Part two

Transcription

Part two

Introduction: dermatology and human rights
155
Part two
156
Health Systems and Skin Diseases: the case of Ethiopia
BIANCA
1. Introduction: health systems and skin infectious diseases. The case of Ethiopia
157
1. INTRODUCTION: HEALTH SYSTEMS
AND SKIN INFECTIOUS DISEASES.
THE CASE OF ETHIOPIA
Aldo Morrone, Gebreab Barnabas
In assigning health priorities, skin diseases are sometimes thought of, in planning terms, as small-time players in the global league of illnesses compared
with diseases that cause significant mortality, such as HIV/AIDS, community-acquired pneumonias, and tuberculosis. However, skin problems are generally among the most common diseases seen in primary care setting in tropical areas, and in some regions where transmissible diseases such as tinea imbricata or onchocerciasis are endemic, they become the dominant presentation. For instance, the WHO’s 2001 report (WHO 2005) on the global burden of disease indicated that skin diseases were associated with mortality rates
of 20,000 in Sub-Saharan Africa in 2001. This burden was comparable to
mortality rates attributed to meningitis, hepatitis B, obstructed labour, and
rheumatic heart disease in the same region.
Moreover skin diseases related to HIV, which may constitute an important
component of the skin disease burden in developing countries, particularly in
Sub-Saharan Africa, lead to an important impact on life quality.
Skin conditions are amongst the commonest causes of morbidity in rural and
urban areas of developing countries, accounting for a high proportion of visits to primary health care centres, which are often underserved and underfunded. The limited time and financial resources available in primary health
care are frequently swamped by this high patient burden to the detriment of
other important health promoting activities, such as immunization programmes or antenatal care. This situation presents a further dilemma in that
skills in the management of skin disease are poorly developed, and inappropriate treatment leads to the wastage of household resource which could be
spent to the benefit of the family and the community.
Most information about the epidemiology of skin disease is based on data
collected from medical records in specialized centres. Unfortunately, this does
not necessarily represent the prevalence of skin disease in the community.
Moreover, when estimating the health needs of the population, these figures
are seldom accompanied by data on community prevalence.
There are limited studies of the impact of skin disease on health care systems
158
in developing countries. In 1992, dermatological disorders were reported as
the second and fourth most frequent complaints at Shebe and Agaro health
centres in the tropical foothill region of Illubabor province, southwestern
Ethiopia.
Tropical dermatology used to be known as colonial dermatology, which has
more of a cultural rather than geographical significance. Today, this terminology underlines the tie between this discipline and the developing countries.
In fact, most cases of dermatological pathologies occur and are increasing in
tropical regions, not necessarily because of climate conditions which, admittedly, can favour the development of certain pathogenetic micro-organisms
or saprophytes, but rather because of the dramatic level of poverty, the lack
of public and personal hygiene, the difficulty in obtaining water, poor housing, malnutrition and the lack of education, especially in the rural areas (all
factors that have little to do with the difference among the races). To these
unfavourable climatic and environmental conditions, political and cultural
influences, often characterized by absurd ethnic conflicts sustained by
wealthy industrialised countries, have to be added.
In the last few years, in the area of dermatology and venereology, these has
been a return of illnesses that, in our national territory, had apparently disappeared some time ago. Is it a result of this migratory phenomenon that sees
millions of people fleeing from the Southern Hemisphere in the hope of finding a future in Europe, in the USA, in Canada or in Australia? Or does it depend on the rise in tourism that sees people from the Northern Hemisphere
look for holidays in more exotic and unexplored places? Certainly the two situations, although for different reasons have something in common: the speed
of movement of large numbers of people reduces the distance between developing tropical countries and the industrial countries of the north, eliminating the borders which once upon a time contained the illnesses. We are in the
middle of a pathology that can be described as omnipresent due to the movement of hundreds of millions of people from one end of the planet to the
other. Viruses, bacteria and fungi no longer seem to be confined within specific boundaries and are spreading in areas where it seemed they had been
eliminated forever.
Undifferentiated use of the terms tropical countries, developing countries, if
not third world, is very frequent, but we fail to understand that nowadays
such words imply very different values and meanings. Confusion often arises
from the fact that 80 percent of the tropical countries also represent the poorest part of the world. Only a fifth of the world population controls 87 per-
1. Introduction: health systems and skin infectious diseases. The case of Ethiopia
159
cent of the world production and 84 percent of the international trade. One
billion one hundred and fifty million people have no future, no job opportunities and live under precarious hygienic and health conditions. Despite the
fact that the majority of this population lives in tropical countries, the climatic environment or the latitude are not the determining factors of poverty or
inadequate, if not absent health care.
Ranking 99 out of 103 on the Human Poverty Index, Ethiopia remains one
of Africa’s poorest states. Close to 80% of the 70 million Ethiopians live with
less than USD 2 per day. Per capita income is under USD 100. Three-quarters of the population do not have access to clean water or proper sanitation.
In the two last decades, major crises, featuring drought, epidemics, displacement and armed conflicts, often combined, have repeatedly occurred.
Ethiopia health status:
• Infant and under five mortality rates are 112 and 169 per 10,000 live
births respectively. Maternal mortality is 850 per 100,000 live births. Life
expectancy at birth is 49 years.
• Ethiopia is one of the most malaria-epidemic prone countries in Africa.
The annual case load has risen from 1.1 million cases in 1995 to 1.5 million in 2001 and peaked at over 6.1 million in 2003. Rates of mortality
and morbidity increase by three to five-fold during epidemics. About 4%
of the population (3,1 million people) might be at risk in 2006.
• About 117,000 new cases of tuberculosis were reported in 2003, for a
prevalence of 593 per 100,000 and mortality rate of 96 per 100,000. As
only about 50% of the population lives within walking distance from
health facilities, TB management poses a special challenge.
• Between July and December 2005, 357 cases of measles were reported in
Afar with a Crude Fatality rate of 4.2%. From July to October 2005, 195
cases, including 14 deaths, were reported in Somali region.
• Along with malaria and measles, acute respiratory infections and diarrhoeal
diseases are major causes of death among children under five, threatening
up to 9.5 million of them in 2006. Massive meningococcal disease also
strikes population intermittently. In 2006, approximately 2.7 million people could be considered as most at risk for meningitis outbreaks.
• In 2005, 21 polio cases were detected after a polio-free four year period.
• The preliminary 2005 Ethiopia demographic Health Survey results show
that 38% of the surveyed population in Ethiopia is underweight, while
47% is stunted. The highest wasting prevalence is found in Somali region,
with a global acute malnutrition of 5.1%. Other regions with a high
160
prevalence of wasting include Beneshangul Gumuz, Amhara, Tigray and
Dire Dawa regions with respectively 16%, 14.2%, 11.6% and 11,4%.
• HIV/AIDS prevalence among adults is around 4.4% which represents 3
million people living with AIDS. An estimated 5,000 people are infected
every week, and AIDS is now recognized as a leading cause of morbility
and mortality.
“Disease weighs heavily on economic development…. But economic development requires more than just healthy individuals…. Economic development is a multisectoral process, and the strategy for economic development
must build on a broad range of social investment as well as strategies to encourage private sector business investments” (WHO, 2001).
If the conditions necessary for the fulfilment of a person’s capabilities are not
available, the health care system may cure patients only to have them return
sick once again. But can health care system contribute to economic development in its broader sense?
Health system can contribute to equitable development and poverty reduction by:
• Proving employment
• Injecting resources into local and national economies through procurement
• Funding research and development in the private health sector
• Engaging education system while providing professional training activities
• Reducing inequities in health by providing preferred access to health care
and promoting health care and promoting health in vulnerable communities
• Decreasing economic disparity by providing development opportunities
in poor neighbourhoods.
In the context of our activity supported by the Italian Development
Cooperation, we aim to provide a complete and, in the sometimes, easy to
consult, textbook in order to make the diagnosis, treatment and follow – up
of infectious skin diseases reliable also in Countries where the diagnostic and
laboratory facilities are not widely available.
In addition the present book is aimed at spreading the knowledge of dermatological diseases also among the health and social operators, beside the medical doctors directly involved in dermatology.
What’s more, we would like to provide a tool to reorganize the diagnostic
flow and treatment options of skin infectious diseases in order to reduce the
health system expenses and consequently make the health facilities accessible
to as many people as possible.
2. Pattern of skin diseases at the first dermatological hospital in Tigray, Ethiopia
161
2. PATTERN OF SKIN DISEASES AT THE FIRST
DERMATOLOGICAL HOSPITAL IN TIGRAY, ETHIOPIA
Aldo Morrone, Valeska Padovese, Margherita Terranova,
Silvana Trincone, Giuseppe Fontanarosa, Gebreab Barnabas
SUMMARY
Skin diseases have only recently been considered as a possible public health
problem in developing countries. Data supporting this matter are scarce. The
aim of this study is to report the experience of a specialized dermatologic centre in Mekele, the capital city of Tigray region (Ethiopia). It is our intention
to provide a comprehensive picture of the problem of skin diseases in an
African developing country. We have prospectively collected all cases of skin
diseases diagnosed during consultations provided at the Italian
Dermatological Hospital (IDH), the only centre specialized in dermatology
in Tigray, during the first 18 months’ medical activity (from January 2005 to
July 2006). In the northern Ethiopia, Malaria, Tuberculosis, Acute Upper
Respiratory Infections (AURI), Diarrhoeal diseases, Skin infections and
HIV/AIDS are among the top disease burdens. IDC is a referral hospital for
diagnosis and care of communicable and non-communicable skin diseases in
Tigray region and a training centre for health workers in collaboration with
Addis Ababa and Mekele University.
Key words: tropical dermatology, Ethiopia, Developing Countries
Communicable diseases and nutritional problems are major health problems
in Developing Countries (DC). Among all diseases, infectious and parasitic
diseases remain the biggest killers, and they account for one-fourth of the
global burden of diseases1. Tigray is the northernmost national regional state
of Ethiopia, a country located in the horn of Africa that counts more than 73
million inhabitants. Ranking 99 out of 103 on the UNDP Human Poverty
Index, Ethiopia remains one of Africa’s poorest states, with 45% of the people living below the poverty line. It is estimated that only about 60% of
Ethiopians live within walking distance from one health facility2. The Tigray
region covers 54,572.6 square kilometres and the population is estimated to
be 4,215,944 of which 82.6% lives in rural areas (Fig.1). The population of
162
A. Morrone, V. Padovese, M. Terranova, S. Trincone, G. Fontanarosa, G. Barnabas
Tigray grows by more than 110,000 people every year and that of Ethiopia
as a whole by more than 2 to 3 million3.
The Civil Hospitals in Tigray are 12 (1:342.750 inhabitants) and the medical doctors 48 (1:58.757 inhabitants), of whom only 12 are specialized. The
main problems that the health system has to face are the unavailability of
drugs, a long waiting time, the lack of facilities (laboratory, medical equipment) and the shortage of health professionals. In comparison with the service provided the costs are too expensive and often people prefer to turn to traditional medicine.
In the northern Ethiopia, Malaria, Tuberculosis, Acute Upper Respiratory
Infections (AURI), Diarrhoeal diseases, Skin infections and HIV/AIDS are
among the top disease burdens3.
Ethiopia has the third largest number of people living with HIV in the world
after South Africa and Nigeria2. Modelled data suggested a rise in prevalence
of HIV in rural areas (2003: 2.6%) and in all Ethiopia (2003: 4.4%), but a
stable or declining prevalence in Addis Ababa (2003: 14.6%) and other urban areas (2003: 11.8%). Modelled HIV incidence, inferred from prevalence
changes, showed a slowly rising trend in Addis Ababa (2003: 2.0%), other urban areas (2003: 1.7%), and rural Ethiopia (2003: 0.46%). The total burden
of HIV/AIDS is expected also to rise substantially due to population growth4.
