may resemble vitiligo.
Nail changes
Nail changes of either the nail matrix, or the nail fold, is sometimes seen in the secondary stage.
These changes have no specific characteristics.
Syphilitic alopecia
Patchy hair loss is characteristic of syphilis. The hair falls leaving small, scattered, irregularly
thinned, "moth-eaten" patches of semi-baldness, never producing complete baldness (fig. 16,
below). The disease can spread to the eyebrows and the beard.
Fig. 15
Fig. 16
Mucus membrane lesions
On the mucous membranes secondary syphilis produces three manifestations: condilomata lata
(previously described), mucous patches, and pharyngitis.
Mucous patches are macerated, grey, rounded and flat papules. The epithelium overlying the
papules sloughs off, leaving non tender abraded areas on the tongue, palate, and inner aspects of the
lips and cheeks. Ulceration is uncommon.
Pharyngitis of variable degrees may be identified in 25% of cases. Diffuse redness of the pharynx
and tonsils may be very mild or severe with oedema and erosions.
Syphilis is known as the "great imitator". The skin manifestations of secondary syphilis are so
variable that this disease must be considered in the diagnosis of all dermatoses that are in any way
"atypical".
With the macular rash, drug eruptions must first be considered. The history, itching and lack of
adenopathy helps. Measles and rubella may cause difficulty but it is pityriasis rosea which is most
often called into question. The presence of a herald patch and the collarette of scales distinguish this
condition from macular syphilis.
With papular eruptions many diseases can cause difficulty in diagnosis. When the lesions are
pruritic and lichenoid, the eruption may be difficult to distinguish from lichen planus and, when the
scaling is thick, from psoriasis.
Exudative syphilic papules on the face can be mistaken for impetigo and in the genital region for
condylomata acuminata. The syphilitic condylomata lata, however, are broad-based in contrast to
the papilliferous condylomata acuminata.
The micropapular varieties of syphilis can be confused with keratosis pilaris, lichen scrofulosorum
and lichen planopilaris.
Eruption on the palms and soles can be strikingly similar to psoriasis and mycoses.
With oral lesions the question of aphtae has first to be considered. The painful nature of the lesions
contrasts with syphilis and the aphtous lesions are markedly areolated.
Tonsillitis or tonsillary papules with multiple lymphadenopathy must be differentiated from
infectious mononucleosis. The differential diagnosis is particularly difficult when infectious
mononucleosis is accompanied by morbilliform rashes and biological false-positive tests for
syphilis.
Systemic involvement in secondary syphilis
Secondary syphilis may produce complications in practically any organ. These include hepatitis,
nephropathy, gastrointestinal involvement, arthritis, periostitis and iridocyclitis. The central nervous
system may be invaded and abnormalities in the cerebrospinal fluid (CSF), such as raised cell count
and increased protein content can be found in at least 15% cases.
LATENT STAGE
The latent stage corresponds to the asymptomatic stage following the secondary phase, which can
be diagnosed solely by positive specific treponemal antibody test. Before the diagnosis of latent
syphilis is accepted a thorough clinical examination should be made, including a CSF examination
and X-ray of the heart and aorta. Differentiation between latent syphilis and asymptomatic
neurosyphilis is important because the latter has a more serious prognosis. This period is divided
into early latent syphilis, within the first 2 years after infection, when the disease must be
considered contagious and late latent syphilis where it is usually not. It has been estimated that
about 30% of patients with untreated latent syphilis subsequently develop demonstrable signs of the
disease. In the others where never develops clinically evident late syphilis, however, the occurrence
of spontaneous cure is in doubt.
ASYMPTOMATIC NEUROSYPHILIS
Haematogenous dissemination of spirochetes to the central nervous system (CNS) occurs in early
syphilis, although it may not be apparent for years.
The diagnosis of asymptomatic neurosyphilis is made in patients who no longer have manifestations
of primary or secondary syphilis, who lack neurologic symptoms and signs, and who have certain
CSF abnormalities (see "examination of CSF) due to T. palidum. In patients with untreated
asymptomatic neurosyphilis, the probability of progression to clinical neurosyphilis is about 20
percent in the first 10 years and is highest in those who show the greatest degree of pleocytosis or
protein elevation. Patients with untreated latent syphilis and normal CSF probably have no future
risk of subsequently developing neurosyphilis.
LATE (TERTIARY) SYPHILIS
The designation benign tertiary late syphilis includes any symptomatic manifestation, after the
secondary and relapsing stages, that does not involve the cardiovascular or nervous systems. The
more commonly involved organs are the skin, mucous membranes and bones, but the characteristic
lesion, gumma, may appear in practical any organ.
LATE BENIGN SYPHILIS OF THE SKIN
Cutaneous manifestations may develop any time after the secondary stage resolves, with
"precocious" lesions noted within the first 2 years and the late syphilides between 2 and 30 years.
Precocious tertiary syphilides were somewhat common in the pre-antibiotic era. Lesions usually
occur during the first 4 years of infection. The skin manifestations have characteristics that border
between secondary cutaneous lesions and consist of localized or generalized grouped papules with
some degree of ulceration. On the skin tertiary syphilis normally produces two types of lesions: one
superficial, the nodular syphilide, and the other deeper, the gummatous syphilide. Transitional
forms also occur.
Nodular and noduloulcerative syphilide (tubercular syphilide)
The lesions begin as superficial, firm, pink to purple, papules or nodules that measure several
millimetres to 2 cm in size. The lesions appear in a grouped configuration, rapidly extending
peripherally in an irregular manner. Over weeks or months, central healing and advancing borders
produce plaques with annular, arciform. serpiginous or polyciclic configurations that may reach
over 30 cm. As the nodules grow, the skin appears red and eventually breaks down, resulting in
ulcerations with raised borders and slightly purulent, crusted surfaces. The lesions of tubercular
syphilide are asymptomatic and have a predilection for the extensor arms, back, and face. Even if
untreated, the lesions heal over the years, leaving non-contractile, atrophic scars with increased or
decreased pigmentation.
Gummas are painless pink to dusky red nodules of various sizes that are more common on the scalp,
forehead, buttocks, and presternal, supraclavicular, or pretibial areas. The infiltration starts in the
subcutis and subsequently involves the dermis, the epidermis and the underlying tissues. A gumma
is nearly always painless. It has a characteristic tendency to necrosis, which begins in the middle
where the tissue turns into a slimy and stringy mass, and which has given rise to the name
"gumma". The gumma may be absorbed without ulceration of the skin but it always leaves a scarlike retraction. Ulceration may occur and is typically cylindrical, punched out, and covered with
adherent yellowish-white slough. Large gummas may have several skin perforations and undergo
necrotic changes that cause destruction of the intervening bridges of skin. Various geometric
configurations are assumed (circles, ovals, etc.).
Mucous membrane lesions of late benign syphilis
The most commonly involved mucous membranes are those of the palate and of the nose. Ulcers in
these areas may cause destruction of the bony and cartilaginous structures (saddle nose) or
perforations that sometimes persist despite treatment. Gummas, nodules, and diffuse inflammation,
with ulcers covered by a grey slough may appear in the tonsils, pharynx and tongue.
On the face lupus vulgaris, epithelioma, sycosis barbae, infiltrated types of rosacea and lupus
erythematosus frequently cause diagnostic difficulties.
On the trunk and limbs tertiary syphilides may resemble circinate psoriasis or mycosis fungoides.
On the legs gummas can be confused with varicose ulcers, Bazin's disease and necrobiosis
lipoidica. The changes in the tongue should not be confused with carcinoma; in these cases a biopsy
must always be taken.
LATE SYPHILIS IN OTHER ORGANS
Almost any visceral organ may be affected in the late tertiary syphilis. The more commonly
involved organs, other than skin and mucous membranes, are bones and joints.
Skeletal changes occur commonly and are classified as gummatous osteitis, periostitis, and
sclerosing osteitis. The chief symptoms are nocturnal pain and swelling, and the most common sign
is tenderness.
Joint manifestations of late syphilis include arthralgias, synovitis, and arthritis and are caused by
adjacent periostitis or gummatous infiltration from adjacent bone and skin lesions.
CARDIOVASCULAR SYPHILIS
Cardiovascular syphilis is essentially a disease of the aorta. Presumably, during the early stages of
syphilis, treponemes invade the aortic wall, where they can remain dormant indefinitely.
Predilection of T. pallidum for the ascending aorta is probably explained by the large number of
lymphatics and vasa vasorum in this portion of the vessel. Infiltration of the vasa vasorum in the
intima layer by lymphocytes and plasma cells produces an obliterative endarteritis, which over the
years, weakens the wall of the aorta. This results is necrosis of the muscular and elastic tissues of
this layer and consequential scarring.
Overt clinical cardiovascular disease occurs around 15 to 30 years following initial infection. Most
frequently, aortitis remains asymptomatic and is usually found inadvertently at postmortem
examination. The diagnosis is suspected when linear calcifications of the anterolateral aortic wall
are present in chest radiographs.
In other cases, aortitis progresses to aortic aneurysm, coronary ostial stenosis and aortic valvular
disease.
NEUROSYPHILIS
Despite the protean nervous system manifestations caused by syphilis, the major clinical categories
of symptomatic neurosyphilis include meningovascular and parenchimatous syphilis (general
paresis and tabe dorsalis). Meningovascular syphilis most commonly presents as a stroke syndrome.
Other symptoms are headaches, vertigo, insomnia and psychological abnormalities. General paresis
reflect widespread parenchymal damage and include a wide variety of CNS disturbances. Tabe
dorsalis presents symptoms and signs of demyelinization of the posterior columns, dorsal roots, and
dorsal root ganglia. The Argyll-Robertson pupil, seen in both tabe dorsalis and paresis, is a small,
irregular pupil which reacts to accommodation but not to light.
CONGENITAL SYPHILIS
Intrauterine infection with T. pallidum may occur at any stage of pregnancy. Untreated maternal
infection may result in foetal loss, prematurity, neonatal death or nonfatal congenital syphilis.
The manifestations of congenital syphilis can be divided into (1) early manifestations, which appear
within the first 2 years of life, often between 2 and 10 weeks of age, that are infectious, and
resemble severe secondary syphilis in the adult; (2) late manifestations, which appear after 2 years
and are non-infectious; and (3) the residual stigmata of congenital syphilis. The earliest sign of
congenital syphilis is usually rhinitis soon followed by other mucocutaneous lesions that include
bullae (syphilitic pemphigus), papulosquamous lesions, mucous patches and condylomata lata.
The most common early manifestations are osteochondritis and osteitis, particularly involving the
metaphyses of long bones. Hepatosplenomegaly, lymphoadenopathy, anaemia, jaundice,
thrombocytopenia, and leukocytosis are also common.
Late congenital syphilis is defined as congenital syphilis which remains untreated after 2 years of
age. In perhaps 60 percent of cases, the infection remains sub-clinical, while the clinical spectrum in
the remainder resembles the acquired late syphilis in the adult. The clinical manifestations include
cardiovascular syphilis, interstitial keratitis, neurosyphilis and gummatous periostitis.
Stigmata of congenital syphilis include Hutchinson's teeth, the centrally notched, widely spaced,
peg-shaped upper central incisors, and "mulberry" molars, sixth-year molars which have poorly
developed cusps, numbering more than the usual four. The abnormal facies of congenital syphilis,
which includes frontal bossing, saddle-nose and poorly developed maxilla, may also be seen.
LABORATORY EXAMINATIONS
Dark-field examination technique
Dark-field examination is essential in evaluating cutaneous lesions, such as the chancre of primary
syphilis, or condylomata lata of secondary syphilis. The surface of the suspected ulcerated lesion
should be cleaned with saline and gauze and than gently abraded further with dry gauze, without
production of bleeding. A drop of the transudate is picked up on the surface of a glass slide, covered
with a cover-slip and examined immediately for T. pallidum with a dark-field or phase contrast
microscope by an experienced individual.
Serologic tests for syphilis
Syphilis produces two types of antibodies, the non specific "reaginic" antibody and the specific
antitreponemal antibody, which are measured by the non nontreponemal and treponemal tests,
respectively. Both tests are reactive in persons with any treponemal infection, including yaws, pinta,
and endemic syphilis.
The nontreponemal antibodies produced in syphilis are directed against a lipodal antigen that results
from the interaction of T. pallidum with host tissues. The most widely nontreponemal antibody test
for syphilis is the Venereal Diseases Research Laboratory (VDRL) slide test. Normally the reaction
becomes positive 5-8 weeks after infection (2-4 weeks after the appearance of the chancre). If
insufficient penicillin treatment is given in the incubation phase, for instance in case of concomitant
for gonorrhoea, the reaction may be delayed for several months. VDRL can be performed not only
qualitative, but also quantitatively. The reagin titer reflects the activity of the disease: a four-fold or
greater rise in titer may be seen during the evolution of primary syphilis: a persistent fall in titer
following treatment of early syphillis provides essential evidence of an adequate response to
therapy.
Because the antigen used in the non-treponemal tests is found in other tissues, it may be reactive in
persons without treponemal infection, although rarely in titers exceeding 1:8. False-positive reagin
tests are classified as acute if they become negative within 6 months and may occur during a variety
of acute infections, such as viral diseases, mycoplasma pneumonia, and malaria, and following
certain immunizations. Chronic reactions, which persist 6 months or longer, occur in intravenous
drug addiction, autoimmune diseases, and aging. In patients with a false-positive reagin test,
syphilis is excluded by obtaining a nonreactive treponemal test.
Treponemal tests
There are three standard treponemal tests: the fluorescent treponemal antibody absorption (FTAABS) test, the T. pallidum hemagglutination assay (TPHA) and the T. pallidum immobilization
(TPI) test.
The FTA-ABS shows reactivity with IgM and IgG antibodies directed against T. pallidum. A
quantitative evaluation has very little value in routine testing. Advantage of the FTA-ABS test
include detection of recent infection, 1 or 2 weeks before other assays, and high specificity and
sensitivity. In addition, determination of IgM might be useful for estimating the activity in late
syphilis. However, performance of the test requires highly trained personnel. It is time-consuming,
and reading the results is tiresome. Thus, FTA-ABS should be applied as a method for confirmation
when reactivity is detected in other assays.
The TPHA renders the most reliable results in syphilis serology among the presently available tests.
Its sensitivity and specificity is superior to the VDRL and to the FTA-ABS, except in primary
syphilis. However, the reagents are rather expensive, and internal quality control and proficiency
testing are very important, due to lack of standardization.
The TPI, in which immobilization of alive T. pallidum is induced by immune serum plus
complement, is the most specific treponemal test (almost 100%), but technically demanding and,
therefore, not available in the majority of laboratories in developing countries. TPI becomes
positive later than the other serological tests.
In summary, for practical purposes, VDRL should be used (l) for testing large numbers of sera for
screening or diagnostic purposes and (2) to assess the clinical activity of syphilis and the response
to therapy, whereas the other assays (TPHA, FTA-ABS and TPI), should be performed (3) for
confirmation of the diagnosis of syphilis in patients with positive VDRL.
EXAMINATION OF CEREBROSPINAL FLUID (CSF)
The examination of the CSF is mandatory in the presence of clinical evidence of neurosyphilis or in
any case of untreated syphilis of more than 2 years' duration. By contrast examination of the CSF in
early secondary syphilis, that has been adequately treated, is unnecessary.
CFS is considered abnormal in the presence of pleocytosis (more than 3-5 lymphocytes per ml),
elevation of protein content (total protein over 40 mg per cent), and positivity to serological tests for
syphilis.
TREATMENT GUIDELINES
Penicillin is the drug of choice for all stages of syphilis. In penicillin allergic patients, other
antibiotics, such as tetracyclines, erythromycin, and cephalosporins can be prescribed. However,
because penicillin is the only effective therapy in neurosyphilis, congenital syphilis, or syphilis
during pregnancy, allergy skin testing and eventual desensitisation is recommended in those
patients reporting a history of penicillin allergy.
Recurrence rates for a given regimen increase as infection progresses. Thus, a longer duration of
therapy is required in the later stages of the disease.
Two-twelve hours after administration of drugs with strong treponemicidal effect (e.g. penicillin), a
febrile reaction often accompanied by an aggravation of the syphilitic symptoms may occur (JarishHerxheimer reaction). The reaction occurs more frequently when early secondary syphilis is treated.
Corticosteroid given simultaneously with penicillin is indicated to reduce the risk for this reaction.
The treatment regimens recommended for syphilis are described below.
Early syphilis (Primary, secondary, and latent syphilis of less than one year's duration).
Benzathine penicillin, in a single dose of 2.4 million units intramuscularly (i.m.), cures over 95
percent of cases of primary syphilis. In secondary syphilis a second dose of 2.4 million units 1 week
after the initial dose in recommended. Because of the accelerated progression to neurosyphilis
associated with HIV infection, early syphilis in HIV-positive individuals should be treated with
penicillin G administered intravenously (i.v.) as in neurosyphilis.
Latent syphilis of indeterminate or more than one year's duration, cardiovascular, and late
benign syphilis (gumma).
Benzathine penicillin, 2.4 million units i.m. once a week for 3 successive weeks (7.2 million units
total) is the treatment of choice of latent and late benign syphilis. However, because up to 25
percent of patients with gummas will also have cardiovascular syphilis or neurosyphilis, careful
examination of the patient and CSF examination is recommended for determination of optimal
therapy. In particular, CSF examination is clearly indicated in certain situations: presence of
neurologic signs or symptoms, treatment failure, non penicillin therapy planned, serum
nontreponemal antibody titer greater than 1:32. If CSF examination demonstrates abnormal
findings, or there are signs of cardiovascular involvement, patients should be treated with the same
regimen as neurosyphilis. Quantitative nontreponemal serologic tests should be repeated at 6 and 12
months after treatment. If titers increase fourfold or if an initially high titer fails to decrease, the
patient should be revaluated for neurosyphilis and re-treated appropriately.
Neurosyphilis
Treatment with benzathine penicillin is not recommended in neurosyphilis because it does not
produce detectable drug concentration in CSF. Intravenously administration of penicillin G in doses
of 12 million units per day for 10 days or longer ensures treponemicidal concentrations of penicillin
in CSF. If CSF pleocytosis is present before treatment, CSF examination should be repeated every 6
months until the cell count is normal. If it has not decreased at 6 months, or it is not normal by 2
years, re-treatment should be strongly considered.
Pregnancy
Routine serologic testing in early pregnancy is considered cost effective in virtually all populations,
even in areas of low prenatal prevalence of syphilis.
Where the prevalence of syphilis is high, and in high-risk patients, syphilis serology should be
repeated in the third trimester and at delivery.
Pregnant women with seropositive results should be considered infected unless treatment can be
verified and sequential serology antibody titers convincingly demonstrate an appropriate response.
Treatment with penicillin is strongly recommended in pregnancy. The only potential serious side
effect is the Jarish-Herxheimer reaction, which may precipitate labour (placental shock).
Infected pregnant women with penicillin allergy should be desensitised and treated. Erythromycin is
prescribed only when penicillin desensitisation is impossible.
Newborn infants of mothers with positive VDRL or FTA-ABS tests may themselves have reactive
tests, whether or not they have become infected, because of transplacental transfer of maternal IgG
antibody. Thus, monthly quantitative VDRL should be performed on seropositive infants even if
they were born to women who were treated adequately with penicillin during therapy. In addition,
as IgM do not pass the placenta, the FTA-IgM test might be helpful to distinguish between actively
produced antibody and passively transferred antibody.
In the absence of infection, nontreponemal antibody titers should be decreasing by 3 months of age
and have disappeared by 6 months of age. Accordingly, treponemal antibodies should not persist
beyond the first year of life. Unless this is the case, the infant should be treated for congenital
syphilis, with penicillin, 50000 units/kg twice a day for 10-14 days.
It is essential to evaluate carefully infants born to seropositive mothers who remained untreated or
received penicillin treatment less than 1 month before delivery or at any time during pregnancy with
a non-penicillin regimen. Also, the offspring of mothers who did not have the expected decrease in
serologic titers after treatment need to be carefully observed. The neonate's evaluation should
include a thorough physical examination, antibody titration, CFS analysis, long-bone x-rays and
chest x-ray. These infants should be treated if they have any evidence of active disease by the above
examinations. Even with a normal evaluation, infants should be treated if their mothers have
untreated syphilis or evidence of relapse or re-infection after therapy.
Treated infants should be followed with nontreponemal antibody titers, which should disappear by 6
month of age. Treponemal tests, however, may remain positive despite effective therapy.
PREVENTION
The prevention of syphilis depends upon use of condoms, and detection and treatment of infectious
cases. The doctor treating early syphilis assumes a great responsibility towards all persons who
have had contact with an infectious patient. Persons sexually exposed to a patient with infectious
syphilis should be evaluated clinically and serologically. It may be advisable to treat
prophylactically persons who were exposed to infectious syphilis within the previous 6 weeks with
a single dose of benzathine penicillin 2.4 millions units i.m., if serologic test results are not
immediately available or compliance appears uncertain (epidemiologic treatment).
Patients who have other sexually transmitted diseases should have a serologic test for syphilis
Alternatively, treatment with the same regimen as in primary syphilis should be considered if
compliance with testing cannot be guaranteed.
REFERENCES
Brown TJ., Yen-Moore A., Tyring SK. An overview of sexually transmitted diseases. Part.
I. J Am Acad Dermatol 1999 Oct., 41 (4): 511-32.
Singh AE., Romanowski B., Shyphilis: review with emphasis on clinical, epidemiologic,
and some biologic features. Clin. Microbiol. Rev. 1999 Apr., 12 (2): 187-209.
Augenbraun MH., Rolfs R. Treatment of syphilis, 1998: nonpregnant adults. Clin. Infect.
Dis. 1999 Jan., 28 Suppl. 1:S21-8.
Gerbase AC., Rowley JT., Heymann DH., Berkley SF., Piot P. Global prevalence and
incidence estimates of selected curable STDs. Sex Transm Infact 1998 Jun., 74 Suppl.
1:S12-6.
Van Voorst Vader PC. Syphilis management and treatment. Dermatol Clin. 1998 Oct., 16
(4):699-711.
Rosen T., Brown TJ. Cutaneous manifestations of sexually transmitted diseases. Med. Clin.
North Am. 1998 Sep., 82 (5): 1081-104.
HIV-AIDS INFECTION IN DEVELOPING COUNTRIES: Clinical features, staging systems
and basic concepts of management1
Anke Bourgeois, E. Delaporte
Introduction
1. Natural History and Classification
The entire sequence of events for an average patient, without any specific treatment against HIV, is
approximately ten years from seroconversion to death. Rates of progression appear similar by sex,
race, and risk category if adjusted for quality of care. Patients with symptomatic primary HIV
infection progress more rapidly than those with asymptomatic seroconversion. Age is an important
variable: for patients aged from 16 to 24 years at seroconversion, the median time from
seroconversion to AIDS is 15 years; for those aged more than 35 years at seroconversion, it is 6
years. It is longer for HIV-2 than for HIV-1. Anyway, the individual patient variation is extensive.
Inserire figura 1
The natural history of HIV infection is divided into the following stages (figure 1):
Viral transmission: HIV infection is usually acquired through sexual intercourse,
exposure to contaminated blood or perinatal transmission.
Primary HIV infection (or "acute HIV infection" or "acute seroconversion
syndrome"): symptomatic primary HIV infection has been reported in all major risk
categories with a frequency of 50-90%. Most symptomatic patients seek medical
consultation, but this diagnosis is infrequently recognised. The time from exposure to
onset of symptoms is usually 2 to 4 weeks. Typical symptoms are fever, adenopathy,
pharyngitis, rash, myalgias or arthralgias, diarrhoea, headache, nausea and vomiting,
hepatosplenomegaly, and thrush. Laboratory findings include lymphopenia, followed
by lymphocytosis with depletion of CD4 cells, CD8 lymphocytosis, and often
atypical lymphocytes. The acute illness is generally accompanied by high level HIV
viremia and so, the patients are highly contagious.
Seroconversion: seroconversion with positive HIV serology generally takes place at
3 to 12 weeks following the viral transmission
Clinical latent period ("stage A" according to the 1993 CDC classification): during
this period, the patient is clinically asymptomatic and generally has no findings on
physical exam, except for persistent generalised lymphadenopathy (PGL), defined as
enlarged lymph nodes involving at least two non contiguous sites other than inguinal
nodes.
Early symptomatic HIV infection ("stage B" according to the 1993 CDC
classification) (table 1). Infections occurring at this stage are generally due to
"aggressive" pathogen agents.
AIDS ("stage C" according to the 1993 CDC classification) or a CD4 cell count less
than 200/mm3. More and more opportunistic infections, due to less pathogen agents,
are occurring.
Advanced HIV infection, characterised by a CD4 cell count <50/mm3.
1
This document is incomplete as many tables and figures are missing.
Table 1: 1993 revised CDC classification
Clinical categories
A
B*
Asymptomatic or PGL or Symptomatic
acute HIV infection
(not A or not C)
1/ >500/mm3
A1
B1
2/ 200-499/mm3
A2
B2
3/ <200/mm3
A3
B3
Note: all patients in categories A3, B3, C1-3 are reported as AIDS, based on the
and/or a CD4 cell count less than 200/mm3.
CD4 cell categories
* Category B: Symptomatic conditions
not included in Category C that are
a) attributed to HIV infection or
indicative of a defect in cell-mediated
immunity, or
b) considered to have a clinical course or
management complicated by HIV
infection.
Examples of B conditions include but are
not limited to:
- bacillary angiomatosis;
- thrush;
- _vulvovaginal candidiasis that is
persistent, frequent or poorly responsive
to therapy;
- cervical dysplasia (moderate or severe);
- cervical carcinoma in situ;
- _constitutional symptoms such as fever
(38.5°C) or diarrhoea more than 1 month;
- oral hair leukoplakia;
- _Herpes zoster involving two episodes
or more than 1 dermatome;
- idiopathic thrombocytopenic purpura;
- listeriosis;
- _pelvic inflammatory disease
(especially if complicated by tuboovarian abscess);
- peripheral neuropathy.
C**
AIDS indicator condition
C1
C2
C3
AIDS indicator conditions
**Category C: Indicator conditions in case definition of AIDS
(adults) 1995
- oesophageal, tracheal, bronchi or lungs candidiasis;
- invasive cervical cancer;
- extrapulmonary coccidioido-mycosis;
- extrapulmonary cryptococcosis;
- Cryptosporidiosis with diarrhea more than 1 month;
- _Cytomegalovirus of any organ other than liver, spleen or
lymph nodes;
- CMV retinitis (with vision loss)
- _Herpes simplex with mucocutaneous ulcer more than 1 month
or bronchitis, pneumonitis, oesophagitis;
- extrapulmonary histoplasmosis
- _HIV-associated demencia: disabling cognitive and/or other
dysfunction interfering with occupation or activities of daily
living;
- _HIV-associated wasting : involuntary weight loss more than
10% of baseline plus chronic diarrhea (>=2 loose stools/day
>=30 days) or chronic weakness and documented enigmatic
fever;
- Isosporis with diarrhea more than 1 month;
- Kaposi's sarcoma;
- _Lymphoma, non-Hodgkins of B-cell or unknown
immunologic phenotype and histology showing small,
noncleaved lymphoma or immunoblastic sarcoma;
- disseminated Mycobacterium avium infection;
- disseminated or pulmonary Mycobacterium tuberculosis
infection;
- Nocardiosis;
- Pneumocystis carinii pneumonia;
- recurrent bacterial pneumonia (>=2 episodes in 12 months);
- progressive multifocale leukoencephalopathy;
- recurrent non typhi Salmonella septicaemia;
- extraintestinal strongyloïdosis;
- toxoplasmosis of internal organ;
- Wasting syndrome due to HIV (as defined above)
2. AIDS definition
In the developing world, access to laboratory facilities being difficult, a clinical definition for AIDS
was necessary. A first definition "the Bangui definition" was elaborated in 1986 (Table 2), and is
still used on the field. The main goal for this definition was the epidemiological follow-up of AIDS
cases. After several validation studies, specificity for this definition was 90%, with a sensitivity of
only 60% for adults. Sensitivity and positive predictive value were poor for the paediatric
definition.
Table 2: AIDS clinical definition in Africa (WHO/Bangui definition)
For adults
Major criteria
- Weight loss >10% of baseline
- Diarrhea > 1 month
- Fever > 1 month (continuous or intermittent)
Minor criteria
- Cough > 1 month
- Generalised pruritic dermatitis
- Recurrent zona
- Oropharyngal candidiasis
- Chronic Herpes
- Generalised lymphadenopathy
Exclusion criteria
- Cancer
- Severe malnutrition
- Other aetiology
For children
Major criteria
- Weight loss >10% of baseline
- Diarrhea > 1 month
Minor criteria
- Persistent cough
- Generalised pruritic dermatitis
- Oropharyngal candidiasis
- Recurrent common infections (otitis, pharyngitis)
- Mother's confirmed HIV infection
- Generalised lymphadenopathy
Exclusion criteria
- Cancer
- Severe malnutrition
- Other aetiology
Aids diagnosis is done in presence of:
- at least 2 major criteria and at least 1 minor criteria Aids diagnosis is done in presence of :
- at least 2 major criteria and
or
- aggressive Kaposi's sarcoma or proved cryptococcal - at least 1 minor criteria
meningitis
3. Laboratory tests
HIV infection is established by detecting antibodies to the virus or by detecting the virus with p24
antigen, nucleic acid-based tests (PCR) or by culture. The standard test is the serology for antibody
detection. There are two types: HIV-1 and HIV-2 which show 40-60% amino-acid homology. HIV1 is divided into subtypes or clades designated group M (major) "A to J", group O (outlier) and
group N. Subtype O shows 55-70% homology with other M-subtypes. Most common assay is an
Elisa screening assay and a confirming Western Blot or Line Immuno Assay on EIA positive
specimens. For laboratories where Western Blot or LIA are not available, the World Health
Organisation (WHO) has recommended an alternative strategy based on a first Elisa test, as
sensitive as possible, followed by a second Elisa test more specific for the reactive samples (Figure
2).
First Elisa
(Very sensitive)
Negative
Seronegative
Second Elisa
(More specific)
Reactive
Reactive
Seropositive
Negative
Seronegative
Fig. 2 – WHO alternative flow-chart for the diagnosis of HIV infection
African specificities
1. Specificities of opportunistic infections in adults living in Africa
General signs:
Most frequent signs in Africa are diarrhea, fever and wasting, generally associated with anorexia
and asthenia. Chronic diarrhea, intermittent and recurrent, is observed in 40 to 90% of the cases,
compared to around 6% in developed countries. Long or recurrent fever without any aetiology is a
common symptom revealing HIV infection in more than 60% of the cases. In 70 to 100% of cases,
the wasting syndrome, "slim disease", is strongly suggestive of AIDS. The weight loss is
significant, with more than 10% of baseline weight.
Dermatological signs:
Isolated pruritus, localised or generalised, is persistent, and often resistant to usual drugs. Prurigo is
the most common dermatitis, occurring in more than 20% of the patients. It is generally associated
with a wasting, and is quite specific of HIV infection. Pruritus is often strong and recurrence is very
frequent. The aetiology is not known, but there might be an allergic component. Hair modifications,
as diffuse alopecia are also quite frequent. Hair is becoming fine, silky, with spontaneous
straightening. Oral candidiasis is banal and can sometimes have severe consequences, preventing
the patient to take food. Cutaneous cryptococcosis is more prevalent in Africa. It has to be
distinguished from Molluscum contagiosum. Chronic herpetic infection, with superficial and
painful ulceration is prevalent, as well as extensive and recurrent zona. Hair leukoplakia is probably
due to the Epstein-Barr virus. Venereal warts and Molluscum contagiosum are often profuse and
recurrent after treatment. Kaposi's sarcoma is less frequent in tropical areas than in the developed
world, by contrast to the endemic Kaposi's sarcoma. Clinical aspect is generally typical.
Digestive signs:
Oesophageal signs, as dysphagia or retrosternal pains, are usually associated with candida
oesophagitis. Herpes simplex virus and Cytomegalovirus can also be responsible of oesophageal
ulcerations. Diarrhea, as written above, is one of the most frequent AIDS sign in tropical areas.
Main causes are bacterial (Salmonella, Shigella...), and parasitological infections (Cryptosporidia,
Isospora, amoebiasis, giardiasis, helminthiasis). The HIV virus itself may be responsible of this
diarrhea.
Respiratory signs:
The most common pulmonary infections are banal pneumopathy (Streptococcus pneumonia,
Haemophilus influenzae...) and tuberculosis. Extrapulmonary tuberculosis seams more frequent in
HIV patients. Pneumocystosis is less prevalent than in industrialised countries.
Neurological signs:
In case of localised neurological sign, cerebral toxoplasmosis must be suspected, and specific
treatment has to be started. Same symptomatology and scanographic aspect is sometimes caused by
cerebral lymphoma, cryptococcome or tuberculome. Cryptococcal neuromeningitis, quite prevalent
in Africa, is responsible of severe headache and fever. Superior functions troubles evocates
papovavirus progressive multifocal encephalitis or HIV encephalitis. HIV or CMV myelitis are not
exceptional. Peripheral neuropathies as multinevritis or polyradiculonevritis are due to HIV.
Ocular signs:
Keenness of vision reduction corresponds usually to CMV retinitis. Vascular lesions appear also
frequent in Africa.
Adenopathies:
Except common adenopathies due to chronic lymphadenopathic syndrome, malignant lymphoma or
disseminated diseases (tuberculosis, atypical mycobacteria, Kaposi's sarcoma, deep mycosis or
leishmania) are responsible of painful adenopathies.
Systemic diseases:
Some infections present only with fever and general alteration. It is the case for minor salmonellas,
but also tuberculosis (often associated with hepatosplenomegaly), or visceral leishmaniosis,
histoplasmosis and coccidioidomycosis.
2. Specificities of opportunistic infections in children living in Africa
The asymptomatic period is shorter than in adults, and the first symptoms occur generally before the
third year of life. The prognosis is worse when disease starts earlier.
First symptoms are failure to thrive, oral thrush and chronic diarrhea. After 1 year, polyadenopathy,
hepatomegaly with or without splenomegaly, often associated with parotiditis and insterstitial
lymphoid pneumopathy were described.
The incidence rate of neurological lesions is high, with psychomotor delay, pyramidal syndrome,
ataxia, extrapyramidal rigidity, convulsions.
3. African specificities concerning antiretroviral treatment
In Africa, clinical particularities have some therapeutic implications. Tuberculosis is quite frequent,
and specific therapy against it complicates ARV prescription and contra-indicates some protease
inhibitors. Viral hepatitis B and C are also very prevalent in all sub-Saharan areas and pose some
problems first for protease inhibitors, especially ritonavir, second for hepatotoxic nucleosides such
as didanosine, zalcitabine and stavudine. The frequency of glomerular lesions, more or less severe,
makes the use of indinavir, which may increase the creatinine rate, difficult. Anaemia, often well
tolerated, is a limiting factor for the prescription of zidovudine, and also cotrimoxazole.
Regimen's choice is limited by the presence of HIV-2 in West-Africa and of HIV-1 group O,
especially in Cameroon. In fact, non nucleoside reverse transcriptase inhibitors are ineffective on
these viruses. It is necessary to evaluate other drugs against HIV-2. The first results with protease
inhibitors are promising for HIV-2 and HIV-1 A and E subtypes. However, G subtype appears less
sensitive in vitro to the protease inhibitors. Nucleoside analogues seam fully effective on the whole
subtypes.
Psychosocial and medical care of persons living with HIV
1. Psychosocial care
Psychosocial care is as important as medical care. If possible, it is better to have a counsellor
specifically trained for the HIV counselling. The first effort to do with people living with
HIV/AIDS is to make them accept their serologic status and to make them understand how to live
positively with HIV/AIDS. Then, it is essential to convince them of the importance of a regular
follow-up. The counsellor has to explain how to prevent reinfection and sexual or blood
transmission. Informations about hygiene, nutrition, sport... have to be given.