Tigray is particularly vulnerable to HIV/AIDS due to additional factors such
as the social disorganization and population displacement related to the protracted armed struggle, the Ethio-Eritrean war, recurrent famines and
drought, rapid urbanization and the huge number of female headed households in both the rural and urban areas. The prevalence of HIV/AIDS in
Tigray in 2005 is estimated to be 4.7% and the epidemic appears to be intensifying3-4.
Many studies and reports indicate that communicable diseases and skin diseases account for more than 85% of the diseases seen in the health institutions5. Most of these diseases cause lifelong disability, due to functional loss,
pain and itch, and serious social and economic problems.6
We report the experience of the first dermatological hospital in Tigray and
our intervention strategy.
Material and methods
After a 20 years’ collaboration on health sector with Ethiopian government
and local NGOs, San Gallicano Institute in Rome has opened on January
2005 the first dermatological hospital of northern Ethiopia, named Italian
163
Dermatological Hospital (IDH)-International Institute of Medical,
Anthropological and Social Sciences (IISMAS). The small hospital, initially
located in a village near Mekele, the capital city of Tigray region, in May
2006, has moved to Ayder University Referral Hospital’s compound, a new
building in the city centre. It is provided with 30 beds for the inpatients department, two rooms for outpatients examination, a surgery room, a pharmacy, a microbiology laboratory, a library and a didactic area for training of
medical students and health operators.
The service is free of charge. A team of local health workers and foreign dermatologists takes care of admitted patients and also deals with outpatients’
examination. From September 2005, Voluntary Counselling and Testing
(VCT) service is available in the hospital and it is free of charge. Microscopic
investigations for fungal, protozoan and bacterial infections are performed in
the hospital’s laboratory whereas biopsy specimens taken in doubtful cases for
histological examination are sent to San Gallicano Institute in Rome.
Theoretical and practical courses on dermatology and communicable diseases
for training of medical doctors and regional health workers are periodically
held in the hospital.
This article reports a prospective study of patients seen at the IDH-MU referral clinic, in 18 months’ medical activity (from January 2005 to June
2006). All new patients attending the dermatological clinic were included in
the study. The percentages given are based on the number of diseases, not the
number of patients, because some of the patients had more than one disease.
Two dermatologists saw all patients.
Results
The total number of patients examined at the IDH was 14,510, while the
number of skin diseases diagnosed was 18,118. Of these patients, 52% were
males and 48% were females. Patients ranged in age from birth to 1 (4.3%),
from 1 to 5 (8.6%) from 6 to 16(16.8%) from 17 to 35 (52.9%) from 36 to
60 (14.1%) and over 60 (3.3%) (Table 1). For a better evaluation and treatment of the skin problem, 469 patients were admitted to the IDH, half of
whom aged less then 15. A total of 475 biopsies specimens were taken for
histopathological examination in doubtful cases.
The patterns of skin diseases are shown in Table 2.
41% of the total skin diseases diagnosed was infectious. Among these, scabies, bacterial and fungal infections were dominating, comprising 6.4%, 6%
and 16.1% of cases respectively. Viral infections represented 3.2% of cases.
164
Mycobacterial infections (cutaneous tuberculosis and leprosy) were diagnosed in 1.4% of cases. Typical tropical infectious diseases accounted for only 1% of all diagnoses.
Among non infectious skin problems we observed Eczematous dermatitis
(22.4%); Pigmentation’s disorders (11%), Acneic dermatitis (6.4%), Lichen
planus (2%), Psoriasis (1.6%), Prurigo (4.3%) and Annexes’ diseases (2.1%).
The HIV prevalence in our patients was 1.8% but only 250 patients examined for dermatological problems in IDC had voluntary counselling and testing. Of these 133 patients (53%) resulted positive.
Discussion
Recently, awareness that certain common skin diseases are an underestimated health problem in developing countries has grown14. Between 5% and
20% of the total number of visits to primary health care centres in this environment have been reported to be the result of skin disease3, which makes
this one of the most common organ-specific reasons for consultation.
Expenditure on these disorders may be high15 and this seems to be affected by
the low level of skills relevant to the management of such disorders among
most general health care workers16–17. The data collected in the IDC confirm
the high prevalence of skin infections and communicable diseases in rural
Ethiopia.
Prevalence in the general population is high for disorders such as pyoderma,
scabies or superficial mycoses, especially in children8-15.
Scabies and streptococcal skin disease are a burden in crowded communities
and are among the most common presentations at health services.16
The skin is probably the organ most commonly affected in patients with
HIV. The range of skin diseases in patients who are HIV-positive is broad,
encompassing both HIV and non-HIV related dermatoses. The immune status of the patient, reflected in the CD4 T-cell count and viral load, is an important parameter since there is often a strong correlation between the CD4
count and the presence of particular HIV-associated rashes19-20. Correlation of
skin diseases and HIV disease staging has long been recognized and used to
guide medical management in resource-limited settings. In our experience,
133 (53%) over 250 patients with evocative skin lesions tested for HIV infection was positive. The most common skin problems we observed in HIV
positive patients were infections including viral, fungal and bacterial, with
atypical and spread manifestations (Fig. 1-2). Pruritus was one of the most
common symptoms encountered in patients with HIV. In the early stage,
165
with a relatively high CD4 count, we observed muco-cutaneous disorders
like herpes zoster, molluscum contagiosum and vaginal candidiasis. The late
stage of HIV infection with a low CD4 count was characterized by the combination of the above mentioned skin infections, especially viral and fungal.
Among our series we didn’t report Kaposi’s sarcoma, considered common in
advanced HIV infection by other authors20. Antiretroviral treatment (ART)
has been introduced only recently in Tigray but the amount of drug is not
sufficient to treat all HIV patients in the region. Early diagnosis and prevention of HIV/STIs transmission remain the only way to fight the infection’s
spreading. Improving the capacity of health professionals and health workers
through training and surveys on skin conditions and their correlation with
systemic diseases is the aim of an operational research project we are carrying
out in Tigray region in collaboration with Tigray Health Bureau, Tigray
Medical Association and Italian Cooperation-HSDP. Knowledge of common
skin manifestations found in HIV-infected patients is essential for all health
care personnel who work in the HIV field. Most skin infections presenting
in HIV-infected patients can be treated effectively if the correct diagnosis and
appropriate referral are made promptly. Moreover, IDC participates to
IPOCM project (Integration and Promotion of Italian Hospitals and Health
Care Centres Worldwide) for the promotion and quality improvement of
health care delivery through the supply of teleconsultation and e-learning
services to doctors and health personnel. The Italian hospitals in the world
are located in 22 countries abroad, and the excellence Hospitals in Italy are
Health Care and Research Institutes and important public and private hospitals, which participate in the project. The main objective of the telematic network is the implementation of clinical-diagnostic and technical-organizational skills among health personnel working in the Hospitals abroad and the
growth of individual and staff skills of health personnel in the Italian
Hospitals world-wide through training activities via e-learning.
Conclusion
It is essential to know the prevalence and the pattern of skin diseases affecting Ethiopian population to program intervention and control strategies for
the early detection of life threatening and disabling diseases. This epidemiological study on skin and communicable diseases is the first in northern
Ethiopia and our findings will provide a useful database for future improvement on the skills of the health workers and on the service provided to the
community. Moreover, through a simple skin examination, it’s possible diag-
166
nose earlier systemic more serious conditions, such as HIV infection, and
prevent the epidemic spreading. To implement the clinical and research activity we believe that it is important to train medical doctors and nurses on
accurate recognition, diagnosis and management of the commonest skin diseases.
We believe that this study represents a significant contribution to improving
the problem of common skin diseases in developing countries, as it establishes for the first time the impact, as well as the practicability, of a specific programme proportionate to the priority profile of the diseases targeted. It may
represent a reasonable solution to a neglected component of primary health
care in many developing countries, which, although not a top priority, would
benefit from a more rational management than so far has been adopted.
Public health measures are a critical first step in disease prevention and control. When prevention has not been successful, rapid diagnosis and prompt
treatment ensure successful control. Establishing a dermatological service in
a region lacking in facilities for skin disease diagnosis and treatment can represent a valid intervention to decrease morbidity, mortality and in some instances long-term disability related to untreated and misdiagnosed skin diseases.
Inadequate interventions and control strategies can cause the re-emerging of
life threatening diseases preventable through approaches such as supply of adequate amount of safe water, control of vectors, expanding vaccination and
educating the people to bring behavioural changes.3
Age group
<1
1-5
6-16
17-35
36-60
61-70
>70
Total
Sex (%)
F
3,6
7,1
17,7
57,7
11,9
1,5
0,4
100,0
M
Total
5,0
10,0
15,9
48,5
16,1
2,8
1,7
100,0
4,3
8,6
16,8
52,9
14,1
2,2
1,1
100,0
Table 1 Age and sex distribution and the relative percentages of patients
examined in the IDH from January 2005 to June 2006.
Tab. 2 Patterns of skin diseases diagnosed at the IDC in the first 18 months
medical activity (from January 2005 to July 2006).
Fig. 1 Tigray Population Pyramid, 1997 EC (2004)
167
168
References
1. Hotez P, Remme J, Buss P, Alleyne G, Morel C, Breman J. Combating tropical infectious diseases: report of the diseases control priorities in Developing Countries project.
Clin Infect Dis 2004;38:871-8.
2. http://www.who.int/hac/crises/eth/background/Ethiopia_Aug06.pdf
3. Tigray Regional Health Bureau HMIS. Tigray Health Bureau Profile 1997 Ethiopian
Calendar (2005 Gregorian Calendar)
4. W Hladik, I Shabbir, A Jelaludin, A Woldu, M Tsehaynesh, W Tadesse. HIV/AIDS in
Ethiopia: where is the epidemic heading? Sex Transm Infect 2006;82(Suppl I):i32–i35.
doi: 10.1136/sti.2005.016592
5. J. Infection, skin disease, and developing countries. Skinmed. 2002 Nov-Dec;1(2):101-6
6. Kint A. Dermatology in current medicine. Verh K Acad Geneeskd Belg 1997;59(1):5-12
7. Bezabih M. Patterns of chronic dermatoses in an Ethiopian central teaching hospital: a
histopatologic approach. Skinmed 2002 Nov-Dec;1(2):87-8
8. Hiletework M. Skin diseases seen in Kazanchis health center. Ethiop Med J. 1998
oct;36(4):245-54
9. Shibeshi D. Pattern of skin disease at the Ethio-Swedish Pediatric Hospital, Addis
Ababa, Ethiopia. Ped Derm 2000 vol. 17 No. 5: 357-359
10. Figueroa JI, Fuller LC, Abraha A, Hay RJ. The prevalence of skin disease among school
children in rural Ethiopia. A preliminary assessment of dermatological needs. Pediatr
Dermatol 1996;13:378-381
11. Mahe A, Cisse IA, Ousmane F, N’Diaye HT, Niamba P. Skin diseases in Bamako (Mali).
Int J Dermatol 1998;37:673-676
12. Shrank AB, Harman RRM. The incidence of skin diseases in a Nigerian teaching hospital dermatologic clinic. Br J Dermatol 1996;88:235-241
13. Manzur J. Skin diseases in Addis Ababa. A preliminary review. Ethiop Med J
1981;19:123-134
14. Skin disease and public health medicine. Lancet 1991;337:1008-9.
15. Verma BL, Srivastava RN. Measurement of the personal cost of illness due to some major water-related diseases in an Indian rural population. Int J Epidemiol 1990;19:169-76.
16. Mahe A. Bacterial skin infections in a tropical environment. Current Opinion in
Infectious Diseases 2001; 14 :123-6
17. Carapetis JR, Currie BJ, Kaplan EL. Epidemiology and prevention of group A streptococcal infections: acute respiratory tract infections, skin infections, and their sequelae at
the close of the twentieth century. Clinical Infectious Diseases 1999; 28:205-10
18. Gibbs S. Scabies. Tropical Doctor 2000; 30:232-5
19. Singh F, Rudikoff D. HIV-associated pruritus: etiology and management. Am J Clin
Dermatol 2003;4(3):177-88
20. Mbuagbaw J, Eyong I, Alemnji G, Mpoudi N, Same-Ekobo A. Patterns of skin manifestations and their relationships with CD4 counts among HIV/AIDS patients in
Cameroon. Int J Derm 2006, 45, 280–284
21. Figueroa JI, Fuller LC, Abraha A, Hay RJ. Dermatology in southwestern Ethiopia: rationale for a community approach. Int J Dermatol 1998;37:752-8.
22. Mahe, Antoine, Faye, Ousmane, N’Diaye, Hawa Thiam et al. Integration of basic dermatological care into primary health care services in Mali. Bull World Health Organ,
Dec. 2005, vol.83, no.12, p.935-941. ISSN 0042-9686.
3. Dermatoes due to bacteria
169
3. DERMATOSES DUE TO BACTERIA
Aldo Morrone, Valeska Padovese
From a systematic point of view we have to distinguish three main groups of
bacterial dermatoses:
• Mycobacterial infections, including leprosy, tuberculosis, Buruli ulcer
• Pyogenic infections
• Non-pyogenic infections
In tropical countries the most common cutaneous infections are pyodermatitis, which can be caused by Staphylococcus or Streptococcus.
In the following chapter we examine:
• Sycosis barbae
• Furuncle
• Necrotic acne
• Hydradenitis suppurativa
• Impetigo contagiosa
Among the non-pyogenic infections we find the following cutaneous infectious conditions:
• Pseudofolliculitis barbae
• Folliculitis keloidalis
• Tropical ulcer
• Erythrasma
9.1 Mycobacterial Dermatoses
9.1.1 Leprosy
Synonyms: Hansen’s disease, hanseniasis.
Leprosy is a chronic granulomatous infectious disease caused by
Mycobacterium leprae with a predilection for cooler parts of the body, especially peripheral nerves and skin. In this multisystem disease, M. leprae
and/or inflammatory cells are found infiltrating the skin and a large number
of internal organs, including the upper respiratory tract, anterior segments of
the eyes, reticulo- endothelial system and the testes.
In 1848, Danielssen and Boeck proposed that leprosy was hereditary.
Discovery of M. leprae by Gerhard Henrick Armauer Hansen in Bergen,
Norway, in 1873 offered a setback to the hereditary theory of causation of
170
leprosy. M. leprae is an acid-fast bacillus (AFB) 0.3 to 0.5 m wide by 4 to 7
m long. It resists decolourization with alcohol and 5% H2SO4 after staining
with Ziehl-Neelsen. It is a compulsory intracellular parasite with tropism for
macrophages and, uniquely, for Schwann cells. These organisms multiply
slowly, with a generation time of 11-13 days, accounting for the disease’s long
incubation period, which varies widely from several months to over 30 years,
with an average period of 2-5 years. The optimal temperature for the growth
of M. leprae is 30-33 C. It remains viable in the environment for up to 10
days. The WHO estimated that in 1997 there were 1.15 million cases of leprosy in the world, compared to10-12 million cases in 1988, as a consequence
of the wide implementation of Multi-Drug Therapy (MDT) programmes.
The leprosy prevalence rate at the global level is 1.25 cases per 10,000 people. It is estimated that about 2.5 million new leprosy patients will be detected in the period 2000-2005. Unfortunately incidence rates have not come
down. Special efforts will be needed to reach the leprosy elimination target in
10 countries: Brazil, Democratic Republic of Congo, Guinea, India,
Indonesia, Madagascar, Mozambique, Myanmar, Nepal, and Tanzania.
Mode of transmission
The inhalation of bacilli laden droplets is regarded as the most likely mode
of entry of leprosy bacilli into exposed individuals. Untreated lepromatous
patients may discharge as many as 100 million leprosy bacilli from their nasal
secretions every day. Other possible routes of transmission include breast
milk from mothers with untreated lepromatous disease and rare cases of cutaneous inoculation. There is increasing evidence in favour of placental transmission of leprosy. The concept of arthropod transmission of leprosy is still
under debate. The transmission of leprosy depends primarily on the infectiousness of the infected person, the susceptibility of the contact person and
the closeness, frequency and duration of the contact.
Age, Sex, Genetic, Environmental Factors
Occurs in all age groups. The incidence of onset peaks in two age groups: 1015 and 30-60 years with a 2:1 male preponderance among adults in most regions, but in children the sex ratio is approximately 1:1. Clinical expression
of the disease in individuals is determined by the cell mediated immunity and
partly by human lymphocyte antigen (HLA) – linked genes. HLA-DR2 and
/ or DR3 are associated with tuberculoid leprosy whereas HLA-DQ1 with
lepromatous leprosy.
171
Clinical Classification
Several classifications have been proposed but the Ridley-Joplings classification based on clinical, bacteriological, histopathological and immunological
parameters is the one widely accepted:
Tuberculoid tuberculoid (TT)
Borderline tuberculoid (BT)
Borderline borderline (BB)
Borderline lepromatous (BL)
Lepromatous lepromatous (LL)
The cell-mediated immunity which has an inverse relationship with the bacteriological load declines from TT to LL. The drawback of this classification
is that it does not classify “indeterminate” and “pure neuritic” leprosy. The
Seven Group classification incorporates these two groups.
For therapeutic purposes, leprosy is classified into two groups, paucibacillary
and multibacillary leprosy.
Clinical features
The extension of the clinical manifestations of the disease is determined by
the patient’s cell-mediated immunity status.
Indeterminate Leprosy (I) : Indeterminate leprosy is a transient stage where
the histological and immunological responses have not yet evolved completely. This stage may herald determinate forms of leprosy or persist as indeterminate, although in 75% of cases the lesions are known to disappear spontaneously. It presents usually as a single or a few bizarre hypopigmented or erythematous macules ranging in size from 1 to 5cm with ill-defined margins
commonly seen over the trunk, or proximal part of extremities or the face in
children, who are often in contact with leprosy patients. Skin texture, sensations and sweating may be slightly altered but they are often difficult to detect. Thickening of nerve proximal to or feeding the patch is variable. Slit
skin smears are usually negative for AFB. The lepromin reaction is unpredictable.
Histopathology shows non-specific cellular reaction with lymphocytic and histiocytic infiltration around the adnexa and blood vessels. Serial sections may
reveal scanty acid-fast bacilli on Fite-Faraco staining in dermal nerve fibres.
Patients should be examined at 3 to 6-month intervals to evaluate the progression of the lesions.
Tuberculoid Tuberculoid (TT) :Tuberculoid leprosy manifests itself with few
skin lesions, often only a single lesion is present. Lesions may be macular or
172
raised, either as a plaque or at the edge with a flat centre. The peripheral
raised margin indicates disease progression while the flat central area indicates healing. Margins are well defined and unbroken. Lesions are hypopigmented on dark skin and erythematous or coppery on light skin. Sensory
loss, absence of hair and dry appearance of the lesion as a result of impaired
sweating are characteristic features. However, sensory impairment may be
difficult to identify on the face because of the generous supply of sensory
nerves. The nerve proximal to the patch may be thickened. Solitary peripheral nerves are frequently enlarged in tuberculoid leprosy and may occasionally be the only presentation. Routine slit skin smears are negative. The lepromin test is strongly positive (2+ to 3+) indicating effective cell-mediated
immunity.
Histopathology is characterized by a compact granuloma containing epithelioid cells with dense peripheral lymphocyte accumulation in skin and nerves.
There is no subepidermal clear zone. An intense infiltration and complete destruction of cutaneous nerves is seen. Acid-fast bacilli are rarely found even
in nerves.
Borderline Tuberculoid (BT): The skin lesions resemble those of TT leprosy but with features suggesting that the disease is not being contained. The
lesions are more numerous (three to ten) and variable in appearance and their
edges are less distinct. The margins may be better or well defined and raised
in a part of the lesion, and poorly defined, flat and vague in another part of
the same lesion. Presence of small satellite lesions suggest local spread.
Hypopigmentation, dryness and scaling are less conspicuous than in TT.
Sensory loss over skin lesions is less intense as compared to TT. Nerve lesions
are more numerous than in TT. The patient may first present with anaesthesia or paraesthesia in the distribution of a nerve as a result of damage to the
nerve. Progressive nerve damage is common. Bacteriological Index (BI)
ranges from 0 - 2+. The lepromin test is weakly positive.
Histopathology reveals granulomas similar to TT but these are more diffuse
and a free but narrow papillary zone is seen. AFB may be found on serial sections.
Histopathology of thickened nerves shows presence of epithelioid cells and
oedema. Even when few fascicles are infected, inflammation in the epineurium and sheath causes compression within the sheath destroying Schwann
cells and axons. Cutaneous nerve twigs, autonomic and sensory, are obliterated by the infiltrate within and around the perineurium.
Borderline Borderline (BB): Immunologically unstable and uncommon form
173
with the propensity to shift rapidly towards BT leprosy or to downgrade towards BL leprosy. Clinical features of BB show a mixture of disease characteristics at the poles. Numerous skin lesions are bilateral but asymmetrical
with a likelihood to become symmetric. They may be hypopigmented or erythematous. Presence of a target lesion with raised erythematous annular border with a vague outer edge and “punched-out” pale centre and impaired sensation suggest that the disease may have begun near the tuberculoid pole and
subsequently has been downgraded. The nerves show asymmetrical thickening. Slit skin smears are moderately positive, BI being 3+ or 4+ and the lepromin test is doubtful or negative.
Histopathology shows sheets of immature epithelioid cells and histiocytic infiltration with oedema of the dermis. Giant cells are unusual. Lymphocytes
are usually scanty and seen loosely scattered throughout the epithelioid cell
granuloma, but there is no localization and development into tubercles. A
clear sub-epidermal zone is seen. Nerves are still recognizable, although they
are infiltrated by epithelioid cells. AFB are numerous and readily found.
Borderline Lepromatous (BL): Skin lesions of BL resemble those of lepromatous leprosy but their distribution is not symmetrical. Numerous lesions of
various sizes and shapes may be present. Small erythematous macules,
papules, nodules, and succulent plaques may develop and, in contrast to tuberculoid leprosy, the lesions do not hamper sensation. They are shiny, copper coloured and more infiltrated in the centre than in the periphery. The
nodular lesions and the diffuse infiltration of the pinna and eyebrows seen in
lepromatous leprosy (LL) do not appear during BL leprosy. Areas of apparently normal skin are found between the lesions. Widespread symmetrical infection of the nerves is typical, especially if the patient has downgraded from
BT leprosy. BI is usually 4+ or 5+. The lepromin test is usually negative.
Histopathology shows diffuse granulomas, located in mid and lower dermis,
composed of clumps of histiocytes, lymphocytes and macrophages containing acid-fast bacilli. An eosinophilic stained subepidermal zone is present.
Acid-fast bacilli are easily demonstrable.
Lepromatous Leprosy (LL): Lepromatous leprosy, a systemic disease with
bacillaemia and multiple organ involvement, is characterized by widespread
involvement of the skin, mucous membranes, nerves and reticulo-endothelial
system. Several of these small lesions are symmetrically distributed, hypopigmented, erythematous, or copper-coloured macules which gradually progress
to form papules, nodules, and even plaques with smooth and shiny surfaces.
The lesions have sloping edges which merge indistinguishably with normal
174
skin. Eventually, the whole skin may be uniformly affected, resulting in diffuse infiltration. In the advanced stage, massive infiltration of the face leads
to the classical appearance of leonine-like face due to prominent ridges and
furrows on the forehead, nodular thickening of earlobes, lateral madarosis
and saddle-nose deformity. Involvement of mucous membranes is frequent
with predilection for nasal, nasopharyngeal and laryngeal mucous membranes, and patients present with nasal blockage and epistaxis. Early macules
of LL are not anaesthetic. Evidence of nerve damage is slow to appear.