2. Medical care
Regular follow-up allows for screening and early diagnosis and treatment of many opportunistic or
non opportunistic diseases. Tuberculosis is one of the commonest infection occuring in Africa,
which is essential to treat as early as possible. Even without antiretroviral treatment, a regular
follow-up will improve the survival and quality of life of HIV/AIDS people. Furthermore, it will
also help to prevent the spread of the epidemic.
a - Prophylaxis by antimicrobial agents
Cotrimoxazole: In Europe and North America, pulmonary pneumocystosis and cerebral
toxoplasmosis incidence were reduced by the use of cotrimoxazole, when the CD4 cell count are
below 200/mm3, and if the haemoglobin rate is more than 7g/dl and the creatinine rate below 130
mM/l. However, 15% to 30% of the patients do not tolerate this prophylaxis (cutaneous rashes,
neutropenia, hepatic or renal toxicity). This toxicity is partially dependant on the dose. Even if the
bacterial environment is quite different in Africa, prophylaxis with cotrimoxazole should be
prescribed to prevent Pneumocystis carinii (even if it is less frequent), Isosporis belli (one of the
most common aetiology for diarrhea), recurrent bacterial pneumopathies and Salmonella
bacteriemia. It seems that it is necessary to give this prophylaxis for patients with a CD4 cell count
below 300/mm3.
Recommended regimen are:
Cotrimoxazole 800/60 mg or 400/80mg po daily or Cotrimoxazole 400/80 mg po 3 x/week
Mycobacterium tuberculosis prophylaxis: tuberculosis is one of the commonest and earliest
opportunistic infection in Africa. It is therefore important to prevent it. Some studies in Haïti,
Uganda and Zambia showed that tuberculosis incidence decrease using isoniazid. However, these
results are not confirmed at long term because of reactivation or reinfection. Moreover, it appears
very difficult, from the point of view of costs and adherence, to propose life-long prophylaxis.
Furthermore, it could lead to the emergence of drugs resistant strains. By contrast, active screening
for tuberculosis among seropositive patients is strongly recommended and cost effective.
In case of personal or familiar tuberculosis history, a prophylaxis could be initiated:
Preferred regimen are:
– INH 300 mg + pyridoxine 50 mg po qd x 12 months
– INH 900 mg + pyridoxine 50 mg 2 x/week x 12 months
Alternative regimen are:
– Rifampicin 600 mg po qd x 12 months
– Rifampicin 600 mg/day plus pyrazinamide 20 mg/kg/day x 2 months
– Rifampicin 600 mg 2x/week plus pyrazinamide 50 mg/kg 2x/week x 2 months.
b - Prophylaxis by immunisation
Principles: HIV-infected persons should not receive live virus or live bacteria vaccines. Killed or
inactivated vaccines pose no danger to immunosuppressed patients. Symptomatic HIV-infected
persons have suboptimal responses to vaccines, hence all single-dose vaccines should be given as
early as possible in the course of HIV infection to obtain an optimal immune response.
Recommendations: Pneumococcal vaccine is recommended as high priority, with revaccination at 5
years. Tetanus-diphteria vaccine should be administered as usual by recommended for adults, every
ten years. Hepatitis B vaccine could be used if necessary, i-e in presence of susceptible injection
drug users, sexually active gay men, prostitutes, sexually active heterosexual men and women with
STDs or more than 1 partner in the last 6 months, and household or sex contacts of HBsAg carriers.
The following vaccines are contraindicated: measles, mumps, rubella, BCG, oral polio, varicellazoster, yellow fever.
c - Management of opportunistic diseases in HIV/AIDS adults
The WHO has recommended some algorithms for the management of HIV infected patients. The
main are described below in a schematic format (for chronic diarrhea, respiratory manifestations,
headache and fever). Table 3 summarizes treatment regimens recommended for opportunistic
infections, table 4 for non-infectious diseases.
Insert 4 management schemes and tables 3 & 4
d - Management of children living with HIV/AIDS in Africa
Primary prevention: Materno-foetal and breast-feeding transmission can be prevented as previously
described. Security for blood products and sterilisation of all materials must be enhanced,
improving the staff training and the furniture purchase.
It is also very important to improve the care of pregnant women because the severity of maternal
infections is directly associated to the materno-foetal transmission rate and the severe clinical forms
of children.
Secondary prevention: It is necessary to treat systematically every infection, even if it appears mild,
particularly for cutaneous, nose-and-throat and bronchopulmonary infections, as well as digestive
candidiasis. Early diagnosis and adequate treatment may reduce mortality due to HIV.
Cotrimoxazole prophylaxis has to be strengthened, because of the increasing risk for pneumocystis
carinii infection, but also to protect against other bacterial infections. This prophylaxis can be given
daily in the first months. The recommended dose is 25 mg/kg/day.
Tuberculosis prophylaxis for children living with infected adults is recommended with the
following regimen: Rifabutine (Ansatipine* 150mg caps) 10 to 20 mg/kg/day once.
Supplementation with vitamin A shows a benefit, especially because of a reduction of diarrhea
episodes. Recommended doses are: 50 000 UI at 1 and 3 months, 100 000 UI at 6 and 9 months,
200 000 UI at 12 and 15 months. The common vaccination program has to be followed, especially
for the BCG at birth:General measures, as nutritional surveillance and food hygiene, have to be
reinforced.
Table 5: Vaccination calendar proposed by the WHO
Birth
BCG + oral polio
6 weeks
Diphteria, tetanus, whooping cough + oral polio
10 weeks
14 weeks
9 months
Measles
1 year
Diphteria, tetanus, whooping cough and polio booster
Antiretroviral therapy
1. Antiretroviral therapy in adults
a - Introduction
The introduction of new antiretroviral drugs (ARV) in industrialised countries has significantly
improved the survival of HIV-infected persons. The effects of ARV consist of a reduction of the
plasmatic viral load, and, more moderately, of the biological fluids or lymph nodes viral load. This
viral load decrease is associated with a partial restoration of the circulating CD4 lymphocytes.
Moreover, the use of AZT during pregnancy allows a very important reduction of perinatal
transmission, in the absence of breast-feeding.
Factors related to the ARV cost and the need of a relative advanced technical equipment have
limited the diffusion of these drugs in the developing world. Nevertheless, ARV should be available
for every HIV-infected person, who is entitled to receive it according to the scientific knowledge.
b - Recommendations
The first step before introducing ARV is to prevent, diagnose and cure opportunistic infections,
particularly tuberculosis. ARV should only be prescribed if adherence and correct patient follow-up,
including communities and persons living with HIV/AIDS associations, are assured. The
serological diagnosis must be reliable and laboratory facilities available. Monotherapy has to be
proscribed because of rapid resistance emergence. Whenever possible, triple therapy should be
used, both for children and adults. ARV treatment for women should be a priority. Treatment must
be established for an indefinite duration. Indications proposed for developing countries according to
clinical situations, CD4 cell count and viral load are summarized in table 6.
Table 6: ARV indications proposed for developing countries
Clinical situation
CD4 cell count
Viral load
< 350/mm3
Any value
350-500/mm3
Undetermined
Asymptomatic
<10 000
<10 000
>500
Undetermined
<10 000
>10 000
Undetermined
Undetermined
Symptomatic
Any value
Any value
Terminal stage
Any value
Any value
ARV treatment
Yes
To be discussed*
Yes
No
To be discussed*
Yes
No
No
Yes
To be discussed (costbenefit ratio
*To be discussed, taking account financial means
c - Therapeutic strategies
Treatment strategies should be regularly adapted to the results of ongoing trials.
Nucleoside analogs bitherapy:
Among associations with zidovudine (AZT), the most current are zidovudine/didanosine
(ddI) and zidovudine/zalcitabine (ddC). Zalcitabine is recommended for early stages.
The association of zidovudine with lamivudine (3TC) is interesting because of a longer delay for
AZT resistance emergence.
Among associations without zidovudine (AZT), Stavudine (D4T) with ddI, and D4T/3TC are
proposed because of their tolerance and efficacy.
Encouraging but discordant results were obtained with ddI/hydroxyurea. The gain is modest for
severe haematology toxicity.
Nucleoside analogs and protease inhibitors bitherapy: The efficacy is high but lower than that of the
correspondent tritherapy :
- zidovudine (AZT) and saquinavir (SQV) < AZT-ddC-SQV
- zidovudine (AZT) and indinavir (IDV) < AZT-3TC-IDV
Other bitherapies, such as stavudine/saquinavir or stavudine/nelfinavir are under evaluation.
Tritherapies including 2 nucleoside analogs and 1 protease inhibitor: It is the best association in
terms of extended virological and immunological efficacy. After 6 to 12 months of treatment, the
mean viral load decrease is from 1.5 to 2 log. In 10 to 15% of the cases, early intolerance is noted.
Furthermore, after 10 to 12 months, there are 10 to 20% of immunovirological failure.
Tritherapies including 3 nucleoside analogs: Some associations (AZT-ddI-3TC and D4T-ddI-3TC)
are under evaluation, notably for the treatment at seroconversion. The advantage is that of
significant viral load reduction without the side effects and drug interactions (rifampicine) of
protease inhibitors.
Associations with protease inhibitors: Some are under study, especially ritonavir and saquinavir.
The goal is to block (for example with ritonavir) the p450 cytochrome with lower doses and so to
increase the action of the second protease inhibitor. The 2 protease inhibitors have to be associated
with 1 or 2 nucleosides analogs. These regimens are limited to patients at late stages who have
already received several drugs.
Table 7: different associations, listed by decreasing interest
2 nucleosidic inhibitors
One of the 5
1-Triple therapy with protease inhibitor
AZT-ddI
possibilities
AZT-ddC
AZT-3TC
D4T-ddI
D4T-3TC
2–Multitherapies less strong and less
studied
– Triple therapies with saquinavir
– Triple therapies with a non
nucleoside reverse transcriptase
inhibitor
3 - Triple therapies with 3 nucleoside
analogs
4. Bitherapy with 2 nucleoside analogs,
especially during anti-tuberculosis
treatment
(Clinical interest validated)
protease inhibitors
One of the 3
Indinavir
possibilities
Nelfinavir
Ritonavir
- Waiting for the EOF
capsules
-Only one association (AZTddI-nevirapine) is validated
Some trials in course: –
AZT-ddI-3TC
– D4T-ddI-3TC
AZT-ddI and AZT-ddC
d - Associations which are contraindicated
– Stavudine/zalcitabine (D4T/ddC): toxicity risk
– Zidovudine/stavudine (AZT/D4T): antagonism, toxicity
– Didanosine/zalcitabine (ddI/ddC): non coherent
– Didanosine/lamivudine (ddI/3TC): non validated
– Zalcitabine/lamivudine (ddC/3TC): non validated
– Indinavir/saquinavir (IDV/SQV): antagonism
e - Tuberculosis treatment associated with antiretroviral treatment
Patient never treated with Protease Inhibitor (PI):
Quadritherapy during 2 months followed by bitherapy (isoniazid + rifampicin) for 4 months.
At the end of this treatment, it is possible to start with PI.
Patients already receiving PI:
– Stop PI during the whole anti-tuberculosis treatment. The tuberculosis is then optimally treated,
but emergence of resistant virus can appear, and the viral load can increase.
– Stop PI during the period of "induction" treatment (isoniazid, rifampicin, ethambutol,
pirazinamid, 2 to 3 months), followed by isoniazid and ethambutol 16 months long, restarting PI.
The short interruption of PI will prevent resistance emergence, but the anti-tuberculosis treatment
will be long and sub optimal.
– Continue the PI, using indinavir (800 mg x 3/day). Quadritherapy using rifabutin (150 mg/day)
instead of rifampicin for 4 months, followed by 6 months of isoniazid + rifabutin. Such regimen
must be further evaluated.
f - Change of ARV
It is based on any clinical, immunological or virological progression.
Patient with prior monotherapy: a bitherapy or better a triple therapy must be prescribed, using
preferentially drugs other than those used before.
Patient with prior bitherapy: if clinical or immunological progression is observed, the best is to
change the 2 nucleoside analogs and, if possible, to associate a protease inhibitor.
2. Antiretroviral therapy by pregnant women
a - Mother to child transmission
In countries where breast-feeding is rare, the estimated risk of perinatal transmission for HIV-1 is
15 to 20%. Studies conducted in african countries where breast-feeding is very common show an
increased risk, from 25 to 30%. For HIV-2, the perinatal transmission rate is only 1 to 2%.
When there is no breast-feeding, HIV is principally transmitted during the latest phase of the
pregnancy and during the labour. In Africa it has not been demonstrated that caesarean section
could reduce the transmission rate. In case of breast-feeding, the most common situation in the
developing world, the transmission is distributed as following: for a global rate of 25 to 30%, 25 to
30% of the transmission happens before 28 gestation weeks, 50 to 60% between the late pregnancy,
the labour and the early breast-feeding period (the first week). Post natal transmission can continue
for long time, and represents 15 to 20% of the global risk for HIV-1 transmission. Studies have also
shown that the risk of transmission is increased by a CD4 count below 200/mm3, maternal vitamin
A deficiency, malaria and breast abscess.
b - Prevention of mother to child HIV transmission
Before 1996, WHO and UNICEF recommended the breast-feeding in the developing world, taking
into account its benefits for the children. In 1996, UNAIDS recommended individual strategies,
based on the specific family conditions, in countries where breast-feeding promotion is the rule.
Monotherapy with AZT was evaluated in a double blind therapeutic trial against placebo, which
was interrupted in 1994 when the first intermediary analysis showed a reduction of the transmission
rate from 25.5% to 8.3%. Several studies with AZT simplified regimen are under evaluation. Other
trials evaluating preventive measures are undergoing: genital desinfection during the labour,
vitamin A supplementation, passive immunisation.
c - Antiretroviral recommendations
In case a pregnant woman who can afford to buy ARV drugs, medical staff has to propose a
screening test for HIV, to advise against breast-feeding and to treat as follows:
- Before delivery: AZT (300 mg 2x/d, 200 mg 3x/d or 100 mg 5x/d) initiated at 14-34 weeks of
gestation and continued to onset of labour
- During labour: IV AZT (loading infusion of 2 mg/kg IV for one hour followed by continuous
infusion 1 mg/kg per hour until delivery
- Infant: AZT for the new-born (AZT syrup at 2 mg/kg every 6 hours) for the first 6 weeks of life
beginning 8-12 hours after birth.
More recent advances in antiretroviral therapy have raised the new issue of antiretroviral therapy of
the pregnant women as well as antiretroviral prophylaxis to reduce the risk of perinatal
transmission. With regard to dosing requirements, only three drugs have undergone
pharmacokinetic analysis in pregnancy: AZT, 3TC and nevirapine. All three are well tolerated and
show pharmacokinetic data similar to those for non-pregnant subjects. There are few studies that
address the safety of many of these drugs in the neonate except for anecdotal clinical experiences,
limited clinical trials, and animal toxicity studies.
3. Antiretroviral treatment after exposure of health care workers
In case of blood, bloody body fluids, semen or vaginal secretions exposure, skin should be first
washed with soap and water, mucous membranes should be flushed with water.
In case of high risk exposure, the association AZT/3TC should be offered. A protease inhibitor
(indinavir or ritonavir) has to be added in case of major danger (deep injection, contaminating
patient at a late stage). These regimens have to be continued for 4 weeks.
4. Antiretroviral treatment by children
a - Introduction
Materno-foetal transmission, breast-feeding, blood transfusion and sexual abuses are the main
routes for the HIV transmission in the developing world. As for adults, prevention and prophylaxis
are the most important means to fight against AIDS, but antiretroviral therapy, when it is accessible,
can also be proposed in certain situations.
b - Antiretroviral drugs
c - Indications
Children under 2 years:
Children infected during pregnancy or at labour, considered as in the primo-infection stage, could
be treated by ARV, particularly if they present signs of disease. Furthermore, in Africa, mortality is
very high during the first 2 years of life. Breast feeding is also the most common situation,
extending the contamination period after the birth. Early diagnosis is difficult because of the lack of
appropriate laboratory equipment (for viral cultures or PCR).
Diagnosis could be based on p24 antigenemia or serological conversion after 10 months, when
breast-feeding was interrupted at least 3 months before.
Older children
Symptomatic children must be treated, particularly those presenting clinical manifestations showing
an important immunodeficiency (as a zona). Treatment regimens follow the same principles as for
adults. Bitherapy (2 NRTI) can be proposed, and triple therapy must be initiated in case of clinical
or biological progression under bitherapy.
BIBLIOGRAPHY
WHO/GPA. Clinical management guidelines for HIV infection in adults. Preliminary
document, April 1991. J.E. Malkin. Prise en charge clinique de l'infection par le VIH en
Afrique. Ch 44.
Ch. Katlama et M. Jouan. Prophylaxie des infections opportunistes au cours de l'infection
par le VIH. Méd Mal Infect. 1996 ; 26 : 742-51
L. Belec, FX Mbopi Keou, N. Cancre et al. Définition clinique OMS/Bangui du sida en
Afrique Noire. Bilan 1986-1991. Ann. Med. Interne, 1992; 143, n° 3, 204-13.
International AIDS society. Place of antiretroviral drugs in the treatment of HIV infected
people in Africa. AIDS 1999 ; 13: IAS1-3.
J. Dormont. Stratégies d'utilisation des antirétroviraux dans l'infection par le VIH. Rapport
1998. Médecine-Sciences, Flammarion.
M. Gentilini. Médecine tropicale. Médecine-Sciences, Flammarion. Ch 8.
J.G. Bartlett. 1998 Medical Management of HIV infection. Johns Hopkins University
School of Medicine, Baltimore, Maryland.
D. Sharpstone, B. Gazzard. Gastrointestinal manifestations of HIV infection. Lancet 1996;
348: 379-83.
D. Greenspan, J.S. Greenspan. HIV-related oral disease. Lancet 1996; 348 : 729-33.
Association between HIV and Tuberculosis: Technical guide. Bulletin of PAHO 1993;27(3):
297-310.
R. Miller. HIV-associated respiratory diseases. Lancet 1996; 348: 307-12.
Cutaneous Manifestations Of HIV Infection
P. Fiallo, S. Talhari
Diseases of the skin and mucous membranes were among the first recognized clinical
manifestations of acquired immuno deficiency syndrome (AIDS) in the early 1980s. Since then
hundreds of disorders occurring on the skin and mucosa have been reported in human
immunodeficiency virus (HIV) disease. There is no skin condition reported so far that is specific for
HIV infection. However, the practice of dermatology has been profoundly changed by the HIV
epidemic. During the course of HIV infection, skin diseases tend to be more chronic, more severe,
more resistant to conventional treatments, and often display unusual clinical presentations,
compared to those seen in the non-HIV infected population. In addition, the HIV epidemic has
brought to attention previously rare and poorly understood skin diseases, such as bacillary
angiomatosis, Kaposis's sarcoma and eosinophilic folliculitis.
It is estimated that more than 90% of HIV-infected patients develop skin or mucous membrane
disorders at some time during their infection. The knowledge of skin manifestations in HIV
infection, thus, is fundamental to medical workers, particularly to those practising in developing
countries. Identification of skin manifestations such as bacillary angiomatosis, Kaposi's sarcoma,
oral candidiosis. And hairy leucoplakia, may provide a clue for diagnosing a previously undetected
HIV-positive status. On the other hand, diagnosing skin disorders such as refractory candidiasis,
disseminated molluscum contagiosum or ulcerating herpes simplex, can be a sensitive and useful
measure by which the progression of HIV infection can be monitored.
Cutaneous Signs Of Primary HIV Infection
Although primary HIV infection is commonly asymptomatic, an acute transitory febrile illness
lasting 1-2 weeks is sometimes identifiable. This flu-like syndrome is accompanied with nonspecific skin lesions in 75% of patients. Cutaneous signs of primary HIV infection include macularerythematous lesions on the trunk, roseola-like or morbilliform eruptions in the upper body or face
and papulosquamous manifestations of the palms and soles. Mucosal involvement in the form of as
enamthem, oropharyngeal or genital erosions has also been reported.
Secondary Mucocutaneous Signs Of HIV Infection
Infections
Viral Infections
Herpes Simplex
Oral and anogenital herpes simplex virus (HSV) infection is common in HIV disease. HSV
infection, presenting as a recurrent self-healing blistering eruption that is clinically and
morphologically indistinguishable from that seen in immunocompetent individuals, may occur at
any stage of HIV infection. As the immunodeficiency progresses, HSV infection become persistent
and progressive. Erosions enlarges and deepen into painful, non-healing ulcers, (fig. 1).
Figure 1: Herpes Simplex
Varicella-Zoster
Herpes zoster is common in HIV patients and may be the first sign of immunosuppression.
However, herpes zoster is not a reliable sign of profound immunodeficiency because it can occur at
any stage of HIV disease. While in the majority of cases the disease runs a typical course with a
vesicular eruption in a dermatomal pattern, some cases develop severe haemorrhagic and necrotic
lesions that may extend over several dermatomes, and eventually disseminate all over the body.
These lesions are varicella like, in most of the patients with disseminated zoster (fig. 2).
Hemorragic and venotic lesions in young-patient are suggestive of HIV infection.
Molluscum Contagiosum
Characteristic lesions, which appear commonly on the face and in the genital regions, include skincoloured umbilicated papules with one or more central hyperkeratotic pores (fig. 3). The clinical
course of mollusca contagiosa in the HIV infected patient differs significantly from that in the
normal host as immunodeficiency progresses. Individual lesions can grow in size, up to 10 mm, and
merge into larger lesions that become disfiguring when located on the face. Molluscum
contagiosum on the face is unusal in adults. This is suggestive of HIV. Widespread lesions are
common and highly characteristic of HIV disease, and must be differentiated from cryptococcal
histoplasmosis and P. marneffei cutaneous lesions.
Fig. 3 – Molluscum Contagiousum
Human Papillomavirus (HPV)
In HIV-infected individuals the incidence of facial and intraoral warts is increased and anogenital
lesions may be florid. However, they do not usually constitute a great problem in these patients.
Intra-epithelial carcinoma has been reported to develope even without HPV types usually associated
with malignancy.
Bacterial Infections
Staphylococcus Aureus
Staphylococcus aureus is the most common bacterial pathogen in HIV disease. Apart from
secondary infection of underlying dermatoses, such as scabies, eczematous dermatititis or herpetic
ulcers, primary staphylococcal cutaneous and soft tissue infections include impetigo, bullous
impetigo, ectyma, folliculitis and cellulitis.
Mycobacteria
Mycobacterium tubercolosis and atypical mycobacteria are important causes of systemic infection
in HIV disease. The cutaneous manifestations of these infections are not characteristics and include
erythema, swelling, painful nodules, ulcers, hyperkeratotic plaques, or subcutaneous abscesses.
Syphilis
Syphilis frequently coexists with HIV infection. Most cases of syphilis occurring in HIV patients
are clinically typical. However, individuals with long-standing HIV infection and some degree of
immunodeficiency may experience an altered course of syphilis: the usually painless chancre of
primary syphilis may become painful due to secondary infection; seroconversion may be delayed,
so that secondary syphilis erupts in the absence of a positive test for treponema antibody; in some
patients the VDRL titre may be very high. Secondary syphilis (fig. 4) may present as "lues
maligna", a rare form characterized by pustules, nodules, ulcers and necrotizing vasculitis
ophthalmologic manifestations may be frequently reported; the disease may rapidly progress to
neurosyphilis or tertiary syphilis within the first year of infection.
Fig. 4 – Secondary syphilis
Bacillary Angiomatosis
This vascular proliferation is caused by organisms of the genus Bartonella. The disease is
characterized by vascular tumors that disseminate systematically. Cutaneous lesions are the most
commonly recognized manifestations of bacillary angiomatosis and may be found in up to 55% of
patients. They consists of violaceous to red papules, often in large numbers and very widespread,
that bleed profusely if injured. The papules may enlarge to nodules, resembling cutaneous lesions
due to Kaposi's sarcoma. Apart from Kaposi's sarcoma, the differential diagnosis includes pyogenic
granulomas, angiomas and disseminated crytococcosis.
Fungal Infections
Systemic mycoses as well as superficial/muco-cutaneous mycoses are commonly encountered in
AIDS because the defective immune system resulting from HIV infection provides an environment
suitable for mycotic pathogens.
Common systemic mycoses in patients infected with HIV include cryptococcosis, histoplasmosis
and sporotrichosis. Skin and mucosal lesions are relatively frequent in these infections. These
include painless reddish papules and nodules (Cryptococcus neoformans), widespread
maculopapular rash, necrotic papules and ulcers (Histoplasma capsulatum fig. 5) and papulonodular
eruptions (Sporotrix schenkii). Although rather non specific, these cutaneous manifestations permit
easy access to tissue for biopsy and may provide valuable diagnostic clues.
Candida spp, Dermatophytes and Malassezia furfur infections are the most common pathogens
responsible for superficial mycoses in HIV infected patients. Their clinical course is often atypical,
and can be masked by other infections.
Fig. 5
Candidiasis
Candida spp are the most common cause of fungal infections in patients with AIDS. Candida
albicans is the most common species, but other species include C. tropicalis, C. kruzei and C.
glabrata.
Candidiasis may affect both oral mucosa and skin. Oropharyngeal candidiasis presents in four
different patterns: l) pseudomembranous (thrush) characterized by whitish or yellowish plaques
within the oral cavity; 2) erythematous or atrophic, characterized by bright red erosions or ulcers
within the oral cavity; 3) hyperplastic, characterized by exuberant yellowish-whitish plaques; and 4)
angular cheilitis, characterized by crusting, fissuring and erythema at the angles of the mouth.
Skin involvement includes intertrigo, folliculitis, paronychia, and/or onychomycosis.
All patients presenting with mucocutaneous candidiasis and having no other predisposing factors
such as prolonged use of systemic antibiotics or corticosteroids, diabetes, poor dental hygene or
history of immunosuppression, should be evaluated for HIV disease.
Mucocutaneous candidiasis in untreated HIV-infected individuals heralds rapid progression to
AIDS.
Dermatophyte Infections
Over a third of HIV patients have superficial infections with ringworm fungi. Some of these
infections may be chronic and unusually widespread, and the morphology may be altered by
enhancement or diminuition of the inflammatory component. Involvement of the soles can give rise
to diffuse hyperkeratosis. Nail involvement is common often affecting all finger nails (fig. 6) and
toe nails, and may occur in an unusual form featuring proximal whitening of nail plate. It is
suggestive of AIDS, also the occurence of subungual wilhist.
Fig. 6
Pityriasis Versicolor
This condition may be unusually extensive and persistent in advanced immunosuppression.
Arthropod Infestations
Scabies
Scabies must always be in the differential diagnosis of pruritus in HIV-infected patients. As
immunodeficiency progresses, HIV-infected patients are more liable to experience crusted
(Norwegian) scabies in which the number of infesting mites can increase enormously (fig. 7). In
these patients generalized scaling-to-marked hyperkeratosis must be differentiated from psoriasis
vulgaris and keratoderma blenorragica of Reiter's syndrome.
Fig. 7
Demodicidosis
Folliculitis due to Demodex folliculorum may cause an itchy papular eruption in HIV patients.
Affected areas include head, neck, trunk and arms.
Tumors
Kaposi's Sarcoma
The clinical course of Kaposi's sarcoma (KS) in patients with AIDS may be localized or aggressive
with widespread cutaneous and systemic lesions. Skin lesions include red, purplish or browncoloured macules, nodules or plaque (fig. 8). Lesions may resemble dermatofibromas, bruises,
pyogenic granulomas, insect bytes or nevi. Any part of the body surface may be affected but
common sites are trunk, legs, face and oral cavity (fig. 9 and 10).
The prognosis has improved with the recent AIDS protocol treatment.
Fig. 8
Fig. 9
Fig. 10
Other Hiv-Associated Malignancies
Lymphomas occasionally produce skin nodules. Intra-epithelial carcinoma has occurred in
association with warts in the anogenital region. Intraoral squamous carcinoma, mostly on the
tongue, has been reported.
Miscellaneous Disorders
Seborrhoeic Dermatitis
The seborrhoeic dermatitis is one of the commonest and earliest skin changes in HIV disease, most
patients having clinical findings at some point during their course of disease (fig. 10). Initially
morphologically typical, it may become unusually widespread over scalp, face, trunk and upper
outer arms with atypical nummular eczematous lesions.
Fig. 11
Psoriasis Vulgaris
These can begin with HIV disease, or pre-existing psoriasis may become severe with widespread
guttate, plaque or pustular lesions or erythroderma.
Reiter’s Syndrome
The prevalence of Reiter's syndrome is increased in HIV-infected patients compared with the
prevalence in healthy population. Articular symptoms can precede onset of immunodeficiency, and
often may be the first manifestation of HIV infection. Mucocutaneous manifestations include
urethritis, conjuntivitis, keratoderma, balanitis and oral ulcers.
Ichthyosiform Dermatosis
Xerosis is seen in up to 30% of HIV-infected individuals. The severity of ichthyosiform dermatosis
do not correlate with the degree of immunodeficiency, but it seems to be directly related to the HIV.
It is more pronounced in severely ill patients.
Papular/Pruritic Eruptions
Pruritus is a common complaint in patients with advanced HIV disease. Although pruritus may
occur without lesions, most patients with pruritus have associated primary and secondary cutaneous
findings. Most of these eruptions are not specific for HIV disease; they include pyogenic and
bacterial infections, Pityrosporum folliculitis, demodicidosis, heightened response to insect bites
and prurigo singlex or nodularis. Eosinophilic folliculitis, although it has been reported in HIVnegative individuals, is the only pruritic eruption that is regarded as a marker of advanced HIVinfection.
Eosinophilic Folliculitis
Eosinophilic folliculitis is a chronic, pruritic, culture-negative folliculitis. Clinically, it is
characterized by multiple follicular and non-follicular, urticarial papules, most commmonly
involving the upper trunk, face, and proximal extremities. Although HIV-related eosinophilic
folliculitis shares some similarities to Ofuji's disease, it is now regarded as a distinct dermatosis
associated with advanced HIV infection.
Adverse Cutaneous Drug Reactions
Cutaneous drug reactions are common in AIDS especially with sulphonamides, which in over 50%
of cases cause a maculopapular eruption within 7-12 days of the first intake. There may also be
urticaria, erythema multiforme and systemic reactions including fever, leucopenia,
thrombocytopenia, hepatitis and nephritis. Rashes with some other drugs, mostly antibiotics, are
also more frequent than expected.
Oral Lesions
All individuals with HIV disease experience disorders of the oral mucosa during the course of their
illness. Some disorders occur early in the course of HIV disease and their detection on routine
physical examination should raise the issue of HIV serotesting. Oropharyngeal candidiasis is the
most common finding, being present in more than 90 percent of untreated HIV-infected individuals.
Apart from oral localization of the previously described cutaneous disorders, two conditions are
relatively distinctive: oral hairy leukoplakia and aphtous ulcers.
Oral Hairy Leucoplakia
These usually asymptomatic, vertically ribbed, keratinized plaques are characteristically situated
along the lateral borders of the tongue, but more extensive involvement of the oral mucosa can
occur. Proliferation of EpsteinBarr virus in the epithelium is thought to be responsible, whereas
candidiasis may coexist but probably is not the cause.
Aphtous Ulcers
Compared to the minor recurrent aphtous ulcerations occurring in the immunocompetent
populations, aphtous ulcers tend to be larger (>1.0 mm in diameter) in persons with advancing HIVinduced immunodeficiency. They consists of painful ulcerations of the oral mucosa, hypopharynx,
and esophagous. In some cases ulcerations may be very extensive, often involving the tongue,
gingiva and lips, and pain upon swallowing may be so severe that rapid weight loss ensues.
REFERENCES
Aftergut K., Cockerell CJ., Update on the cutaneous manifestations of HIV infection.
Clinical and pathologic features. Dermatol. Clin. 1999 Jul.; 17 (3):445-71.
Barton JC., Buchness MR. Nongenital dermatologic disease in HIV-infected women. J Am
Acad Dermatol. 1999 Jun.; 40 (6 pt 1): 938-48.
Porras B., Costner M., Friedman-Kien AE., Cockerell CJ. Upadate on cutaneous
manifestations of HIV infection. Med. Clin. North Am 1998 Sep. 82 (5):1033-80.
Wright SW., Johnson RA. Human immunodeficiency virus in women: mucocutaneous
manifestations. Clin. Dermatol. 1997 Jan.-Feb.; 15 (1):93-111.
Greenspan D., Greenspan JS. HIV-related oral disease. lancet 1996 Sep. 14; 348
(9029):729-33.
Tschachler E., Bergstresser PR., Stingl G. HIV-related skin diseases. lancet 1996 Sep. 7;
348 (9028):659-63.
HIV-STD INTERACTIONS
J.P. Coulaud
A - Links Between HIV and other STDS
Both HIV and the traditional STDs share a common mode of transmission through sexual contact,
and the same behavioural risk factors. It makes sense that there might be some connection between
HIV infection and other STDs. In 1984, health authorities in Kinshasa, Zaire, reported first that
50% of AIDS cases had a past history of STD compared to 14% of controls. A past history of STDs
was reported in 35% (Tanzania) and 70% (Rwanda) of HIV/AIDS infected persons ( 1-2).
On the other hand, the proportion of HIV seropositive among STD clinic attenders compared to the
overall population was 9.2% vs. 4.4% in Tanzania, 29% vs. 9% in Zambia, 18.5% vs. 4.3% in
Burundi and 30% vs. 1.4% in rural Rwanda, respectively (2). The association between STDs, and
HIV seemed stronger with increasing episodes of STD infection (3). The first studies have been
performed in prostitutes and pregnant women, the latter being a marker of the young sexually active
"general population".
Three mechanisms are mentioned in the literature which explain in what manner STDs and HIV
may interact with one another. The first is termed "epidemiological synergy" (4). Under this
mechanism, co-infection with HIV prolongs or increases infectiousness of the person with the STD.
The STD further facilitates HIV transmission, at the community level. The two infections, mutually
reinforce one another. This mechanism may be applicable to chancroid, genital herpes and syphilis.
The second mechanism acts in a unidirectional way in which the STD may promote HIV
transmission but HIV infection does not cause an increase in the prevalence of the STD.
Gonorrhoea, chlamydia and trichomaniasis may behave in this fashion.
The third mechanism acts also in a unidirectional way representing the traditional opportunistic
infection pattern. HIV infection may alter the natural history of the STDs. Genital warts and
hepatitis B or C may be implicated here.
There are biological explanations for these three mechanisms. Under the theory of "epidemiological
synergy", there is increased presence of lymphocytes and macrophages when one is infected with
some STDs. These cells are targets of HIV infection. In the HIV/negative individual with genital
ulceration, there are more target cells which may be infected. In the HIV-seropositive person with
genital ulceration, the ulcerations are further exacerbated by HIV infection and their pathogens are
passed on to the partner. HIV has been isolated from the surface of genital ulcers and from cervical
and vaginal secretions (5,6). Especially for women, the presence of genital ulcers increases the risk
of HIV infection. For men, the lack of circumcision, concomitant with genital ulcers is a cofactor in
HIV acquisition. In addition, for women, disruption of the epithelial cells in the genital tract is
common. Early sexual activity is more conducive to this epithelium breakage due to immaturity of
the genital tract cells and to cervical ectopy which is usual in young adolescent. This has profound
implications for Africa since the cultural pattern is one of relationships between older men, with
many different sexual partners, and young women (7) or even now, very young girls. In the
presence of genital ulcer disease,(GUD) bleeding is easily induced during sexual intercourse. A
portal of entry for the HIV virus is then present, making infection easier.
It is reasonable to think that the immune systems of poor people with multiple sex partners are in a
continually activated state, making these individuals more susceptible to many diseases including
HIV/STD. Repeated reactivation of T lymphocytes may weaken the body's immune response
towards HIV acquisition and/or progression of HIV.
There are very few studies that look directly at circumcision and STDs. A study in the US at a
public health STD clinic found the prevalence of current syphilis was higher in uncircumcised men
than in circumcised (OR = 4.0 95% CI = 1.9, 8.4), as was the prevalence of gonorrhoea (OR = 1.6,
95% CI = 1.2, 2.2) (9). A study of genital ulcers in Kenya reported a higher prevalence among the
ethnic group which is traditionally uncircumcised (10). A case-control study from the same
population (men presenting with an STD) confirmed that chancroid and other genital ulcer disease
develop more commonly in uncircumcised men (11).
A review of epidemiological studies (8), identified 30 relevant studies concerning circumcision and
HIV transmission. A cycle appears to be emerging in which genital ulcer disease enhances HIV
transmission, HIV infection increases genital ulcer disease frequency, and the lack of male
circumcision augments the transmission of both (12). But the interpretation of most of these results
is limited by the poor assessment of sexual behaviour and other potential confounders.
B - Sexually transmitted diseases enhance the risk of HIV transmission
1. The first studies
Many of them have been done in sub-Saharan Africa.
a) Role of genital ulcers diseases
Chancroid
The available data support a significant association between the genital ulcer diseases (GUD), and
HIV infection. Chancroid, in particular, has been found to be a true risk factor for HIV transmission
and acquisition rather than simply being a marker for high-risk behaviour. Among several crosssectional and case-control studies, three studies showed an association between a past history of
GUD and HIV infection: a study of truck drivers in Nairobi, Kenya (13) one among men attending
an STD clinic in Nairobi (14), and one from a random sample of people from Mwanza, Tanzania
(15). In a population-based survey and a case-control study from the same population group in
Masaka, Uganda, a recent history of genital ulcer was found to be a significant risk factor for HIV
infection in adults (16).