Eventually anaesthesia is extensive and is accompanied by anhydrosis.
Multiple nerve thickening producing glove and stocking anaesthesia is a late
feature. Weakness usually starts in the intrinsic muscles of hands and feet.
Bacteriological index is strongly positive (5+ or 6+) and lepromin test is always negative.
Histopathogy is characterized by scattered granulomas (lepromas) containing
numerous foamy macrophages in the lower dermis. Macrophages fail to specialize into epithelioid cells. Presence of Virchow cell (lepra cell) with vacuolated, foamy cytoplasm is cardinal. Lymphocytes are absent or scanty. The
sub-epidermal clear zone is well marked. The texture of the nerves is well preserved . Schwann cells reduplicate in an attempt to repair the damage and
may form concentric rings around nerve fibres giving rise to the ‘onion-peel’
appearance on histological section. The acid-fast bacilli are numerous.
Special Forms of Leprosy
Histoid leprosy: Wade in 1963 described a distinct expression of multibacillary leprosy, called histoid leprosy. It is characterized by firm, erythematous,
round or oval, shiny, glistening nodules, appearing over an apparently normal
skin of patients whose disease is relapsing either because they have discontinued treatment or because leprosy bacilli have become drug resistant. Histoid
leprosy is also rarely encountered in untreated patients. Patients with histoid
leprosy have a heavy bacillary load with BI being 5+ to 6+.
Histopathology consists of elongated or spindle-shaped histiocytes containing
bacilli that are oriented in a storiform pattern.
Lucio’s leprosy (Synonyms: diffuse lepromatous, Latapi):
A rare form of polar lepromatous leprosy occurs in Mexicans of mixed
Spanish and Amerindian ancestry. Patient presents with slowly progressive
diffuse shiny infiltration of the skin of the face and rest of the body (“lepra
bonita” - beautiful leprosy). Thickening of eyelids gives the patient a sleepy
or sad appearance. Loss of body hair including eyebrows and eyelashes, nasal
175
congestion, hoarse voice, numbness and oedema of hands and feet, and widespread sensory loss due to involvement of dermal nerves eventually develop.
This form of LL is vulnerable to the development of Lucio phenomenon,
which is a severe reactional state occurring as a result of obstructive vasculitis
in the skin producing dermal infarcts and irregular ulcers usually in the absence of constitutional symptoms.
Pure neuritic leprosy: Pure neuritic leprosy manifests itself with neural signs
in the absence of skin lesions. Pure neuritic leprosy involving more than one
nerve should be treated as multibacillary.
Peripheral nerve involvement: The three physiological functions of nerves–
sensory, motor and autonomic – may be equally involved but the sensory
component is usually the earliest and most seriously affected. In tuberculoid
leprosy nerve involvement begins early and progresses rapidly. In lepromatous leprosy nerve damage is widespread but progression of damage is slow.
Nerves at superficial sites, where the nerve trunks are cooler, more readily
traumatized and often anatomically constricted, are preferentially affected.
These include ulnar, median, lateral popliteal, posterior tibial, radial, radial
cutaneous, greater auricular, supraorbital and sural nerves. Deformities include claw hand, foot drop, claw toes and wrist drop. Fifth and seventh cranial nerves may also be affected.
Lymphnodes: The superficial or external lymph nodes draining the skin such
as cervical, inguinal, axillary and epitrochlear are the most commonly affected groups. The lymph nodes may be enlarged and painless with the consistency of soft rubber but may become swollen and tender during reactions.
Palpable lymphadenopathy is present in 90% of patients with LL, as compared to 70% in paucibacillary disease. Infiltrations of lymph nodes by lepra
cells and AFB depend on the degree of involvement of the drained organs.
Kidney (Renal system) : M. leprae does not invade the kidney but the kidneys may be damaged by immune complex mediated glomerulonephritis.
Glomerulonephritis, usually the mesangio-proliferative type, occurs in both
paucibacillary and multibacillary patients with a reported incidence of 6% to
50%. Renal insufficiency due to secondary amyloidosis has also been reported in patients with long standing multibacillary disease, particularly those
who suffer from recurrent type 2 reactions.
Testes: Testicular involvement is common and occurs in about 90% of lepromatous patients. Testicular atrophy can result in sterility and gynaecomastia.
Epididymo-orchitis, sometimes severe, may occur during lepra reactions.
Musculoskeletal system: Nerve involvement leads to muscular paralysis and
176
muscle atrophy, especially of the interosseous muscles of the hands. Both
smooth and striated muscles are invaded. Erectors pilorum and dartos may
contain many bacilli.
Bone changes in LL are confined to the skull and limbs, predominantly
hands and feet. Aseptic necrosis of the bone accompanied by concentric bone
atrophy is followed by resorption of the fingers and toes and shortening of
digits. Sensory loss can lead to the development of Charcot joints in the fingers, toes, wrists and ankles. Elderly female leprosy patients and hypogonadal
male leprosy patients may develop osteoporosis. Bones may be invaded in LL.
Marrow of phalanges is replaced by bacilli laden foam cells which in turn may
invade cancellous bone, forming cysts leading to destruction of the bone.
Cortical bones are also occasionally involved. Osteoporosis contributes to increased susceptibility for bone fractures. Osteomyelitis due to chronic ulceration of overlying skin is yet another complication. Sacroilitis and inflammatory arthritis of the small and large joints may occur in patients with all types
of leprosy. Atrophy of the anterior nasal spine and the maxillary alveolar
process occurs. Destruction of the alveolar process causes the upper central
incisor teeth to fall out.
Eyes: The anterior structures (cooler portions) of the eye are commonly affected whereas the posterior structures and optic nerve are usually spared.
Infiltration of the ciliary body, iris, choroid, scleral, corneal and periorbital
tissues can occur. Ocular involvement may manifest as pterygium, corneal
scarring, corneal anaesthesia, reduced corneal reflexes, lagophthalmos, iridocyclitis, conjunctivitis, ectropion, dry eyes, scleritis, uveitis, keratitis, cataract
or glaucoma. Eye damage can end in blindness in the absence of early appropriate ocular management.
Liver: Kupffer cells of the liver phagocytose M. lepae, which multiply there
and become the focus of multiple small lepromas. The term “lepromatous
hepatitis” is used to describe infiltrative, well limited, portal and centrilobular granulomas made up of Virchow cells with or without lymphocytes, minimal fibrosis and usually multiple AFB. Hepatic involvement is usually
asymptomatic with normal liver function tests. Hepatomegaly due to amyloidosis of the liver is more common in lepromatous patients.
Respiratory system: M. leprae affects the upper portions of the respiratory
tract. In 80% of lepromatous patients invasion of skin is accompanied by invasion of the mucous membrane of the nose and sometimes throat.
Destruction of the anterior nasal spine and invasion of the nasal cartilage
leading to ulceration and collapse of the nasal septum as well as tracheal in-
177
volvement are seen in multibacillary leprosy. Epiglottis is the most commonly affected part of the larynx. Laryngeal involvement may be ulcerative or fibrotic and present with cough, hoarseness or breathlessness.
Nails: Nails may appear dry, lustreless, narrowed and longitudinally ridged.
Growth of the nail can be affected and the nail may appear curved, brittle and
thin.
Figure 1 Lepromatous leprosy with
typical saddle nose deformity
Diagnosis
Diagnosis is based on clinical findings and confirmed by bacteriological,
histopathological and immunological investigations.
Cardinal signs of leprosy
• Anaesthesia : Anaesthetic skin lesions or anaesthesia in the distribution of
the involved nerves.
• Thickened nerves.
• Skin lesions : hypopigmented in dark skin, copper coloured or erythematous in light skin.
• Identification of bacilli.
Two of the first three cardinal signs or the fourth should be present to make
a diagnosis of leprosy.
178
Bacteriological examination: Examination of slit – skin smear of AFB is an
important diagnostic tool. The smears are taken from the skin lesions, ear
lobes, and eyebrows, by tightly squeezing and holding a fold of skin between
the thumb and fore finger to render it avascular and making an incision with
a small bladed scalpel. The blade is turned at right angles and the wound
scraped several times to obtain the test material. The cells and fluid obtained
are smeared on a glass slide and stained by the Ziehl-Neelsen technique and
the slide is evaluated for the BI and MI.
BI is the bacteriological index on a logarithmic scale of 1+ to 6+ and is an indicator of the bacillary load and the MI, morphological index, is the percentage of solid staining AFB in smears which indicates the viability of M. leprae.
Histopathology: Skin biopsy is indicated for accurate classification of leprosy lesions. Serial biopsies carried out at regular intervals are valuable in assessing response to treatment and prognosis.
Immunologic test: The lepromin (Mitsuda) test is an intra-dermal test performed to elicit the cell – mediated immune response of the patient to M.
leprae. Various antigens used include integral lepromin, Dharmendra antigen,
leprolin and leprosin. The lepromin test is not of diagnostic help in leprosy
but helps in classifying the established cases and is a prognostic indicator. It
is strongly positive in TT and negative in LL, whereas in borderline cases it
may be weakly positive or negative.
Sweat function tests : Anhydrosis is a common sign of autonomic nerve damage presents with dryness of the skin. Pilocarpine nitrate and acetylcholine
sweat function tests are some of the sudomotor tests employed for the diagnosis of leprosy and it.
Newer diagnostic investigations: Several serodiagnostic techniques are now
available which facilitate the early diagnosis of leprosy. These include lymphocyte transformation test (LTT), fluorescent leprosy antibody absorption
test (FLA-ABS), detection of specific antigen of M. leprae, PGL-1 (surface
glycolipid unique to M. leprae), anti-PGL-1 antibody, DNA probes specific
for M. leprae, and polymerase chain reaction. Immuno-cytochemical techniques can be used to detect neural involvement and AFB in biopsy sections.
Differential diagnosis
A number of diseases may mimic leprosy. Differential diagnosis can be described under the following groupsMacular lesions: Vitiligo, occupational leucoderma, pityriasis versicolor,
pityriasis alba, nutritional dyschromia, post-kala-azar dermal leishmaniasis
179
(PKDL), onchocerciasis, herpes zoster, naevus anaemicus or naevus achromicus.
Infiltrated lesions: Tuberculosis verrucosa cutis, lupus vulgaris, lupus erythematosus, granuloma annulare, granuloma multiforme, pellagra, annular
syphilis, seborrhoeic dermatitis, PKDL, oriental sore, tinea circinata, sarcoidosis, psoriasis, pityriasis rosea.
Nodular lesions: PKDL, cutaneous leishmaniasis, syphilis, onchocerciasis,
sarcoidosis, leukaemia cutis, mycosis fungoides, Von-Recklinghausen’s disease
and Kaposi’s sarcoma.
Conditions mimicking polyneuritic leprosy:
Peripheral neuropathy pattern: Carpal tunnel syndrome, syringomyelia, lead
toxicosis, diabetes mellitus, congenital insensitivity to pain, and meralgia
paraesthetica.
Thickened nerves: Primary amyloidosis of nerves, hereditary sensorimotor
neuropathy.
Therapy
The WHO has recommended drugs and dosage regimens for leprosy.
Three treatment groups have been proposed:
• Paucibacillary single-lesion leprosy.
• Paucibacillary leprosy patients with 2-5 skin lesions.
• Multibacillary leprosy patients having more than five skin lesions or any
patient with a positive skin smear irrespective of the clinical picture.
A single dose of combination therapy has been recommended to cure single
lesion paucibacillary leprosy.
Rifampicin 600 mg
Ofloxacin
400 mg
Minocycline 100 mg
Half the adult dose of the 3 medications is recommended in children.
Treatment for paucibacillary leprosy consists of combination therapy with
Rifampicin and dapsone for 6 months.
Adult 50-70 kg
Child 10-14 yrs
100 mg
Given daily
50 mg
Given daily
Rifampicin
600 mg
Given once a month under supervision
450 mg
Given once a month under supervision
180
Rifampicin and dapsone in combination with clofazimine is administered for
12 months to treat multibacillary leprosy.
Adult
50-70 kg
Child
10-14 yrs
Dapsone
Rifampicin Clofazimine
100 mg
600 mg
50 mg
AND
Given daily Given once Given daily
a month
under
supervision
300 mg
Given once
a month
under
supervision
50 mg
450 mg
50 mg
AND
Given daily Given once Given every
a month
other day
under
supervision
150 mg
Given once
a month
under
supervision
Newer antileprosy drugs include fluoroquinolones, namely ofloxacin and pefloxacin, as well as minocycline, a tetracycline derivative. The other drugs under trial are clarithromycin, a macrolide, phenazine derivatives, including rifabutin (LM-427), rifapentine (DL-473), and R-76-1.
Immunotherapy: Research is in progress to develop vaccines for immunoprophylaxis and immunotherapy. The various vaccines under trial are BCG,
heatkilled M. leprae, BCG and heatkilled M. leprae, ICRC vaccine and vaccines developed from soil mycobacterium, M.w. and M. habana.
Leprosy reactions
Leprosy reactions are immunologically mediated episodes of acute inflammation occurring during the course of the disease. Reaction can be either type1 (lepra) which is a delayed hypersensitivity reaction or type-2 (erythema nodosum leprosum-ENL) which is an immune complex mediated response.
Type – 1 reaction can either be upgrading or downgrading. This reaction occurs in the immunologically unstable borderline groups BT, BB and BL sparing the TT and LL groups.
There are several factors that trigger reactions, including:
• Multidrug therapy, especially with dapsone;
• Vitamin A, iodides and bromide;
• Intercurrent streptococcal infection, malaria and filaria;
• Tetanus, BCG, and other vaccinations;
• Pregnancy, puerperium, and lactation; and
• Other physiological, psychological and physical stress.
181
Type-1 (lepra) reaction: The existing skin lesions enlarge, become erythematous, swollen and tender. Involved nerves become swollen and tender. In upgrading reactions, the preceding changes are confined to one or a few lesions.
Motor function of the muscles supplied by affected nerves may be compromised in upgrading reactions. These changes affect almost all lesions in downgrading reactions. Furthermore, appearance of new lesions and constitutional symptoms such as fever, malaise, and loss of appetite may be associated.
Type-2 (ENL) reaction: Complicate LL and BL leprosy. This is characterized
by sudden appearance of erythematous, tender, evanescent cutaneous and/or
subcutaneous nodules usually distributed over the extensor surface of the
limbs and face. At times, the nodules may ulcerate to form erythema necroticans. Peripheral nerves may be thickened, tender, or both. Systemic involvement in the form of conjunctivitis, keratitis, iritis, iridocyclitis, hepatosplenomegaly, orchitis and lymphadenopathy may occur. Type 2 reaction
is accompanied by marked constitutional symptoms. Fever, malaise, anorexia, arthralgia and myalgia may be associated distressing features.
Treatment of leprosy reactions : Eliminate the possible precipitating factor
and continue anti-leprosy treatment in full dosage without interruption. Rest
and adequate analgesia are essential during the period of active neuritis.
Rapid control of neuritis is achieved with corticosteroids in patients with a
type 1 lepra reaction. Prednisolone should be started with a single daily dose
of 40-60 mg, depending on the severity. Once there is evidence of improvement on a serial voluntary muscle and sensory testing, the dose is reduced
over 6 weeks to 20mg/day and this is continued for some months before
gradually stopping. Therapy is usually required for 4-6 months, but may have
to be continued longer in MB cases. Mild ENL responds to aspirin or nonsteroidal anti-inflammatory drugs, increased clofazimine dosage and rest.
Moderate or severe episodes and those with neuritis require prednisolone,
usually starting with 40-60 mg/day.
The response is rapid and the prednisolone can be tapered over 2-3 months.
Clofazimine at a higher daily dose of 300 mg suppresses ENL after 4-6
weeks, and can be used to prevent further episodes. Other drugs like chloroquin are also helpful in mild intermittent, type 2 reactions. The drug of
choice for recurrent ENL is thalidomide administered in a dosage of 400
mg/day for 2-3 weeks, and then 100-200 mg/day as maintenance. Its use
should be restricted to males and post-menopausal patients under strict supervision because of its teratogenic potential. Iritis responds to local treatment with corticosteroids and atropine drops.
182
LUCIO phenomenon: Lucio phenomenon occurs exclusively in lucio leprosy. Patients with advanced forms of lucio leprosy may develop severe type
2 (ENL) like reactions called lucio phenomenon which is characterized by
dermal infarcts and extensive bizarre, painful ulceration of the skin, usually
unaccompanied by constitutional symptoms. The onset is a gradually spreading purplish erythema that later forms a haemorrhagic infarction or plaque
followed by a blister. The blister ruptures to form a bizarre ulcer with jagged
margins. Such lesions occur over the legs, thighs, forearms, and buttocks.
Recurrences are usual. Abundant AFB are seen in the endothelial cells and
patients have high titres of immune complexes and cryoglobulin.
9.1.2 Tuberculosis
Synonyms: Koch’s disease, maladie de Koch, Tuberkulose.
Tuberculosis of the skin is caused by the bacteria Mycobacterium tuberculosis,
M.bovis and under certain conditions, the Bacillus Calmette-Guerin (BCG),
an attenuated strain of M.bovis. Cutaneous tuberculosis has varied clinical
presentations determined by the pathogenicity of the infecting mycobacterial strain, route of infection and state of cellular immunity.
Tuberculosis with a significant global prevalence has been responsible for devastating morbidity and mortality. Cutaneous tuberculosis occurs in 10% of
all cases of extrapulmonary tuberculosis. It has a worldwide distribution;
while previously more prevalent in regions with a cold and humid climate ,
it now occurs in the tropics also. The incidence of cutaneous TB has shown
a steady decline over the past decades which paralleled the decreasing incidence of pulmonary TB. However, attention has now been focused on the
resurgence and increasing incidence of mycobacterial infections, in temperate regions as well as in tropical countries. Factors contributing to the resurgence include immigration from endemic countries (particularly Asia and
Africa), increased movement of refugees, the HIV pandemic and poverty.
Tuberculosis is increasing worldwide especially in developing countries. One
third of the world population is thought to have been in contact with the infection at some time in life. The number of cases was estimated at 8.8 million in 1995 and projected to reach 11.9 million in the year 2005. The global increase in TB is related to HIV infection as many regions of the developing world where TB is common are also areas of high HIV infection rate. It
is estimated that in Africa, with a high HIV infection rate, the number of cases of tuberculosis will increase by at least 50% by the end of the decade.
183
Incubation period
Varies from 2-4 weeks.
Classification
A widely accepted scheme of classification is the one proposed by Beyt et al
in 1981, with slight modification.
I.
Inoculation tuberculosis
(exogenous source)
II. Secondary tuberculosis
(endogenous source)
A. Contiguous spread
B. Auto-inoculation
III. Haematogenous tuberculosis
(endogenous source)
IV. Eruptive tuberculosis
(the tuberculids)
A. Micropapular
B. Papular
C. Nodular
Tuberculous chancre (Primary
Inoculation tuberculosis – infection
of the non-immune host)
Tuberculosis verrucosa cutis (warty
tuberculosis)
Lupus vulgaris (some)
Scrofuloderma
Orificial tuberculosis
Acute miliary tuberculosis
Tuberculous gumma
(Metastatic tuberculous abscess)
Lupus vulgaris (some)
Lichen scrofulosorum
Papular or papulonecrotic
Erythema induratum (Bazin)
Nodular vasculitis (some)
Clinical manifestation of cutaneous tuberculosis is a reflection of continuous
immuno-pathological spectrum. A more effective cell-mediated immune response is reflected in lupus vulgaris (LV) where CD4+ lymphocytes predominate, whereas there is a preponderance of CD8+ lymphocytes in scrofuloderma which has a relatively retarded response. Tuberculosis verrucosa cutis
(TBVC) occupies an intermediate position. The immunological status of the
patient is a crucial factor which influences the clinical variants and the course
of the disease itself.
Clinical types
Cutaneous tuberculosis may evolve as a primary or secondary infection.
Primary infection occurs in a previously uninfected, non-sensitized host
manifesting as either tuberculous chancre or acute disseminated miliary tuberculosis. Alternatively, secondary infection occurs in a presensitized host in
the form of reinfection or reactivation.
184
“Reinfection tuberculosis” may be due to secondary infection with another
strain of M.tuberculosis, with LV and TBVC as its distinct manifestations.
“Reactivation tuberculosis” occurs due to reactivation of the dormant “persister” mycobacteria, which follows impairment of cell mediated immunity and
manifests itself as either scrofuloderma or tuberculosis cutis orificialis.
Tuberculous chancre: This is now an uncommon form of primary cutaneous
tuberculosis, except in Asia. It occurs chiefly in children and affects the face
or extremities. Tubercle bacilli cannot penetrate the intact cutaneous barrier.
The usual site of entry is minor trauma to the skin in the form of abrasions
and pyodermas. Procedures like circumcision, ear and nose piercing, tattooing and injection with unsterilized needles also may inoculate the bacteria.
The earliest lesion appearing 2 to 4 weeks after inoculation is a reddish brown
papulo-nodule that rapidly enlarges and erodes to form a sharply demarcated ulcer. The triad of tuberculous chancre, enlarged lymphatics, and painless
regional lymphadenopathy is analogous to Ghon’s complex in the lungs and
is referred to as cutaneous primary complex. The primary lesion heals with
scarring. It may rarely evolve into LV or TBVC. The regional lymph nodes
may break down, producing scrofuloderma.
Histopathology is not characteristic in the early stages but later a tuberculoid
granuloma with giant and epithelioid cells develops. Caseation is seen in late
stages.
Warty tuberculosis (Synonyms: Tuberculosis verrucosa cutis, anatomist’s warts,
verruca necrogenica, prosector’s warts, lupus verrucosa) : A common form of tuberculosis in South-East Asia, has a tendency to localize over the lower extremities; while a rare condition in the Northwestern European countries,
tends more often to involve the hands. The clinical features are variable, but
verrucosity is always found. Lymphadenitis is rare unless there is secondary
pyococcal infection. It begins as a solitary indurated nodule with a keratotic
warty surface. It gradually extends in a serpiginous manner producing irregular reddish- brown warty plaque. Surface is crossed by deep clefts and fissures. The lesion pursues a chronic course with centrifugal progression and
central healing.
Histopathology: shows hyperkeratosis and acanthosis with an acute inflammatory infiltrate beneath the epidermis. A characteristic feature is the presence
of pseudoepitheliomatous hyperplasia and focal areas of abscess. Epithelioid
cells,giant cells and tuberculoid granulomas with caseation necrosis are usually present in the mid-dermis. Tubercle bacilli are more numerous than in
lupus vulgaris.
185
Scrofuloderma (Synonyms: King’s evil, tuberculosis cutis colliquativa): It
represents a form of reactivation tuberculosis which occurs due to direct extension into the skin of an underlying tuberculous focus present in either
lymph nodes, bones, joints, or epididymis. The lesion begins as a progressively adhering deep-seated nodule. Subsequently the swelling suppurates, softens and perforates with resultant ulceration and sinus formation. Margins of
the ulcer are blue, the edges undermined and the floor is covered with soft
granulation tissue. It heals with characteristic puckered spiral-like scars.
Histopathology: Non-specific changes like an abscess or ulceration are demonstrated in the center of the lesion. Tuberculoid granulomas with necrosis and
pronounced inflammatory infiltrate are seen in the deeper portions and at the
periphery of the lesion. Tubercle bacilli may be found.
Tuberculosis cutis orificialis (Synonym. Acute tuberculous ulcer): This is
a type of reactivation tuberculosis which develops in the skin and/or mucous
membrane adjacent to an orifice draining an active tuberculous infection in
individuals with impaired cell-mediated immunity. It is most common
around the nose, mouth and anal orifice. Starts as an oedematous red papule
that ulcerates and develops undermined edges. The ulcers are painful and resistant to treatment.