Several other studies report an association between the presence of GUD and concurrent HIV
infection: in Kampala among male and female STD clinic patients, and among male STD clinic
patients in Durban, South Africa (17). A cross-sectional study of male STD clinic attenders in
Zimbabwe showed that male-to-female transmission of HIV is facilitated by the presence of genital
ulcers in infected men (18). Another cross-sectional study in Abidjan among male STD clinic
attenders showed prior and current genital ulcers to be associated with HIV (19). Chancroid was the
primary cause of ulcers in the study of male STD clinic patients in Nairobi (11) where a history of
GUD and current GUD was associated with HIV infection. In two prospective studies in Nairobi,
men presenting to an STD clinic with GUD were nearly 5 times as likely to seroconvert and female
prostitutes with GUD had a threefold increase in the risk of HIV seroconversion (20-21).
Syphilis
A majority of cross-sectional studies have found significant associations between HIV infection ant
T. palladium antibodies. HIV infection was associated with TPHA positive reaction in studies of
pregnant women in Kinshasa, (Zaire)(22), Yaoundé (Cameroon)(23), and Malawi (24); and among
STD clinic patients in Zimbabwe(27) and in Cameroon (26). In a random selection of population in
Mwanza, (Tanzania)(15), the presence of syphilis was associated with HIV infection. After
adjustment for risk variables linked to sexual behaviour, a study of gynaecological inpatients in Dar
es Salaam found syphilis infection associated with a more than two times higher risk of HIV
infection (27). Thirty-three percent of HIV-seropositive pregnant women were RPR positive
compared to 9.5% of HIV-seronegative pregnant women (p < 0.05) in study in Soweto, (South
Africa)(28). In a case-control study of women attending family planning clinics in Nairobi, RPR
positivity was associated with a three/fold increase in HIV infection (29).
But a few cross-sectional studies found no significant associations between syphilitic antibodies and
HIV infection including a study of Zambian prisoners (30), prostitutes in Tanzania (31), outpatients
in south-western Uganda (32), or in STD patients in Tanzania (33).
Genital herpes
Herpes simplex 2 virus (HSV) is the other major cause of genital ulceration found in Africa.
However, it may only cause 5-15% of ulcerations in the region (34) In other countries, studies
reviewed suggest that herpes may be an independent risk factor for HIV infection. A case-control
study of patients attending STD clinics in the US (35) found HSV infections associated with an
increase risk of HIV (OR=2.0, 95% CI = 1.2-3.2). A cross-sectional study of prostitutes in
Kinshasa, Zaire, reported HSV as the identifiable cause of 12% of GUD, and that HSV was more
common among HIV positive women (96% vs. 76%) (36). A study conducted in Zimbabwe found
that a past history of herpes in the man was a factor for HIV serologic concordance between
married couples (2).
b) Role of non ulcerative STDs
Gonorrhoea
Many of the first studies did not find significant differences between HIV seropositive and
seronegative individuals and current gonococcal infection (3). In Zaire, cross-sectional studies of
pregnant women showed no difference in current gonococcal infection and HIV seropositivity (3738-39). Two other studies of high-risk women in Kinshasa, concluded that there was no significant
association between current gonococcal infection between HIV-positive and HIV negative women
(40-41). Cross-sectional studies of prostitutes in Tanzania (31), male blood donors in Zimbabwe
(42), and pregnant women in Kigali, Rwanda (43) found no association between gonococcal
infection and HIV seropositivity. Also, a prospective study of pregnant women in Nairobi, Kenya,
found no difference in the incidence of gonococcal infection between HIV-positive and HIVnegative women (44).
However, a study in Mwanza (Tanzania) found genital discharge as a risk factor for HIV infection
(15). A cross-sectional study in Uganda, focusing on a history of gonorrhoea, found a greater risk of
HIV infection with increasing number of gonorrhoea episodes (45). A prospective study of HIVnegative prostitutes in Kinshasa found incident gonorrhoea was associated with an increased risk of
HIV seroconversion (46). In Malawi, a cross-sectional study of pregnant women found HIV
infection significantly associated with gonorrhoea (47) and a prospective study of pregnant women
found incidence of gonorrhoea significantly higher among HIV-seropositive women (48). A crosssectional study of women attending family planning clinics in Nairobi found that both a history of
gonorrhoea and a positive gonorrhoea culture were associated with a twofold increase in HIV
infection (29).
Chlamydia
Overall, evidence demonstrating a link between chlamydia and HIV infection is scanty. Crosssectional or case-control studies of pregnant women in Kinshasa (22-38), or female prostitutes in
Kinshasa (36), or prostitutes in northern Tanzania (31), and STD clinic patients in Nairobi (49),
found no association between chlamydia and HIV serostatus.
A prospective study of high-risk women in Kinshasa, however, showed incident chlamydial
infection associated with an increased risk of HIV seroconversion in women (46). Two other studies
found significant differences between HIV positive and negative individuals and presence of
chlamydial infection (28-50). This might be attributable to an accompanying inflammatory response
associated with chlamydia infection, which attracts lymphocytes.
Trichomoniasis
Research linking trichomoniasis with HIV is limited. A few studies have documented an association
between trichomoniasis and HIV infection. A prospective study of pregnant women in Malawi
found trichomoniasis as a risk factor for seroconversion (51). A cross-sectional study of pregnant
women in Kinshasa, Zaire, reported an association between trichomoniasis and HIV (22). After
adjusting for sexual behaviour, a cross-sectional study of gynaecological inpatients in Dar es
Salaam found trichomonas vaginalis infection associated with nearly three times higher risk of HIV
infection (52). A prospective study of prostitutes in Kinshasa found incident trichomoniasis
associated with an increased risk of HIV seroconversion in women (46). However, two crosssectional studies in Kinshasa, one of prostitutes and one of pregnant women revealed no significant
associations between trichomonas infection and HIV serostatus (36-38).
c) On the whole, ulcerating and non ulcerating STDs enhance the risk of HIV transmission with a
mean OR of 3 to 7. As STDs are usually considered as at least 10 fold more frequent in developing
countries than in Western industrialized countries, the risk of sexual transmission is in average 50
fold higher in Africa than in Europe. We may add also a 10 fold higher risk due to multiple
simultaneous partnership and it becomes obvious than the risk may be easily 500 fold higher for a
young African than for a young European of same sex and age.
In an other hand, ulcerative STD such as chancroid (OR = 5) may appear the most dangerous but in
an epidemiological point of view their attributable risk is lower than for gonococcal and chlamydial
infections (OR between 3 and 4) which are extremely common whilst chancroid cases remain
scanty.
At last most of these reports were cross-sectional or case control studies, and therefore failed to
document the temporal sequence of STD and HIV infection. Consequently, the interpretation of
these studies include: l) STDs are cofactors that increase an individual's susceptibility to, or
transmissibility of HIV; 2) STDs are more easily identified in HIV-infected individuals; or 3) STDs
are surrogate markers of high risk behaviour that puts the individual at risk of HIV infection (53).
Longitudinal cohort studies that follow HIV-uninfected individuals prospectively to determine the
incidence of HIV and STDs have the advantage of documenting whether or not an STD preceded
the HIV-infection. But these longitudinal studies, with the exception of discordant couple studies
cannot accurately measure sexual behaviour, however, and give little information on the sexual
partner(s) of study participants.
2. The recent studies
Data from recent reports, provide further evidence of the enhancing effect of STDs on HIV
transmission, by examining the impact of the treatment of STDs on HIV shedding and incident HIV
infection in a community-based trial.
Several studies from Africa, Europe and the USA have documented an increased prevalence of HIV
shedding in the genital tracts of individuals with either STDs or endogenous infection. At an STD
clinic in Mombasa, Kenya, investigators tested 189 endocervical specimens and 87 lateral vaginalwall specimens from HIV-1-infected women for HIV-l infected cells, using an HIV- 1 DNA
polymerase chain reaction (PCR) assay (54). The detection of endocervical HIV- 1 DNA was
independently associated with Neisseria gonorrhoeae (odds ratio 4.5) but not with chlamydia
trachomatis.
In a preliminary report from Abidjan, Cote d'Ivoire (55) investigators found that HIV-1, measured
by PCR on the supernatant of cervico-vaginal lavage specimens of 381 HIV-1-infected female sex
workers, was more frequent in those with visible ulcers (47% versus 21%), in those with N.
gonorrhoeae (30% versus 20%), and in those with C trachomatis (40% versus 23%). After treatment
for STDs, the persistence of HIV-1 in the cervico-vaginal lavage was less frequent in those sex
workers who were cured than in those who were not cured, although the decrease in frequency was
not significant. Specifically, HIV-1 was detected in one out of three women with healed ulcers
compared with eight out of 10 with persistent ulcers, and in seven out of 21 women with
gonococcal infection compared with six out of eight who had persistent gonococcal infection.
The impact of the treatment of urethritis in men on HIV-1 shedding in urethral secretions and
seminal plasma has been reported in four studies. These studies show that urethritis increases HIV
shedding in men, and that providing effective antibiotic treatment results in a rapid reduction of
seminal HIV in a study from Nairobi, Kenya, (56). HIV DNA was detected in 44% of 48 men with
gonococcal urethritis and 19% of 26 men without urethritis. After successful treatment of the 48
men who had gonococcal urethritis, urethral HIV-DNA detection decreased to 21%. In a report on
one HIV-1 infected man with chlamydial urethritis a 50-fold post-treatment reduction in HIV-1
RNA was noted in seminal plasma (57).
In an other report on the effect of treating four men with gonococcal and non-gonococcal urethritis,
copies of HIV-1 DNA decreased from two-to four-fold 10 days after effective treatment (58). In
Malawi, semen collected before treatment and 2 weeks after treatment from 78 men with urethritis,
and at enrolment and 2 weeks later from 45 men without urethritis (controls), was tested to measure
the concentration of HIV-1 RNA. At enrolment, men with urethritis had a significantly higher
median HIV-1 concentration compared with the controls; 125000 copies/ml versus 17000
copies/ml, respectively. There was a significant decline in HIV-1 shedding after treatment in the
men with urethritis. At 2 weeks post-enrolment, the median HIV concentration was not statistically
different between treated patients and controls, 37000 copies/ml versus 23000 copies/ml,
respectively (59).
These reports show the increase of shedding of HIV in the presence of STDs, and the dramatic
effects of STD treatment. In contrast, there is little data on the potential mechanisms by which
STDs might increase an HIV-seronegative individual's susceptibility to HIV infection. A study of
20 women with non-ulcerative STDs and 22 women with no infection reported a localized increase
in endocervical CD4 lymphocytes in the women with STDs compared with the women without
STDs.
In an other study in US, it has been shown that local CD4+ cells increase obviously during
chlamydia trachomatis cervicitis and come back to baseline one week after therapy discontinuation
(60).
On the other hand, prospective studies from Asia, Africa and the Caribbean continue to report a
strong association between HIV seroconversion and STDs. In a discordant partner study from Haiti
(61), incident HIV infection was more common in sexually active partners who did not use
condoms, in female partners of HIV-infected men, and in the presence of STD syndromes.
Interestingly, seroconversion was more common when the STD was present in the seronegative
partner. In the HIV-seronegative partner, new HIV infection was more likely to occur in persons
with genital ulcerations (relative risk 6.89) positive syphilis serology (relative risk 2.9) and with a
vaginal or urethral discharge (relative risk 2.6).
A cohort of 891 HIV-1-seronegative high-risk patients attending an STD clinic in India, who were
followed every 3 months was evaluated for HIV infection and behavioural risk factors. The stronger
risk factors for HIV seroconversion in this cohort were genital ulcerations (relative risk 4.3) and
cervicitis or urethritis (relative risk 3.0)(62). Similar results, underlining the risk of urethritis, were
observed in a prospective two years studies of Thai military recruits.
All these data obviously showed the potential major benefit of an intervention strategy of STDs
prevention and treatment.
The first longitudinal study has been done in Zairian prostitutes (Kinshasa) (46). During the two
years follow up with surveillance and counselling and condoms providing, rates of STDs and HIV
seroconversion gradually declined similarly in women who regularly were using preservatives.
More recently the Thai 100% condom project obtained the same result in Thai prostitutes of
Bangkok brothels and their customers (63). Two randomised community-based trial have been
completed.
The Mwanza trial gave the major results. In Mwanza, after randomising six paired communities on
the basis of baseline HIV prevalence, improved STD control of symptomatic patients presenting to
health facilities was implemented at the intervention sites. Investigators demonstrated an overall
42% reduction in HIV incidence over the 2 years of the study, from 1.9% in the control
communities to 1.2% in the intervention community (risk ratio 0.58; p = 0.007). HIV incidence was
lower in each of the six intervention communities compared with controls, and was reduced in both
sexes and in all age groups (64). There was no difference in the reported sexual behaviour or
condom use between the intervention and the control communities. The Rakai district study in
Uganda (65) is a community-based randomised clinical trial on the impact of intensive STD control
on STD and HIV transmission. Intervention and control communities have been tested for STDs
every 6 months using DNA amplification technology and serology. In the intervention communities
all adults between the ages of 15 and 59 years are treated with antibiotics, covering all major
bacterial and protozoal STDs. The study hopes to identify which STDs are most strongly associated
with HIV transmission. The preliminary results of this trial have documented a high prevalence of
asymptomatic STDs, and a significant reduction in STD prevalence 6-9 months after the first
community treatment. The fact that many STDs are asymptomatic favours preventive intervention
since half of STDs infection are not identified and therefore are not treated.
The final results confirm the decrease of a STD transmission after intervention but HIV 1
transmission remains stable in this area; probably because when prevalence is high in the general
population, the part of STD attributable risk is limited.
D - HIV and the immune deficiency may effect STDs natural history
Since the beginning HIV epidemics, clinical and biological abnormalities have been described in
STDs occurring in HIV infected persons. Length of symptoms may be increase and treatment
failures are relatively common. Some of these STDs may appear as authentic opportunistic
infections
1. Chancroid
In a case-control study of men in Nairobi (66-67) presenting with chancroid, the HIV-positive
group had more ulcers per patient and treatment failure at day 7 was more common in the
HIV/positive group.
According some authors, treatment failures at day seven with conventional drugs such as
cotrimoxazole or Erythromycin may be a marker of HIV seropositivity and they recommend HIV
testing of the patients.
2. Syphilis
The prevalence of syphilis and serological response to standard therapy did not differ in
HIV/positive and HIV-negative prostitutes in Kinshasa (68). In a case control study in New-York
(69), HIV-positive patients with primary syphilis were less likely to be considered as "serologically
cured" than patients with primary syphilis who were HIV negative. Many others studies gave
discordant results. In summary, if we consider all the reports devoted to syphilis-HIV co-infection,
the natural history of syphilis may be totally normal with typical clinical pattern of both primary
and secondary syphilis (but some giant ulcers and increase of cases of severe secondary syphilis
with neurological involvement may occur), with typical pattern and progression of serology (but
more patients may remain seropositive than usually), with the same rate of successful treatment (but
the failure rate may be higher). On a practical point of view, there is no need to increase the doses
of Benzathine Penicillin. Cefriaxone does not seem more effective than Penicillin G during
secondary syphilis. In an other hand, diagnosis of syphilis may be difficult in patients with severe
immune deficiency due to lack of significant positive serology (disappearance of specific antibodies
related to immunodeficiency).
3. Genital herpes
The possible impact of HIV on Herpes simplex includes increase of shedding, larger lesions, longer
duration, higher recurrence rate of genital lesions and an increased incidence of acyclovir resistance
(70). In this case, Foscavir by intravenous route may be needed. In developing countries where
Acyclovir is often lacking, genital and perineal lesions, especially in women, may become
extremely painful with large and deep ulcerations which may be super-infected and be a cause of
death.
4. Gonorrhoea and Chlamydia Infections
There are no data which indicate that HIV infection alters the clinical presentation of gonorrhoea or
chlamydia (4). However, there are some indications that previously acquired HIV infection may
promote development of gonococcal complications, such as pelvic inflammatory disease (PID) and
increase in penicillin resistant strains of gonorrhoea (4). In Nairobi (71), a prospective study of
prostitutes found that HIV-positive women were three times as likely to acquire cervical gonorrhoea
and about three times as likely to acquire gonococcal PID than were HIV-negative women. One
study suggests (72) that HIV infection may alter the clinical course and response to therapy of PID.
Two other recent studies, one from the US and one from Abidjan,(73-74) Côte d'Ivoire, suggest that
HIV prevalence is high in women with PID, that the illness is more severe at presentation in HIVpositive women but the response to therapy is similar, (similar length of hospitalisation and similar
rate of sequelae).
More recent studies confirm the common occurrence of PID in HIV seropositive women, probably
due to sex practices and behaviour. There are currently no published data which document any
changes in the natural history of chlamydial infection or trichomonas infection as a result of HIV
infection. Success rate after treatment are similar in both seropositive and seronegative women.
5. Human Papilloma virus (HPV infection)
Genital warts are very common in HIV seropositive men and women with florid extensive lesions
and recurrences difficult to treat (75-76-77). In homosexual and bisexual men, anal lesions may be
the cause of anal carcinoma and systematic examination must be counselled to receptive partners.
HPV infection is better known in women. Many studies in US but also in West Europe have
underlined the risks in HIV seropositive women.
– HIV shedding is more frequent
– Oncogenous subtypes (mainly HPV 16 and HPV 18) are more frequently found. Pap smears
abnormalities concern more than 50% of infected women
– Dysplasia and especially grade 2 and 3 lesions are more common, more persistent and more
recurrent.
– Local treatments (laser...) fail more frequently than in seronegative women.
Occurrence and severity of HPV lesions are correlated with the CD4+ cell decrease and may be
considered as an authentic opportunistic infection. CDC guidelines recommend Pap smear at first
visit and colposcopy in case of inflammation or presence of koilocytes. If the first smear is normal,
surveillance has to be done yearly. If the first smear is inflammatory, surveillance has to be done
each six months.
Since 1993, the invasive cervix carcinoma is an AIDS defining event. But this event is less common
than it was initially thought and only 2% in US and France of women AIDS new cases correspond
to that event. With the lengthening of survival related to antiretroviral therapy, the risk of cervix
carcinoma occurrence may increase in the next decade.
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SEXUALLY TRANSMITTED DISEASES AND REPRODUCTIVE HEALTH
Q. Islam Mounir
Reproductive tract infections (RTIs) including sexually transmitted diseases (STDs), are a neglected
area in public health in most countries, both in the developing and developed parts of the world.
This is despite overwhelming evidence for their impact on health, particularly that of women, young
people and neonates. It is estimated that 333 million curable STDs occur globally every year, most
of them in developing countries(1). In many developing countries STDs rank among the top five
conditions for which adults seek health care service, while post-abortion, postpartum and postnatal
infections due to RTIs are major causes of maternal death. Whereas in most industrialised countries
there has been a spectacular decline in the incidence of STDs, particularly gonorrhoea and syphilis,
they are on the rise in most developing countries. A total of 33.4 million adults and children is
estimated to be living with HIV/AIDS as of end 1998. It is also estimated that a total of 13.9 million
adults and children will have died because of HIV/AIDS since the beginning of the epidemic, with
2.5 million deaths in 1998. Approximately one-fifth of these deaths during 1998 occurred in
children and 45% of the estimated adult deaths were in women(2). HIV and AIDS particularly
affect young people. In fact, 50 per cent of HIV infections have occurred in the age group 15-24.
This has an important impact on the economy of many countries since the group most affected
constitutes the bulk of the workforce.
The epidemic of RTIs and STDs in the developing world is characterised by a high incidence and
prevalence, a high rate of complications, an increasing problem of antimicrobial resistance,
especially for most STDs, and the increased risk of HIV infection (3). Important factors
contributing to the problem in developing countries are population pyramids that are heavily
weighted towards young individuals, fast increasing urbanisation and the low status of women.
However, until recently, prevention and control of STDs was not a priority for most countries and
development agencies.
The victims
STDs and other RTIs have become a silent epidemic that is adversely affecting women’s lives. Each
year, thousands of women suffer physically as well as socially, or die needlessly from the
consequences of these infections, including infertility and pregnancy wastage, cervical cancers,
ectopic pregnancy, acute and pelvic infections, and puerperal infections. The burden of reproductive
ill-health falls overwhelmingly on women in developing countries (see text box 1) (4).
For example, over 90% of all maternal deaths occur in the developing world. Women are especially
vulnerable to sexually transmitted diseases and still bear most of the responsibility of contraception,
including the consequences of contraceptive failure. For many women, this happens because they
receive medical attention too late, if at all. The irony of this is that the vast majority of illnesses
especially RTIs and STDs are curable; early diagnosis of, and treatment for most RTIs and STDs do
not require high technology health care and therefore, morbidity and mortality due to these illnesses
is preventable. Across the world, millions of adolescent girls and boys are suffering from unwanted
pregnancies and STDs, and their severe consequences. In most countries one third of the STDs
occur among adolescents below the age of 20 years. Adolescents are at risk of serious reproductive
health illnesses including STDs because they lack access to the necessary information and service,
or they receive poor quality services from providers who are judgmental or moralistic, untrained to
diagnose and provide appropriate care or to deal with sex and sexuality, poorly supervised, or ill
equipped.
Reproductive Ill-Health
Category
World wide affected persons
Couples with unmet family planning needs
120 million
Infertile couples
60-80 million
Maternal deaths annually
586 thousand
Cases of maternal morbidity annually
20 million
Prenatal deaths annually
7.2 million
Unsafe abortions
20 million
Adults with HIV/AIDS
20.1 million
Annual adult incidence of HIV infection
2.75 million
Annual incidence of curable STDs
333 million
Women living with invasive cervical cancer
2 million
New cases of cervical cancer annually
450 thousand
Women with genital mutilation
85-110 million
Text Box 1 (4)
Women, especially young women, are more vulnerable than men in regard to STD and its
complications. The high prevalence of STD among women attending antenatal, family planning, or
gynaecological clinics in developing countries indicates the extent of the STD problem. For
example, in studies in developing countries up to 19% of pregnant women have gonorrhoea or
chlamydia and up to 20% have syphilis (see text box 2) (5-25).
Prevalence of STD in pregnant women
Country
GC (%)
Botswana
14
Chile
1
Gambia
7
Haiti
11
India
8
Kenya
18
Malaysia
54
Senegal
19
South Africa
12
Thailand
11.9
Zaire
2
Note: GC – Gonorrhoea, CT – Chlamydia
Text Box 2 (5-25)
CT (%)
6
7
10.1
20
12.5
11
12.8
6
Syphilis (%)
7
17
11
4
4
3.3
20.8
7
1
Biologically women are more susceptible to most sexually transmitted diseases than men, at last in
part because of the greater mucosal surface exposed to a greater quantity of pathogens during sexual
intercourse. In addition, the risk of transmission of STDs, including HIV infection, is greater
whenever the mucosa is damaged. As a result of such factors most STDs, including HIV infection,
are transmitted more readily from men to women than from women to men. Women with STD are
more likely than men to be asymptomatic, and therefore are less likely to seek treatment for STD,
resulting in chronic infections with more long-term complications and sequelae (see text box 3) (7,
8, 26-29).
Women and sexually transmitted diseases
It is estimated that 165 million new cases of curable STDs occur globally each year among women aged 1549 years. Case numbers are distributed as follows with many women having more than one disease:
• syphilis
6.5 million
• gonorrhoea 3.1 million
• chlamydia
47.0 million
• trichomonas 80.0 million
STDs in women are not easily identified and cured for a number of reasons • over 50% of STDs in women are asymptomatic;
• diagnosis is difficult
• women’s access to services is frequently poor, because STD management is rarely provided as part
of an integrated approach to women’s health needs.
• This leads to complications and sequelae which seriously impair the health of women in developing
countries causing considerable morbidity and mortality:
• STDs cause pregnancy-related complications, premature birth, stillbirth and congenital infections;
• 1-5% of all maternal mortality is due to ectopic pregnancy mostly attributable to STDs;
• 35% of postpartum morbidity is attributed to STDs;
• almost two-thirds of cases of infertility among women are attributed to STDs;
• 17-40% of all gynaecological admissions are due to PID, mostly due to STDs;
• almost half a million new cases of cervical cancer occur each year in the world. Cervical cancer is
the second most common cancer in the world.
World wide, the disease burden of STD in women is more than 5 times that of men.
Text Box 3 (1-7, 8, 26-28)
The factors that contribute to the higher rate of STD as well as HIV in women are mostly related to
economic and gender inequalities. Poverty and urbanization in many developing countries drive
men to cities for work, resulting in concentrations of men away from their families and in demand
of sexual services. These same factors drive women into prostitution as a survival strategy, and
limit access to proper health care. Where cultures expect women to be passive and subservient to
men, women have little or no control over decision-making relating to sexuality, nor do they have
control over sexual behaviour of their male partners or the use of condom for prevention of
STD/HIV or pregnancy. The awareness of reproductive health problems and need for care in
women is generally low, so symptoms of STD may not be recognized as such. Stigmatisation and
various cultural norms impede appropriate health care seeking behaviour, while acceptable and
accessible services for diagnosis and treatment may not be available for those who do seek health
care.
In addition to all the above factors, many STDs increase the probability of transmission and
acquisition of HIV infection. The presence of HIV alters the morbidity of STDs, making control
more difficult. Although RTIs and STDs seriously undermine the success of other health initiatives,
they have been ignored because of widespread beliefs that they are not serious, do not kill, or are
too complicated and expensive to control. RTIs/STDs have also been neglected because deeply held
attitudes and values make them socially taboo subjects among women and men at all levels of
society. This culture of silence prevents changes in long standing behaviour related to sexuality and
gender, and has inhibited the development of effective information and services. It is now time to
re-evaluate long standing assumptions about the impact and feasibility of systematic prevention and
control efforts, and to examine critically the national and international policy implications of RTIs
and STDs in the developing world.
The impact
Even though there are millions of people infected with HIV, we are only at the beginning of the
epidemic of illness associated with HIV and AIDS. In 1990, about half a million people required
care for AIDS; in the year 2000 this figure will be 2.2 million. In hard hit cities, AIDS patients
already occupy half or more of hospital beds. The weak health and social systems of many countries
are finding it difficult if not impossible to cope with the growing numbers of people falling ill. The
epidemic is having devastating effects on individuals, families, and entire communities.
For women, HIV infection has added its burden to the one they carry from diseases related to STD,
pregnancy and childbirth. Women’s risk of HIV infection has climbed steadily and the proportion
of women represented 40% of all new AIDS cases; up to 50% of all new cases of HIV infections
were in women, mainly those aged 15-24 years29,28. Female vulnerability has become increasingly
clear in Africa and Asia. By the year 2000, an estimated 14 million women will have been infected
with HIV and about 4 million will have died of AIDS. Related to women’s infection comes the risk
that their infants will be infected before or during childbirth or during breast-feeding. The risk of
mother-to-infant transmission in Africa is around 35-40% while in the developed countries it is
typically under 20%.
Young people are particularly affected by HIV and AIDS. In fact, 50% of HIV infections have
occurred in 15-24 years old. This has an important impact on the economy of many countries since
the group most affected constitutes the bulk of the workforce. The costs of lost production are
generally thought to be 10-20 times greater than direct medical care costs.
The socio-economic burden of sexually transmitted infections, in terms of direct and indirect costs,
is growing. The AIDS threat to the economy again stems from the age group most affected - young
and middle-aged adults. In its World Development Report for 1993, the World Bank estimates that
for adults between 15 and 44 years of age in the developing world, STDs not including HIV
infection are the second cause of the burden of disease in women, after maternal morbidity, and
mortality. In men, HIV infection ranks first, before tuberculosis, motor vehicle injuries, and
homicide and violence. If HIV infection is combined with conventional STD, sexually transmitted
infections account for nearly 15% of all health lost in this critical age group for society (figure 1)
(30,31).
As the principal caretakers in the home, the woman’s burden is particularly great both during her
spouse’s illness and after his death - and, many are battling HIV infections themselves. Where there
is no social security and legal protection, women who become AIDS widows may have to face the
loss of land, housing, goods, inheritance, and even custody over their children.
Of the three fundamental determinants of population size - births, deaths and migration - the most
obvious effect of the epidemic will be on the death rate. Unlike most other diseases, the majority of
deaths due to AIDS occurs during the most productive years of life. For example, in Thailand, 78
per cent of the reported AIDS cases are between the ages of 20 and 4932. In some cities in the
United States and sub-Saharan Africa AIDS is the leading cause of death among adults between 15
and 49.
HIV infection in Uganda has been responsible for 44 per cent of all mortality, and 89% of mortality
in adults between 25 and 34 from 1989-199033. HIV has also shown to be responsible for negating
advances in child survival in countries such as Tanzania, where it is estimated that child mortality in
1995 will be equal to that in 1980 despite decreasing trends in child mortality which began in 1980
as a result of immunization and diarrhoeal disease control programmes34 (figure 2).
The interrelation family between planning and HIV/AIDS is another important issue which needs
urgent attention. Way and Stanecki projected that without AIDS, the population of Uganda in the
year 2010 would be expected to be about 33 million but with AIDS it is instead estimated at 24.5
million35. This has prompted some policy makers in the region say that there is no demographic
rationale for fertility regulation in sub-Saharan Africa. This attitude will affect family planning
initiatives in the region.
Reproductive health
Conventional STD control programmes, directed primarily at men and at high risk groups, are
typically inaccessible to women and young people in the general population. Women are
constrained from using these services because of social censure, and financial and personal costs.
Conventional STD programmes, which serve mostly men, often fail to inform and serve the
partners, especially stable partners. STD care services are not integrated into existing family
planning and maternal and child health care service because of fear of stigmatisation of these
services. One of the better mechanisms for identifying and serving women at high risk of infection,
and their partners, is thus lost. RTIs/STDs and their sequelae are intertwined with key health-related
development programmes, such as those concerned with family planning, child survival, women’s
health, safe motherhood, adolescent health, and HIV prevention. RTIs/STDs have profound
implications for the success of each of these initiatives. Conversely, each of these initiatives
provides a crucial opportunity for the prevention and control of RTIs/STDs.
Change of emphasis
The current emphasis on reproductive health began when human rights and women’s health
advocates began to question the rationale of traditional policies that mainly focused on reducing
population growth through the provision of family planning services. During the 1980s, attention
was focused on the child. Child survival strategies and programmes were developed with the
objective of reducing infant and child mortality. Family planning and child survival programmes
were dealt with separately and with great intensity and investment of international and national
efforts and resources. The combination of maternal and child health and family planning (MCH/FP)
represents the first attempt to bring the two components together and deal in a more comprehensive
manner with aspects of reproductive health. The increasing prevalence of STDs and AIDS sparked
further discussion on the best ways of managing and providing MCH/FP services. Client
expectation also began to change over the years. At the International Conference on Population and
Development in 1994 in Cairo, there was consensus among national delegations on the need for a
more comprehensive, client centred view of reproductive health and for the implementation of
reproductive health programmes in addition to family planning. Co-ordinated planning is designed
to lead to conceptually balanced and technically sound approaches that best serve people’s needs.
There is conceptual overlap and strategic interdependence among programmes such as family
planning, safe motherhood, women’s health, adolescent health, child survival, and prevention of
RTI’s STDs and HIV. Integrated programmes, co-ordinated allocation of resources, and concerted
action can achieve a critical mass of resources and effectiveness where separate programmes are
ineffective because of limited financial or human resources.
There appears to be a considerable potential for increasing the effectiveness of reproductive health
programmes by integrating elements to prevent RTI/STD related morbidity and mortality.
Current programmes
Most countries have programmes dealing with particular components of reproductive health.
Generally, they have tended to be fragmented and vertical, with a focus either on a particular
disease such as STD or HIV/AIDs, or on a general area such as family planning or maternal and
child health. Vertical programmes often overlap. Because of the interdependence of the service, a
more integrated approach, establishing links between information and various services for
promotion and prevention as well as care would have many advantages. Such an approach would
improve access to and quality of services, be more responsive to clients’ needs, more cost effective,
more humane and comprehensive and more likely to reach groups such as women and young people
who are currently poorly served. In developing countries, the need for integrated services is even
more acute because so few facilities are available.
Moreover, access to services is usually more cumbersome and time-consuming. Therefore, when
clients make the effort to obtain one particular service, the full range of preventive care should be
offered.
Although there is general consensus on the need to work towards the development of a
comprehensive approach to RTI/STD control, in practice, programme development will require
prioritisation on the basis of countries’ need and available resources within the context of
reproductive health. In most developing countries, 80-90 per cent of the population is dependent on
primary health care services such as dispensaries and health centres. In order to make maximum use
of scarce resources, it is essential that appropriate public health strategies for the prevention and
control of RTIs/STDs be implemented and integrated into basic health care, maternal and child
health care, and family planning services.
Such strategies are more responsive to the needs of individuals and the community, improve access,
quality and use of services, are more cost-effective and can meet the needs of groups at risk and not
adequately reached by existing services.
Priority interventions and actions
Policy makers, who are working with programme managers, health care advocates, service
providers, clients and others, need to determine, from an array of proposed reproductive health
options, what package of services to provide. Programmes will have to expand the range of services
offered and at the same time increase access to and improve the quality of existing services. Policy
makers must decide on the structure of expanded reproductive health programmes, funding
requirements and the sources of funding. These decisions will be difficult, since programmes will
require co-ordinated efforts and will compete with other priorities for limited domestic and
international funding.
There is no single strategy. A global strategy will need to be translated into various approaches at
national and local levels, and simultaneous activities will be needed on a variety of fronts.
Nevertheless, there are guiding principles that apply everywhere. The strategies for the attainment
of reproductive health, and the prevention and care of RTIs including STDs must be based on the
underlying principles of human rights and the operational principles of national ownership, a
participatory process involving providers, users and planners in the planning, implementation and
evaluation of programmes; and multisectoral action, with partners contributing according to their
comparative advantages.
Action
Response to the challenge of reproductive health, including RTIs and STDs, should focus on -
Environment: Establishment of a supportive, enabling environment. This includes a number of
actions to change the social, economic, cultural and political environment conducive to better
reproductive health and HIV/AIDS and STD programmes. It includes a variety of possible actions.
There is a strong need for advocacy to promote interventions and action. Soliciting international
community support is needed, including agencies and nongovernmental organisations, to increase
resources, develop some common guiding principles and establish collaboration and partnerships
for programme implementation.
Advocacy should draw the attention of communities and decision-makers to the issues of
reproductive health, RTIs and STDs, and point towards nationally relevant solutions. National
advocacy should provide the rationale for greater allocation of national resources.
Health Promotion: Relevant information should be developed, as well as education and
communication (IEC) programmes to build knowledge, motivation and skills. IEC programmes
need to be developed based on a full understanding of the individual and broader socio-economic
factors that influence individual, institutional and group behaviour. They should focus on fostering
health and responsible behaviour. IEC could also be used to promote ideas of equality, to increase
male responsibility in pregnancy and the prevention of STDs and HIV, and to promote informed
reproductive health choices, especially for women. The overall programme should aim to develop
individual skills to make informed decisions and to create a demand for timely and quality services.
Health services: Strengthening of health services, improvement of delivery and quality, and
establishment of strong linkages across services. These should include early and prompt
management of bacterial STDs: Bacterial STDs and RTIs are treatable and early case management
should be a basic strategy of every programme. Case management is more than giving a pill or an
injection. A patient contact for a sexually transmitted disease should provide an opportunity for
education about risk reduction and condom use. In most settings, including in the industrialised
world, laboratory tests are not available to support a treatment decision on the spot. In addition,
current laboratory tests, with the exception of microscopic study and the rapid plasma reagin test,
are too technically demanding and expensive for many populations. For these reasons, simple flow
charts using syndromic approach are being used increasingly at the primary care level. The
development of cheap and simple diagnostic tests should also be high on the research agenda.
Functional linkages should be established, coordinating or integrating prevention and care
programmes for RTI, STD and HIV into family planning and MCH services including primary
prevention of RTIs and STDs through interpersonal counselling at the health facility and
community outreach to reach underserved populations and promote supportive environments.
Targeted interventions should be introduced for populations at higher risk. The awareness of
reproductive health problems, need for care and availability of services in high-risk groups is
generally lacking. Health care seeking behaviour needs to be improved. Stigmatisation, economic
conditions and various socio-cultural norms impede appropriate health care seeking behaviour,
while acceptable and accessible services for diagnosis and treatment may not be available for those
who want to seek health care.