Histopathology: The ulcer shows non-specific inflammatory infiltrate.
Tuberculoid granulomas with pronounced necrosis are found deep in the dermis. Tubercle bacilli are readily demonstrated.
Miliary tuberculosis (Synonym: Tuberculosis cutis disseminata): The
acute haematogenous dissemination of tuberculosis chiefly affecting infants
and children whose state of immunity has been impaired/compromised.
Most reported instances of cutaneous tuberculosis seen in patients with AIDS
are of this type. Any exanthematous rash in a patient suffering from tuberculosis should a suggest immediate treatment because prognosis is poor.
Histopathology: The centre of the papule shows a microabscess containing
neutrophils, cellular debris, and numerous tubercle bacilli, which is surrounded by a zone of macrophages with occasional giant cells.
Lupus vulgaris: Usually a reinfection tuberculosis of the skin, it can also result from the direct extension or haematogenous and lymphatic spread from
a tuberculous focus. Occurs in a person with a moderate or high degree of immunity. It is now uncommon in Europe and the USA. Cool, moist and dark
conditions appear to favour its development. The most common site affected
in Western countries is the face, with predilection for the nose and cheeks,
whereas in the tropics and sub-tropics the lower extremities, especially the
186
buttocks, are more often involved. At initial presentation, the skin shows
small areas of brownish–red discoloration, which subsequently become infiltrated to form plaques of gelatinous consistency which are soft on probing.
Fine scaling may or may not be present. Diascopy reveals characteristic “apple
jelly” nodules. The morphological variants of lupus vulgaris, depending on the
local tissue response to the infection, are: plaque form, ulcerative and mutilating forms, vegetating, tumour-like and papular and nodular forms (hypertrophic type). Although, it is a chronic condition, spontaneous resolution may
occur, after which scarring, contractures and tissue destruction occur.
Histopathology: Tuberculoid granulomas composed of epithelioid cells and giant cells usually of Langhan’s type are present with lymphocytic infiltration.
Caseation necrosis within the tubercles is slight or absent. Tubercle bacilli are
demonstrated very rarely.
Tuberculous Gumma: Is seen to occur in poorly nourished children following haematogenous spread from a primary focus.
Histopathology: Caseation necrosis with a rim of epithelioid cells and giant
cells is seen. Acid-fast bacilli are scanty.
Lichen scrofulosorum (Synonym: Tuberculosis cutis lichenoides): An
eruption of grouped, closely set, minute lichenoid papules, often perifollicular. It may occur in children or adults who have tuberculosis of the bones or
lymph nodes. The tuberculin test is always positive in individuals with lichen
scrofulosorum.
Erythema Induratum (Bazin): Erythema induratum is considered to be a form
of panniculitis precipitated by cold conditions occurring in association with TB.
It has a persistent or recurrent course. Presents with bilateral indolent eruption
of erythematous, tender, ill-defined subcutaneous nodules or plaques on the
back of lower legs of women with an erythrocyanotic circulation. Nodules may
initially regress but eventually persist and ulcerate. Ulcers are shallow with a
ragged, irregular and bluish edge. Ulcers heal slowly with atrophic scars.
Histopathology: It is non-specific. Tuberculoid granulomas, fat necrosis,
caseous as well as coagulative, foreign body giant cell reactions with a mainly lobular panniculitis have been frequently observed.
Diagnosis
The diagnosis of cutaneous tuberculosis is based on absolute and relative criteria and accompanying supportive immunological evidence.
Absolute criteria:
• Demonstration of acid-fast bacilli on Ziehl-Neelsen or Kinyoun staining
of the smear or with the recent method of auramine rhodamine staining
187
and fluorescence microscopy.
• Positive culture of M.tuberculosis from the lesion on Lowenstein-Jensen
medium after 4-6 weeks of inoculation. Rapid cultural diagnosis within 23 weeks is possible with Middle brook 7H10 and the liquid media with
radiometric growth detection (BACTEC 460).
• Recovery of M.tuberculosis from guinea pig inoculation.
• DNA identification by polymerase chain reaction (PCR) is a specific rapid and sensitive test for the diagnosis of M.tuberculosis infection. PCR detects a 65-KDa antigen of M.Tuberculosis complex DNA.
Relative Criteria:
• The presence of active proven tuberculosis elsewhere in the body.
• The clinical history and morphological features.
• The histopathology showing evidence of a tuberculoid granuloma.
• Strongly positive Mantoux test indicates active tuberculosis. An induration of 5mm should be considered a positive test in HIV infected patients.
• The effect of specific therapy.
Ulcerative form – Lymphogranuloma inguinale, coccidioidomycosis, actinomycosis, blastomycosis, leishmaniasis, filariasis, schistosomiasis, amoebiasis,
ulcerative colitis and Crohn’s disease.
Verrucous form – Pyoderma vegetans, verruca vulgaris, and hypertrophic lichen planus.
Treatment
Cutaneous tuberculosis can be treated with the 6-month regimen recommended for patients with pulmonary tuberculosis. The short course regimens
comprise two phases:
Initial intensive or bactericidal phase: The aim of this phase is to achieve rapid bacterial killing and render the patients non-infectious using at least three
drugs, given for 2 months.
Continuation or sterilizing phase: Targets and eliminates the semidormant
“persisters” and is administered for 4 months
Dosage recommendations for initial therapy of tuberculosis in adults
Drug
Isoniazid
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Dosage
Daily
5 mg/kg, max. 300mg
10 mg/kg, max. 600mg
15-30 mg/kg, max. 2g
15-25 mg/kg
15 mg/kg, max. 1g
Thrice Weekly
50-70 mg/kg, max. 3mg
25-30 mg/kg
25-30 mg/kg, max. 1.5g
188
In both adults and children a 2-month initial phase of isoniazid, rifampin
and pyrazinamide followed by a 4-month continuation phase of isoniazid
and rifampin is recommended. In some patients, ethambutol (or streptomycin) are included in the first 2 months or until the results of drug susceptibility testing become available. Treatment may be given daily throughout
the course or intermittently (either three times weekly throughout the course
or twice weekly following an initial phase of daily therapy).
Several newer drugs whose role in antituberculous regimens is yet to be determined include quinolones, ciprofloxacin, oflaxacin and sparfloxacin, the
rifamycin derivatives rifabutin and rifapentine; betalactam-beta lactamase inhibitor combinations, e.g. amoxycillin-clavulanic acid; and clofazimine.
Surgical therapy: Scrofuloderma may require surgical intervention in addition to antitubercular drugs. A persistent nodule of lupus vulgaris and lesions
of TBVC may have to be excised. The lupoid nodules within the scarred areas may be destroyed by cryotherapy or electrocautery.
HIV disease: HIV testing is recommended for all patients diagnosed with tuberculosis, because they may require longer courses of therapy. For HIV infected patients, isoniazid and rifampicin should be taken for 9 months (i.e.
for 7 months after the initial 2 months of quadruple therapy) or for 6 months
following negative culture results.
Multidrug resistant tuberculosis (MDRT): The term MDRT has been
adopted by the World Health Organization to refer to strains that are resistant to isoniazid and rifampicin with or without resistance to additional
drugs. Resistance rates are higher among HIV-infected patients and may be
due to non-compliance. Between 50 and 100 million people worldwide are
thought to be infected with strains of drug resistant tuberculosis. MDRT is
difficult to manage and is often fatal. Owing to the variations in the patterns
of drug resistance, regimens must be designed for each patient on the basis of
in vitro susceptibility.
DOTS: In order to enhance compliance, the WHO proposed the strategy of
Directly Observed Therapy, Short course. It aims at ensuring cure by providing the most effective treatment in the form of combined drugs and intermittent therapy, and reassuring that it is properly followed.
9.1.3 Mycobacterium ulcerans infections
Synonyms: Buruli’s ulcer, Searle’s ulcer, Buruli Ulkus.
Definition: Buruli’s ulcer is caused by Mycobacterium ulcerans, which enters
the skin at sites of minor trauma by cuts or pricks from vegetation. This in-
189
fection characteristically occurs close to bodies of water draining tropical or
warm temperate rain forests, predominantly in Australia, Africa, Mexico,
Central and South America and South East Asia. M. ulcerans has an incubation period of 3 months and usually occurs in children and young adults.
Clinical features: The infection commences as a solitary, firm, painless, mobile, subcutaneous nodule which later ulcerates and extends rapidly and irregularly, developing a deeply undermined edge which is sometimes hyperpigmented. There is a predilection for the occurrence of these ulcers on the
extremities. The floor is formed of necrotic fat and may be associated with a
clear mucoid discharge. Satellites rarely develop. Ulcers may become very
large, up to 25 cm in diameter, surrounded by extensive and deep induration,
exposing the muscle and bone of an affected extremity. Constitutional symptoms are usually absent. There is no regional lymphadenopathy. The infection has a prolonged course and spontaneous healing may occur after several
months or years, causing appreciable scarring.
Scarring deformity, lymphoedema, and squamous cell carcinoma are the
complications that reportedly occur secondary to buruli’s ulcer . It has been
postulated that mycolactone, a polyketide toxin from M. ulcerans, may be responsible for the necrosis and ulceration. The toxin does not cause cell death
but instead arrests cells in the G1 phase of the cell cycle.
Diagnosis
Bacteriological examination of smears or biopsy specimens shows clumps of
acid-fast bacilli which are characteristically extracellular. They can be cultured
at a low temperature in liquid media containing albumin. M. ulcerans grows
at a restricted range of temperature from 24∞C to 31∞C. Skin test with ‘burulin’ gives a positive response. PCR is the diagnostic investigation.
Histopathology of the lesion shows extensive involvement of subcutaneous fat
as a septate panniculitis with a “ghost” outline of the normal tissue structure.
There is presence of granulation tissue with giant cells also. Deeper dermis
will show features of leukocytoclastic vasculitis, affecting small and mediumsized vessels. AFB are present in early lesions but are rare in the healing stage.
Phase of subcutaneous nodule: panniculitis, nodular vasculitis, foreign body
granuloma, nodular fasciitis. Phase of ulceration:deep fungal infection, pyoderma gangrenosum and suppurative panniculitis.
Treatment
Extensive excision of the lesion, debridement and split-thickness skin grafting is the best form of treatment. Hyperbaric oxygen may be useful.
190
Controlled heat therapy has also been tried. Medical management, while disappointing, may be tried and either rifampicin, clofozimine or co-trimoxazole are often included in the treatment. There are recent reports of clarithromycin as a promising drug. BCG vaccination has a moderately protective effect.
9.2 Pyogenic infection
9.2.1 Sycosis Barbae
Synonyms: folliculitis simplex barbae, sycosis vulgaris, barber’s itch, sycosis
de la barbe, Bartflechte.
Definition: Sycosis barbae is a subacute or chronic deep folliculitis with perifollicular inflammation caused by Staphylococcus aureus. It is clinically characterized by the appearance of inflammatory papules and pustules – with a
tendency to recur in the bearded and upper lip regions.
Clinical features: Occurs in males after puberty usually in the third or fourth
decade. Emotional stress, seborrhoeic dermatitis and trauma produced by
shaving are the predisposing factors. It initially starts as inflammatory follicular papules or pustules pierced by hairs. Involvement of neighbouring follicles produces raised plaques studded with pustules. The subacute form manifests itself as scattered or grouped lesions especially on the upper lip and below the angles of the jaw with recurrent episodes at irregular intervals, whereas the chronic forms which persist for a long time are typically clustered into
plaques, especially on the upper lip and chin. Hairs become loose and are
readily epilated. ‘Lupoid sycosis’ refers to a deep, chronic form of sycosis barbae, characterized by active pustules and papules that surround a central pink
atrophic scar giving the appearance of lupus vulgaris. Common site of involvement is the front of the ear or under the chin. Scalp may be extensively
involved (Folliculitis decalvans). Lesions tend to persist indefinitely.
Diagnosis
Diagnosis is mainly clinical. Culture yields S. aureus.
Histopathology: The affected follicle is packed with polymorphonuclear
leukocytes infiltrating its wall. Chronic granulomatous infiltrate containing
lymphocytes, plasma cells, histiocytes and foreign-body giant cells are seen
around the follicle in chronic lesions. This may result in destruction of the
sebaceous gland, or the whole follicle.
191
The condition has to be differentiated from pseudofolliculitis barbae, tinea
barbae, acne vulgaris and herpetic sycosis.
Treatment
The subacute forms are treated with topical antibiotics. The chronic forms
may need steroid-antibiotic combination. Resistant cases often require systemic antibiotics.
9.2.2 Furuncle
Synonyms: Furunculosis, boil, furuncle, Furunkel, eiterbeule.
A furuncle is a deep seated infection in and around the hair follicle. Preceding
folliculitis may evolve into a subcutaneous abscess. Staphylococcus aureus is the
most common aetiologic agent.
Clinical features
A furuncle begins as a firm, tender, red folliculo-centric nodule, that enlarges
and becomes a pustule which undergoes central necrosis and ultimately ruptures and heals with a scar. The lesions may be single or multiple, and tend
to appear in crops. Fever and constitutional symptoms are usually mild.
Furuncles arise in hair-bearing sites, particularly in regions subject to friction,
occlusion and perspiration such as the neck, face, axillae, buttocks and the
anogenital region.
Predisposing factors include poor hygiene, malnutrition, nasal or perineal
carriage of S. aureus, mechanical damage of the skin, alcoholism, blood
dyscrasias, defects in neutrophil function, iatrogenic or immunosuppression
including AIDS and probably diabetes mellitus.
Diagnosis
Clinical appearance, Gram-stain of pus showing clusters of Gram-positive
cocci, or isolation of S. aureus on culture confirm the diagnosis.
Histopathology reveals an area of perifollicular necrosis containing fibrinoid
material and neutrophils. An abscess is present at the deep end of the necrotic plug, in the subcutaneous tissue.
Cystic acne, hidradenitis suppurativa (axillae and anogenital region), ruptured epidermal inclusion cyst and furuncular miyasis (e.g., Dermatobia hominis) should be considered in the differential diagnosis.
Treatment
Warm compresses relieve discomfort, localize the infection and promote
drainage. A systemic antibiotic is indicated if there is associated fever or cel-
192
lulitis. Penicillinase-resistant penicillin or a first-generation cephalosporin
should be given orally in a dose of 1 to 2 gm/day. Erythromycin (250 to 500
mg orally every 6 hours) is an alternative in patients allergic to penicillin.
Ideally drug sensitivity should be checked. If MRSA is implicated or suspected, vancomycin (1.0 to 2.0 gm IV daily in divided doses) can be given.
Intranasal application of a 2% mupirocin calcium ointment in white, soft
paraffin base for 5 days has shown to eliminate nasal carriage of S. aureus. The
other effective options are rifampicin, 600mg orally daily for 10 days, combined with cloxacillin, 500mg four times daily, or low dose clindamycin,
150mg daily for 3 months.
9.2.3 Acne Necrotica
Synonym: Acne varioliformis, acne frontalis
Definition: Acne necrotica occurs because of a chronic follicular necrotizing
process and manifests itself as recurrent cycles of inflammatory papulo-pustules which heal, leaving behind characteristic, deeply pitted varioliform
scars.
Clinical features: Acne necroticans is seen in young and middle-age adults
on the scalp or adjacent areas and is commonly seen to involve the frontal
hairline. The exact aetiology is unknown but is thought to be due to the
host’s response to various microorganisms, of which staphylococcus aureus and
propionibacterium acnes are the popularly accepted ones. Emotional stress is a
frequently associated finding. The typical primary lesions are itchy umbilicated follicular papulopustules 2-5mm in diameter, which become necrosed,
and develop adherent haemorrhagic crusts, which gradually separate over a
period of 3 to 4 weeks to form permanent, deeply pitted, varioliform scars.
Cheeks, nose, midline of chest and back may rarely be affected.
Diagnosis
Histopathology of early lesions shows a marked perifollicular lymphocytic infiltrate with exocytosis of lymphocytes into the external root sheath. Necrosis
of the hair follicle and of the perifollicular epidermis is a late occurrence.
This condition should be differentiated from papulo-necrotic tuberculides
and tertiary syphilis.
Treatment
Treatment is with culture directed antibiotics or tetracycline in case of culture
negative cases. Adjuvant therapy with topical clindamycin and doxepin have
been recommended. Doxepin provides dual benefit with its psychotropic and
193
antipruritic effects. Resistant cases have been treated successfully with
isotretinoin.
9.2.4 Hidradenitis Suppurativa
Synonyms: Apocrinitis, hidradenitis suppurativa axillaris, apocrine sweat
gland abscesses.
Definition: A chronic and often painless relapsing inflammatory disease primarily affecting apocrine gland follicles, which may extend subcutaneously
causing induration, scarring, destruction of skin appendages and sinus formation.
Distribution: The prevalence is estimated at 4% of women in the general
population. A tropical environment favours the development and intensification of hidradenitis suppurativa, but the disorder can occur under diverse climatic conditions. Hidradenitis generally begins after puberty with female
preponderance, and it may well persist into old age.
Aetiopathogenesis
Comedonal occlusion of the ‘apocrine gland follicle’ unit obstructs the outflow of both apocrine and sebaceous gland and may thus initiate hidradenitis. Genetic factors play an important role and often involve a single gene.
Association with HLA-A1, and HLA-B8 may predispose patients to a more
severe disease. The role of hormonal influences in the development of the disease is controversial. Improvement during and relapse after pregnancy, and
premenstrual and menstrual exacerbation, suggest that low-levels of estrogen
predispose to disease activity. Defects in cell-mediated immunity may exist in
some patients. Obesity is not a constant feature of hidradenitis suppurativa.
Hidradenitis is not a true infectious process and bacterial infection, if present, is only secondary. Staphylococcus aureus, anaerobic streptococci, notably
the microaerophilic organisms Streptococcus milleri and Escherichia coli, are
the organisms most commonly demonstrated in the draining sinuses.
Proteus, pseudomonas and anaerobes have been cultured occasionally.
Lithium is known to induce follicular hyperkeratosis causing hidradenitis
suppurativa.
Clinical features
As the skin containing apocrine glands is affected, commonly involved sites
are axillae, buttock, inguinal, perianal, mammary and inframammary areas.
Characteristic polyporous comedones are present in or beside affected skin.
The earliest clinical lesions are erythematous tender nodules, 0.5 to 2 cm in
size, that are initially firm but are fluctuant and painful later. The abscess
194
gradually increases in size and if untreated may open to the surface, yielding
purulent or seropurulent discharge, forming chronic draining sinuses. The
inflammation subsides gradually. Recurrent episodes of inflammation are the
rule. Fibrosis eventually becomes prominent, but healing is incomplete.
Bands of scar tissue restricting the mobility of the tissue are the late sequelae.
Acute episodic eruptions intervene indefinitely. Regional lymphadenopathy
is common. The lesions have a foul smell secondary to bacterial overgrowth
and colonization.
Hidradenitis suppurativa is sometimes associated with acne conglobata, dissecting cellulitis of the scalp or a pilonidal sinus (follicular occlusion triad or
tetrad).
Diagnosis
The diagnosis is based chiefly on clinical manifestations. Acute stages may be
associated with high erythrocyte sedimentation rate, leukocytosis and low
serum iron. Bacteriological analysis reveals underlying organisms.
Histopathology
In the early stages there is evidence of follicular hyperkeratosis with plugging,
and inflammatory changes within and around the apocrine glands. The ducts
may be distended with leukocytes. Later, the adjacent and subcutaneous tissues may show chronic inflammatory cell infiltrate with histiocytes and giant
cells in relation to remnants of glandular epithelium and keratinous debris.
Skin appendages are obliterated by scarring. Extensive fibrosis may be seen in
areas of healing, along with sinus tracks lined partly by granulation tissue and
partly by squamous epithelium.
In the early stages, a solitary abscess resembles a carbuncle, lymphadenitis or
an infected epidermoid cyst. The disease has to be differentiated from scrofuloderma, actinomycosis, lymphogranuloma venereum, granuloma inguinale, Crohn’s disease, and ulcerative colitis.
Treatment
Hurley’s clinical staging of hidradenitis suppurativa is helpful for planning
treatment.
Stage I: Solitary or multiple isolated abscess formation without scarring or sinus tracts.
Stage II: Recurrent abscesses, single or multiple widely separated lesions, with
sinus tract formation and cicatrization.
Stage III: Diffuse or broad involvement across a regional area with multiple
interconnected sinus tracts and abscesses.
195
Medical management alone may be helpful in Stage I, whereas surgery is the
treatment of choice for Stage II and Stage III of the discase.
Full doses of appropriate antibiotics should be instituted in most cases.
Generally preferred antibiotics are erythromycin, tetracycline, doxycycline or
minocycline. About 25-50% of patients respond to isotretinoin therapy.
Etretinate or acitretin may be more useful than isotretinoin.
Systemic corticosteroids are helpful in managing severe flares. Intralesional
triamcinolone therapy (5mg/ml) is useful in reducing inflammation in new
lesions.
A combination of cyproterone acetate (100mg/day) and ethinyl estradiol (50
mcg) has been reported to result in substantial improvement.
Surgery is considered in refractory cases. Exteriorization, curettage and electrocoagulation of sinus tracts for stage II disease and a simple or wide excision with direct closure or grafting for stage III disease are recommended.
CO2 laser therapy is a new method of treatment which has been found to be
a safe and effective procedure.
9.2.5 Impetigo
Synonyms: Fox’s impetigo, Pemphigus neonatorum in newborns.
Definition: Impetigo is a superficial contagious bacterial infection of the
skin predominantly occurring in children. The two clinical patterns recognized are bullous and non-bullous (impetigo contagiosa). Bullous impetigo is
a staphylococcal infection chiefly of group II phage types 71 and 55 whereas
non-bullous form accounting for 70% of cases of impetigo may be caused by
group A Streptococcus pyogenes but predominantly by Staphylococcus aureus.
Staphylococcal non-bullous impetigo is more common in temperate climates
whereas the streptococcal form is frequently seen in warmer and humid areas. Overcrowding and poor hygiene predispose to infection. The peak seasonal incidence is in late summer and early autumn.
Clinical features
Pruritic non-bullous impetigo manifests itself initially as a thin-walled vesicle
containing clear yellow fluid on an erythematous base which becomes cloudy
and rapidly ruptures resulting in honey-coloured “stuck on” crusts. Gradual
irregular peripheral extension occurs without central healing, and adjacent lesions may coalesce. Eventually the crusts dry and separate leaving behind erythema, which fades without scarring.
In comparison, the thick-walled flaccid bullae of bullous impetigo have
sharply demarcated margins without an erythematous halo and measure 1-2
196
cm in diameter. They last for 2-3 days and rupture forming thin “varnishlike” brown crusts. Central healing and peripheral extension may give rise to
circinate lesions.
Lesions may affect any part of the body, the most common sites being the
face, especially around the nose and mouth, and the limbs. Regional adenitis
is a rare manifestation of bullous impetigo and occurs in 90% of patients
with non-bullous impetigo. Lesions normally resolve in 2 to 3 weeks without
treatment.
In HIV infected patients, impetigo occurs more often in the axillary, inguinal
and other intertriginous locations. Furthermore, the earliest lesions are
painful red macules that rapidly evolve into superficial vesicles. These on rupturing lead to sero-purulent discharge containing potentially infective HIV.
Untreated, invasive infection can cause cellulitis, lymphangitis, acute
glomerulonephritis, erythema multiforme, pneumonia, osteomyelitis,
meningitis, and septicaemia.