Research and development: There are two priority areas: 1. Research to develop appropriate and
effective interventions, including operational research. Such research should cover, for instance:
a) Research on service delivery, such as what the barriers are and how to improve access to
service by women and young people; on effective ways of integrating STD services into
family planning or primary health care; operational research on improving supplies and
storage of drugs, condoms etc.
b) Research on appropriate communication approaches, such as exposure to different channels
of communication, on reach and effectiveness of programmes using various channels, on
perceptions and understanding of messages and on effectiveness of peer education or school
education curriculum. Policy analysis and research to assess the effect on programmes, such
as research on effectiveness of policies and regulations promoting condom use; on health
policies etc.
c) Research on new tools and technologies: Research on new technologies that prevent RTIs
and STDs, HIV and pregnancy, and that prevent STDs and HIV without preventing
pregnancies (microbicide, virucide, female condoms, new barrier methods etc.); Research on
optimal strategies for diagnosis and management of asymptomatic RTIs, including STDs;
Development of simple, cost-effective diagnostic tests for RTI and STDs; Operational
research to identify new ways of motivating people to adhere to safe and responsible sexual
practices; mobilising community networks and support systems to facilitate informed
decision making and appropriate use of reproductive health services; and strengthening
environments to facilitate responsible sexual behaviour.
It is clear that there is no simple solution for the prevention and care of RTI, STD and AIDS, nor for
meeting all reproductive health needs. What is needed is a right combination of approaches,
combining prevention and care, and combining medical, behavioural and societal and contextual
interventions. Suitable and highly cost-effective interventions are available.
Much creativity and energy is needed to make use of this momentum of opportunities to contain
HIV/AIDS and STDs, and to ensure improved sexual and reproductive health for all.
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STD CONTROL AS A COMPONENT OF HIV CONTROL STRATEGIES
Anne Buvé
Introduction
Nearly two decades after the first cases of AIDS were identified the HIV/AIDS pandemic remains
one of the biggest challenges in public health worldwide. UNAIDS estimates that in 1997 5.8
million people became infected with HIV, of whom more than 90% were living in developing
countries (1). Over the last three years spectacular progress has been made in the treatment of HIV
infection, which is at least in part responsible for the decrease in AIDS incidence and mortality in
industrialised countries since 1995-1996. Unfortunately, due to the high cost of the drugs and other
operational constraints, in the foreseeable future treatment for HIV infection will remain
unavailable for the vast majority of infected persons in developing countries. Also the prospects of
having a vaccine ready soon, are rather slim. For many years to come prevention of the spread of
HIV to as yet uninfected persons will remain the main strategy to combat the immense human
suffering associated with the morbidity and mortality due to HIV infection.
The majority of the world's HIV infections are acquired through sexual intercourse, making HIV
infection the most serious and deadly STD (sexually transmitted disease). The other STD's1 include
diseases caused by a range of micro-organisms including viruses, bacteria and protozoa. The latter
are the most widespread STD's and include gonorrhoea, chlamydial infection, syphilis and
trichomoniasis. They are relatively easy to treat and are curable. An estimated 333 million of these
curable STD's have occurred worldwide in 1995 (2). The highest incidence rates have been
estimated for sub-Saharan Africa, Latin America and the Caribbean, and South and South East
Asia.
Although most of the "other" STD's and their complications have been known for many years, their
public health importance is only fully acknowledged since the advent of the HIV/AIDS pandemic
and since it became clear that there is interaction between other STD's and HIV infection. It is now
widely accepted that control of other STD's ought to be an essential component of any programme
aiming at reducing the spread of HIV.
In this paper we will first examine the rationale for STD control as part of HIV control programmes.
Then we will go on to discuss the main strategies for the control of other STD's, with an emphasis
on the control of curable STD's.
Factors determining the spread of HIV
Whether an uninfected person will acquire HIV through sexual intercourse will depend on the
probability that he/she has intercourse with an infected partner; and secondly on the probability that
the virus is transmitted through sexual intercourse (see Figure 1).
Exposure to infected
partner
Uninfected
Sexual Behaviour
Transmission of HIV
Co-factors
Figure 1
The probability of exposure to an infected partner is determined by sexual behaviour. Since the start
of the HIV epidemic many studies have documented the overlapping risk factors for HIV infection
and other STD's in terms of sexual behaviour. Frequent partner change and sexual contact with
commercial sex workers have been identified as important risk factors for both HIV infection and
diseases such as syphilis, gonorrhoea, chancroid, chlamydial infection etc. On the other hand
condoms have been shown to be an effective barrier against the transmission of HIV, as well as
other STD's.
The transmission probability of HIV during sexual intercourse between men and women has been
estimated at around 0.001 to 0.005 per sex act. This is much less than for instance the transmission
probability of gonorrhoea and of hepatitis B. Several behavioural and biological factors have been
identified which decrease the transmission of HIV (e.g. condom use) or enhance the probability that
the virus is passed on to the uninfected partner. Among the factors that enhance the transmission of
HIV, the presence of another STD in one of the two partners or in both takes a prominent place.
From a public health point of view other STD's are among the most important co-factors in the
transmission of HIV because of their high incidence and prevalence in many populations and
because of their vulnerability to intervention.
"Other" STD's as co-factors for HIV transmission
The question whether other STD's enhance the transmission of HIV during sexual intercourse has
been debated and researched for many years. First, cross-sectional studies found that men and
women who had a history of STD were more likely to be HIV infected than men and women with a
similar sexual behaviour pattern but no history of STD. Longitudinal studies among clients of sex
workers in Nairobi and among sex workers in Kinshasa and Nairobi, established the causal link
between presence of another STD and the acquisition of HIV infection (3,4,5). For instance Laga et
al. found that HIV negative sex workers in Kinshasa had a higher risk of acquiring HIV infection in
a certain time period, if during that time period they had suffered from gonorrhoea or chlamydial
infection (4). This suggests enhanced susceptibility of HIV uninfected people if they are suffering
from another STD.
The strongest epidemiological evidence so far for an enhancing role of other STD's in HIV spread
has been provided by a community intervention trial in Mwanza, Tanzania. Twelve communities
were selected within the catchment area of health centres and dispensaries. A programme was set up
of improving STD case detection and management at primary health care level. This programme,
the so-called intervention, consisted of a refresher course for health care workers; supply of
appropriate antibiotics for the treatment of STD's; and regular supervision. The intervention was
first introduced in 6 communities. Over two years the incidence of HIV infection was found to be
42% lower in the intervention communities than in the control communities, which received the
intervention at a later date (6).
The last piece of the puzzle of the interaction between HIV infection and other STD's has recently
been provided by studies on shedding of HIV in genital secretions. Female sex workers in Abidjan
were found to be shedding more HIV in their genital secretions when they had another STD and this
increased shedding was reversed by treatment of the STD (7). Likewise, a study in Malawi found
that men with urethritis shed more HIV in their semen than men without urethritis and men who
were treated for their urethritis (8).
These latter studies point to an increased infectiousness of HIV infected persons when they are
suffering from another STD, be it a non-ulcerative STD or a genital ulceration. As mentioned
before the study among sex workers in Kinshasa pointed to an increased susceptibility for HIV
infection in the presence of another STD. Indeed, the presence of another STD in an HIV infected
person increases his/her infectiousness, while an HIV uninfected person is more susceptible to HIV
infection if he/she is suffering from another STD. As such it has been hypothesized that one of the
explanations for the much more rapid spread of HIV infection in some populations in developing
countries compared to industrialised countries, is the higher prevalence and incidence of other
STD's in the former populations. In Thailand for instance it has been estimated that the probability
of transmission of HIV infection from sex workers to army recruits is 0.031 per sex act which is
substantially higher than the probability of female-to-male transmission of 0.001 which has been
estimated in studies of discordant couples in industrialised countries (9).
Strategies for the control of "other" STD's
Broadly speaking there are two strategies for the control of “other" STD's. The first aims at
reducing the probability that an uninfected person is exposed to a person with a sexually transmitted
infection. This is achieved by changing sexual behaviour towards safer sex, e.g. by avoiding sex
with high risk partners, such as commercial sex workers, and by using condoms. The second
strategy aims at reducing the pool of infected persons in the community, i.e. reducing the
prevalence and incidence of STD's. This can be achieved by changing sexual behaviour but also by
"removing" infected subjects from the population through treatment.
Both these strategies intervene on factors that also determine the rate of spread of HIV infection.
Safer sex leads to less exposure to persons infected with a sexually transmitted infection, including
HIV infection. A reduction in the prevalence and incidence of other STD's will reduce the
prevalence of an important co-factor in the transmission of HIV infection and will thus decrease the
overall transmission probability of HIV during sexual intercourse. We will now discuss these two
strategies.
Changing sexual behaviour
Controlling the spread of STD's through changing sexual behaviour has for many years been
neglected because the most widespread STD's were curable and because sexual behaviour change
was not considered feasible nor cost-effective. Under the threat of the HIV/AIDS epidemic attitudes
towards this strategy have changed. It became clear that our knowledge about sexual behaviour was
rather patchy and blurred by prejudices and taboos. Since the early 1980's however a lot of research
has been done on sexual behaviour and its determinants. And innovative approaches have been tried
out to address and change high risk sexual behaviour. Interventions to change behaviour towards
safer sex range from population based interventions, such as mass media campaigns and social
marketing of condoms, to individual counselling by peer educators or professional staff at
counselling centres and STD care services.
Any behaviour change is a slow process but some remarkable successes have been booked in the
area of sexual behaviour. The Thai government for instance launched a large scale campaign for
condom use in brothels, soon after the start of the HIV epidemic in Thailand in the mid 1980's. The
proportion of commercial sex acts where a condom was used increased from 25% in 1989 to 94% in
1993; in the same time period the number of men presenting with gonorrhoea at government
services decreased from 84.675 to 14.750 (10). Also in several other countries social marketing
programmes for condoms have led to substantial increases in condom sales.
It is now generally accepted that advising patients on safe sex ought to be part and parcel of STD
care. A clinic visit for an STD offers a unique opportunity for providing sexual health education to
individual patients. Patients seeking care for an STD are more receptive to information and advice
in order to avoid suffering from the same disease in the future, especially if advice is given in the
context of good clinical care. This was for instance demonstrated in a group of sex workers in
Kinshasa, Congo (formerly Zaire), who attended a specialised clinic. The women were more
receptive to prevention advice and started using condoms more frequently once they realised they
were receiving good quality care at the clinic (11). Sexual health education in the context of STD
care should include information on the nature of the disease and treatment, advice on risk reduction,
including condom use, and partner notification.
Reducing the pool of infected persons in the population: detection and treatment of STD cases.
Some of the most widespread STD's, such as gonorrhoea, chlamydial infection, syphilis and
trichomoniasis, are caused by bacteria and protozoa and can be cured by relatively simple and cheap
means. Prompt cure by treatment constitutes an additional strategy for the control of these STD's by
reducing the time during which STD patients are infectious and would transmit the infection to their
sex partners. In order for case detection and management of STD's to contribute to the control of
STD's in the population the coverage of STD patients by effective curative services needs to be
maximal. Keeping this in mind what are the issues in STD case detection and management as
control strategy of STD's?
The lack of cheap, simple and reliable diagnostic tools for the detection of STD's is generally
perceived as an important obstacle in the efficient management of these infections. Also the
increasing resistance of N. gonorrhoea and, to a lesser degree, H. ducreyi against commonly used
and relatively cheap antibiotics is raising a lot of concern. These however are only a few of the
factors that determine how many cases of STD that occur in the community will ultimately be cured
by the health services. Figure 2 depicts the steps a person with an STD takes before he/she can be
considered cured by the health services.
Fig. 2: Different steps from STD infection to cure by health services
Sexually transmitted infection
Awareness of Symptoms
Utilisation of health services
Problem suspected by health care worker
Correct diagnosis made
Treatment received
Treatment taken
Treatment prescribed is effective
Patient cured
Ideally all individuals with a sexually transmitted infection are symptomatic and immediately aware
that they have a health problem. They promptly seek care from health services that are competent to
provide cure. The health worker immediately suspects the patient of suffering from an STD and
makes an accurate diagnosis. The patient receives a prescription for efficacious medication, collects
the drugs and takes them. He/she complies with safe sex advice and informs his/her partners. In
reality however at each of these steps something goes wrong leading to a sub-optimal cure rate. The
cure rate achieved by health services depends on the proportions of patients that go from one step to
the next.
A first obstacle to the effectiveness of case detection and management of STD's are the many
infections that remain asymptomatic and thus go undetected by patients and health workers.
Population based studies, as well as studies among women attending antenatal clinic or family
planning clinic and studies among partners of STD patients, revealed high proportions of
asymptomatic infections among persons infected with N. gonorrhoea or with C. trachomatis. It is as
yet unclear which role these asymptomatic infections play in the epidemiology of STD's, in
particular whether they are as infectious as symptomatic infections and whether they are as
important in enhancing the transmission of HIV infection. At the same time however they constitute
an important pool of infections in the population.
Utilisation of health services by patients with an STD depends on the accessibility, in geographical
and economic terms, and the acceptability of these services. Clinical services for STD's pose special
problems due to the stigma that is attached to STD's in most cultures. Privacy and confidentiality
are major concerns of potential users of STD clinical services, even if they are known to provide
efficacious treatment. Studies conducted in Tanzania, Malawi and Swaziland found the proportion
of STD patients who would attend public health services to seek care for their STD, to be at most
50%. There was a strong preference for private practitioners and traditional healers who were
perceived as more understanding than the health workers in the public services. On the other hand
there is evidence that improving services for STD patients also improves care seeking behaviour in
the sense that more STD patients will come forward for treatment. This has been shown for instance
in Mwanza Region, Tanzania, where improving the quality of care of STD patients raised the
proportion of STD patients in the community who attended the public services (H Grosskurth,
personal communication).
Confirmation of the sexually transmitted infection depends on the level of suspicion of the health
care worker and on the diagnostic techniques used. In low resource settings laboratory diagnosis is
usually not feasible because it is too costly or too complicated. Health workers have to rely on
clinical algorithms. The performance of these algorithms varies but in general their sensitivity is
quite acceptable in symptomatic patients, while the specificity is often too low, especially in
women, which leads to over treatment of patients.
Whether or not a patient is prescribed the correct treatment and receives the medication depends on
several factors. Resistance against commonly used antibiotics is an increasing problem for
gonorrhoea and to a lesser degree chancroid. Regular testing for the emergence of resistance and
adaptation of the treatment guidelines is essential to prevent this problem from becoming
uncontrollable. Other factors relate to the functioning of health services. Health care workers need
to be aware of treatment guidelines and need to be compliant with them. Also availability of even
basic drugs can not be taken for granted in most health services in developing countries.
The list of potential obstacles to effective case detection and management of STD's is long. On the
other hand many problems, such as the provision of efficacious drugs and the supervision of health
care workers in STD services, are related to the functioning of health services and are in principle
vulnerable to interventions. The one exception remains the asymptomatic infections. Which
alternatives are available to address this problem? Regular screening of certain population groups is
a theoretical option. Screening for chlamydial infection in young women has for instance been done
in Sweden for a number of years, with good result. Such strategies however are too costly and not
feasible in many industrialised country settings, let alone in low resource settings. As long as there
is no cheap, simple and non-invasive test for the detection of gonorrhoea and chlamydial infection,
screening for asymptomatic STD's remains an illusion. These problems as well as the operational
problems of passive case detection and management of STD's in low resource settings has led to the
suggestion that mass treatment of STD's should at least be considered an option. In the past attempts
have been made to control STD's with mass treatment. The effect was found to be transitory.
Moreover the logistic difficulties of reaching high numbers of people within a short time span make
such strategy rather problematic, as well as costly. On the other hand contact tracing, which is a
well established strategy for the detection of asymptomatic STD's in many industrialised countries,
has for long been considered too labour intensive and not cost-effective to be seriously taken into
consideration in low resource settings. Recent experiences from a variety of developing countries
however have shown that contact tracing for STD's can be feasible at low cost. An intervention
study in Zambia for instance showed that individual counselling of male STD patients led to an
increase in the number of sex partners that came forward for treatment after being notified by the
index patient himself (12).
In addition to good quality STD services for patients in the general population, special STD services
may need to be considered for marginalized groups such as commercial sex workers and even
adolescents, who would not attend regular health services for a variety of reasons. A number of
small scale intervention projects in a research context have demonstrated the feasibility of setting up
specialised services for sex workers that achieve reductions in incidence of STD's and HIV
infection in this high risk population. Such interventions can be highly cost-effective because they
reduce the pool of infections in a so-called "core group", i.e. a group of individuals who are highly
sexually active and who maintain STD's in the population at endemic levels.
Concluding remarks
The interrelationship between HIV infection and other STD's offers a unique opportunity for
prevention of the spread of HIV, i.e. controlling one infectious disease that is more easily
controllable to control another, more difficult to manage disease. That it is possible to reduce the
incidence of HIV infection by improving case detection and management of other STD's has
convincingly been shown by the community intervention trial in Mwanza, Tanzania. It ought to be
pointed out that this intervention was not a "high tech" intervention but actually consisted of
activities that are normally part and parcel of every well functioning health system. For instance, it
was estimated that before the intervention drugs prescribed for gonorrhoea would cure at most 25%
of cases presenting to the public health services. Following a survey of the sensitivity of N.
gonorrhoea treatment guidelines were changed and health centres were provided with
cotrimoxazole for the treatment of gonorrhoea instead of tetracycline and penicillin. The former
antibiotic has an estimated efficacy in Mwanza Region of over 90%.
One last word of caution however is still needed. In Mwanza, improving STD case management led
to a 42% percent reduction in incidence of HIV infection. Such large impact is unlikely to be
generalised to other situations. The impact of STD case management on HIV incidence will depend
on the incidence and prevalence of STD's and the prevalence of other factors that determine the rate
of spread of HIV in the population. Control of "other" STD's is an essential component of every
HIV control programme where the predominant route of transmission is sexual intercourse. It can
however not be considered a "magic bullet" and should be part of a comprehensive package of
interventions which also includes interventions to reduce risky sexual behaviour, prevention of
percutaneous infection and of mother-to-child transmission.
REFEFENCES
1. Report on the global HIV/AIDS epidemic. UNAIDS, December 1997.
2. An overview of selected curable sexually transmitted diseases. Global Programme on AIDS.
STD/GPA/WHO/ESTIMATES/95. 1.
3. Cameron DW, Simonsen JN, D'Costa LJ et al. Female to male transmission of human
immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989, ii: 403407.
4. Laga M, Manoka A, Kivuvu M et al. Non-ulcerative sexually transmitted diseases as risk
factors for HIV-l transmission in women: results from a cohort study. AIDS 1993; 7: 95102.
5. Plummer FA, Simonsen JN, Cameron DW et al. Cofactors in male-to-female sexual
transmission of human immunodeficiency virus type 1. J Infect Dis 1991; 163: 233-239.
6. Grosskurth H, Mosha F, Todd J et al. Impact of improved treatment of sexually transmitted
diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346:
530-536.
7. Ghys PD, Fransen K, Diallo MO et al. The association between cervicovaginal HIV
shedding, sexually transmitted diseases and immunosuppression in female sex workers in
Abidjan, Cote d'Ivoire. AIDS 1997; 11: F85-F93.
8. Cohen MS, Hoffman IF, Royce RA et al. AIDSCAP Malawi Research Group. Reduction of
concentration of HIV-l in semen after treatment of urethritis: implications for prevention of
sexual transmission of HIV-l. Lancet 1997; 349: 1 868- 1873 .
9. Mastro TD, Satten GA, Nopkesorn T, Sangkharomya S, Longini IM. Probability of femaleto-male transmission of HIV-l in Thailand. Lancet 1994; 343: 204-207.
10. Hanenberg RS, Rojanapithayakorn W, Kunasol P, Sokal DC. Impact of Thailand's HIVcontrol programme as indicated by the decline of sexually transmitted diseases. Lancet
1994, 344: 243-245.
11. Laga M, Alary M, Nzila N et al. Condom promotion, sexually transmitted disease treatment,
and declining incidence of HIV-l infection in female Zairian sex workers. Lancet 1994; 344:
246-248.
12. Faxelid E, Tembo G, Ndulo J, Krantz I. Individual counseling of patients with sexually
transmitted diseases. A way to improve partner notification in a Zambian setting? Sex
Transm Dis 1996; 23 (4): 289-292.
STD CONTROL IN PHC SETTINGS
A. Matteelli, G. Carosi*
STI CARE SERVICES
The provision of STI care is an essential component of any Sexually Transmitted Infection (STI)
control programme. STI care services represent an important setting to prevent new infections (by
means of education of STI patients) and to reduce the duration of already established infections,
thus reducing overall STI incidence and prevalence.
Taking care of persons with STI symptoms should be considered a priority in most developing
countries as STI rank in the top ten reasons for medical consultations. Caring for symptomatic
people is also a priority for any STI control programme because it is widely recognised that a
population will not accept preventive interventions for STI (including HIV) unless effective
curative services are already in place.
Patients with STI in developing countries have a choice among a wide variety of services from
which they can seek care. A list of possible sources is shown in table 1.
Table 1: List of potential sources of STI care
The public sector
• Specialised STI clinics
• Outpatient departments of hospitals
• Primary Health Care setting, including health centres and dispensaries
• Reproductive health / Maternal and Child health clinics
• Family planning clinics
The private sector
• Private STI clinics
• Outpatient departments of private hospitals
• Private physicians and specialists
• Pharmacists (where it is legal to dispense antibiotics without prescription)
• First level care through nongovernmental organisations
• Workplace clinic services
The informal sector
• Traditional healers
• Pharmacists (where it is not legal to dispense antibiotics without prescription)
• Unqualified medical practitioners
• Vendors of antibiotics
From Sexually transmitted diseases: policies and principles for prevention and care UNAIDS
documents/97.6
This chapter will briefly review the concepts and difficulties of the integration of STI prevention
and care activities into health care systems. STI care providers need to deliver accessible,
acceptable and high quality service. Advantages and disadvantages of the potential sources of STI
care in the public sector are briefly reviewed. The choice on the most appropriate source may vary
according to the epidemiological situation and the health structure system.
The private sector
In addition to government facilities, other facilities provide much of STD care, although they may
frequently be ignored by the public programs. Other sector providers include both licensed and
unlicensed practitioners. These sources are widely accepted and utilised by the people mainly for
the privacy they ensure, but also for the common belief that they are more effective that the public
health system. For these reasons, people often accept to pay to obtain services in the private sector
more than what they would pay in the public one. The quality of the STD care provided in the
private sector is difficult to assess and may vary substantially. Although evaluating STI care at
private sectors is difficult, planning of a comprehensive programme will need to consider
strengthening health care providers in the private sector as well. One possible tool is represented,
for instance, by the organisation of information and training courses targeted to private and informal
sector health care providers.
Integrated government programs should have two objectives while confronting with the private
sector. First, they should offer a competitive service, delivering high quality care at lower prices, in
order to limit the diversion of patients from the public to the private sector. Second, they should
anyway ensure the co-ordination of efforts between the public and the private sector, in order to
ensure that even the subjects using the private services may obtain appropriate case management.
Specialised dermato-venereology clinics
Specialised STI clinics have received a lot of attention and support (from external donors
especially) in the past because they represent a highly visible form of intervention. As case
management is likely to be very efficient, specialised STI clinics have been considered an optimal
tool in the contest of STI control programmes.
Specialised STI clinics have indeed several advantages in terms of provision of STI care: staff
allocation and training is usually adequate, drugs and other supplies regularly available, reporting is
accurate and management and monitoring of activities are under the direct responsibility of the
central unit.
However, it is virtually impossible to provide specialised clinics that are easily accessible to all
population in both urban and rural areas. In addition, attendance to such clinics may be stigmatising,
particularly for women. These clinics are expected to drain patients with STI who have been
referred by PHC centres, but this is in an unlikely event, and most clients are first-contact patients.
In facts, most patients with an STI who are referred to a second, frequently far-away clinic, usually
report to alternative and often unlicensed health care sources. Referral of patients is therefore not
recommended as it determines the loss of the opportunity to break at an early point the chain of
transmission and to prevent later complications.
In general, specialised clinics are an inappropriate source of STI care for the general population, but
they may still serve as reference centres. They can serve as training centres for health care
providers, can provide essential epidemiological information to steer programme planning and
monitoring, and perform operational research activities. In some urban settings specialised STI
clinics can provide STI care for specific population groups at increased risk for STI, such as sex
workers and their clients, migrant workers, truckers, and any other group with poor access to health
care.
STI care in the PHC setting
An alternative to specialised STI clinics is the offer of case management in an integrated way using
general outpatient agencies at Primary Health Care (PHC) facilities, including dispensaries or health
centres. Only the PHC setting can allow for a wide accessibility, which represents an essential
element of the care process for patients affected by an STI. Other services, such as Family Planning
(FP), Ante Natal (AN) and Mother and Child Care (MCH) clinics offer a great potential for further
extension of the network of health care services and should be involved in STI management as far
as possible.
Integration of STI prevention and care activities into the existing health care system networks is a
tough challenge: it is reasonable to fear that integration may mean adding tasks to unqualified and
already overburdened staff, which leads to dilution of specific efforts and even poorer delivery of
services. Two ways can be pursued to avoid this:
• the overall strengthening of the decentralised health care system
• the sharing of responsibilities by programs, units and departments
The STI package in decentralised health care systems
The integration of STI services into a decentralised health care system requires the existence of a
package of possible intervention: the STI package. The package aims to provide highly effective,
accessible, and acceptable care services at the first point of contact, and merges the two cornerstone
principles of efficacy and simplicity.
Efficacy
Case management needs to be effective to stop current symptoms which have brought the patient to
the care facility, to prevent the development of late complications, to reduce the risk of further
transmission of the etiologic agent to sexual partners, to contain the possibilities that the current
STD infection facilitates transmission or acquisition of HIV infection.
Stopping the symptoms is essential to maintain the trust of the people towards the facility. Which,
in its turn is essential to avoid diversion of the clients to other sectors of health care constituted by
unlicensed providers. An example: vaginal candidiasis is a very frequent condition in the female
population presenting with vaginal discharge; although it is not sexually transmitted and may not
determine direct complications to the women, it should be cared for, in order to clear the associated
symptoms.
In practical terms, effective case management is achieved by an appropriate diagnostic flow and the
use of drugs of high efficacy, as described below.
Simplicity
The STI package should be as simple as possible so that it can be easily incorporated into the
everyday routine of health facilities. The less the routine is disturbed, the less resistance there will
be from the staff.
Components of the STI package
Preventive and curative interventions should be merged in an STI package, a comprehensive tool
which needs to be tailored on specific countries need, but which should still contain all the basic
components of STI case management: diagnosis, treatment, education and counselling, treatment of
partners, and case reporting.
Syndromic diagnosis
Etiologic diagnosis, the ultimate target as far as infectious diseases are concerned, established by
microscope, laboratory culture, or serological tests is expensive, and involves delays in obtaining
the results. Required techniques are simply unavailable in most settings in developing countries.
Clinically oriented diagnosis, the usual alternative method, avoids expenditures for laboratory tests
and is done on the spot. However, it is inaccurate or incomplete (mixed infections always
unrecognised) in the majority of instances, leading to an unacceptable drop of effectiveness of case
management.
Syndromic management has been proposed to overcome the limitations of etiologic and clinical
diagnosis: it consists in identifying the syndrome the presenting patient complains of, and deliver
treatment towards all the epidemiologically relevant agents causing that syndrome. Flow-charts are
used to help the health care provider to reach a treatment decision. This approach is effective and
complete; though over treatment certainly occurs, it has a competitive cost-effective profile
considering that prevents late complications.
Laboratory tests
Syndromic diagnosis allows for appropriate case management in the absence of laboratory facilities,
however, laboratory tests may be added whenever possible. Few tests are applicable to PHC setting,
provide on-the-spot results and are therefore useful for STD case management:
• wet mount of vaginal samples to diagnose trichomoniasis, candidiasis and bacterial vaginosis in
women presenting with vaginal discharge
• Gram stain of urethral samples to identify intracellular diplococci (suggestive of gonococcal
infection) and leukocytes in men with urethral discharge
• syphilis serological tests (RPR or VDRL) at AN clinics for screening of the infection in pregnant
women
Details on all the above tests are given in the relevant chapter of this book.
Risk score method in syndromic diagnosis
Women with vaginal discharge pose significant problems in syndromic case management, due to
the difficulties in differentiating vaginal infections (yeasts, trichomonas, bacterial vaginosis) which
are not, except for trichomonas, STI in strict terms, from cervical infections (gonorrhoea,
chlamydia), which are true STI. To help in managing this specific problem the WHO has proposed
and tested a system which considers the presence of markers of behaviours at increased risk of
sexual exposure. These systems have been applied with some success to symptomatic women in
countries of sub-Saharan Africa. The identified markers include young age, single status, history of
multiple partners in the last month or of a new partner in the last three months. The presence of
symptoms in the current sexual partner is also associated to the presence of cervicitis.
Treatment
The availability of effective drugs is an essential requirement for appropriate STI management. STI
treatment should offer a cure rate of at least 95%. Using less costly but less effective drugs does not
eradicate infection in a substantial proportion of cases, may lead to carrier state with transmission to
sexual partners, and erode the confidence in health services. Preference is given to drugs which are
given as a single dose because this increases substantially adherence to treatment. Preference is also
given to orally administered drugs, thus avoiding risk of needle-prick accidental exposure to HIV
among health personnel and the clients. Pregnancy is a condition which requires special caution
and, sometimes, second line drugs.
It is a specific task for the central level to envisage drugs which are acceptable and available in the
country (Table 2). Co-ordination with the Essential Drug Programme is essential.
Education and counselling
Case management of a patient with an STI offers a unique opportunity to educate subjects who are
likely to be very sensitive to the problem in order to prevent future acceptance of high risk
behaviours.
Education involves giving patients practical information about their disease, its name, symptoms
and treatment. It is also about helping a patient to understand how STI spread and why it is so
important to treat them. Another vital part of education is helping patients to understand how they
can protect themselves, their partner and children in the future.
Counselling is a face to face communication between a person with a problem and a person who
tries to help solving the problem. Counselling of STI patients involves a whole range of skills from
listening to their problems to giving them the motivation to follow medical advice.
Education and counselling of a person with an STI requires special skills, as these diseases involve
the deeper part of an individual and are the targets for several prejudices. To this aim, the health
care providers should receive training in counselling.
Condom supply
Condoms should be available throughout all regular health care services and, specifically, to
patients with STIs. This is complementary to condom distribution through social marketing
mechanisms.
Treatment of partner(s)
Partner(s) notification and treatment is a specific and essential component of STI case management,
intended to interrupt the chain of transmission. The aim is to treatment all sexual partners (at least
within the previous three months) of the index case for the same conditions as in the index case.
Whenever implemented, contact tracing needs to observe the principle of confidentiality and noncompulsion as an essential prerequisite.
However, it seems reasonable to proceed to more intensive contact tracing activities only once
routine STI prevention and care are functioning.
Case reporting
Case reporting has several purposes:
• assess disease burden, by providing an indicator of minimum incidence of recently acquired
infections
• monitor trends in incidence of recently acquired infections
• provide information of which provider in the health care system is seeing STI patients, to assist in
planning and managing programme efforts
• provide data necessary for managing health services (e.g. pharmaceutical distribution)
Syndromic case reporting is simple. An example of a reporting form, adopted at PHC clinics in the
Indian Ocean countries, is shown in table 3. It should be noted that the adoption of a specific form
for STI is impractical and unnecessary in an integrated system: the information should be contained
in the general reporting form of the clinic.
Table 3: Form for syndromic cases reporting of STI patients
Syndromes
Age
<15
Vaginal discharge
Urethral discharge
Genital ulcers male
Genital ulcers female
Abdominal pain
Inguinal bubo males
Inguinal bubo females
Neonatal conjunctivitis
15-19
Total
20-40
>40
Acceptability of services
Acceptability is mainly related to the capacity not to stigmatise clients: in this respect the PHC
setting offers clear advantages compared to specialised clinics. However, the judgmental attitude of
the caring staff may reduce clients acceptability even in a decentralised health care system. This
issue should be included in retraining courses of staff.
Acceptability of the service may be reduced by other constraints, which may include, for example,
inconvenient opening times, long waiting periods, or unattractive physical facilities. Ideally,
services should be offered after usual working time as STI patients may delay seeking treatment or
choose self-medication rather than asking for time off work. Appropriate time should be available
for consultation of STI patients, as counselling and education, two essential elements of appropriate
case management, require at least 20 minutes, a time which is hardly available in settings which are
usually overcrowded by patients with all kind of health problems. The premises should also be
appropriate: STI patients need privacy, both in case genital examination is required, and during the
education and counselling activities.
Free services versus cost recovery methods
One factor which may reduce substantially accessibility of health care services is the cost of care.
Although some countries are still offering free basic health care services for the entire population,
many other have realised that cost-recovery systems are essential in order to sustain the costs of
health at public facilities, as the regular health budgets in most developing countries are insufficient
to afford acceptable standards. In many countries patients are used to pay for drugs, or at least
making some contribution, and a policy of cost recovery may be considered as an option. However,
the introduction of cost-recovery mechanisms should not discriminate against STI patients and
should not ignore people needs. The introduction of cost recovery methods may turn into a decrease
of the number of STI patient consultations, as it has been demonstrated in several settings. Costs
should always be kept to a minimum, because a proportion of symptomatic subjects may still find it
impossible to attend for financial constraints. However, since the private sector is not free, the
minimum requirement for public health facilities is to offer a competitive service, delivering highly
effective care at lower costs than those of the private sector.
Most common problems in STI delivery at PHC setting
Delivery of STI care in an integrated and decentralised setting is far from being an easy and
automatically achievable task. It makes little sense to integrate STI care into a virtually non-existent
or poorly functioning structure. Work overload and low salaries are common constrains. These
represent the major structural draw-backs of the PHC system in most countries. These problems can
be overcome by profound structural changes only, which are far beyond the scopes of integration of
STI care into the PHC system.
Examples of some common obstacles that may additionally hamper integration of STI care into the
PHC system are detailed in the section below.
Premises are not appropriate
STI case management requires privacy. Overcrowding, sharing the rooms with other patients or
health care providers significantly hamper the possibility of privacy during clinical examination,
and prevent the establishment of an appropriate climate for counselling and education.
Upgrading of premises is an example of investment costs that donors may wish to make to assist
health development programmes, provided that this intervention fits into a comprehensive initiative,
and that recurrent costs originated by the upgraded premise can be met locally. In a cost-recovery
system, part of the savings should go to maintenance of the premises.
Personnel is not adequate in number
This is an example of structural deficiency. It cannot be solved while implementing integration of
STI services into the system. Great attention should be paid to limit new charges for STI and to
maintain introduced practices as simple as possible.
Guidelines for STI care are not available
National guidelines for the management of a patient with STI must be produced and distributed by
the central office (with the collaboration of the district management). Guidelines should be prepared
through a large consensus of health care providers at central and peripheral levels.
Personnel not specifically trained for STI care delivery (and use of guidelines):
Once guidelines have been distributed health care providers need to be trained to use them
appropriately. This can usually be achieved by means of decentralised, on-job, short-course training
(one-day courses may be sufficient). Decentralised training requires a training of trainers approach
organised by the central office.
Guidelines are not followed
The usual cause of this problem is the lack of training of the staff (see above). Lack of regular
supervision, which is necessary to maintain an acceptable rate of observance to the guidelines, may
be an additional reason. Alternatively, the algorithms proposed in the guidelines may either be too
complicated or ineffective. Guidelines may therefore be revised to make them simpler. The efficacy
of the proposed algorithm needs to be measured regularly and, if efficacy drops below an acceptable
standard, the algorithm needs to be revised. Low efficacy of the algorithms may be due to wrong
estimates or assumptions related to the following parameters
- spectrum of etiological agents causing the syndromes
- perception of symptoms by the patient
- antibiotic resistance
- availability and price of drugs
Gynaecological examination is not feasible
Gynaecological examination is not essential in the frame of syndromic case management. If the
guidelines call for gynaecological examination appropriate premises, facilities (beds, specula, etc.)
and specific training need to be in place.
The algorithms call for lab tests which are not available
This is a frequent mistake. Laboratory tests are attractive to policy makers, due the common belief
that they make the intervention more visible, and to the clients, who have the impression of a higher
quality management. Whenever laboratory investigations are included in standard management
practices at PHC level, regular supply of reagents, appropriate stocking of reagents and quality
control of tests need to be in place.
Recommended drugs are not available
The availability of effective treatment is an absolute requirement in an STI care setting. It is a
specific task for the central level to envisage drugs which are acceptable and available, and to
guarantee the regular supply of recommended drugs at the PHC network. In fact, unavailability of
recommended drugs is one of the more common consequences of the financial problems faced by
the public health system in many countries. Cost recovery methods may represent a solution in
some settings.
Counselling is not performed
Poor staff communication skills is a common problem. It takes special efforts to appreciate the
different disease perceptions, especially of adolescents. Appropriate and specific training on
counselling skills need to be planned, performed, and evaluated.
Educational tool may be specifically prepared and distributed (flip charts, leaflets etc.).
Condoms and other means of education are not available
It is the responsibility of the STD control programme to ensure that condoms are widely available
throughout all regular health care services. Whether condoms need to be distributed freely to STD
patient is a matter of political decision.
There is no case recording
Registration of cases is done almost everywhere. Sometimes, however, the information registered is
not useful or sufficient for the sake of case reporting of STI patients and monitoring of
appropriateness of the use of the algorithms. Registers might need to be modified according to the
scope.
There is no case reporting
It is not advisable to have a special reporting system for STI. Therefore it is essential that the
official reporting form will include STI syndromes. Thereafter, the problem of regular reporting is
common, not specifically related to STI. In special instances a specific surveillance system may be
put in place, but this will generally be at sentinel sites and monitored by the STI units themselves.
Partners are not notified or treated
This is one of the major problems at PHC level, where it is difficult to dedicate special effort to this
activity. A system of tags is advisable: tags are given to the patient to be passed to all partners under
the responsibility of the patients him(her)self. The partners will be treated as the index case, being
identified by the tag they present on consultation. Initially, the success rate of partner notification is
usually very low, but it can be increased by appropriate counselling and education of the index case.
Coercitive means of partner notification are impossible at the PHC level and are definitely
counterproductive.
REFERENCE
1. Joint United Nations Programme on HIV/AIDS (UNAIDS). Sexually transmitted diseases:
policies and principles for prevention and care. Document UNAIDS/97.6, 1997.
2. AIDSCAP / Family Planning International. From Control of Sexually Transmitted Diseases,
a Handbook for the design and management of Programmes. Dallabetta G, Laga M, and
Lamptey P Editors 1997.
3. World Health Organisation. Management of sexually transmitted diseases.
WHO/GPA/TEM/94.1, 1994
4. Department for International Development. Sexually transmitted infections: guidelines for
prevention and treatment. Health and population occasional paper, 1998.
STD CONTROL IN FEMALE COMMERCIAL SEX WORKERS IN AFRICA
Elizabeth N. Ngugi, D. Jackson
Introduction
This paper will be divided into three sections. The first will describe briefly the STD/HIV/AIDS
problem in Africa, the second strategies and intervention that have been tried and the third will
suggest the way ahead into the next millennium.
Africa is still experiencing an explosive epidemic of sexually transmitted diseases (STD) including
human immunodeficiency syndrome (HIV) which will continue well into the next millennium if
drastic measures are not taken to slow down the transmission.
According to the World Health Organization estimation 1995, 333 million cases of curable sexually
transmitted diseases (STDs) occurred in the world, 65 millions of which were from Sub-Sahara
Africa alone. The vast majority were between 15-49 years of age.
Table 1: Number of cases of STD by type for Africa in 1995
Sexually transmitted disease
New cases (in millions)
Syphilis
3.5
Gonorrhoea
16
Chlamydia
15
Trichnomoniasis
30
Total
64.5
Source: World Health Organisation, STD Estimated Cases, 1995 (1)
Given the sexual behaviour of the female commercial sex workers (FSWs) in Africa i.e. frequent
partner change (2-10 per day with an average of 4) and lack of condom negotiation skills, poor
power relations and low economic status the STD attack rates is higher in this population. The
importance of holistic management of these diseases cannot be overemphasised as "the presence of
STDs suggests a marked risk of concurrent HIV infection (2)".
In view of these rates of STD infections, high HIV prevalences have been reported in Africa. For
example, more than 10 percent of women attending antenatal clinics in the 80's surveyed in urban
areas of Kenya, Malawi, Rwanda, Tanzania, Zambia and Zimbabwe have been found infected with
HIV. Similar patterns of HIV spread have expanded to Botswana, Lesotho, Swaziland and South
Africa. The situation is even more explosive in FSWs where HIV sero prevalence ranges between
55% in Abidjan to 80% in Nairobi (3).
Targeted intervention is not easy as this latter population is hard to reach. However, although
prostitution is illegal in these countries, sometimes, the Administration is tolerant to the practice as
is the experience in Kenya (although intermittent harassment continues) which makes mobilization,
education, counselling, condom provision and referral for STD treatment more manageable. The
most difficult of these groups are street walkers and bar pick ups compared to home based and other
institutionalised forms of commercial sex.
Once FSWs are organized, it becomes easier for them to make collective decision about consistent
condom use and regulate their charges to avoid exploitation and safeguard their income (4).
Considering the importance of transforming FSWs into agents of change by, first becoming safer
sex practitioners, secondly protecting their clients from STD/HIV, thirdly educating their peers and
fourthly seeking prompt treatment when infected, this paper seeks to examine targeted interventions
across the African region starting with Zimbabwe.
The Zimbabwe study was done to describe and evaluate an intervention to reduce STD transmission
among FSWs and their clients. The design included formation of two committees, one of the
professional staff and the other one of FSWs. The women were given cards after examination
without which they could not enter premises to practice their trade. They were examined monthly
for STDs. The result indicated that total case of STDs among males dropped from 452 cases in
March 1988 to 117 in December, 1988 in a country where prostitution is illegal. The conclusion
was that regular testing and treatment of STD of FSWs is effective in reducing transmission rates
which in turn would lower the HIV transmission rates. The limitation of the study was that the
women could use one another's card (5). The writers' view is that the card can also be used by
authority to harass the women and the same can/does break confidentiality, thus forcing the women
underground to hide their profession.
Another project in Nigeria was set to describe and evaluate an HIV prevention programme among
FSWs. Full time prostitutes in 19 states including a sea port were recruited. A total number of 1150
FSWs and 1600 clients were thus reached and 4000-5000 condoms distributed monthly. The
number of STD patients increased from 16135 in 10 months presumably due to this advocacy.
Condom use increased from 12.2% at baseline to 24.2%.
The programme "faced obstacles including apathy, lack of trust etc. (6)" It is suggested that the
itemised problems could be reduced by understanding the structures of the target population as part
of the design.
An intervention to implement and evaluate an HIV prevention programme among 595 FSWs in
Nairobi, Kenya was carried out between January and May 1985. A committee comprised of the
researchers and the study population was set to oversee the implementation. The study population
was divided into 3 groups namely, those who received intensive education and counselling (N=91),
those who received less intensive education and counselling (N=67) and the control group (N=205).
All groups received free condoms. Results indicated that condom use at baseline among three
groups was 10%, 7% and 7% respectively. STD assessment was carried out and treatment given
appropriately.
In November, 1986, condom use was found to have increased to 81%, 70%, 58%. This shows a
dose response relation between increased exposure to health education and increased condom use.
There is also a clear a dose response relationship between condom use and decreased risk of HIV
seroconversion. The conclusion was that "the high efficacy of condoms in preventing HIV infection
could in part, reflect a multiplier effect of condoms use. Reduced incidence of STDs was identified
and this increased condom use resulted in a 3 fold reduction of HIV seroconversion. Therefore
proper condom use with all sexual partners is vital with any population that has high frequency of
partner change and high prevalence of STD. Of importance is that the FSWs must be part of the
process of education and counselling. They have the same knowledge as their peers, and unique
language, having lived through the experience themselves (7).
Interventions in Kenya and Zimbabwe were carried out to describe and evaluate two HIV
prevention programmes. In Kenya the experience of successful intervention at Pumwani, Nairobi
set the stage for replication in four other sites namely, Korogocho slum, Nairobi, Machakos, Nakuru
and Thika. This was through informal contact and use of key informants at the entry point. Sexual
Educational Barazas or Open Meetings, were carried out and weekly peer education and social
meetings were held. These were supervised monthly by the researchers. Condoms were made freely
available at no cost and traditional and other appropriate media such as drama, songs, dance,
posters, pamphlets and video were used. Counselling was provided for those with STD/HIV/AIDS
allowing difficult issues such as condom negotiation, increase of charges uniformly for a single sex
act to be discussed and resolved. These activities resulted in more cohesive group formation.
Of the women reporting any condom use (virtually all women) it was shown that a 3-fold reduction
in incidence of HIV infection occurred. Reported condom use among FSWs rose from virtually nil
in 1986 to about 80% of all reported sexual contacts by 1989, and has remained at that level since.
Declines in STD rates; for example, the mean annual gonorrhoea incidence rate fell from 2.85 cases
per woman in 1986 to 0.66 cases per women in 1989. It is estimated that over 10,000 new cases of
HIV infection are prevented each year by the Pumwani programme which covers about 500 FSWs
(8). A decline in STD has been observed in the number of men from Pumwani attending the main
Nairobi STD clinic.
Evaluation carried out in the four new Kenyan sites (mentioned above), one year after
implementation showed that the number of women who reported "always" using a condom
increased from 4.6% at baseline to 36.5% (P=002).
An evaluation done in Bulawayo Zimbabwe in 1992 showed 4400 community meetings were held
with 380,000 attendees. More than 2.4 million condoms were distributed to this population.
However, the programme identified lack of funding, lack of political commitment (for sex worker),
deficiencies in planning, lack of management and human resources (9).
A well planned and implemented intervention in Kinshasa, Democratic Republic of Congo
(formerly Zaire), provided excellent information as well as encouragement for further interventions
(10). It was a combined behavioural intervention (largely condom promotion) and monthly STD
screening and free treatment. A cohort of 531 initially HIV-1 negative female CSW were followed
from 1988 to 1991. Study participants were seen every month for interviews and STD laboratory
diagnosis, and screening for HIV-1 antibodies every 3 months. Women received individual health
education and free condoms monthly. In addition, every 3 months group sessions for condom
promotion were held. HIV-1 incidence declined steadily from 11.7 per 100 PY during the first 6
months of follow-up to 4.4 per 100 PY over the last 6 months of follow-up, 3 years later (p<0.001).
There was a significant relationship between incidence rates and different levels of clinic use. The
HIV-1 incidence rate increased from 2.7 per 100 PY among the most frequent clinic visitors to 7.1,
20.3, and 44.2 per 100 PY among regular, medium and irregular visitors, respectively. Condom use
was also associated with regularity of clinic visits, but the declining trend of HIV-1 incidence with
increasing regularity of clinic visit remained significant for both regular and irregular condom users.
This is evidence that use of the clinic, with STD care, had an independent impact on the incidence
of HIV-1, in addition to its impact on condom use. A recurrent theme in CSW interventions is that
the main obstacle for reaching 100% condom use was male clients' refusal, highlighting the urgent
need for additional chemical or physical barrier methods which are under the control of women.
A "saturation effect" can occur when the incidence of HIV infection declines due to the fact that the
most susceptible individuals seroconvert first, whether or not there is a preventive intervention. The
lower risk individuals in the cohort get infected at a lower rate because they are people who engage
in less high risk behaviour, or because of other constitutional factors which remain to be fully
elucidated. The Zairian CSWs who seroconverted did not report a significantly higher mean number
of partners that those who did not seroconvert, suggesting that they were not a higher risk group. On
the other hand, people who comply with requests to attend health facilities regularly are more likely
to be compliant with other facets of the intervention, in ways which are not fully measured. These
factors which were not fully taken into consideration in the analysis but can influence the result,
called residual confounding, are potentially present in every intervention. Examples of potential
sources of residual confounding in CSW intervention research are client mix and elements of client
choice, and this phenomenon can interfere with accurate interpretation of the results for the
purposes of introduction of an appropriate intervention method mix.
The increasing difficulty in the African region, experienced by women to convince men to use
condom for prevention of STD/HIV and the continued rapid spread of these infections have
highlighted the urgent need for the scientists to discover a method of prevention that are under
direct control of the woman be it a female sex worker or otherwise. It is with this in mind that a
prospective, randomised placebo-controlled trial was initiated in Nairobi, Kenya's female sex
workers. This was to determine the efficacy of N- 9 contraceptive sponge in preventing sexual
acquisition of HIV.
In this study, 138 HIV seronegative FSWs were enrolled of whom 74 were assigned to N-9 sponge
use and 64 to placebo use, an oil based vaginal suppository as a placebo sponge was not possible to
manufacture. The two groups did not significantly differ with respect to demographic
characteristics, sexual practice, or prevalence of genital infections at enrolment, except for a lower
number of sex partners per week and a higher initial prevalence of genital ulcers among women
assigned to N-9 sponge use. Among the 116 women who returned for follow-up, the mean duration
of follow-up were 14 and 17 months for the two groups, respectively.
The result indicated that N-9 sponge use was associated with an increased frequency of genital
ulcers and vulvitis. Twenty seven (45%) of 60 women in the N-9 sponge group and 20 (36%) of 56
women in the placebo group developed HIV antibodies. The hazard ratio for the association
between N- 9 sponge use and HIV seroconversion was 1.7 (95%, CI, 0.9 to 3.0). Using multivariate
analysis to control for the presence of genital ulcers at enrolment, the adjusted hazard ratio for the
association between N-9 sponge use and seroconversion was 1.6 (95%, CI, 0.8 to 2.8).
Genital ulcers and vulvitis occurred with increased frequency in N-9 sponge users. We were unable
to demonstrate that N-9 sponge use was effective in reducing the risk of HIV infection among
highly exposed women11. A large randomised controlled study in FSWs in Cameroon showed no
beneficial effect of and use of N-9 film in prevention of HIV infection.
Considering the majority of FSWs in Africa are driven into it by poverty, a study was carried out in
Kenya to identify and measure safer sex practices including condom use as well as reported status
of gTDs as a result of improved social economic status. This method was used due to lack of
laboratory support.
The 30 women were educated, counselled, and provided with condoms. They were also individually
supported and trained to start alternative income generating activity of their choice. Finance to
support their small businesses were provided ranging from US $ 75 to US $ 220 payable in 12
months.
Their income through alternative generating activity improved i.e. those earning US $ 15 increased
from 27% to 33% and US $ 8 increased from 33% to 43%. Significant decrease is those earning US
$ 3 to US $ 6 per month i.e. from 37% to 23%.
Sexual partners decreased from 2-10 per day to 0-5 per day. Two of the 30 women suspended
having sex and are not sure how long this will go for. Negotiation for safer sex even with the
"lover”,” husband" which is most difficult to change increased to 93.3% within about one year.
It is noteworthy that 80% of the women had suffered an STD a year before the study compared to
zero STD during the study period. Their self-esteem was noticeable in all of them. Drinking of
alcohol decreased from 73.3% to 43.5% and smoking from 16.6% to 0%. All in all, the change in
these women was remarkable. This is because for once, they were engaged in an income generating
activity of their choice and not being forced into commercial sex due to lack of an alternative.
Suggestions for The Way Ahead Into the Next Millennium
There is just not sufficient coverage and targeted interventions for FSWs and their clients in African
countries. Some have not even attempted to address the issue of STD/HIV/AIDS in relation to
FSWs as a group that needs destigmatised holistic services. In our view, integrating FSWs
interventions within the existing primary health and social/economic structures will yield greater
and faster results. This should go hand in hand with youth and women STD/HIV prevention and
control programmes. The rationale being advanced here is that FSWs clients are youth and men in
the general population who also have other sexual partners including wives and girlfriends.
Proposed programme components:
1) Sensitise policy makers to enact laws which lead to tolerance of FSWs. This will be a
cornerstone to destigmatisation and allow these women to enjoy a greater degree of human rights.
It will also allow the government to set aside specific funding and to solicitate further input from
the donor community.
2) Mobilization of FSWs for a systematic STD/HIV/AIDS prevention course that includes
participatory education, prevention, and positive living when infected and peer counselling.
3) Proper use of condom always even with the "lover". This is crucial in the absence of a vaccine or
cure. Storage and disposal methods should be covered in education. It is also important for FSWs to
know where to get condoms from i.e. clinics, chemists and peer educators. The condoms should be
free or at a price the FSWs can afford.
4) The FSWs should be trained and offered opportunities for alternative income generating
activities. This is because according to the writer’s experience, well over 90% of women in Africa
are in commercial sex due to poverty and lack of an alternative. The low economic status also
interferes with condom negotiation and therefore should be addressed.
5) Although condom is the prevention method of choice, it is not 100% efficient due to breakage or
slipping, meaning that some FSWs will still get infected. Therefore prompt and proper management
of STDs which includes counselling, condom use, contact tracing and compliance is vital for
prevention of HIV transmission.
Treatment of STDs as a strategy for HIV prevention is well documented in Mwanza. In Tanzania
early treatment in a rural population has been associated with a 42% decline in the rate of newly
acquired HIV infections (12).
In view of the foregoing, it is suggested that well articulated STDs programmes be an integral part
of Primary health care settings, and that STD clients be they FSWs or otherwise get the service
advantage where they live and work. This service should also be affordable and should have
sufficient as well as proper drugs for treatment.
The World Health Organization has suggested use of appropriate (well tested) flow charts for
management of STDs where laboratory support is scarce or unavailable. Kenya and other African
countries, have been using syndromic management of STDs for over 5 years. It has assisted in
improving access to good STD care, and has proved popular with staff and clients alike.
Training of all operatives at various levels is imperative. Training of Trainers Course (TOT) should
be taught by well prepared facilitators in community mobilization with focus to special groups such
as FSWs and clients.
The TOTs in turn should be supported to train sufficient number of health care providers and related
fields (i.e. social workers) to carry out the task in holistic manner and in a way that ensures
maximum coverage of target population.
Female commercial sex workers peer educators is another strategy necessary to ensure that
ownership and continuity are maintained. This also bridges the gap between the FSWs and the care
providers in health and social sectors.
It is also important to include all the 5 components discussed in this paper in each country's preservice training for health care providers, the clinicians e.g. Doctors, Nurses and Clinical Officers,
getting the whole package and the non clinical cadre i.e. public health technicians, laboratory,
pharmacy etc. getting the education package that has STD/HIV/AIDS education, counselling,
community mobilization and condom promotion only.
Conclusion
In conclusion, the issue of FSWs in Africa can no longer be swept and left under the carpet, but
should be part of inclusive (integrative) strategy for prevention of HIV transmission and reduction
of its impact such as overcrowding in hospitals, deaths and orphans.
REFEFENCES
1. World Health Organization Estimated STD Cases in the World, 1995.
2. Tarantola D, Lamptey P. The Status and Trends of the HIV/AIDS/STD Epidemics in SubSahara Africa - Provisional Report Abidjan Cote D'Ivoire, Dec. 1997.
3. UNAIDS: The Status and Trends of Global HIV/AIDS Pandemic July 5-6 1996 Final
Report.
4. Ngugi E.N.: Personal interview with CSWs from Kenya, Tanzania and Uganda, 1997.
5. Chipfakacha V.: Prevention of Sexually Transmitted Diseases: the Shurugwi Sex-workers
Project, 50 Afar. Med. J 1993; 83:40-41.
6. William E. Lamson N., Efems S. Weir S. Lamptey P.: Implementation of STDs Prevention
programme among prostitutes in the Cross River State of Nigeria. AIDS 6(2): 229-30.
7. Ngugi E.N., Plummer F.A., Simonsen J.N., Cameroon D.W., Bosire M., Waiyaki P., Ronald
A.R., Ndinya-Achola J.O.: Prevention of Transmission of Human Immunodeficiency Virus
in Africa: Effectiveness of Condom Promotion and Health Education Among Prostitutes.
Lancet 1988; 2:887-90.
8. Ngugi E.N. Njeru E.K. Kariuki B.K., Muchunga E.K., Moses S., Plummer F.A.: Dynamism
of Focused AIDS/STD Education/ Counselling: A Cohort Study of Wome with High
Frequency Partner Change (Prostitution).
9. Ngugi E.N., Wilson D.,Sebsted J., Plummer F.A., Moses S.: Focused Peer Mediated
Educational Programmes Among Female Sex Workers to Reduce Sexually Transmitted
Diseases and Human Immunodeficiency Virus Transmission in Kenya and Zimbabwe. J of
Inf.Diseases 1996; 174 (suppl. 2): S240-7.
10. Laga M., Alory M., Anzala N., Monoko A.T., Behets F., Goeman J., St.Louis M., Piot P.:
Condom Promotion, Sexually Transmitted Diseases Treatment and Declining Incidence of
HIV1 Infection in Female Zairian Sex Workers. Lancet 1994; 334:246-48.
11. Kreiss J., Ngugi E.N., Holmes K., Jeckonia N.A., Waiyaki P., Ruminjo I., Sajabi R., Kimata
J., Feeming T.R., Anzala A., Holton D., Plummer F.A.: Efficacy of N-9 Contraceptive
Sponge Use in Preventing Heterosexual Acquisition of HIV in Nairobi Prostitutes.
12. Ngugi E.N., Staugard F., Gallachi A., Njoroge M., Waweru A.L Social Economic
Empowers Commercial Sex Workers to Reduce Reported Attack Rate of STDs. Xth
International Conference on AIDS and STD in Africa, Abidjan, December 1997. (C. 290).
DESIGNING STD SURVEILLANCE SYSTEM IN THE TROPICS
A. Gerbase, Silvia Titan, W. Levine
Introduction
The global burden of sexually transmitted diseases (STDs)
STDs are a major cause of morbidity throughout the world. The World Health Organization has
estimated that in 1995 there were 333 million cases of curable STD (gonorrhoea, chlamydia,
syphilis, and trichomoniasis infections)l. Although the incidence of bacterial STDs has declined in
many developed countries, incidence and prevalence rates of STDs in developing countries remain
high.
The consequences of STDs are most severe for women and children. In high prevalence areas, these
diseases rank second as a cause of healthy life lost in women aged 15 to 45 years, after maternal
morbidity and mortality (not including HIV)2. Untreated chlamydial and gonorrhoeal infections can
lead to acute pelvic inflammatory disease and its complications which include infertility, ectopic
pregnancy, and chronic pelvic pain. Human papillomavirus infections have been strongly associated
with cancer of the uterine cervix.
There are also the well-known effects of STDs on the foetus such as spontaneous abortion,
stillbirth, prematurity, and congenital syphilis. Another important sequela of untreated infection is
ophthalmia neonatorum, a result of N. gonorrhoeae or C. trachomatis ocular infection during
delivery.
STD control is important not only to prevent these consequences, but also because of the
relationship of STDs with HIV infection and transmission. Numerous studies have shown that both
ulcerative and non-ulcerative STDs facilitate HIV transmission3-8. Therefore, STD control is now
recommended as an important way to enhance HIV prevention efforts. In a community-based,
randomised trial in the Mwanza Region, Tanzania, STD syndromic treatment resulted in a 42%
reduction in HIV incidence9. Furthermore, as HIV and other STDs share the same behavioural risk
factors, behavioural interventions to control the former will have beneficial consequences on the
latter.
STD surveillance can be coordinated with HIV surveillance activities. First, ongoing activities in
each area can be used to provide data about the other (for example, performing syphilis testing in
HIV serosurveillance sites or performing HIV testing in selected populations that are routinely
screened for syphilis). Second, according to the pattern of the HIV epidemic in a country, STD
surveillance activities can be modified to better target and evaluate the impact of HIV prevention
programs. These concepts are discussed further below.
Importance of STD surveillance
Despite its importance, surveillance data on STDs have been scarce and those that have been
available are problematic and cannot be used to accurately assess the global STD situation. An
improved STD surveillance program aims to:
• evaluate the magnitude and regional distribution of STD, i.e., the prevalence and incidence
rates;
• identify trends in infection rates;
• identify groups with high incidence and prevalence of disease;
•
•
•
•
•
define aetiologies of STD syndromes;
monitor antibiotic resistance;
establish realistic outcome objectives for prevention programs;
define resources that are necessary and advocate for support; and
evaluate effectiveness of control programmes over time.
Accurate STD surveillance information is necessary to develop activities to interrupt STD
transmission, to prevent their complications, and to reduce HIV transmission. A major question,
however, is how to design an STD surveillance program.
Alternatives for STD surveillance
Universal case-reporting
Systems of universal case-reporting rely on the collection and reporting of data by health care
providers throughout the country. A system of universal reporting can be useful to the event that it
provides information on the whole population and not only on a sample. Also, it makes use of the
existing infrastructure for communicable disease surveillance. However, universal case-reporting
can yield information of limited quality on the true disease burden since its reliability depends on
the extent to which patients seek health care (especially important for STD), on consistent use of
case definitions, on the validity and completeness of case-reports, and on quality of diagnostic
methods. Frequently, there is no accurate information on population-level denominators, making the
interpretation of data even more difficult. Even countries with well-organized health care systems
have high rates of under diagnosis and under reporting of STDs.
However, universal case-reporting data can be very useful to the extent that they are a source of
information on which health care providers (and, in some countries, laboratories) are diagnosing
STDs. Sites that are not reporting, or where reporting has suddenly declined, should be contacted to
determine if the decline is due to lack of drug availability, lack of trained personnel available to
diagnosis STDs, or if it is only a problem of submitting case-reporting forms. Data from a system of
universal reporting can be made even more useful if they are compared with other sources of
information (e.g., prevalence surveys).
Sentinel sites and populations
In a sentinel-site case-reporting system, selected clinical sites report STD cases on a regular basis.
Selection of sentinel sites (or "enhanced surveillance sites") make it possible to work more
intensively with designated clinics to systematically collect data and to obtain high quality
information. If the cost of these surveillance activities is minimized, this activity may be integrated
into existing services.
Ideally, sentinel case-reporting sites should be chosen to obtain some representation of the whole
population attending clinical services. Sites should be selected in most geographic areas (urban and
rural), include different types of clinics where STDs are usually seen (primary health care, general
outpatient departments, specialized clinics, private and public sectors), and which can provide
reliable information on the overall clinic population (denominators). Even if some of these
conditions cannot be met but the data are collected consistently, they may be of some use.
If patterns of clinic attendance (including overall numbers and types of patients) do not fluctuate
substantially over time, data collected from these sites may be used to monitor trends in numbers of
STD cases, in proportions of clinic attendees with STDs, and in types of STDs. However, if this
condition is unlikely to be met, or if placing emphasis on sentinel case-reporting sites detracts from
efforts to integrate STD care more broadly into primary health care, it may be preferable to
strengthen the universal reporting system rather than to use scarce resources for sentinel-site case
reporting.
It is well known that many patients with STDs do not seek health care from clinicians, and self-treat
their infections using drugs they have obtained from pharmacies. Others may receive treatment
from traditional healers. Ideally, pharmacies should also be included in sentinel surveillance in
order to make data more representative; however, the feasibility and utility of this approach have
not yet been demonstrated. Another approach may be to perform special surveys to estimate how
many patients with STD do not reach the formal health care system.
For monitoring STD prevalence (an activity distinct from case-reporting), among the most
important sentinel populations is pregnant women, seen either at antenatal clinics or examined at
delivery. Although pregnant women at these sites can be quite representative of women in the
general population, as they are seeking health care for reasons unrelated to STD symptoms, data
obtained on this population does have biases. Women with reduced fertility are under represented;
infertility is an important consequence of untreated STD. In some settings, pregnant women who
have multiple sex partners may be less likely to seek clinic-based care than those who only have
stable partners. In addition, women who are consistently using condoms are less likely to become
pregnant (and thus will not be presenting for care at these sites).
It is especially important to obtain data on STD prevalence among female sex workers, and other
persons at high risk. This is especially important as part of basic surveillance activities because
limited data are being collected. Findings of high STD prevalence in persons at high risk can serve
as a warning signal regarding the general population. Other sentinel populations that can be used for
assessing STD prevalence include blood donors, military recruits, and factory workers. Their
representativeness depends on the socio-cultural characteristics of each group.
Special surveys
Universal case-reporting and sentinel surveillance activities can be used to provide data on trends in
incidence and prevalence of disease (this will be discussed below). However, when further
information is needed, additional STD surveillance related data need to be obtained. Among the
most important supplement activities include monitoring of N. gonorrhoeae resistance and studies
of proportional distribution of aetiologies associated with each major STD syndrome.
Syndromic and etiologic reporting
In most countries, laboratory examinations for diagnosing STDs are not widely available.
Diagnostic and therapeutic decisions are made syndromically, therefore case reports should also be
syndromic. This approach is feasible since it is rapid, does not depend on laboratory confirmatory
examination nor on specialized staff, and can yield useful information. Case-reporting of syndromes
characterized by symptoms which present acutely (e.g., urethral discharge and genital ulcer disease)
can be used to monitor trends in STD incidence.
Countries (or even isolated sites) that have sufficient resources to routinely identify etiologic agents
of STDs should do so. If a country has the capacity to report only some cases etiologically,
syndromic and etiologic reports should be reported separately. Most developing countries however
will not be able to report cases etiologically.
Basic and advanced STD surveillance activities
Basic STD surveillance activities are used to obtain the minimum data necessary to evaluate the
STD situation within a country, despite lack of resources. Countries with enough resources (human
and/or financial) may also perform advanced STD surveillance activities.
Basic STD surveillance activities include case reporting of genital ulcer disease and urethral
discharge (universally or at sentinel sites); congenital syphilis case reports (universally); syphilis
prevalence in pregnant women attending antenatal clinics or seen at delivery (at sentinel sites); and
studies of gonococcal resistance and aetiology of STD syndromes in only a few sites.
Vaginal discharge cases may also be reported to assist in health services management and
pharmaceutical distribution; however, vaginal discharge syndrome is too non-specific to be a useful
measure of STD incidence or prevalence, and need not be recorded for these purposes.
According to the stage and type of HIV epidemic some modification of STD surveillance activities
is recommended. In order to prioritise HIV/AIDS surveillance activities it has been proposed that
countries be categorized according to their HIV epidemic stage: low-level (few cases of AIDS, low
HIV prevalence (<5%) in high risk groups), concentrated (high HIV prevalence in high risk groups
but low prevalence in the general population) or generalized (>5% HIV prevalence in the general
population, with increasing equalization of HIV prevalence between urban and rural areas).
In countries with nascent and concentrated HIV epidemics, basic STD surveillance activities should
include (at a minimum) assessment of syphilis, gonorrhoea, and chlamydia prevalence in persons at
high risk. In countries with generalized HIV epidemics, these assessments should be done both in
sentinel populations at high risk and in the general population (at least in pregnant women). Clearly,
the expansion of data collection is limited by human and financial resources.
Advanced STD surveillance activities include etiologic case reporting; syphilis, chlamydia,
gonorrhoea and trichomoniasis prevalence studies in sentinel populations; more accurate data about
aetiological proportions for each syndrome (for example, HSV, chancroid, and syphilis testing on
genital ulcers); and reporting of ophthalmia neonatorum.
We now focus on the details of basic STD surveillance activities.
Standards for basic STD surveillance
Incidence monitoring
Only urethral discharge and genital ulcer disease are considered useful for monitoring trends in
STD incidence because of their acute, symptomatic onset, and their specificity for recently acquired
infection with an STD agent. Persistent, asymptomatic and recurrent infections cannot be used to
monitor trends in incidence (e.g., endocervical infection, genital warts, vesicular ulcers, latent
syphilis).
Syndromic reporting
Minimum data items - age, sex, date, residence, and reporting site.
Urethral discharge
Case definition: Urethral discharge in men with or without dysuria. (This syndrome is most
commonly caused by N. gonorrhoeae and Chlamydia trachomatis; other infectious agents associated
with urethral discharge include Trichomonas vaginalis, Ureaplasma urealyticum, and Mycoplasma
spp.
The syndromic reporting of urethral discharge can be useful for monitoring trends in N.
gonorrhoeae and Chlamydia trachomatis infections in men since these are usually acute,
symptomatic and self-limited infections. Although these agents do cause asymptomatic infections,
and other agents can cause of urethritis, the high proportion of symptomatic cases due to these
pathogens makes reporting of this syndrome useful for monitoring trends.
Genital ulcer disease
Case definition: Ulcer on penis, scrotum, or rectum in men and on labia, vagina, or rectum in
women, with or without inguinal adenopathy. (This syndrome can be caused by syphilis, chancroid,
lymphogranuloma venereum, granuloma inguinale, or atypical cases of genital herpes.)
Since non-vesicular ulcers may be due to atypical cases of HSV (and because HSV lesions often are
recurrences of a persistent infection that was acquired long before), non-vesicular genital ulcer
disease is only a fair indicator of incident STD. In settings where patients are attending health
services for reasons unrelated to STD symptoms (e.g., routine sex worker examinations), prevalence
of genital ulcers may also be useful as one measure of STD prevalence.
As a large proportion of ulcers in women go unnoticed, case reports of genital ulcer disease are a
much better indicator of STD incidence in men than in women.
However, it is worth emphasizing that even with under-detection of disease, these syndromic casereports can be useful when other data on prevalence and incidence are lacking. Vaginal discharge
Case definition: Abnormal vaginal discharge (indicated by amount, colour, and odour) with or
without lower abdominal pain or specific symptoms or specific risk factors. (This syndrome is most
commonly caused by bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis; it is less
frequently caused by gonococcal or chlamydial infection.)
This syndrome is less useful as an indicator of STD than urethral discharge or genital ulcers because
many etiologic agents associated with vaginal discharge are not sexually transmitted (Candida
albicans, bacteria associated with bacterial vaginosis).
Aetiologic case-reporting
As mentioned above, countries with enough resources or even isolated sites that have good
laboratory infrastructure can report STD cases aetiologically. In order to report etiologically, it is
important to stress that these data can only be useful if the quality of laboratory testing is certain.
Therefore, for etiologic reporting, clinicians and laboratories must have sufficient material and
reagents, trained staff, adequate specimen collection, and quality control. If this cannot be achieved,
it is preferable to report syndromically. The only aetiological reporting that is considered a basic
surveillance activity is reporting of congenital syphilis cases.
• Minimum data items - age, sex, date of specimen collection, residence, and reporting site.
• For etiological report the following laboratory diagnosis should be included in the case
definitions:
o Acquired syphilis - positive non-treponemal tests (RPRIVDRL) confirmed by
treponemal tests (TPHA/FTA-Abs). (Syphilis should be reported by stage of
disease).
o Chancroid - Positive culture for Haemophilus ducreyi
o Granuloma inguinale (donovanosis)- direct microscopy showing typical
lntracytoplasmic inclusions (Donovan bodies)
o Lymphogranuloma venereum - positive culture for Chlamydia trachomatis or antigen
detection test on a genital ulcer or from a lymph node aspirate.
o Gonorrhea - presence of Gram negative diplococci within polymorphonuclear
leukocytes (in men); or positive culture or antigen detection test for N. gonorrhoeae
(in men or women).
o Chlamydia - positive culture or antigen detection test.
o Trichomoniasis - positive wet mount preparation of vaginal fluid or positive culture.
o Congenital syphilis - an infant born to a woman with untreated or inadequately
treated syphilis at delivery.
Although congenital syphilis case-reporting will underestimate the impact of congenital syphilis (in
part, because spontaneous abortions will be missed, and usually many stillbirths), it is important to
collect these data because this is one of the most serious sequela of untreated STD. The case
definition requires a positive syphilis serologic test of pregnant women at the time of delivery;
ideally, a confirmatory treponemal test should also be performed on the woman, and the infant
should be evaluated for clinical and laboratory evidence of congenital syphilis.
Prevalence assessment
Prevalence of persistent STD tends to be much higher than prevalence of acute symptomatic STDs.
Often, these persistent STDs are in an asymptomatic stage (e.g., latent syphilis). Therefore, for
prevalence assessment, laboratory testing is necessary. To gain insight into the burden of disease in
the general population, prevalence is best measured by testing patients who seek health care for
reasons unrelated to STD symptoms (primary health care, prenatal clinics, family planning clinics,
military recruits, etc.).
Syphilis in pregnant women
Although it may be difficult to interpret non-treponemal tests and distinguish treated from untreated
disease, syphilis screening is the only way to obtain data on syphilis prevalence. Pregnant women
are fairly representative of women in the general population. All women attending sites for
antenatal control or delivery should be tested for syphilis; where feasible confirmatory treponemal
tests should also be performed. In this population it may also be possible to perform HIV
counselling and testing.
The non-treponemal tests (VDRL and RPR) are a better indicator of recent infection than are
treponemal tests (FTA-ABS, MHA-TP) because the non-treponemal tests usually become nonreactive after treatment, although this may take months or years. False-positive nontreponemal tests,
and persistently positive non-treponemal tests are two factors that diminish the utility of syphilis
serologic testing for monitoring of incidence or prevalence. However, most false positive results are
at low tires, and use of a cut-off point (e.g., 1:4) may diminish this source of error. Once positive,
the treponemal examinations can remain so for life; they are not useful as measures of syphilis
incidence (although in adolescents, reactive treponemal test results may more likely reflect recently
acquired infection).
Other populations (for example, military recruits, blood donors)
STD prevalence can also be assessed in other populations, such as blood donors, military recruits,
factory workers, and students; however, in interpreting these data, it is important to assess the extent
to which the population selected may be representative of the general population.
As a basic surveillance activity, countries with nascent and concentrated HIV patterns should
evaluate prevalence of syphilis, gonorrhea, and chlamydia in populations at high risk. Countries
with generalized epidemics should also perform these studies in some general population groups.
Countries with sufficient resources can perform these studies in all sentinel populations enrolled.
Using sera from HIV prevalence studies to assess STD prevalence
Many countries already have a sentinel HIV seroprevalence system. It may be possible for some of
these sentinel sites to provide data on the prevalence of other STDs. Since sera are already obtained
for HIV testing, syphilis serology can also be performed; however, syphilis serologic testing should
be performed in an unblinded fashion, and treatment must be available.
Assessment of aetiologies of urethral discharge, genital ulcers, and vaginal discharge
If a country is reporting STD syndromes, it is essential that a few centres perform special studies on
the proportion of pathogens associated with each major syndrome (urethral discharge, genital ulcer
disease, and vaginal discharge). If pathogen distribution for each syndrome is known in a few
sentinel sites and these sites are fairly representative of the general population, it may be possible to
extrapolate this pattern to other areas. This is important both for syndromic case management
(treatment) and for tracking trends in the aetiology of different syndromes.
Monitoring antimicrobial resistance in N. gonorrhoeae
Centres that are well equipped should provide data on antibiotic resistance, especially gonococcal
resistance. These data are not required for individual case management but are of the utmost
importance for deciding on guidelines. Resistance must be monitored at regular intervals to evaluate
antimicrobial susceptibility within a population. At a minimum, the less expensive and more
commonly used antibiotics should be tested.
References
1. World Heath Association/Global Program on AIDS: Global prevalence and incidences of
selected curable sexually transmitted diseases: overview and estimates. WHO/GPA/STD
95.1, pp 1-26.
2. World Development Report, 1993: Investing in Health. The World Bank. New York:
Oxford University Press, 1993.
3. De Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by
heterosexual partners. European Study Group on Heterosexual Transmission of HIV. NEngl
JMed 1994; 331:341-346.
4. Cameron DW, D'Costa LJ, Maitha GM, et al: Female to male transmission of human
immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989; ii:
403-407.
5. Plummer FA, Simonsen JN, Cameron DW, et al: Cofactors in male-female sexual
transmission of human immunodeficiency virus type 1. JInfect Dis 1991; 163:223-239.
6. Laga M, Manoka A, Kivuvu M, et al: Non-ulcerative sexually transmitted diseases as risk
factors for HIV-l transmission in women: results from a cohort study. AIDS 1993; 7:95-102.
7. Hayes RJ, Schulz KF, Plummer Fa: The cofactor effect of genital ulcers on the perexposure
risk of HIV transmission in sub-Saharan Africa. J Trop Med Hyg 1995; 98:1-8.
8. Pepin J, Plummer FA, Brunham RC, et al: The interaction of HIV infection and other
sexually transmitted diseases: an opportunity for intervention. AIDS 1989; 3:3-9.
9. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of STD on HIV
infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346:530-36.
10. Levine WC. Improving Measurement of STD Incidence and Prevalence in the Americas.
Working paper for Informal Technical Working Group Meeting on STD Surveillance in the
Americas. Washington, D.C., Pan American Health Organization, 1995.
THE STD LABORATORY
E. Van Dyck
Role of the laboratory in STD control
The primary role of the STD laboratory is to support decision making in clinical practice and for
public health. Strengthening of laboratory infrastructure should always be subordinate to
requirements for STD control interventions.
Clinical practice
Laboratory tests improve the diagnostic specificity of symptomatic STDs as well as the diagnostic
sensitivity of symptomatic STDs. A laboratory can become involved in three types of STD control
activities:
1. Diagnosis of symptomatic patients: the role of the laboratory is to assist in management of
patients seeking health care for symptoms of STD. Given that symptoms and signs of lower genital
tract infections are not specific, particularly in women, laboratory tests are helpful to differentiate
serious infections, i.e., cervicitis, from milder but more common infections, i.e., vaginitis. Simple
laboratory tests incorporated in syndromic management of urethral discharge also help distinguish
mixed and single infections, reducing the administration of unnecessary antibiotics.
2. Case finding in asymptomatic individuals: the laboratory can play an important role for the
detection of STDs in patients seeking health care for other reasons. Laboratory tests increase
substantially the sensitivity of STD diagnosis. Case finding of asymptomatic STDs is most
important in female patients who carry the burden of STD complications and sequelae. STD case
finding in pregnant women is extremely important for prevention of adverse consequences of
syphilis, HIV, gonococcal and chlamydial infection in newborns.
3. Screening of populations: laboratory testing is essential for assessment of STD among (target)
populations not seeking health care.
Public health
Laboratory tests play a key role in public health decision making. They help document the
epidemiology of STDs in target populations, regardless of the symptoms. Results are used to
advocate STD control interventions and assess their impact. Laboratory tests are essential for
operational research such as validation of guidelines for syndromic management of symptomatic
STDs or definition of appropriate STD treatment guidelines. Reference laboratories are also used to
monitor the quality of results produced by clinical laboratories and to train their staff.
Criteria for laboratory test selection
The criteria for determining which laboratory test to use are similar to those for choosing any
evaluation indicators and include validity, reliability, feasibility, and acceptability (affordability).
Validity: refers to test sensitivity (percent of true positives) and specificity (percent of true
negatives) of a test compared to those of the gold standard. The gold standard is the best available
diagnostic test for a disease. In some cases, no single diagnostic test is available, and a combination
of tests is needed, such as the "expanded gold standard", e.g. positive culture or confirmed DNA
amplification technique, presently in use for the diagnosis of Chlamydia trachomatis infection.
Laboratory test sensitivity partly depends on the prevalence of the disease. As the prevalence
increases, so does the probability of encountering the disease in its acute stage with higher
concentrations of detectable particles. Usually, cost increases with validity.
Reliability: is the ability to produce similar results for the same biological sample. Reliability
increases with the validity of the technique, but also depends on the ease of use. Techniques
involving automated measurement of substances, such as enzyme immunoassays (EIAs), are
intrinsically more reliable than those involving the technician's interpretation, such as microscopy.
Direct fluorescent antibody testing (DFA) for C. trachomatis can be extremely sensitive and reliable
in expert hands, but even a simple test as Gram stain examination of urethral discharge can have a
low validity when it is used by a sloppy technician.
Increasingly reliable techniques ("idiot-proof") are constantly being developed by test
manufacturers, but they can be extremely expensive. In addition, even the most reliable technique
yields poor results when it is improperly standardised and not monitored through quality control
procedures.
Feasibility: beyond the ease of use, the technical feasibility of a test for a laboratory depends on the
operational requirements for the test, such as space, clean water, stable power supply, sophisticated
equipment, and refrigerated storage of reagents. As health facilities become more distant from
urban centres, these requirements become more difficult to meet. Even in major central level and
reference laboratories, provision of spare parts and reagents is frequently overlooked.
Acceptability: of a test for patients usually depends on the type of biological sample requested.
Saliva and urine production is painless and easier than having blood drawn. In some cultures blood
samples can be extremely difficult to obtain. Not surprisingly, urethral swabbing in men is probably
the least acceptable. Painful or invasive specimen collection techniques may be more acceptable to
symptomatic patients, but painless and non invasive sampling is critical for case finding or
screening of asymptomatic individuals. Acceptability also increases when results are obtained
quickly, which in turn depends on the organisation of laboratory activities. Acceptability also
includes affordability when patients must pay for laboratory services. As a general rule, laboratory
expenditures should not exceed the treatment costs saved by testing. Acceptance of laboratory
expenditures is the lowest for case finding or screening of asymptomatic subjects, including
asymptomatic contacts of STD patients.
Laboratory organisation for clinical practice
Clinical infrastructure in the public sector is organised at three successive levels. Most patients are
seen in peripheral (primary health care or first-encounter level) health units. Patients who need to be
referred are sent to intermediate (regional) health facilities and eventually from there to central
(national) facilities. Clinical laboratories are generally organised at the same three levels (see Table
1 on next page).
Peripheral laboratories are attached to health centres and first referral (health district) hospitals.
Laboratory procedures at this level usually include microscopic examination of fresh and stained
specimens. In syndromic management of urethral discharge, microscopy help single out
nongonococcal infection. For vaginal discharge, microscopy helps differentiate trichomoniasis from
candidiasis and bacterial vaginosis.
Laboratory procedures may also include rapid HIV tests and simple nontreponemal syphilis tests
(RPR or VDRL).
Intermediate-level laboratories are commonly situated in regional or provincial hospitals. Their
diagnostic requirements are greater, and better infrastructure and skilled manpower are available.
Laboratory tests might include culture of Neisseria gonorrhoeae and identification of penicillinaseproducing strains. They might also include antigen detection of C. trachomatis, depending on staff
workload and available resources. Serology might include enzyme-linked immunosorbent assays
(ELISA) or particle agglutination for HIV as well as confirmatory microhaemagglutination test for
syphilis.
Central laboratories are usually located in the capital city or in an university hospital. The range of
diagnostic tests performed varies according to the available human, material, and financial
resources and the workload. There is no sharp distinction between what should and could be
performed at the intermediate versus the central level. These decisions depend on the organisation
of health services in a country. One central reference laboratory may be quite satisfactory in a small
country. In big countries centralisation of reference activities in the capital city is unrealistic;
therefore some decentralisation of laboratory services at the regional level is necessary.
Constraints to providing laboratory services in developing countries include:
• Shortages of supplies and reagents
• Failure of water and power supplies
• Inadequate maintenance of equipment
• Weak technical ability of personnel
• Lack of supervision and quality control
• Absence of continuing education and training
• Lack of primary and continuing education for health care providers on the usefulness of
laboratory diagnostics.
All these factors contribute to low motivation among laboratory technicians and may result in
poorly maintained and dirty workplaces, delays in specimen processing, use of out-of-date reagents,
mislabelling of specimens, poorly maintained registers, and frequent personnel absences.
Introduction of STD diagnostic activities tests is difficult and expensive. In planning STD
laboratory development and diagnostic activities, it is essential to consider the following factors:
• The prevalence of STDs should be of sufficient magnitude to justify the effort.
• Sufficient logistic support and financial and human resources should be available to
maintain the laboratory.
• The technology and methodologies used should be appropriate for the technical capacity and
educational levels of laboratory staff.
• Clinicians should choose treatment or preventive measures based on laboratory test results.
• Additional tests should not be introduced at the expense of higher priority needs; the most
cost-effective STD case management approach should be employed.
• Follow-up, evaluation, coordination, and quality control should be assured.
Public health laboratory services
Among the major public health needs for STD control are prevalence studies for guideline
validation or HIV/STD surveillance and antimicrobial susceptibility surveillance of N. gonorrhoeae.
The most important requirement for public health data is reliability, which depends on skilled
manpower and quality control procedures. It is critical that centralised laboratories are reliable
because samples taken for public health purposes should be forwarded from different sites in the
country to one reference laboratory, usually located in the capital city. When this is not technically
feasible, however, some decentralisation should be considered.
The cost of public health testing should be supported by the public sector, since patients cannot be
expected to pay for tests they have not requested. Also, because people do not request these tests,
the least invasive methods of specimen taking should be used to increase acceptability.
Total separation of public health and clinical testing is not a cost-effective use of equipment and
trained personnel. In fact, some laboratories combine both activities because fees for clinical tests
help raise money for public health testing. However, the two should not be combined at the expense
of public health priorities.
Cost of laboratory testing
Careful attention should be given to the cost-effectiveness of laboratory testing. Such testing is
expensive and adds to the complexity of providing care. In many low-income countries, per capita
health care expenditures are less than $ 10 per year; therefore, widespread testing for most STDs,
including HIV, using currently available tests is unlikely. Detailed cost-effectiveness studies of
health care based on laboratory testing and diagnosis are very complex and require assessment of
indirect costs. Direct costs, which include equipment, supplies, reagents, drugs, and labour, can be
calculated more easily. An illustration of how to calculate the direct costs for screening and
treatment of syphilis is given in Table 2.
Table 2: Cost of rapid plasma reagin (RPR) screening in an asymptomatic population of 10,000 people
for three different prevalence rates of disease (RPR sensitivity 85%, specificity 98%)
Prevalence
1%
5%
25%
Positive Predictive Value (PPV)
30%
69.1%
93.4%
N of true positives detected
85
425
2,125
Total N of reactives detected
283
615
2,275
Screening costa (U.S. dollars)
$ 9,000
$ 9,000
$ 9,000
Cost for management of reactives
detectedb:
• laboratory (RPR titration)
$170
$369
$1,365
• medical care
$849
$1,845
$6,825
Total cost
$10,019
$11,214
$17,190
Cost to detect one true positive
$107.90
$22.00
$4.90
Total cost per true positive
$117.90
$26.40
$8.10
a blood collection: $0.5; Laboratory testing: $0.4
b Laboratory testing: $0.6; medical care: $3.0
* For a prevalence of syphilis of 1%, a test with a sensitivity of 85% and a specificity of 98% will detect in a
population of 10,000 people 85 cases of syphilis (true positives) and 198 reactive cases who do not have the
disease (false positives); 15 true cases of syphilis will not be detected (false negatives) and 9,702 people will
correctly be identified as not having the disease (true negatives)
Syndromatic STD management approach
Developing-country health providers at all levels, in both the public and private sector, are likely to
be confronted with many STD patients. Primary health care facilities in resource-poor settings face
several constraints to the optimal management of patients with STDs. These constraints include:
• Lack of access to the laboratory technology, necessary for making an aetiological diagnosis
• Shortage of well-trained staff
• High workloads with limited time available per patient.
•
•
•
•
The syndromic approach to STD case management involves the detection of a syndrome
(symptoms and signs) associated with a number of well defined aetiological agents. This
allows health care workers to make a correct diagnosis in many patients:
without sophisticated laboratory tests
without specialized skills
within a short time, and preferably without the need for a repeat visit by the patient.
Once a syndrome has been identified, adequate treatment can be provided for the majority of the
organisms responsible for that syndrome.
Although of adequate sensitivity for urethritis in males and genital ulcers in both sexes, the
syndromic approach shows relative low sensitivity and specificity when used for management of
female genital discharge. Recently, attempts have been made to supplement identification of signs
and symptoms with risk assessment questions and with non-specific simple diagnostics like
leukocyte esterase in vaginal fluid or in urine with varying success. On the other hand, management
of certain STD conditions, such as pelvic inflammatory disease, requires a syndromic approach,
regardless of available resources.
Diagnostic laboratory approach
Urethral discharge
Cases of urethral discharge can be treated on clinical examination according to syndromic
management guidelines, but laboratory tests are required to distinguish between nongonococcal and
gonococcal urethritis. The presence of leukocytes and typical intracellular diplococci (gonococcal
urethritis) or the presence of leukocytes without intracellular diplococci (nongonococcal urethritis)
can be detected through microscopic examination of a smear of urethral exudate stained with
methylene blue, safranin or Gram's method. Concomitant gonococcal and nongonococcal infections
will not be identified with this method.
Since microscopy of stained smears has a sensitivity of greater than 95 percent for symptomatic
gonococcal urethritis, culture for the isolation of N. gonorrhoeae is not essential for diagnosis and
clinical management1. However, isolation of gonococci, along with clinical monitoring of treatment
response, may be important in monitoring antimicrobial susceptibility trends.
For screening or case finding of urethritis among asymptomatic men, the collection of urethral
specimens is an invasive method, not much appreciated by the participants. A non-invasive
alternative is the collection of first-catch urine for the detection of leukocyte esterase. This method
has a reported sensitivity for detecting infectious urethritis ranging from 41 to 100 percent, but it
does not allow differentiation between gonococcal and nongonococcal urethritis. The specificity of
the leukocyte esterase test varies between 35 and 100 percent; consequently, the predictive value of
a positive test may be very low (2-7).
For screening of urethritis in male populations, the newer DNA amplification techniques for the
detection of N. gonorrhoeae and C trachomatis can be performed on first-catch urine samples.
Vaginal discharge / Lower abdominal pain
Wet mount microscopy is very useful for the diagnosis of trichomoniasis, candidiasis, and bacterial
vaginosis (BV). A pH test and a KOH sniff test may help diagnose BV, but the most reliable
diagnosis is based on a Gram stained smear to detect the typical bacterial flora and the presence of
clue cells. Diagnosis of gonococcal and chlamydial cervicitis, infections with potentially serious
sequelae, is even more important, but unfortunately, simple methods for diagnosing these infections
are not available. Gram stain microscopy has a low sensitivity for detecting gonorrhoea among
women; culture remains the method of choice8. Diagnostic assays for C. trachomatis include DFA,
EIA, DNA hybridisation, cell culture and DNA amplification techniques (9).
Genital ulcer disease
Genital ulcers may result from syphilis, chancroid, herpes, donovanosis, or (rarely)
Lymphogranuloma venereum (LGV). Management of patients can be based on clinical examination
and application of treatment algorithms. Essential procedures for definite diagnosis of the different
genital ulcer diseases are:
• Darkfield or DFA microscopy for treponemes
• Wright or Leishman stain for Calymatobacterium granulomatis
• Culture for Haemophilus ducreyi
• Culture or direct immunoassay for herpes simplex virus
• Serology for syphilis and LGV
• Multiplex PCR for syphilis, chancroid, and herpes.
Aetiological laboratory diagnostic procedures
Gonorrhoea
Gonorrhoea produces a purulent exudate, but signs and symptoms of disease may either be absent
or indistinguishable from those of chlamydial infection; therefore, laboratory tests are needed for
diagnosis and case finding as well as for test-of-cure. Accurate methods for the diagnosis of
gonorrhoea are direct microscopy of a stained urethral discharge smear in men and culture or DNA
amplification of all other types of specimens.
Direct microscopy (for males)
Simple staining of a urethral specimen with methylene blue or safranin may offer a quick and
reliable diagnosis of gonorrhoea in men, but the Gram stain, which give more specific results for
specimens containing mixed bacterial flora, remains the standard method.
Culture and identification
Specimens are cultured on selective enriched media such as (modified) Thayer Martin or New York
City. The observation of oxidase-positive Gram-negative diplococci with a gonococcus like colony
morphology on 24-48h cultures offers a sufficient and reliable identification of N. gonorrhoeae for
routine diagnosis in genital specimens. For extragenital isolates as well as for research, further
characterization is recommended (10). Carbohydrate degradation tests (glucose, maltose, lactose,
and sucrose) are commonly used, sometimes in combination with enzymatic substrate tests (11-14).
An immunologic confirmation assay using monoclonal antibodies is a very reliable but more
expensive alternative (13-l5).
Non-culture gonorrhoea detection techniques
Different culture-independent tests for gonorrhoea detecting oxidase, endotoxin, antigen, or DNA
have been compared with a standard culture technique. All these procedures are less efficient and
most are more expensive than a culture technique for extragenital specimens and for specimens
containing small numbers of organisms. The only technique that can compete with culture is DNA
amplification (10, 16-19).
Several antibody techniques have been used to detect gonococcal antibodies in serum. None of the
currently available methods are useful for diagnostic purposes because they cannot differentiate
recent from past infection.
Chlamydia trachomatis infection
Chlamydia trachomatis is an important cause of urethritis and cervicitis. Symptoms and signs of
chlamydial infection may be extremely mild or totally absent, making early diagnosis and treatment
less likely than with other STDs. Untreated chlamydial urethritis in men can evolve to epididymitis.
In women, the cervix is most commonly infected and infection frequently spreads to the urethra;
Chlamydia can also invade the endometrium and fallopian tubes, resulting in endometritis or
salpingitis. Coinfection with gonorrhoea is common.
With the advent of new technologies, the current reference test (expanded gold standard) for
diagnosing C. trachomatis infection is either positive tissue culture or positive DNA amplification
test confirmed by another test using a different technique, such as DFA, or the same DNA
amplification technique directed toward a different target such as a major outer membrane protein
(9). The culture procedure, however, is expensive, slow, labour-intensive, technically difficult and
beyond the capacity of most laboratories. In competent hands, the specificity of culture is 100
percent, its sensitivity is estimated to be no more than 70 to 85 percent compared to DNA
amplification. Cervical culture for C. trachomatis has a 65-90 percent sensitivity compared to DNA
amplification of first-catch urine (9).
Other non-culture techniques (DFA, EIA, DNA hybridisation) developed during the 1980s, which
are easier to perform and less expensive than culture, are still widely used. Unfortunately, all those
tests show lower sensitivity than culture and extremely low sensitivity (45-60 percent) when
compared to the expanded gold standard (9,20).
Direct microscopy (for males)
In a patient who has a history of acute onset of urethral discharge and has not received antibiotic
therapy, a Gram stain of a urethral specimen demonstrating polymorpholeukocytes without the
presence of Gram-negative diplococci has a high predictive value for chlamydial infection.
Cell culture
Many cell lines are suitable for the growth of Chlamydia, but the method of choice in most
laboratories is to add centrifuged specimens to cycloheximide-treated McCoy cell monolayers,
incubate them at 36°C for two or three days, then stain them with fluorescein-labelled monoclonal
antibody (21,22). The addition of a blind passage enhances the sensitivity of the culture method, but
may create a clinically unacceptable delay in diagnosis (23,24).
Direct fluorescent antibody (DFA) test
Fluoresceine-labelled monoclonal antibodies to the species-specific epitope of major outer
membrane proteins can detect elementary bodies (EBs) of C. trachomatis in clinical specimens25.
The procedure is rapid and simple to process, but labourious and tedious to read and not
recommended for processing large numbers of specimens. Microscopic reading of results is
subjective, and the reliability of the test depends on the expertise of the observer (26,27).
Investigators do not always use the same cutoff number, or number of EBs necessary to consider a
specimen positive, which influences the sensitivity of the method (28,30). Overall, DFA shows
acceptable accuracy for diagnosis in symptomatic patients and for case finding in high prevalence
populations, but lacks the sensitivity to detect the small numbers of organisms often found in
asymptomatic subjects, particularly in low prevalence populations (31,32).
Enzyme immunoassay (EIA)
EIA methods are more suitable than DFA for batch processing of large numbers of specimens. This
method is also more objective than DFA because the results are read with a photometer. The overall
sensitivity and specificity of EIA and DFA are similar (32). Most of the currently available ElAs
include a confirmation (neutralisation or blocking) assay to be performed on positive specimens,
during retesting by EIA, the presence or absence of chlamydial antigen in a sample previously
reactive in EIA can be confirmed by selective inhibition of the antigen by Chlamydia-specific
immunoglobulin (33,34).
Newer easy-to-use membrane immunoassays enable rapid diagnosis of chlamydial infection under
field conditions. These methods have a lower sensitivity and are therefore less accurate than the
more classic immunoassays (9,35,36).
DNA assays
DNA hybridization methods have been applied to chlamydial diagnosis since the 1980s (37).
Commercially available tests are easy to perform and have been shown to be highly specific, but
their sensitivity appears to be similar to that of DFA and most ElAs (9). Amplification of DNA
sequences with polymerase chain reaction (PCR), ligase chain reaction (LCR), and transcription
mediated amplification (TMA) offer very high sensitivity (38-40). However, the high cost of these
assays, the specialised laboratory equipment necessary, and the ease with which contamination with
DNA can occur in the laboratory currently limit the use of these methods in routine diagnosis.
Urine specimens
Obtaining urethral specimens by swab from men is an invasive method that causes some
discomfort. The collection of cervical swabs from women requires a clinical setting, skilled
personnel and a speculum examination. Urine samples are easier to obtain in both sexes and this
makes diagnosis and screening of chlamydial infection more feasible. Several studies have shown
significant lower sensitivities of EIA, DFA, and cell culture from urine specimens than those from
urethral and cervical swab specimens (41-44). Results obtained by DNA amplification techniques
on urine specimens from both men and women have shown that this approach is at least as good as
cell culture on classic genital swab specimens (45-47). Another promising approach to noninvasive
testing is the use for DNA amplification of vaginal introitus specimens self-collected by the patients
(48).
Antibody detection tests
Various serological methods (complement fixation (CF), micro-immunoflourescence (MIF), EIA)
have been used to study chlamydial infections in special situations, but their use for diagnostic
purposes remains limited. Similar to serologic confirmation of other infections, serologic evidence
of chlamydial infection can be obtained by demonstrating seroconversion or by a fourfold or greater
rise in antibody titer in paired sera two weeks apart. The use of a single high titer for diagnosis of
chlamydial urethritis and cervicitis is unreliable, it is diagnostically suggestive for LGV, reactive
arthritis, epididymitis and pelvic inflammatory disease (27,49).
Active LGV infections in general have CF titres of 1:64 or greater. However, high CF titres can be
found in asymptomatic individuals and those with chlamydial infections with the non-LGV
serovars. MIF is more sensitive that CF because it is possible to determine the antigenic type of the
infecting chlamydial strain. MIF, however, is not routinely available and is used in few specialised
laboratories (50).
Syphilis
Venereal syphilis is acquired by sexual contact with an infected person with an open ulcer or with
mucocutaneous secondary lesions. Transmission of Treponema pallidum requires exposure of noninfected mucous membranes or skin abrasions to infectious lesions.
No structural or metabolic difference has been found that distinguish between spirochetes that cause
venereal syphilis (T. pallidum), endemic syphilis (T. endemicum), yaws (T. pertenue) and pinta (T.
carateum). Therefore, these organisms cannot be differentiated by laboratory tests, but only by
clinical manifestations and through epidemiological studies, including inquiries to determine the
mode of transmission.
Syphilis is a chronic infection with diverse clinical manifestations occurring in distinct stages, and
each stage requires a different diagnostic approach. Treponemes can be identified in the primary
and secondary stages. In the primary stage, treponemes are microscopically detectable in skin or
mucosal lesions at the site of entry (primary chancre). During the secondary stage, they can also be
detected in papular rash lesions or in condylomata lata.
During the early primary stage serological tests are negative; antibodies usually appear one to four
weeks after a lesion has formed. During the secondary stage, all serological tests are positive, and
nearly all patients will show high antibody titres (>1:8) in nontreponemal tests. Serology remains
positive during latency and the tertiary stage, however, approximately 20 percent of patients during
late latency and 30 percent of patients with tertiary-stage syphilis may have nonreactive
nontreponemal tests.
Congenital syphilis is acquired by transplacental transmission of T. pallidum from a pregnant
women to a foetus. Diagnosis of congenital syphilis is based on (1) microscopic demonstration of T.
pallidum in nasal discharge or skin lesions, when present; (2) detection of specific IgM antibody in
serum; (3) demonstration of rising nontreponemal test antibody titres in serial serum samples during
the first eight months of life.
Direct microscopy
Darkfield microscopy is the standard method to provide an instant diagnosis of syphilis in the
primary and secondary stages. For reliable results, however, appropriate technical conditions
usually found only in specialised laboratories are essential, including well trained staff and adequate
equipment and time.
The direct fluorescent antibody (DFA) test may be a more practical alternative to darkfield
microscopy because the clinical specimens are fixed on a slide with methanol or acetone and
laboratory examination can be done after transport. DFA also eliminates confusion with other spiral
organisms and does not require motile organisms for syphilis diagnosis, so its specificity and
sensitivity are higher than that of darkfield (51). Failure to visualise the organism, however, does
not exclude a diagnosis of syphilis. A negative result may mean that:
• An insufficient number of treponemes were present in the lesion
• The patient was treated or partially treated recently
• The lesion was approaching natural resolution
• The lesion was not syphilitic
Nontreponemal tests
All the current nontreponemal tests for syphilis are flocculation tests using cardiolipin, lecithin, and
cholesterol as antigen. The Venereal Disease Research Laboratory (VDRL) test was the first in the
series of slide flocculation methods, and the basic antigen composition in all newer tests is that of
the VDRL (52). The antigen used in the VDRL test is not stabilised, so a working suspension must
be prepared fresh daily. The VDRL should be performed on serum heated at 56°C before testing,
and results must be read with a microscope at 100x magnification. This microscopic test, VDRL, is
the only appropriate test for spinal fluid. Another microscopic method, the unheated serum reagin
(USR) test, can be performed with a stabilised antigen on unheated serum (53).
In other flocculation tests, the reaction is visible to the naked eye. The most popular of these macrovue methods is the rapid plasma reagin (RPR), which uses plastic-coated cards in place of slides
and a stabilised antigen to which charcoal particles are added. The antigen is not coated on these
particles. Instead, it is trapped in the lattice performed by the antigen-antibody complex in positive
samples, making the reaction visible to the naked eye. The test may be performed on unheated
serum or plasma54. Modifications of the RPR include the reagin screen test (RST), which uses a
lipid-soluble black dye in place of charcoal, the VDRL carbon antigen test, which is similar to the
RPR, and the toluidin red unheated serum test (TRUST), which uses toluidin red in place of
charcoal to make the reaction visible (55-56).
Treponemal tests
Specific treponemal tests detect antibodies against treponemal cellular components. The three
different test procedures are: indirect immunofluorescence, haemagglutination and enzymelinked
immunosorbent assay. The fluorescent treponemal antibody-absorption (FTA-Abs) test is the most
sensitive of all syphilis tests, but is technically the most difficult. Standard reading, high-quality and
appropriate dilution of the conjugate, and the use of good antigen slides are essential for the
reliability of the test (57). Microhaemagglutination assay for antibodies to T. pallidum (MHATP),
T. pallidum haemagglutination assay (TPHA) or haemagglutination treponemal test for syphilis
(HATTS) are easier to perform than FTA-Abs, have fewer variables, and are more practical for
batch processing of large numbers of specimens (58-59). Enzyme-linked immunosorbent assays
(EIAs) are designed for batch processing and are suitable for automation of serology (60-61). The
different treponemal tests have comparable sensitivity and specificity, except for primary-stage
syphilis, where FTA-Abs is more sensitive than the other methods.
Appropriate use of serological tests
The sensitivity and specificity of nontreponemal and treponemal syphilis tests for the different
phases of the disease are shown in Table 3. A reactive nontreponemal test may indicate a primary
infection, a recent infection treated or not treated, or a false positive result. False positive results
occur in populations at a rate of 1 to 3 percent. The vast majority of false positive sera show
antibody titres of m 1:4. However, low titres do not exclude syphilis and are often found in early
primary, late latent and tertiary syphilis. Determination of nontreponemal serum titres through a
quantitative procedure may be helpful for more accurate interpretation of results and for evaluation
of patients after treatment. To exclude false positive results, it is necessary to perform a specific
treponemal test.
Table 3: Sensitivity and specificity of serological tests for Syphilis
Sensitivity (%) by phase of Syphilis infection
Test
VDRL
RPR card
FTA-Abs
MHA-TP
Primary
80 (74-87)
86 (81-100)
98 (93-100)
82 (69-90)
Secondary
100
100
100
100
Latent*
80 (71-100)
80 (53-100)
100
100
Late*
71 (37-94)
73 (36-96)
96
94
Specificity
%
98
98
99
99
A reactive treponemal test may indicate a primary or early infection, recent infection treated or not
treated, or past infection. Once infected with pathogenic treponemes, the majority of subjects
remain treponemal antibody-positive in tests for years - even for a lifetime - whereas nontreponemal
tests usually revert to negative over time after successful treatment.
For borderline reactions, discordant nontreponemal-positive treponemal-negative reactions, and
discordance with clinical impression, the tests should be repeated on a new serum sample. If
disagreement persists, a different treponemal test may be done for final judgement. In incubating
syphilis all antibody tests are negative. In early primary syphilis, different combinations of results
may be obtained (nontreponemal-positive microhaemagglutination-negative, nontreponemalnegative microhaemagglutination-positive, or nontreponemal-negative microhaemagglutinationnegative). To diagnose or exclude syphilis, the tests must be repeated after two to three weeks on a
new serum sample. In such cases, it may be helpful to perform an FTA-Abs, since it is the most
sensitive test for primary syphilis. Finally, when adequate treatment is started early in primary
syphilis, patients may remain antibody-negative.
Seroreversion of nontreponemal tests to negative in patients adequateley treated usually occurs
within a period of six months to a few years and is associated with the duration of infection,
previous infection, and the antibody serum titer at the moment of treatment. Seroreversion of
treponemal tests also occurs within a few years in a minority of patients; this phenomenon is not yet
clearly understood.
For diagnosis as well as for case finding of syphilis, serum samples should first be screened with a
nontreponemal test. To date, the most popular nontreponemal test is the RPR 18-mm circle card test
with mechanical rotation. In poorly equiped laboratories with low numbers of specimens to test,
hand rotation of the card is appropriate. The sensitivity of a "hand rotation" RPR is only slightly
lower than that of a RPR with mechanical rotation. Thus, some samples with low antibody titer of
m1:2 may appear negative with the hand rotation procedure (62). Specific treponemal antibody tests
are used to confirm positive nontreponemal samples as well as for epidemiological studies. The
most appropriate of these tests for routine work is the TPHA.
With nontreponemal tests, undiluted serum samples with high antibody titer occasionally appear
nonreactive because of excess antibody. This phenomenon, known as prozone effect, is sometimes
observed in patients with secondary syphilis. Consequently, nonreactive undiluted samples from
symptomatic patients should be diluted 1:16 to 1:256 and retested with a quantitative procedure.
Demonstration of treponemal IgM in serum
The synthesis of specific IgM antibodies is the first humoral immune response after infection in
syphilis as well as in other bacterial or viral infections. In syphilis, treponemal IgM antibody is
present not only in patients with early primary syphilis, but may also be found during the latent
period and in patients with late disease. IgM decreases more slowly after spontaneous resolution of
infection than after successful therapy.
Detection of IgM antibody is also very useful for the diagnosis of congenital syphilis. The presence
of IgM antibody in the blood of newboms indicates prenatal infection of the child. In most children,
however, IgM antibody only appears a few weeks to a few months after birth. The appearance of
IgM in the cerebrospinal fluid (CSF) of patients with an intact serum/CSF barrier (i.e. normal
serum/CSF albumin ratio) indicates active neurosyphilis because the molecular size of IgM prevents
it from passing the intact serum/CSF barrier as well as the placental barrier.
The sensitivity of treponemal IgM detection is not optimal, but its observation may contribute to a
more reliable interpretation of congenital syphilis, early primary syphilis, late syphilis, and
reinfection of patients with a previous history of syphilis or other treponematoses. Disappearance of
IgM can be a helpful test-of-cure for patients with early infection before seroreversion of
nontreponemal tests is observed.
Genital herpes
Herpes simplex virus (HSV) belongs to the group of alpha-viruses that become latent and cause
persistent infections. Genital herpes is caused by HSV-2 in approximately 85 percent of cases; the
remainder are caused by HSV-1. Primary HSV infection may be asymptomatic or characterised by
the appearance of extensive vesicular or ulcerative genital lesions associated with inguinal
Iymphadenopathy, dysuria and fever. Recurrent genital herpes episodes are usually milder (except
in an immunocompromised host) and are nearly always caused by HSV-2. Genital herpes is mainly
diagnosed on clinical grounds; laboratory diagnosis is usually not essential.
Neonatal herpes is the most serious consequence of genital herpes infection. The virus is
transmitted from the infected mother to the child during vaginal delivery. There is a need for rapid
and reliable laboratory tests to detect HSV in asymptomatic infected pregnant women shortly before
delivery, as well as to monitor neonates exposed to HSV at delivery.
Virus culture
Isolation of HSV in tissue culture remains the diagnostic laboratory method of choice. Culture
performed on fresh vesicular lesions has a sensitivity of more than 90 percent. Culture from pustular
lesions is positive in 70 to 80 percent of cases, whereas only 25 percent of crusted lesions give a
positive culture result. Cultures from primary infection lesions recover a significantly higher
amount of virus than culture from recurrent lesions (63-65).
Cytopathic effect (CPE) typical of HSV can be recognised by a rounding of scattered culture cells,
visible after one to seven days of incubation, depending on the concentration of virus in the clinical
specimen. Other viruses may exhibit CPE similar to HSV; definite identification of HSV is
recommended when an unusual type of CPE occurs or when specimens come from asymptomatic
people. Identification and typing of HSV may also be useful for epidemiological and research
purposes. Virus isolates can be confirmed as HSV and typed as HSV-1 or HSV-2 by neutralisation
tests, immunologic assays or nucleic acid hybridization.
Direct detection methods
Nonculture procedures are more practical for routine diagnosis of HSV infections because tissue
culture facilities are not widely available. Detection of HSV antigen by immunologic techniques is
currently the most common rapid diagnostic method. Immunologic procedures include
immunofluorescence, immunoperoxidase, and enzyme-linked immunosorbent assay. The sensitivity
of these antigen detection methods seems to vary between 70 and 95 percent (66,67).
A more recent approach to rapid HSV diagnosis is DNA hybridization (68). The amplification of
DNA sequences by polymerase chain reaction offers a highly sensitive method useful for detecting
HSV in asymptomatic pregnant women at term (69).
Papanicolaou and Tzanck staining are no longer considered appropriate techniques for the diagnosis
of genital herpes (63). Although they are simple, inexpensive methods and can be used to
demonstrate cytologic changes, such as giant cells or cells with intranuclear inclusions in smears
from lesions and cervical specimens, they are not specific for HSV and have a low sensitivity
compared to cell culture.
Serology
Serological tests for HSV antibody detection can contribute to diagnosing a primary infection
episode if seroconversion or a fourfold or greater rise in antibody titer is observed between an acute
phase serum sample and a convalescent serum obtained 10 to 14 days later. In patients with
recurrent infection, a significant antibody rise occurs in less than 10 percent of cases.
HSV antibody procedures include complement fixation, indirect immunofluorescence,
neutralisation technique, latex agglutination, haemagglutination, and enzyme immunoassay. All
these methods are sensitive for detection of IgG antibodies but cannot discriminate between recent
and past HSV infection on a single serum sample. Most of the commercially available tests cannot
effectively differentiate between HSV-1 and HSV-2 infection because of extensive cross-reactivity.
The major targets of serum antibodies are viral surface glycoproteins, and most of the immunogenic
epitopes are common to both HSV-1 and HSV-2 types. Recently several new proteins specific for
HSV-1 and HSV-2 have been defined, including the glycoprotein gG of HSV-1, which differs
significantly from the gG of HSV-2, and solid phase ELISA procedures using purified recombinant
gG2 glycoprotein to specifically detect antibody to HSV-2 have become available. These tests can
be used to determine specific IgG antibodies in patients exposed to HSV-2, including individuals
who were previously infected with HSV-1 or other herpes viridae (70).
Chancroid
Chancroid is caused by Haemophilus ducreyi and is transmitted sexually by direct invasion of the
organism through healthy or abraded skin and mucosa. The disease starts with a painful papule at
the site of infection, resulting in a single or in multiple ulcers. Inguinal Iymphadenopathy may be
present in up to 50 percent of patients. Extensive and persistent genital ulcers without inguinal bubo
development may be observed in patients with immunosuppression caused by HIV infection. Due to
the atypical presentation and superinfection of the ulcers, the accuracy of a clinical diagnosis varies
between 40 and 80 percent.
Isolation and identification of H. ducreyi
To date, an accurate diagnosis of chancroid depends on the ability to culture H. ducreyi. Different
media formulations have been used to isolate the organism with varying success. It has been shown
that parallel use of both gonococcal (GC) and Mueller-Hinton (MH) media may increase the
isolation rate of H. ducreyi from ulcers to above 80 percent.
A presumptive identification of H. ducreyi may be based on colony characteristics, Gram stain,
production of ß-lactamase and oxidase reaction. Colonies are nonmucoid, raised, granular, grayishyellow in colour, and can be pushed intact across the surface of the agar with an inoculating loop.
They can be either translucent or opaque, and this variability in opacity gives the impression of a
mixed, nonpure culture. H. ducreyi is a fastidious organism with limited biochemical activity.
Haemin is required to initiate growth. Nitrate reduction and alkaline phosphatase are also important
characteristics. H. ducreyi is oxidase-positive when tested with tetramethyl-p-phenylenediamine
and almost 100 percent of isolates are ß-lactamase positive.
Direct detection methods
Direct examination of ulcer material on Gram stained smears may contribute to the diagnosis of
chancroid if typical small, Gram-negative bacilli grouped in chains or as “schools of fish" are
observed. These typical features, however, are infrequently seen on smears from patients with
culture-proven chancroid, resulting in a sensitivity of much less than 50 percent for the direct Gram
stain (71-73). In addition, because most genital ulcers harbour polymicrobial flora due to secondary
contamination, the presence of Gram-negative bacilli may be misleading and frequently results in a
false-positive diagnosis (73-74). As a result of its low sensitivity and low specificity, a Gram
stained smear is not recommended for the diagnosis of chancroid.
Non-culture antigen and nucleic acid methods for H. ducreyi have been developed, but are not yet
used in routine diagnosis. Fluorescein-labelled and enzyme-labelled monoclonal antibodies have
been used to detect H. ducreyi in clinical specimens with varying success (75,76). DNA probes
have been shown to be 100 percent sensitive and specific for the identification of bacterial isolates,
but their usefulness for direct diagnosis is not been established (77,78). DNA amplification of
different H. ducreyi sequences offers diagnostic technology superior to culture. The most accurate
diagnostic procedure for diagnosing genital ulcer disease is a multiplex PCR to detect
simultaneously T. pallidum, herpes simplex virus, and H. ducreyi (79).
Serology
The usefulness of serological tests for the diagnosis of active H. ducreyi infection is very limited,
but serology has proven to be valuable for research and epidemiologic purposes.
The development of reliable serological tests depends on detailed information about the host
immune response as well as antigen presentation by the infectious organism. Data on these
mechanisms for chancroid and H. ducreyi are very limited. Clinical experience and experimental
inoculation studies in humans suggest that there is probably no acquired immunity to H. ducreyi.
More research is needed, however, to determinate its antigenic composition, including specific
immunogenic epitopes, and the kinetics of the humoral immune response to H. ducreyi in treated
and nontreated patients with primary and repeated episodes of chancroid.
Circulating serum IgG and IgM antibodies to H. ducreyi have been detected with dot
immunobinding and enzyme-linked immunosorbent assays (75,80). With both methods, a
qualitative and quantitative variation in antibody response is observed in patients with recent or past
history of chancroid but the factors influencing these response variations are not yet clearly
understood.
Antimicrobial susceptibility testing
During the past two decades chromosomal resistance and high-level plasmid-mediated resistance
have significantly increased among H. ducreyi isolates. Resistance patterns of clinical isolates,
however, can vary greatly in geographically diverse areas. It has been observed that chancroid
treatment failures are much more common in HlV-positive patients, but it is not yet clear whether
treatment failure is significantly associated with HIV status or with increased antimicrobial
resistance of H. ducreyi isolates.
To date, no standardised procedures exist for susceptibility testing of H. ducreyi; the only practical
and reliable method is the agar dilution technique for determining minimum inhibitory
concentrations. Commonly used media are MH agar or GC agar enriched with 1 percent
haemoglobin, 5 percent foetal calf serum, and 1 percent IsoVitaleX. Antimicrobial susceptibility
testing of H. ducreyi is a cumbersome technically delicate procedure and can only be successfully
performed in specialised reference laboratories.
Donovanosis
Donovanosis (granuloma inguinale) is a chronic infection involving the skin, mucous membranes
and lymphatics of the genitalia and perineal area. The disease starts with a subcutaneous nodule at
the site of infection. This nodule erodes through the skin to form a beefy, red, granulomatous ulcer.
Inguinal Iymph nodes may become involved; the disease may spread haematogenously and may
even result in cutaneous lesions at extragenital body sites.
Donovanosis is caused by Calymatobacterium granulomatis, which cannot be cultured on artificial
media. Laboratory diagnosis depends on the visualisation of Donovan bodies in smears from
clinical lesions.
Direct microscopy
The sensitivity of microscopy of tissue samples crushed between two slides is below 40 percent for
patients with clinically suspected lesions of donovanosis. Histological aspects in sections of a
biopsy may be helpful to differentiate between donovanosis and other conditions. An ulcer with a
mixed inflammatory infiltrate of plasma cells, neutrophils and histiocytes and with a conspicuous
absence of Iymphocytes, suggests granuloma inguinale. Demonstration of characteristic
intracellular organisms (Donovan bodies) by Warthin-Stary silver impregnation is diagnostic (81).
Serology
Antibodies to C. granulomatis have been observed using a complement fixation method in sera
from patients whose lesions persisted for more than three months. More recently, a successful
indirect immunofluorescence technique has been described. Sera from patients are applied to biopsy
tissue sections containing Donovan bodies and treated with antihuman IgG conjugated with
fluorescein isothiocyanate. In the absence of culture methods or reliable and simple nonculture
detection tests, this serological assay may prove valuable for the diagnosis of donovanosis (82).
Candidiasis
Vulvovaginal candidiasis is caused by Candida albicans in approximately 85 percent of cases, with
the remaining cases caused by other species, particularly by C. glabrata (83). Classic clinical
symptoms and signs of candidiasis include vaginal itching, vulvar burning, external dysuria, curdy
white discharge (that looks like cottage cheese) without malodour, and erythema of the labia and
vulva. Symptoms and signs, however, are often less specific, and laboratory diagnosis is essential
for accurate differential diagnosis.
Direct microscopy
The yeast form is easily recognised in a wet mount preparation of vaginal fluid as round to avoid
cells of 4 mm diameter with typical budding. Adding a drop of 10 percent KOH to the preparation
may facilitate the detection of yeasts, in particular the recognition of mycelia (pseudohyphae).
Yeasts are Gram-positive and can easily be observed in a Gram-stained smear. The sensitivity of a
wet mount, however, is superior.
Culture
Culture remains the most sensitive method currently available for the detection of Candida.
However, it should be stressed that a positive culture does not necessarily indicate that Candida is
responsible for vaginal symptoms, as more than 20 percent of healthy women may harbour Candida
in the vagina Microscopy has a much higher diagnostic value. Few patients with symptomatic
vaginal candidiasis have negative microscopy. Consequently, culture may only be useful if vaginal
candidiasis is clinically suspected in the presence of a negative wet mount preparation (84).
Colonies of yeasts appear after one or two days incubation at 36°C and are white opaque to creamy.
The only important identification of isolates consists of microscopic differentiation from bacteria.
Additional confirmation is not essential for routine diagnosis of vaginal candidiasis.
Trichomoniasis
Trichomoniasis is considered mainly sexually transmitted. Nonvenereal acquisition through fomites
may be possible, but is not well documented. Trichomonas vaginalis elicts an acute inflammatory
response resulting in vaginal discharge containing large numbers of polymorphonuclear neutrophils
Typical symptoms associated with trichomoniasis include vaginal itching or irritation and frothy
gray to green-yellow discharge. Vaginal malodour and dysuria may be present.
The infection is caused by T. vaginalis, an ovoid globular, pear-shaped flagellated protozoon.
Although certain symptoms and signs are predictive for trichomoniasis, visualisation of the parasite
is required to establish the diagnosis (85).
Direct microscopy
Trichomonads are easily recognised in a wet mount preparation of vaginal fluid by their typical
jerky motility. An increased number of polymorphonuclear leukocytes is usually observed, but
small numbers of leukocytes do not rule out infection.
Other diagnostic methods
Culture of T. vaginalis is currently the most sensitive method for diagnosing trichomoniasis and
may be recommended when vaginal infection is suspected despite negative wet mount results, for
diagnosis of trichomoniasis in men, and for research.
Various direct detection methods for T. vaginalis, including immunofluorescence, latex
agglutination, and enzyme-linked immunosorbent assay, have been described. A recently developed
antigen immunoassay seems to be comparable in sensitivity and specificity to culture (86). Several
methods for antibody detection against T. vaginalis in serum and in vaginal washings have been
evaluated but did not contribute to a more adequate diagnosis of trichomoniasis.
Bacterial vaginosis
Bacterial vaginosis (BV) is a clinical entity characterised by slightly increased quantities of
malodourous vaginal discharge. It is associated with overgrowth of the normal bacterial flora of the
vagina with Gardnerella vaginalis, Mycoplasma hominis and various anaerobic bacteria, such as
Bacteroides and Mobiluncus species.
Diagnostic procedures
The diagnosis of BV is based on the presence of at least three of the four following characteristics
(87,88):
• Homogenous white-gray adherent discharge: Interpretation of this clinical sign is subjective.
Discharge seen in women with BV is often not markedly increased over that seen in healthy
women; the application of vaginal douches may reduce the amount of discharge.
• Increased vaginal pH: The normal mature vagina has an acid pH of w 4.0. In BV, the pH is
generally elevated to more than 4-5. The vaginal pH test has the highest sensitivity of the
four characteristics, but the lowest specificity. An elevated pH is also observed if vaginal
fluid is contaminated with menstrual blood, cervical mucus or semen, and in T. vaginalis
infection.
• Malodour: Women with BV often complain of vaginal malodour, which is due to the release
of amines produced by anaerobic bacteria that decarboxylate Iysine to caverdine and
arginine to putrescine. If a drop of 10 percent KOH is added to the vaginal fluid, the amines
immediately become volatile, producing a typical fishy amine odour.
• Presence of clue cells: These cells are squamous epithelial cells covered with many small
coccobacillary organisms. Microscopy of a wet mount shows stippled granular cells without
clearly defined edges because of the large numbers of adherent bacteria present and an
apparent disintegration of the cells. The adhering bacteria are predominantly G. vaginalis,
sometimes mixed with anaerobes.
Confirmatory laboratory testing
A Gram stain of a vaginal smear has a higher specificity for the detection of clue cells than a wet
mount preparation. Moreover, a Gram stain allows good evaluation of the vaginal bacterial flora.
Normal vaginal fluid contains predominantly Lactobacillus species and exceedingly low numbers of
streptococci and coryneform bacteria. In BV, lactobacilli are replaced by a mixed flora of anaerobic
bacterial morphotypes and G. vaginalis. The Nugent scoring system for Gram stain is a weighted
combination of lactobacilli, G. vaginalis or Bacteroides (small Gram-variable or Gram-negative
rods) and curved Gram-variable rods (Mobiluncus) (89). This standardized 0-10 scoring system is
presented in Table 4. Each morphotype is quantitated from 1 to 4 + with regard to the number of
morphotypes per oil immersion fied. The sum of the weigthed quantitations of the three
morphotypes yield a score of 0 to 10. The criterion for BV is a score of 7 or higher, a score of 4 to 6
is considered intermediate, and a score of 0 to 3 is considered normal.
Table 4: Nugent’s scoring system for Gram-stained vaginal smearsa
Scoreb
Lactobacillus
morphotype
Gardnerella &
Bacteroides spp
morphotypes
Curved Gram variable
rods
0
4+
0
0
1
3+
1+
1+ or 2+
2
2+
2+
3+ or 4+
3
1+
3+
4
0
4+
a: Morphotypes are scored as the avarage number seen per oil immersion field. Note that less weight is given
to curved Gram-variable rods. Total score = lactobacilli + G. vaginalis and Bacteroides spp + Gram-variable
rods.
b: 0 = no morphotypes present; 1 = <1 morphotype present; 2 = 1 to 4 morphotypes present; 3 = 5 to 30
morphotypes present; 4 = > 30 morphotypes present.
HIV
Several different types of laboratory tests for detecting HIV antibody in human serum exist today.
The selection of the most appropriate test or combination of tests to use depends on three criteria:
(1) the objectives of HIV testing, (2) the sensitivity and specificity of the tests being used, (3) the
prevalence of HIV infection in the population being tested.
Objectives of HIV antibody testing
The three main objectives for which HIV antibody testing is performed are:
• Transfusion and transplant safety: Screening of blood and blood products, and of organs,
tissues, sperm or ova from donors.
• Surveillance: Unlinked and anonymous testing of serum for monitoring the prevalence and
trends in HIV infection over time in a given population.
• Diagnosis of HIV infection: Voluntary testing of serum from asymptomatic individuals or
from persons with clinical signs and symptoms suggestive of HIV infection or AIDS.
Sensitivity and specificity of HIV tests
Sensitivity and specificity are two major factors that determine a test's accuracy in distinguishing
between infected and uninfected persons. Only tests of the highest possible sensitivity should be
used when there is a need to minimize the rate of false negative results (e.g., in transfusion). A test
with a high specificity will have few false positive results and should be used when there is a need
to minimize the rate of false positive results (e.g., in diagnosis).
Prevalence of HIV infection
The probability that a test will accurately determine the true infection status of a person varies with
the prevalence of HIV infection in the population from which the person comes. In general, the
higher the HIV prevalence, the greater the probability that a person testing positive is truly infected.
Thus, with increasing prevalence, the proportion of false positive samples decreases; conversely,
the likelihood that a person with a negative test result is truly infected, decreases as prevalence
increases.
Strategies for HIV antibody testing
As HIV antibody assays have become extremely sensitive over the years, the probability of a false
positive reaction in two assays based on a different principle is not negligible. Therefore, if test
combinations are not carefully selected, individuals may be wrongly diagnosed as HIV seropositive.
Conversely, the most specific assays are slightly less sensitive as compared to the average HIV
antibody test, which may result in a false negative diagnosis. The choice of the most appropriate
HIV tests also depends on the HIV variants present in a particular geographical area (e.g. HIV-1
group O).
Studies have shown that combinations of ELISA and/or simple rapid assays such as dot
imrnunoassays and agglutination can provide results as reliable, and in some instances more reliable
than the ELISA/Western blot (WB) combination, and at much lower cost. Confirmatory tests such
as WB or line immunoassays, should only be used to resolve indeterminate results for diagnostic
purposes.
Strategy I (for transfusion/transplant safety)
All serum/plasma is tested with one ELISA or simple/rapid assay. Reactive samples are considered
HIV antibody positive and nonreactive samples are considered HIV antibody negative. The test
selected for this strategy should preferably be a combined HIV-1/HIV-2 assay which is highly
sensitive. The specificity of the choosen test should be at least 95 percent. If a blood or tissue donor
is to be notified of a test result, testing strategy III for diagnosis must be applied.
Strategy Il (for surveillance)
All serum/plasma is first tested with one ELISA or simple/rapid test. Any sample found reactive on
the first assay is retested with a second ELISA or simple/rapid assay based on different antigen
preparation and/or different test principle (e.g., indirect versus competitive). Samples that are
positive on both tests are considered HIV antibody positive. Samples, nonreactive on the first test,
are considered HIV antibody negative. Any sample that is reactive on the first test but nonreactive
on the second test, should be retested with the two assays. Concordant results after repeat testing
will indicate a positive or negative result. If the results of the two assays remain discordant, the
sample is considered indeterminate. For surveillance no further testing is needed; indeterminate
results should be reported and analysed separately.
Strategy III (for diagnosis)
All serum is first tested with one ELISA or simple/rapid assay, and any reactive samples are
retested using a different assay. Serum that is nonreactive on the first test is considered HIV
antibody negative. Serum that is reactive in the first test but nonreactive in the second assay should
be repeated with both tests. Concordant negative results after retesting will indicate HIV antibody
negative. Sera found positive in the first assay and positive or negative in the second assay, even
after retesting, should always be tested with a third assay. Serum reactive on all three tests is
considered HIV antibody positive. Samples reactive in the first test only or reactive in two of the
three tests are considered indeterminate for individuals who may have been exposed to HIV in the
last three months and negative for those who have not been exposed to any risk for HIV infection.
For newly diagnosed HIV seropositives, an additional blood sample should be obtained and tested
to help eliminate possible technical or clerical error.
Serum from people with clinical signs of AIDS may have an indeterminate result due to a decrease
in antibodies. In this case, serum does not normally need to be retested.
For diagnosis of HIV infection in asymptomatic individuals, with an indeterminate result, a second
blood sample should be obtained after a minimum of 2 weeks following the first sample and should
be tested with the same strategy. If the second serum sample also produdes an indeterminate result,
it should be tested with a confirmation test (WB or line immunoassay). However, if this result is
also indeterminate longer follow-up may be required. If the results remain indeterminate after one
year, the person is considered to be HIV antibody negative (90).
Antimicrobial susceptibility surveillance of N. gonorrhoeae
Rationale
Surveillance of the antibiotic susceptibility of N. gonorrhoeae is a major public health issue. In
many countries antibiotics currently recommended by the World Health Organisation (WHO) or
Centers for Disease Control (CDC) for gonococcal infections are neither available to nor affordable
for STD patients. It may be possible to recommend less expensive drugs (i.e.
trimethoprim/sulfamethoxazole or kanamycin), provided their efficacy is regularly monitored.
Susceptibility surveillance data are used primarily to help develop and update appropriate treatment
guidelines for managing gonococcal infections at the primary health care level. Susceptibility
testing on an individual basis is not justified.
Susceptibility testing may be recommended in the following circumstances:
• In reference laboratories for epidemiological investigations to provide susceptiblity
information and monitor trends in drug resistance.
• In STD laboratories that conduct a high volume of tests to help monitor the clinical efficacy
of recommended treatment regimens.
• In studying new antimicrobial agents.
• In providing information to clinicians in cases of treatment failure.
It is important to remember that treatment failure may be due to gonococcal resistance to currently
recommended drugs, but more common reasons include poor compliance with therapy, reinfection
or coinfection with Chlamydia trachomatis. If performed without rigorous standardisation, in vitro
antimicrobial susceptibility testing may generate unreliable results.
Antibiotics to be tested
Penicillin and tetracycline are tested for epidemiological rather than practical purposes, since
gonococcal resistance to both drugs is usually high in many countries. Less expensive drugs that
should be tested include trimethoprim/sulfamethoxazole and the aminoglycosides. Resistance to
fluoroquinolones is rapidly increasing when they are widely used, making monitoring essential.
Spectinomycin and second- and third-generation cephalosporins are still highly effective, but
monitoring could document the emergence of resistant strains.
Laboratory methodology
Antimicrobial resistance in N. gonorrhoeae is both chromosome- and plasmid-mediated.
Penicillinase-producing N. gonorrhoeae (PPNG), also termed beta-lactamase-positive gonococci,
refers to plasmid-mediated resistance to penicillin, which is detectable with simple and inexpensive
tests. Tetracycline-resistant N. gonorrhoeae (TRNG) refers to plasmid-mediated resistance to
tetracycline. No simple test can detect TRNG. The corresponding plasmid must be identified with
biomolecular techniques. Alternatively, resistance to tetracycline is assumed to be plasmidmediated when reaching levels far beyond those observed with chromosomal resistance.
Antimicrobial susceptibility testing
The agar-plate dilution technique is the reference method for quantitative testing of chromosomemediated resistance to antibiotics (91). Bacterial growth is examined on culture media with various
concentrations of antibiotics incorporated. Results are expressed in minimal inhibitory
concentrations (MlCs). Unfortunately, the technical requirements for this mehtod make it
inaccessible in developing countries, except in a few experienced reference laboratories.
The disc-diffusion technique involves examining bacterial growth on culture plates around
calibrated paper discs impregnated with antibiotics. It is both economic and simple to use.
Unfortunately, with N. gonorrhoeae, this method has been standardised only for penicillin,
tetracycline, spectinomycin, and cephalosporins (92).
The more recent E-test, produced by AB Biodisk of Sweden, combines the advantages of the agardilution technique with the simplicity of disc testing (93). Plastic strips with continuous antibiotic
gradients, allowing MIC determination, are applied onto the surface of culture plates. Several
studies have shown that the E-test is a reliable alternative to agar-dilution for N. gonorrhoeae.
However, it is expensive and has not yet been fully recognised as a reference method.
Detection of plasmid-mediated antimicrobial resistance
PPNG: Common rapid ß-lactamase detection techniques include (1) the acidometric method, which
uses a pH indicator to detect increased acidity from cleavage of the ß-lactam ring of penicillin; (2)
the iodometric method, which detects a colour change caused by the reduction of iodine by
penicilloic acid, (3) the chromogenic cephalosporin method, which detects a colour change of a
chromogenic cephalosporin after hydrolysis of the ß-lactam ring (94-96).
TRNG: High-level tetracycline-resistant isolates of N. gonorrhoeae carrying a conjugative plasmid
have become endemic in different geographical areas. TRNG can be determined by testing its
ability to grow on a medium containing 10 mg of tetracycline per liter. The MIC of tetracycline is $
16 mg/liter (97).
Sampling for surveillance
Some Western countries conduct ongoing gonococcal susceptibility surveillance in sentinel STD
clinics throughout the country. In developing countries, however, surveillance data are used
primarily to validate treatment guidelines. Guideline validation is an intermittent process, so
susceptibility surveillance may be conducted through specific surveys at regular intervals,
particularly when laboratory resources are limited.
It is estimated that 100 to 150 gonococcal isolates need to be collected to measure a significant shift
in antibiotic resistance between two surveys.
Consecutive male patients with visible urethral discharge attending primary health care facilities are
the first choice for the sample population because gonococcal yields are the highest and it is easier
to take specimens from men than from women. Enrolled patients should be representative of STD
patients at first-encounter level within the formal health sector. Patients entering the survey should
not have been referred from other health care services. Self-medication, widely practiced in many
developing countries, should not lead to exclusion from the survey but should be noted in the data
collection process.
In some countries, male patients are very hard to reach because the stigma associated with STDs
leads to widespread self-medication. Female commercial sex workers may be a second best option
for a sample population, but specimen taking is more difficult because they are women, gonococcal
prevalence may be lower, and the representativeness of the overall population questionnable.
The number and geographical distribution of sites included in the survey should depend on how
representative each site is of resistance patterns in the country as well as logistical constraints.
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MANAGEMENT OF PERSONS LIVING WITH HIV/AIDS AND OTHER SEXUALLY
TRANSMITTED DISEASES
T. Troussier, Fatma Timol
Counselling as primary prevention for Sexually Transmitted Diseases
Definition
Counselling should be regarded as a technical approach which allows decision making and a way to
solve problems. In the context of primary prevention, counselling is a psychological approach
which is adapted to the needs of a client or those of a group of clients. It is a very adaptable tool
which requires marginal medical competence and can be practiced by all categories of educators.
Aims
In general terms, the tasks of counselling for primary prevention should include the following:
• To promote changes in individual behaviors.
• To ensure support to each of the different phases of the decision process leading to
behavioural changes.
• To propose actions which may realistically adapt to the specific client’s situation.
• To help clients in translating into actions their own knowledge on disease and risk. When
applied to the prevention of STD/HIV, counselling has the following scopes:
• To explain to the client, in a way which is easily understandable and appropriate for the
culture, the need to modify sexual behaviours and practices in order to decrease the chances
to both acquire and transmit an STD.
• To encourage people living with HIV infection or AIDS to stop practices and behaviours
which may lead to transmit the infection to others.
• In the context of tertiary prevention (management of persons who have already acquired the
infection), to reach the best possible psychological and social equilibrium for the clients
themselves and those who care for them.
Schematically, four components of counselling can be identified:
• Active listening
• Help
• Support
• Education
Active listening
Counselling is based on classical communication steps:
• Being physically present.
• Reformulate any message into a verbal structure.
• Reformulate any feelings into a verbal structure.
• Personalize problems, feelings, and matters.
• Make matters concrete.
• Define each step you are going through (Robert R. Carchuff).
Two points deserve special remarks:
• Individual’s schemes should always be respected, avoiding any attempt of interpretation.
• Never try to justify current behaviours with situations occurred in the past, better try to help
the individual using just the current contest (Gestalt-therapy).
Help
Individuals being counselled need help to solve problems. However, it is important that the
counsellor maintain a balance between steering and supporting attitudes. The two situations which
need to be avoided are those of victim/persecutor/ saver, and parents/ children.
Educators should be confident in behavioural changes which are personalized to the individual’s
needs. The awareness of the availability of positive behavioural alternatives is important to make
counselling effective (Transactional Analysis).
Support
Support originates from sharing experiences in the material, psychological, and affective domains.
A supportive atmosphere allows for the manifestation of specific feelings like frustration, anger, or
gratitude, which are often disproportionate and amplified. By definition, the support component of
counselling has precise limits in terms of time. The aim of this phase is to allow counselling
recipients to understand and accept the defensive mechanisms which are normally elicited by the
offer of new and alternative behaviours; such mechanisms develop into well codified stages and
require specific support, including counselling in a crisis situation, a problem-solving counselling,
and a decision-making counselling.
Education
Education needs to be based on the understanding of the believes and values of the person being
counselled, because it is essential to elicit the personal interest of the individual. The educational
process requires a continuous balance of the client's needs and counsellor's plan of education. It is
necessary to stress the existence of hopes in order to avoid a sense of condemnation. In the case of
HIV infection, at present, available treatment does not allow a cure, but may still be regarded as an
important support for affected people. The use of transactional analysis may be effective in the
implementation of such an educational approach.
Ethical limitations
The health domain, specifically in the field of prevention, is interested by a number of conflicts of
interest: between the single individual and the population as a whole, between what is ideal and
what is real, between knowledge and practice.
To implement a preventive intervention, or to accept to be the object of a preventive intervention,
requires having a positive perspective of prevention. But is prevention really a positive action?
Prevention is implicitly linked to positive values. However, it is interesting to examine what are the
tools necessary to put preventive interventions into practice. The principles of prevention are based
on medical and scientific knowledge. Prevention, targeted to both individuals or populations, is
managed by either professional or voluntary staff. Although the aim of prevention is definitely
positive, the tools used to apply it strongly interfere with the intimate part of the individual, with its
way to relate with him/herself, the others, and his/her cultural background.
Prevention means taking actions before, and to avoid the occurrence of specific situations. It
requires dealing with a complex contests in order to make an individual have an easier choice.
Starting from a stated information, the individual is supported to develop his/her own thoughts of
the nature and magnitude of risks, and is put in a position to take decisions which are nested in
his/her specific contest. The major ethical limitations of prevention are in facts represented by this
process of interference with the freedom and autonomy of the individual.
During the seventies lawyers and philosophers had an ethical debate on the rights of self
determination of the individual based on four principles: the autonomy of a person, justice, the
good-aiming of actions, and the avoidance of bad-aiming of actions. Being aware of the existence
of these principles and the ethical limitations of prevention is important in order to avoid the risk
that good wishes turn into bad actions.
The autonomy of a person may best be respected by answering to the following questions:
• Are the knowledge at the basis of specific preventive actions really sound ? What is the costbenefit profile of the action ? What level of satisfaction the action may generate in the target
individual?
• Have different perceptions been linked to specific cultural contests and different educational
background appropriately been considered in the intervention?
• What are the effects of the action in terms of the individual perception of health, disease,
and risk?
The freedom of an individual may be endangered as a consequence of the following issues:
• The message we pass: should it be complete or partial, and how to pass it? The facts which
are implicitly carried on by the message and the arguments the message can induce in the
individual need to considered.
• The power we have while passing a message, which is a function of the place we hold, and
the right we have to use it to modify behaviours
• The right to propose "normal" models of practices and to pretend that individuals comply to
the model
• The effect of messages on a public which is forced anyhow to respect rules made by others:
such as children at school, workers in a firm, prisoners in a prison etc.
• Group actions which raise questions of the limits between the freedom of the individual and
that of the community
• The possibility to create feelings of guilt in persons who are not willing or not able to adhere
to behaviours presented as the ideal model.
In the contest of prevention we can identify the person giving the message, the message itself, and
the recipient of the message. The person giving the message needs to tailor his/her educational tools
on the knowledge and comprehension capacities of the recipient. The very aim of health promotion
is to develop in the recipient a sense of responsibility towards the well-being of the individual as
well as that of the community, and to improve the capacities to control the determinants of such
well-being.
To make counselling effective, messages which may lead to social control in a coercive way should
be avoided.
A balanced intervention consists of supporting the client’s efforts to become aware of his/her own
values and to take decisions in order to maintain personal and communal well-being. Autonomy can
be supported by different means: by satisfying essential needs; by maintaining social links; by
recognizing his/her own social role; by increasing the self-esteem; by obtaining educational degrees
etc. Reaching an acceptable level of autonomy is essential to make a person acknowledge and
accept his/her own responsibilities towards the community.
Ensuring freedom means:
• To operate within the limits of the position covered respecting the boundaries between
public and private space.
• To maintain the awareness of the power of the role.
• To not forget the essentials of the role of someone giving a message, in particular the need
to comply with the characteristics and the needs of the recipient.
Counselling as secondary prevention for Sexually Transmitted Diseases
A. Definition
Secondary prevention is centred on screening activities, which provide the opportunity of early
diagnosis and treatment, as well as appropriate follow-up. Screening may be passive, carried out on
selected subjects, identified for example during a medical consultation for genital symptoms.
Screening may also be active, as is the case of blood donors: in this contest screening is systematic,
and all donors are aware that they will undergo HIV testing as a consequence of their decision to
donate blood.
Several problems may be considered:
• the subject’s choice of the health care provider, based on reliability and confidence criteria
• the development of the consultation
• the consignment of test results
• the search for sexual contacts if required
B. Reliability
The patient in the health care provider’s perspective: This perspective is influenced by personal and
professional experience about • sexuality
• a "noble" concept of medicine and the social impact of diseases (theory of justice in the
world)
• what is normal/abnormal
• prejudices
• doubts (from reasonable doubts to incredulity)
The health care provider in the patient’s perspective: This perspective is also influenced by personal
experience and its interactions with knowledge • confidence in his/her own intimacy
• feeling of fears and blame
• lack of knowledge and heterogeneity of information
• importance of the doctor’s figure and professional secrecy
C. Confidence during medical interview
Confidence during medical interview is influenced by the capacity of the counsellor:
• to agree that sexual manifestations are a normal component of any human being
• to be aware of his/her own prejudices
• to dedicate enough time to the consultation
• to express in verbal terms his/her own malaise
• to be simple and sincere
• to give the chance to express questions
• to explain and reassure
D. Individualized dialogue
1. Anamnesis
2. Antecedents
3. Questions related to risky behaviours:
3.1 Objective: to improve comprehension, facilitate diagnosis
Question: single or multiple sexual partnership
3.2 Objective: to have a quantitative measure of risk
Question: mean number of sexual partners
3.3 Objective: to evaluate the likelihood of specific diseases
Question: sex with usual or occasional partner(s)
3.4 Objective: to define the contest of sexual activity
Question: usual or occasional partner
3.5 Objective: to better investigate anatomical sites
Question: type of exposed anatomical sites, by active or passive way; genital, oral, anal,
exchange of objects.
3.6 Objective: to investigate adoption of preventive measures
Question: type of preventive measures used; regular or occasional use.
4. Questions in the contest of HIV screening
Depending on the risk degree, we can propose a pre-counselling questionnaire for restricted or
general screening, as well as specific screening for HIV infection:
4.1 Objective: to evaluate the client’s awareness of risk factors
Question: would you think you are at risk for acquiring AIDS?
4.2 Objective: to evaluate the knowledge on HIV transmission modalities
Question: how could you have got AIDS?
4.3 Objective: to evaluate the correct understanding of the timing in the chain of events
Question: when you last had a risky sexual relation?
4.4 Objective: to explore the client’s feelings about AIDS
Question: express a feeling and make the client reformulate it
4.5 Objective: to explore the expectations for the future of an HIV infected individual
Question: let’s imagine that one week ago you made the test and today I give back to you a
positive result
4.6 Objective: to verify the attitude towards HIV prevention
Question: what would you do in case of a negative result?
5. Questions concerning factors which may limit the client’s capacity to adopt safe sexual
behaviours
5.1 Objective: to evaluate the risk related to the partner(s)
Question: did he/she make an HIV test?
If he/she did it and the result is positive, remember that the periods at increased risk of
transmission are both the early and late stages of the natural history of HIV infection.
If he/she did the test and the result is negative, we need to consider the time lag since the
test, the existence of a conversion window, and the type of sexual exposure.
If he/she did not perform an HIV test and the client does not use condom, the offer of the
test should be based on the knowledge of HIV prevalence in the reference population, the
history of extra-couple relationships, fidelity, etc.
5.2 Objective: to investigate the type of exposure
Question: vaginal or anal intercourse?
Answers will show the attitude of the clients with respect to type of sexual contacts (vaginal,
anal, oral - active or passive exposure), existence of cofactors of HIV transmission (genital
ulcerations, other STDs, sex during menses, violence during sex)
Question: do you use condom?
This will address the issue of self estimate, the capacity to negotiate with himself/herself and
the others, condom acceptability and accessibility, appropriate use (quality of condom,
correct use of lubricants, etc.)
E. Genital examination
Genital examination is intended to explore:
• skin and mucous membranes
• inguinal lymph nodes
• abdominal (pelvic) organs
• genito-anal region in females
• genito-anal region in males
F. Consignment of the HIV test
The consignment of the test aims at orienting the patient according to the positive/negative result
and at providing counselling (tertiary prevention) for those with a positive test.
G. Partner tracing
Requires the full cooperation of the HIV infected person, which often may be obtained only after
some time. Allowing the patient to understand the basics and aims of partner(s) tracing will make it
possible to identify contacts before and after the supposed time of contamination.
H. Answers to common questions
1. What is an HIV test?
It is a laboratory test which detects the presence of antibodies to the HIV virus in the body of the
person being tested. The simple collection of a blood sample is required. The laboratory performs
HIV testing only upon specific request from the health care provider. This test is not performed
during regular check-ups. In case of first positive result the test needs to be confirmed by additional
laboratory investigations.
2. What is the most common method to make a diagnosis of HIV infection?
The most common method to detect HIV infection is the detection of specific antibodies in the
blood. There are three major techniques to verify HIV antibodies in the blood: an ELISA test, a
Western Blot, and an immunofluorescence test. A persons carrying the antibodies is currently
infected by the virus and can contaminate others. Such a person is usually referred to as a
"seropositive" individual; such a condition will last life-long. Being seropositive is not the same as
being affected by AIDS. A reactive serological test may often be detected several years before a
person develop AIDS-defining diseases. Antibodies to the HIV are not produced immediately after
viral infection: it usually takes 4 to 6 weeks after the contamination for the HIV test to become
positive. Hence, a person can be infected by the HIV and can transmit the HIV even if seronegative,
if the test has been performed at a too an early stage.
3. What are other available methods to detect the HIV?
a) an antigen detection test, which aims at identifying a part (antigen) of the virus in the blood. A
positive HIV antigenemia usually develops early (usually 15 days) after infection, well before the
antibodies are detectable. Thereafter the antigen usually disappears from the blood for several years,
to reappear at a later stage to indicate the reactivation of viral replication. The presence of a positive
antigenemia immediately after infection does not always last until the appearance of the antibodies
in the blood: therefore there is always the possibility that soon after infection neither the antibody
not the antigen detection test are positive, though the person is actually infected.
b) A PCR (Polymerase Chain Reaction) test. This test identify the presence of the HIV genome
within the cells of an individual. It is a recently developed technique, which, for a variety of
reasons, is not yet applied to screening programs. This test would be positive in the "window"
period soon after infection, when both antibody and antigen detection tests may be negative:
however, this property is currently exploited only in the contest of research, rather than routine
diagnosis. The PCR test is useful for the diagnosis of HIV infection in babies born to HIV infected
mothers, as the presence of antibodies is not a reliable tool in this contest: maternal antibodies may
persist in the newborn blood for several months, even if the newborn did not in fact acquire the
infection.
c) Viral load. This technique allows to measure the quantity of the HIV virus in the blood of an
infected person. The viral load provides important information for the management of a person with
HIV infection:
CD4> 500 / mm3 and viral load > 104 copies /ml = monitoring, and discuss indication to treatment
CD4< 500 / mm3 and viral load < 104 copies /ml = monitoring
CD4< 500 / mm3 and viral load > 104 copies /ml = indication to treatment
4) What is an anonymous test? How much does it cost? Where can we do it?
When a blood sample is collected a coded number is put on the label to replace the name of the
person, who, therefore, remains unknown. Such a test is called anonymous.
Some persons are afraid that the result of the test, especially should it be positive, be divulgated
generating stigma, social discrimination and, in some case, loss of the job. It is important to make it
very clear that all possible precautions are taken to maintain the privacy. A test can always be kept
anonymous if the patient requires it.
The costs of an anonymous test in France and Reunion Island is approximately 80 French francs
(sometimes more than this, if a confirmatory test is automatically performed after a positive ELISA
test). In many countries, however, at least one or a few offices are available where the HIV test is
performed without any charge.
5) Why should a person know if he/she is seropositive?
Possible advantages of knowing someone’s seropositivity state are:
a) to get access to health care at an early stage
b) to get access to appropriate treatment at an early stage
c) to take precautions during sexual intercourse not to pass the infection to the partner(s)
d) to evaluate carefully the risk of a pregnancy (risk of vertical transmission to the newborn)
6) Should regular testing be performed to be sure about one’s serological state?
The ELISA test is sensitive, provided that it is performed not less than 6 weeks after exposure to a
possible source of contamination. The test should thereafter be repeated only in case of eventual
exposures. That is why it is so important to discuss about risks and prevention at the moment of the
request or the offer of an HIV test.
7) Why some persons are scared by the offer of an HIV test?
Someone believes he/she can have a better life with the doubt of being seropositive than with its
certainty. They need time to acquaint to the possibility of being seropositive. Trying to force them
to make the test may cause the disruption of the trustful climate with the counsellor. Should they be
forced to make the test, they would be likely not to come back to collect the result, or would not
anyway accept a positive result.
At present, effective antiretroviral therapy does exist for subjects with symptomatic HIV infection
or with low immune levels; hence, whenever antiretroviral therapy is actually available, we have a
strong argument for the offer of an HIV test. In addition, case management and medical follow-up
may be offered to those being positive to the HIV test.
8) What method is currently available to detect HIV infection in the newborn?
During the first 15 months of life, the seropositive state of the infant may be the result of the
passage of maternal antibodies through the placenta during the gestational period; hence, the
detection of antibodies is not a suitable test for HIV infection in a newborn from an HIV infected
mother. Alternative diagnostic tests include:
• the presence of clinical signs of AIDS
• the persistence of HIV antibodies after 15 months of age
• a positive HIV culture from peripheral lymphocytes (or a positive PCR test)
9) Why is it so important never to perform a screening test to a person without his/her knowing
about it?
The scope of a screening test is to help decreasing the diffusion of the HIV in the population and to
allow for an early care of HIV infected persons. Hence, when informing a person that he/she is
seropositive you wish him/her:
• to avoid risky behaviours which may cause the passage of the infection to others
• to seek care at an early and still asymptomatic stage
When a person is informed about the HIV test he/she is going to have, it is reasonable to expect this
person to have an attitude of confidence with the health care provider proposing the test. The
favourable climate may therefore increase the capacity to accept a positive result of the HIV test
and to take care of him/herself and the others. The offer of the test gives an important chance for
discussion, which may greatly help initiating a process of behavioural changes if the test will result
to be negative.
10) When to propose the HIV test?
The test should be offered to all persons having, or having had, risky behaviours: frequent change of
partner, presenting with an STD, having commercial sex, being an intravenous drug user (IVDU),
having an IVDU sexual partner, or having a partner from a country at high endemicity for HIV. It is
not always easy to recognize all these conditions, and the health care provider needs to plan for
appropriate time to discuss these issues with the client. Clients are often prevented from requesting
a test by the fear of being judged.
Health care providers should think about offering the test while facing clinical conditions which
may suggest a state of immune deficiency: pneumonia not responding to standard treatment in
persons with a history of risky behaviours, tuberculosis, a herpes zoster infection, severe oral
infections, etc.
11) What is a false positive result?
The HIV test is remarkably sensitive (it detects all infected persons if appropriate timing is
respected). However, it may happen that a positive test is not later confirmed by a second test
(confirmatory test). The person is not infected. This is a toll we have to pay to the great sensitivity
of the screening tests.
Counselling as tertiary prevention for Sexually Transmitted Diseases
A. Definition
This type of counselling aims at preventing the psycho-social and affective consequences of HIV on
infected persons and their relatives. The scope is to provide support throughout the sequential stages
of the disease. It also aims at producing changes in the community towards the AIDS problem, in
order to limit social exclusion and the relevant consequences.
B. Postulates
• Help the patient to exploit his/her own resources
• Respect the patients’ schemes and timing to go through the different phases
•
•
•
•
Never make judgements
Establish an empathic climate
Be flexible
Help "here and now"
C. Relational skills
They include communication skills useful to interact with the patient:
• Physical listening
• Reformulation of messages and feelings
• Personalisation of objectives
• Peer dialogue, avoiding both "parent/child" and "saver/saved" types of relations
• Avoidance of a questioning approach
• Preparation of a positive and constructive atmosphere for both protagonists
D. The different stages
1. The initial crisis
The reactions face to the information that a person has HIV or AIDS are well defined and
reproducible in a wide variety of cultural contests, and are similar to those described by E. Kubler
Ross for persons in the final stages of other incurable diseases.
1.1 The phase of the shock
It is the phase of awareness of having an incurable disease which affects the most intimate
part of an individual. It is a shock because the problem involves the entire society with no
racial or social limitations; because it affects persons in the reproductive age and the infants
of infected mothers; because it obliges a person to think about oneself, own personal and
social relations; because it revives the fear of death associated to that of sex.
The objective of counselling is to facilitate persons to regain self-confidence, despite
emotional derangement and paralysis caused by the magnitude of the problem. The type and
extent of the crisis may be defined by the person experiencing it only. The counsellor need
to start from where the patient is at that moment and explore the crisis, without minimising it
and without trivialising the feelings of those who play a role of a victim. The first priority of
active listening will be not to deny, to respect the feelings, and to help rebuilding self-esteem
and self-control. This implies that the counsellor should have thoughts about these problems
in order to share considerations, and should be able to inform in a clear way to contribute to
the re-elaboration process of the patient.
1. 2. The phase of the denial
It is an unavoidable passage, "it is not me, it is somebody else !" Such a reaction is necessary
to rebuild oneself. It is advisable to make the individual express his/her feelings, as the most
these feelings are verbalised, the less negative actions will be taken. Often, during the phase
of the denial, a person shows his/her feelings with an aggressive attitude.
The objective of counselling is to help the individual to explore the very intimate parts of
oneself here and now, and to guide him/her in verbalising feelings and messages. The aim is
to reach the third phase.
1.3. The phase of the response or the retreat
The individual is depressed and he/she talks of sadness and despair. The counsellor will
need, once again, to help the individual expressing his/her feelings, to observe and confirm
the loss of control. The counsellor will then need to explore and assess the client’s physical
and psychological capacities to analyse his/her own situation.
1.4. The phase of the revolt
Anger is the characteristic reaction. The counsellor will allow the complete expression of
such anger: "you are angry with the society.... with myself.......we both need to know what is
going on...... what is threatening us". By reformulating and personalising the feeling of
anger, the counsellor will help to take initiatives, which represents the next phase.
1. 5. The phase of acceptance
The existence of the problem is admitted and accepted: now it is possible to start managing
it. This represent the end of the phases of shock, denial and response. From now onwards it
is possible to start counselling to take decisions and drive actions.
2. Solving problems
The objective is to understand the consequences of the HIV/AIDS on the real life of the individual,
to establish and strengthen the capacity to face the problems associated to the risk of further
transmission, and to facilitate behaviours intended to protect oneself.
The counsellor will have to demonstrate a real interest and never minimise any sort of problem
raised by the counselled person. He/she will have to help examining the different aspects of
problems, to talk openly of the fear of further transmission of the infection, and to explore any
possible action personalised to the needs of the counselled person. The client is reassured that any
reaction is normal and start building a programme of actions.
3. Taking decisions
The objectives are to:
• Help the individual to think about issues which are usually difficult and disturbing, and to
help him/her in exploring changes in behaviours which may be required by the new
situation.
• Recognize resource persons who may help in putting such changes into practice and
establish a dialogue with persons who may have similar problems. Help the client
communicating within the family and work environment, after having assessed whether this
is feasible.
• Explore the consequences on usual and unusual sexual behaviour
4. Difficulties in behavioural changes
One of the scopes of counselling is to identify the difficulties of behavioural changes. The
counsellor will often need to underline, repeatedly and in different ways, the factors preventing
behavioural changes. Knowing something does not imply that relevant changes will be put into
practice. Some individual may think that a fact is not relevant for his/her own situation, or may
think against proposed changes (for example, proposing condom use may destroy the confidence in
him/herself or the partner). Changes may sometimes be in contrast with cultural or religious
believes. Behaviours are usually modified only if a real gain is perceived by the person who need to
apply them.
5. Psychological support to patients receiving treatment
Providing support to patients receiving antiretroviral therapy is intended to improve adherence.
Effective support requires regular updates in the field of available drug regimens (multi-drug
regimens, early indication to treatment, adverse events of new compounds), their increasing
efficacy (decrease in the number of notified AIDS cases, reduction in hospital admissions), and the
advances of behavioural science. Adherence is a more appropriate terminology than compliance, as
it implies a direct involvement of the patient.
Adherence will depend on three factors:
The attitude of the health care provider: this is influenced by the availability of drugs, his/her
specific knowledge, personal experience, communication skills (from the offer of HIV test to post
test counselling and to the dialogue established with those being infected), costs, framework of
treatment (clinical trials, research protocols, etc.), capacity to link with the patient and his/her
general practitioner, capacity to appreciate and manage adverse events of therapy.
The drug: frequency and type of adverse events, number of pills, knowledge on the mode of action,
length of therapy, costs, drug-drug interactions, specific contraindications (pregnant women and
children, etc.)
The patient: age, gender, ethnicity, social status, medical history, time since knowing to be
seropositive, clinical stage, comprehension of side effects, personal motivation or difficulties,
perception of the importance of missing pills, insurance problems, existence of a supportive
network, comprehension of the mode of action of drugs and the length of therapy, the desire and
expectations to be cured and to maintain a "status quo-ante".
The three most important factors influencing adherence seem to be the length of therapy (the shorter
the best); an optimistic attitude of the patient towards treatment (the patient feels to play an active
role in his/her cure); adverse events (the deeper the initial explanation on the nature and frequency
of adverse events, the best the adherence).
All the above factors will need to be taken into account at the time of each consultation: it is
therefore easy to appreciate that consultations require time, and that availability of time is indeed
the most important factor to allow the patient to participate actively in this process.
E. Answers to common questions
1. I am seropositive, I could never tell it to my wife (husband)
The burden of being seropositive is increased by the lack of communication and discussion with the
partner, relatives and friends. By inviting the individual to express his/her feelings (fear, remorse,
blame, etc.) the counsellor may facilitate the process of focusing on major problems and
implications of the new situation on the day-to-day life. The confrontation with the partner is part of
this process.
2. I am seropositive, I fell in love with somebody, do I have to talk about my condition?
It is easy to imagine how difficult it is to tell some body you love that you are infected by the HIV.
Will the person decide to stop seeing you?
Nevertheless, how continuing the relation with such a secret burden to carry?
How long will it take to the person to know the truth?
What is the future of such a couple?
The counsellor cannot as well ignore the risk that the client will infect the partner.
The most important thing in this difficult issue is that the client will feel that we share his/her
problems. The attention and confidence the client may obtain from the counsellor will later
facilitate his/her decision to take care of the well-being of the partner.
3. I am seropositive, but I don’t use preventive measures with my partners
This person demonstrate a need to talk to somebody of his practices and, maybe, to test the
reactions of the others. Solitude, tension and despair are the most common determinants and
consequences of these practices.
The normal reaction of the counsellor is that of shock; often, the client has an aggressive attitude
while presenting the problem, which may be interpreted as a complete lack of remorse.
However, if we start immediately talking about preserving the well-being of the partner(s) who may
be contaminated, the client will have the impression that we don’t care enough about his/her own
well-being. We may risk that the client will continue his/her risky practices out of spite. The scope
of counselling in this instance is to make the client aware of the suffering that surely motivate
his/her behaviours.
4. Now that I know that I am seropositive, shall I tell to my sexual partners?
This issue is particularly problematic, especially if the counsellor do not know the partners. The
partner may not only terminate the relation, but may also divulgate the information, worsening the
isolation of the seropositive person. It is our responsibility to discuss this with the client, keeping in
mind that our first task is to avoid him/her further suffering and isolation. If the client will decide
not to tell the partner(s), the counsellor will need to encourage him/her to take all necessary
precautions not to transmit the infection to others.
5. I have done the HIV test thrice, always with a negative result, but still I don’t feel safe and I
believe I have symptoms of AIDS.
The counsellor need to assess the magnitude of the HIV risk of the client’s behaviours. Sometimes
the risk is high, and the client may be referred to specialised services to repeat the screening.
Most of the times, however, the risk is minimum. The common situation is that of a person blaming
him/herself for the behaviours which led to taking the HIV risk, usually an extramarital relation.
The person is not able to forgive him/herself and awaits for the punishment, possibly under the form
of HIV infection. The task of counselling is to make the person discuss about infidelity, the cause of
his/her feeling of blame, in order to take consciousness that the HIV risk is unreal.
6. I fear dying
When a person fear dying, sometimes it is easier to discuss it with persons who are not so close and
directly touched by the event, as a counsellor can be. It is surely difficult to listen to somebody
talking about his/her death because it reminds us of our incapacity to help (there is nothing else to
do that listening), but this is still an important contribution. It is certainly important to differentiate
between a situation in which death is really unavoidable and that in which it is just feared of.
Seropositive persons have many years of healthy life to spend and the prognosis is constantly
improving. Despite this, infected persons are right to think that this time is short. In addition,
somebody will experience the infection as a death sentence as they will have to give up to many
projects: marriage, children, career. Usually, with appropriate time, these persons will reconsider
their projects and will adapt them to their new condition. It is important to offer the chance to
cancel previous projects and start rebuilding new ones.
On the contrary, persons who are really in the proximity of their death, should not be deceived
about the length of the remaining life. These persons often take advantage by having somebody to
listen to them: life summary, regret for what they may have missed, fear of dying, life beyond
death, etc.
7. I am seropositive, but I would like to have a baby
We need to consider that the risk of vertical transmission from an infected mother is around 20%,
and can be reduced to less than 10% by the use of appropriate treatment in the mother and the
newborn. However, whether an individual newborn is actually infected or not may presently be
assessed not earlier than the age of 15 months. Pregnancy may worsen the course of HIV infection,
hence reducing the chances that the mother will be able to care for the infant and grow him up.
Despite the lack of optimism of this picture, we can understand the desire of pregnancy of young
women with HIV infection. It is important that these women can discuss their desire without feeling
of being judged.
8. I had risky behaviours but I do not want to know whether I got the HIV infection
The expectation of being seropositive is unbearable to some persons: fear of being rejected,
remorse, fear of the disease, of death, not to be loved any more, etc. These persons may feel
incapable of standing a possible positive result of the HIV test.
However, some circumstances may stimulate these persons to solve the doubt (a new stable partner,
for instance). Knowing about the HIV status would have the advantage of giving access to treatment
and other health care standards at an earlier stage of infection.
9. I need to go to the hospital but I am afraid I will not get out of it
It is important to establish the basis of this fear. Why the person is being admitted to the hospital? Is
it the first time he/she has the fear of dying while getting into the hospital? What are the physical
conditions? What is the opinion of the doctors? Is the person confident of the medical team? Does
he/she receive psychological support from the medical team? Does she/he feel like having less
resources to fight the disease?
By posing some or all the above questions the person may be helped in identifying the real causes
of his/her fear and increase the confidence of his/her own resources.
10. I am seropositive, I am going to commit suicide
By listening to these persons we may allow them to be aware of the specific reasons for which they
believe that being seropositive is an unbearable condition. Is it discrimination? The fear not to be
loved? The physical decline? The shame? The feeling of dependence? The feeling of injustice? The
fear of dying?
It will be important to assess what the person did to avoid getting the infection and how he/she
assessed he/she was actually infected. Sometimes, by a paradox effect, persons are attracted by
what they fear most.
11. I am seropositive but I do not want to be cared for
It is somehow understandable that some person prefer to live a shorter but normal life rather than
trying to live longer by behaving as a sick person for many years. It is important to advice this
persons to consult a doctor at least once, to be explained in details what does the follow-up of an
HIV positive person consist of. These persons will therefore be able to take an informed decision.
We can also offer, in addition or as an alternative to medical follow-up, a psychological follow-up
which may not be centred on the problem of HIV infection. We should always work to leave an
open door to persons who initially decide they do not want to be cared for.
POPULATION MOVEMENTS AND STD/HIV HAZARDS
A. Matteelli, L. Signorini
Migratory flows have always been associated to human societies.
Despite common occurance of conflicts between old and new establishments, migratory flows have
contributed significantly to human development. Nowadays there is no single country in the world
which is not interested by either immigratory or emigratory flows, due to environmental (climate,
geological disasters), political (wars, repression), and economic (job offer and demand) reasons.
According to recent estimates of migratory flows of the United Nations there are at least 130
million people living in foreign countries, and 4 million people cross the boundaries each year. In
addition, there are at least 23 million refugees worldwide, while the numbers of clandestines is
actually unknown (1). As the world population grows differential pressure on ecosystems will
invariably lead to larger and larger population movements. Population policies, environmental
protection and economic development may provide the long term answer to many problems brought
about by migration. In the short term, however, we need to face and solve current health problems
arising from population movements.
The migration process interferes with human sexual practices and therefore with the risk of
acquiring or transmitting communicable agents through the sexual route. The history shows that
STD may travel with man and therefore affect populations in which they were virtually unknown
before: the syphilis epidemics in the Middle Age were strongly influenced by the discovery of
America and the opening of the trade channels with South East Asia. A similar model has been
proposed for the role of human movements on the diffusion of the HIV epidemic. The
heterogeneous distribution of STD in the world is very well documented today: estimated
prevalence rates of curable STDs among adults is of 120 million and 53 million cases in the South
East Asia and sub-Saharan Africa respectively, compared to 8 and 10 million in the North of
America and Europe respectively (2). Little is known, on the contrary, on the distribution of viral
STDs.
The human kind is not a passive carrier of STD. Moving away from the familiar environment
breaks established links, by splitting fixed sexual partnership, and remove many social taboos
which strongly affect human sexual habits. Settling in a new environment may expose to adverse
conditions of cultural isolation which facilitate the establishment of casual sexual relationships. The
motivation for travel, the length of stay outside the native environment, and the type of the hosting
environment strongly affect the risk of STD acquisition and transmission.
Below we review epidemiological data of STD prevalence and risk in three heterogeneous groups
of travellers, namely migrants from southern to northern countries, and either long and short term
travellers from northern to southern countries. The identification of such groups is largely artificial,
but may help in defining different risk patterns and possible control interventions.
We will not examine in this contest the problem of internal temporary migration within countries of
the Southern hemisphere, though this phenomenon is very likely to play a significant role in the
dynamics of the HIV epidemic. One well established example of such situation is represented by
temporary labourers movements in large parts of Africa. In Uganda a longitudinal cohort study at
population level over a 3-year period showed an increasing trend of HIV prevalence from 5.5 to
11.5 and 16.3% among subjects who did not leave the village, those who travelled away, and those
who moved into the village during the study period respectively (3). The reported numbers of
lifetime sexual partners were higher in those who changed residence (3). A similar association
between HIV seroprevalence and travel has been reported from Senegal, related to both movements
within the country (4) and outside the country (5).
Migrants and refugees into Northern countries
Wars, political unrest, poverty and unemployment are the major motivations for migration into
northern countries of people coming from the tropical belt or, more recently, from Eastern Europe.
The living conditions of migrants in the host country are usually unfavourable: they experience
cultural and social marginalisation and occupy the poorest fringes of the society. Although migrants
may soon start the process of integration into the host society, a situation of disadvantage may last
for long periods and represent the roots of ethnical marginalisation in multiracial societies like in
the USA (6). Low socio-economic standards, discrimination and marginalisation facilitate use of
illegal drugs and casual sexual contacts with sex workers (7, 8).
The sex industry itself sometimes represents the specific reason for migration. This is an expanding
phenomenon in many European countries, where the offer of cheap sexual services encounters an
expanding demand. Immigrant commercial sex workers present a risk of acquiring STD and HIV
which is significantly higher than that of local sex workers. For example, a significant proportion
(28%) of Romanian female sex workers in Turkey were first time in prostitution and had little
knowledge and awareness on the exposure to STD/HIV and the measures to avoid infection (9). In
Italy, in the contest of the recent phenomenon of massive immigration, the number of female
immigrant prostitutes significantly increased: most of the women started the activity after moving to
the host country in order to survive, or at the very time of immigration being part of a true trading
system (10).
Even if prostitution is not illegal in many countries, however, most women have no access to the
health security system of the host country. They are excluded from STD/HIV preventive efforts
channelled through standard education campaign for cultural reasons, and may find it difficult even
to get curative services unless when in emergency situations (11). The same curable STDs which
have almost disappeared from high resource countries may re-emerge in these population fringes
which cannot share the benefit of the economic wealth with the local population. As a whole, STD
prevalence and incidence rates in migrant sex workers reflect much more the standards of living in
the host country, rather than the STD prevalence rates in the home country (8, 12).
Migration per se may increase the risk of acquiring the HIV infection regardless the country of
origin of the immigrant (13). In Italy, the sentinel surveillance system for STD in migrants suggests
that 77.5% of new HIV infections in this population are acquired in the host country (14).
Log term travellers to southern countries
Most available observations on this category of travellers refer to personnel of voluntary
organisations employed in countries of the tropical belt. Exposure to STD/HIV in likely to occur in
this setting. About 60% of 1080 American peace corp volunteers reported sexual relationships with
at least one new partner during the stay abroad (15). About 40% of them had a local partner and
only a third of them reported using condom. Regular use of condom was inversely associated to
alcohol abuse among male volunteers, and inversely associated to the number of new partners
among female volunteers (15). In this instance, effective protective measures were actually adopted
by those who mostly needed them, possibly due to a higher level of awareness of the risks of sexual
exposure.
Soldiers on military service abroad represent another group at increased risk for STD/HIV. Among
recruits of a Dutch battalion posted in Cambodia for a period of 6 months almost half reported
having sex with local female commercial sex workers (16). From one side, these recruits reported
very high rates of regular condom use, possibly as a consequence of specific information and
education campaign targeted to the group. On the other side, however, almost one third of regular
condom users reported failure of the barrier method during one or more acts: either the condom
slipped off or broke. This observation reminds that recommending condom use is not enough, and
underlines the importance of explaining the correct use of condoms to those staying abroad.
Expatriates residents in southern countries for long periods are also likely to be at increased risk of
STD/HIV but data are scanty. Thirty one percent of the male and 13% of the female German
expatriates reported casual sexual contacts while staying abroad, of whom, only a quarter used
condom (17). More than 50% of Belgian expatriates in Central Africa reported extramarital sex, and
one third reported regular contacts with commercial sex workers (18).
Short term travellers
Increased sexual promiscuity is likely to occur during short term travels, and, sometimes, sex is the
specific purpose of the travel (sexual tourism). During tourist travels people have the opportunity to
escape standardised behaviours commonly regarded as acceptable by the society. An increased
sexual demand by tourists often matches an increased offer of sexual services as these, in many low
income countries, represent a way to increase the revenues and may contribute significantly to the
family survival. In a recent questionnaire study on Swiss tourists to tropical countries, 30% reported
casual sexual contacts during the holiday period (19). Males were more likely to practice casual sex
abroad and more often reported sex with local females, while travelling women were more likely to
have casual sex abroad with other foreigners (20).
The travel usually amplifies specific individual behaviours. Practicing casual sex in the home
country has been independently associated to casual sex abroad. Among Swiss tourists, the
proportion of subjects reporting casual sex during last travel was 18% in those practicing casual sex
at home compared to 1.6% of those who did not (20). Casual sex abroad among Swedish women
was associated with several behavioural characteristics: earlier coitarche, a higher number of
lifetime partners, more frequent alcohol abuse, and more frequent extramarital sex (21).
These observations may be important: education and counselling may represent effective tool to
decrease unsafe sexual behaviours, but they need to be targeted to the subgroup of travellers who
are actually likely to engage in risky behaviours.
Prevention and control
A travel is a situation in which the risk of acquisition or transmission of an STD is specifically
increased, and people living for sometime away from home country may be at persistently high risk.
The rationale and options to prevent STD are not different from the standard ones: primary
prevention is based on information, education and condom promotion, while prevention of sequelae
and complications (as well as further transmission of the infection) may be achieved by means of
early recognition of infection and effective treatment. Since some of the STD are presently
incurable, such as HIV, HBV, and HPV infections, primary prevention may represent the only
effective option.
The strategies used to translate into practice the general principles specified above, may actually
vary.
Primary prevention requires changes in human behaviours. Passing information and providing
educational messages may not actually result in modifications of behaviours in the target population
and safe sexual behaviours may perfectly be understood but not put into practice. Whether or not a
specific educational message will be put into practice by the recipient basically depends on three
factors: a) perception of personal susceptibility to the specific hazard b) perception of the true
consequences of the hazard; c) individual elaboration on how difficult to apply the new behaviour
and how great the benefits this can determine (22). In a recent study medical advice concerning
proposed behavioural changes were followed by only 40% of the recipients (23). When sexual
behaviours are concerned, this rate is likely to decrease further, as sex behaviours are guided by
emotions rather than a rational choice. The content of information and education in the field of
STD/HIV prevention is very well defined. Where we need to be much more effective is in the
identification of tools which facilitate behavioural modifications. As far as travel related STD/HIV
hazard is concerned, the very heterogeneous conditions of the different groups of travellers require
specifically tailored interventions.
Migrants and refugees
Levelling of the STD/HIV risk can ultimately be achieved only by the integration in the host
country. However, specific interventions have been proposed and implemented in the health sector.
First, preventive an curative services should easily be accessible to all subjects. This requires that
people be entitled to care, even beyond the limits of juridical recognition. Even more important,
effective care requires recognition of the cultural diversity, and may imply the existence of
specialised services. Stigmatisation is a specifically important barrier to the management of
STD/HIV infections, and should carefully be avoided when delivering STD services. Counselling,
an extremely important component of case management, requires optimal ways of communication
between the health care provider and the client, in both linguistic and cultural terms.
Preventive messages may need to be targeted to ethnic minorities and specific population groups.
Long-term travellers
Travellers who belong to international organisations, the army, or non-government organisations
should receive specific information and education. As mentioned above, the content is not a
problem, but the way it is passed to the recipient is frequently inappropriate. Adequate time should
be allocated to STD/HIV prevention during pre-travel advice in order to discuss with the traveller
any possible barrier against the adoption of safe sexual behaviours.
The regular availability of condoms, especially in the case of private companies and camps, should
be ensured by the organisation itself.
HBV is the only STD which is currently a vaccine preventable infection. The incidence rate of
HBV among European expatriates has been estimated to be in the range of 80 to 420 cases per
100,000 per month (24). HBV vaccination should be recommended for long term travellers. In this
setting, it would be essential to strengthen the concept that other STD, like HIV, are not preventable
in the same way, in order to avoid false feelings of being protected.
Short term travellers
Sexual behaviours during short term travels are strongly affected by usual sexual behaviours in the
home country, therefore, continual sexual education is important to prevent STD hazard during
travels abroad. Leaflets to inform about STD hazard have been proposed and used for short term
travellers. Recent observations demonstrate that leaflets are consulted significantly more frequently
by subjects who will thereafter practice casual sex during travel compared to those who do not (20).
In addition, in a questionnaire study, the large majority of travellers stated, at departure, they would
use condom during casual sex, but the proportion of actual users declined dramatically upon return.
Both observations indicate that informing does not imply changing behaviours, and that intentions
not always translate into practice (20).
Contrary to long-term travellers, the provision of pre-travel counselling on STD preventive
practices to all short term travellers seems to be unfeasible. There are indications that travellers at
increased risk may be identified in order to restrict the target for counselling activities (25). The
information package should include discussions on the nature and consequences of STD, the way to
prevent them, and the factors which may create obstacles to the adoption of safe behaviours. The
effects of alcohol and other drugs abuse on self-control should be discussed. Demonstration of
correct condom stocking and use should be included. Condom use during commercial sex is usually
determined by the client decision if the client is a male (26); in the case of female clients condom
use is much more likely to be bargained. The female condom, which is less known and less widely
available but as effective as the male condom can be proposed as an alternative. The sex worker
preference has a major role also in the case of men who have sex with men (27); this make it
possible to have educational campaign on both the side of the traveller and that of the sex worker in
the home country.
Curative services should be in place for travellers as secondary prevention measures. The case
management of long term travellers of big organisation may be done at travel clinics where
appropriate case management, following the syndromic approach, would need to be implemented.
Screening for STD upon return from international travels may be proposed but is largely unfeasible.
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LIST OF AUTHORS
Bastos Rui, Professor auxiliar na Fac Medicina na UEM, Acessor clinico do Programa de Luta
contra SIDA e as DTS (STD) - Director, Serviço de Dermatologia Department of Dermatology,
Hospital Central de Maputo, CP 1164 Maputo, Mozambique, Tel. e Fax: +258-1-428319
E-mail: [email protected]
Benzaquen Adele, MD, Ginecologista, Fundação “Alfredo da Matta”, Manaus, Amazonas, Rua
Codajas, 24 - Cachoerinha, 69.065-130 Manaus, Amazonas, Brasil, Fax (92) 663 3155
Bissek Zoung-Kanyi, Assistant Lecturer in Dermato-Venereology, University of Yaoundé
B.P. 4129 Yaoundé, Cameroun
Bouvè Anne, STD/HIV Research and Intervention Unit, Department of Microbiology, Institute of
Tropical Medicine Nationale straat 155-2000 Antwerpen, Belgium, Tel. +32(3)2476320 - Fax
32(3)2476333
Burgeois Anke, ORSTOM, BP 1857 Yaoundé, Cameroun. Tel. +237.226258 - Fax +237.201854
Coulaud Jean-Pierre, Services de Maladies Infectieuses et Tropicales, Groupe Hospitalier Bichat
Claude Bernard, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. Fax +33(1)40361699
Delaporte Erik, Laboratoire Retrovirus, ORSTOM, 911 Avenue Agropolis, BP 5045, 34032.
Montpellier Cedex I. France, Tel. +33(4)67416156 Fax +33(4)67619450
Fiallo Paolo, MD, Assistant Professor of Dermatology, University of Genoa; Genoa, Italy.
Viale Benedetto XV, 7, 16132 Genova, Italy - Tel.: +39-010-3538865
Fax: +39-010+3538427
Foster Susan, Prof. of International Health, Boston University School of Public Health, 715
Albany Street, Boston, MA 021182526, USA, Tel.: +1(617)6385234 Fax: +1(617)6384476.
Gerbase Antonio, Office of HIV/AIDS and secually Transmitted Diseases, World Health
Organisation, 1211 Genova 27, Switzerland. - Tel. +41(22)7914459 Fax +41(22)7914834
Jackson D., Department of Community Health, University of Nairobi, PO Box 19676, Nairobi,
Kenya. - Fax +254(2)724639
Levine William, Centers for Diseases Control and Prevention, Atlanta, USA.
N. Ngugi Elisabeth, Department of Community Health, University of Nairobi, PO Box 19676,
Nairobi, Kenya, Fax: +254(2)724639
Nunzi Enrico, Professore di Dermatologia, Dermatologia Sociale, Università degli Studi di
Genova, Viale Benedetto XV, 7; 16132 Genova, Italy, Tel: +39-010-3538400 Fax: +39-0103538427
Orsi Ana Tereza, Dermatologista, Nùcleo de Dermatologia, Fundação Instituto de Medicina
tropical, Av. Pedro Teixeira, 25 - 69.040-000 Manus, Amazonas, Brasil, Fax: (92) 2387220
Q. Islam Mounir, Family Planning and Population, World Health Organisation, 1211 Geneva 27,
Switzerland. Tel. +41 (22)7912111 Fax: +41(22)7914189
Signorini Liana, Clinica Malattie Infesttive e Tropicali, Università di Brescia, Piazza Spedali Civili
1, 25125 Brescia, Italia Tel: +39(030)3995671 Fax: +39(030)303061
Talhari Sinésio, MD Department of Dermatology/STD/AIDS University of Amazonas and
Institute of Tropical Medicine, Manaus, Amazonas, Brazil
Timol Fatma, Consultant de Formation et Comunication Santé, 12 rue de la Falaise 97460 St. Paul,
La Reunion. Tel/Fax: +262.454509
Titan Silvia, Office of HIV/AIDS and sexually Transmitted Diseases, World Health Organisation,
1211 Genova 27, Switzerland.
Troussier Thierry, Ministere du travail et des Affaires Sociales, Direction Generale de la Santé,
Bureau des Maladies Trasmissibles, DGS/VS2, 8 Avenue de Segar, 75350 Paris 07SP, France.
Fax: +33(1)40565056
Van Dyck Eddy, STD/HIV Research and Intervention Unit, Department of Microbiology, Institute
of Tropical Medicine Nationalestraat 155 - 00 Antwerpen, Belgium. Tel.: +32(3)2476320 Fax:
+32(3)2476333.

Sexually transmitted diseases in the tropics

Transcription

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