Figure 1 - face impetigo. The
characteristic honey-like crust
can be noticed.
Diagnosis
Diagnosis is established by the clinical appearance; Gram-stain and culture
growth identify the infective pathogen.
Histopathology
Shows vesicles arising in the subcorneous or granular region. In contrast to
impetigo contagiosa, only a few or no neutrophils are seen within the bulla
cavity of bullous impetigo. Gram-positive cocci may be seen in the blister fluid. The stratum malpighii underlying the bulla is spongiotic, and contains
neutrophils. The upper dermis contains a moderately severe inflammatory infiltrate of neutrophils and lymphoid cells.
197
Treatment
Removal of crusts and strict precautions regarding hygiene are essential.
Depending on the severity, topical or systemic antibiotics should be administered based on the culture and sensitivity profile Mupirocin ointment is effective. Antiseptics like chlorhexidine and povidone iodine provide a useful
adjunct to systemic treatment.
9.3 Non-pyogenic infections
9.3.1 Pseudofolliculitis Barbae
Synonyms: Pili incarnati, ingrown hair, ‘shaving bumps’.
Definition: Pseudofolliculitis barbae are inflammatory follicular papules or
pustules in the beard area involving growing hairs that curve back and pierce
the skin as ingrowing hairs, setting off an inflammatory reaction. It is more
common in Black men having curved follicles and it occurs due to the close
shaving of such hairs
Clinical features: Presents with perifollicular papules and pustules on the
sides of the neck and over the angles of the jaw. Some lesions may form nodules which heal with unsightly scars. Although the beard area is the most
common site of involvement, pseudofolliculitis may involve any site that is
shaved, including the scalp and pubic region
Diagnosis: Clinical manifestations which are typical, usually clinch the diagnosis of pseudofolliculitis barbae.
Differential diagnosis: Differential diagnoses to be considered include acne
vulgaris, tinea barbae, and sycosis barbae.
Treatment: Solitary hairs may be epilated. Laser hair removal appears promising. Growing a beard is an alternative. Use of electric clippers, chemical depilatories or a manual razor, and adjunctive antibiotic therapy, are helpful.
Shaving only every second or third day will increase compliance with the depilatory agents.
Figure 9.3.1.1 Pseudofolliculitis barbae: multiple papules lesions, with follicular localisation.
Figure 9.3.1.2 Pseudofolliculitis in North African patient.
Figure 9.3.1.3 Pseudofolliculitis localised in the neck region.
198
9.3.2 Acne Keloidalis
Synonyms: Folliculitis keloidalis, acne keloidalis nuchae, dermatitis papillaris
capilliti, keloidal acne.
Definition: Acne keloidalis results from persistent folliculitis and perifolliculitis at the nape of the neck. Lesions eventually undergo fibrosis and form
firm papules. Coalescence of the papules form keloidal plaques. Risk factors
are irritation from incurving sharp hairs into the skin following close shaving
or friction from the shirt collar. S. aureus is often isolated from the lesion.
Clinical features
This condition is common among young adult African or Asian men and
manifests itself as follicular papules or pustules on the nape of the neck just
below the hair line extending occasionally upwards into the scalp. These lesions evolve into perifollicular cicatricial papules and keloidal plaques.
Occasionally the lesions may be persistent with formation of undermined abscess and discharging sinuses.
Figure 9.3.2.2 acne
keloidalis nuchae: in a
patient from Ethiopia.
Diagnosis
Clinical features and corroborative skin biopsy findings establish the diagnosis. Histopathology shows evidence of deep folliculitis that progresses into a perifolliculitis. The infiltrate is composed of polymorphonuclear leukocytes, lymphocytes, plasma cells, mast cells and sometimes foreign body giant cells. The
normal connective tissue is later replaced by dense hypertrophic scar tissue.
Perifolliculitis capitis ascendens et suffodiens forms an important differential
diagnosis.
199
Treatment
Treatment should be aimed at arresting the active inflammation and decreasing or surgically removing the fibrous lesions. Long-term antibiotics such as
tetracyclines have to be administered. Intralesional steroids (2.5 to 5.0 mg/ml
of triamcinolone acetonide) or topical steroids may reduce scarring and inflammation. Other modalities of treatment tried include excision and grafting, treatment with carbon dioxide laser and allowing healing by secondary
means.
9.3.3 Tropical Ulcer
Synonyms: Tropical phagedenic ulcer, tropical phagedena, tropical sloughing
phagedena, Aden ulcer, Malabar ulcer, jungle rot
Definition: Tropical ulcer is a painful, foul-smelling, necrotizing, rapidlygrowing ulcer of the skin and subcutaneous tissue, usually occurring on the
foot or leg. Predilection for the lower leg is probably related to exposure to
contamination, dependence on the lower leg and poor blood supply.
Microbiological studies indicate that it occurs as a result of interaction between various microbes: fusobacterium (F. nucleatum), a spirochete
(Treponema vincenti) and other aerobic and anaerobic organisms.
Malnutrition and poor hygienic conditions are thought to be contributory
factors.
This condition is virtually limited to the tropics and subtopics.
Clinical features
Lesions start as papules, bullae, or as small painful tender erythematous and
oedematous areas at sites of potential trauma such as lower legs and the foot.
These lesions rapidly enlarge, become haemorrhagic and break down over
two to three weeks to form sharply-defined painful ulcers – measuring 2 to 4
cm in diameter. The floor is covered with a foul-smelling purulent slough and
the ulcers have an indurated and raised margin. Constitutional symptoms
may be present.
Untreated, the ulcers persist for many months or years. Chronic ulcers may
involve deeper structures like fascia, muscles, tendons and periosteum.
Healing occurs with fibrosis forming a paper-like tissue scar which is very delicate. Squamous cell carcinoma can develop at the ulcer site.
Diagnosis
Diagnosis is chiefly based on the clinical appearance together with the classical evolution of the condition especially in endemic areas. Causative organisms may be identified from the floor of the ulcer.
200
Buruli ulcer, mycoses, diphtheritic ulcers, yaws, leishmaniasis, syphilitic
gumma, venous ulceration, arterio-sclerotic ulcers, ulcers of blood dyscrasias
and ulcers of Kaposi’s sarcoma are other causes of chronic leg ulcers.
Treatment
Management involves surgical debridement of dead tissue followed by bland
applications. This has to be supplemented with penicillin (500. 000 to 1
million units, IM daily for 7–20 days) and/or metronidazole (800 mg twice
daily for 1 to 2 weeks). Skin grafting may be necessary for chronic lesions.
9.3.4 Erythrasma
Synonyms: èrytrasma, saprophytic disease of the skin, nocardiosis.
Definition: A mild, chronic, localized superficial bacterial infection of the
skin caused by Corynebacterium minutissimum. A warm, humid tropical climate favours the infection more than a temperate climate does. Commonly
occurs in adult men. Obesity and diabetes mellitus are the predisposing factors. It does not appear to be significantly contagious.
Clinical features
The most frequently affected site is the toe cleft, especially the fourth web
space, manifesting itself as a hyperkeratotic white macerated plaque.
In the genitocrural, axillary and inframammary regions, the lesions present as
well-demarcated, reddish-brown, superficial, finely scaly and finely wrinkled
plaques having uniform appearance. Lesions may be asymptomatic or intensely pruritic. Irritation of the lesions, which is seen particularly in the
tropics, may lead to excoriations and lichenification.
Diagnosis
Diagnosis is based mainly on clinical findings and confirmed by Wood’s lamp
illumination which shows a characteristic “coral red” fluorescence caused by
coproporphyrin III. Gram-staining and culture of pulverized stratum
corneum on Tissue Culture Medium 199 (without antibiotics) with 20% calf
serum and 2% agar yields the organism.
Pityriasis versicolor, tinea cruris, tinea pedis, candidiasis and inverse psoriasis
must be considered under the differential diagnosis.
Treatment
If untreated, lesions tend to persist indefinitely with spontaneous fluctuations
in severity. Systemic erythromycin (250 mg four times daily for 1 week) is the
drug of choice, especially for a widespread involvement as they also reduce
201
the incidence of relapses. Alternatively topical fusidic acid, imidazoles, clindamycin (2% solution) or oral tetracycline can be effective.
Toe cleft infection may be treated with benzoyl peroxide wash or 5% gel.
Prophylaxis for relapsing cases include long-term antiseptic soaps like povidone iodine, and drying agents like powders.
A multidrug-resistant C. minutissimum strain has been recently reported in
an HIV infected patient.
202
Suggested Readings
9.1 Mycobacterial Dermatoses
9.1.1 Leprosy
1. Awofeso N. Potential impacts of poverty alleviation activities on reducing leprosy transmission. Lepr Rev. 2004 Jun;75(2):196-8.
2. Ghorpade A. Tuberculoid leprosy confined to glans penis in two cases. Lepr Rev. 2004
Jun;75(2):188-91.
3. Gidoh M, Namisato M, Kumano K, Goto M, Nogami R, Ozaki M. Nihon Hansenbyo
Gakkai Zasshi. 2004 Feb;73(1):65-7. Guideline for the treatment of leprosy by new
quinolones.
4. Kumar B, Dogra S, Kaur I. Epidemiological characteristics of leprosy reactions: 15 years experience from north india. Int J Lepr Other Mycobact Dis. 2004 Jun;72(2):125-33.
5. Kumarasinghe SP, Kumarasinghe MP. Should large lesions of leprosy be considered as
“multibacillary” for treatment purposes even if the total number of lesions is less than five?
Int J Lepr Other Mycobact Dis. 2004 Jun;72(2):173-4.
6. Meima A, Smith WC, van Oortmarssen GJ, et al. The future incidence of leprosy: a scenario analysis. Bull World Health Organ. 2004 May;82(5):373-80.
7. Mohanty KK, Joshi B, Katoch K, et al. Leprosy Reactions: Humoral and Cellular Immune
Responses to M. leprae, 65kDa, 28kDa, and 18 kDa Antigens. Int J Lepr Other Mycobact
Dis. 2004 Jun;72(2):149-58.
8. Report on the sixth meeting of the who technical advisory group on the elimination of leprosy
Geneva, 9 and 10 February 2004
9. Scollard DM. Classification of leprosy: a full color spectrum, or black and white?
Int J Lepr Other Mycobact Dis. 2004 Jun;72(2):166-8.
10. Stump PR, Baccarelli R, Marciano LH, et al. Neuropathic pain in leprosy patients. Int J
Lepr Other Mycobact Dis. 2004 Jun;72(2):134-8.
11. Travaglino C., Morrone A., La malattia di Hansen tra mito e realtà. In: Morrone A,
Salute e società multiculturale, 1995, Cortina Editore, Milano, pp.209-35
12. WHO Leprosy Elimination Project Status Report 2003 Draft World Health Organization,
Geneva 2004
13. WHO, Intensified control of neglected diseases. Report of an International workshop,
Berlin, december 10-12, 2003.
Tuberculosis
1. Barbagallo J, Tager P, Ingleton R, Hirsch RJ, Weinberg JM. Cutaneous tuberculosis: diagnosis and treatment. Am J Clin Dermatol. 2002;3(5):319-28.
2. Barbagallo J, Tager P, Ingleton R. et al. Cutaneous tuberculosis. Diagnosis and Treatment.
Am J Clin Derm, 2002,3(5),319-28
3. Mahaisavariya P, Manonukul J, Khemngern S, et al. Mycobacterial skin infections: comparison between histopathologic features and detection of acid fast bacilli in pathologic section. J Med Assoc Thai. 2004 Jun;87(6):709-12.
4. Sehgal VN, Ahuja P, Shaema VK. Cell-mediated immunity in cutaneous tuberculosis. Br J
Dermatol, 118: 730, 1988.
203
5. Sehgal VN, Gupta R, Bose M et al: Immunohistopathological spectrum in cutaneous tuberculosis. Clin Exp Dermatol, 18: 309-313, 1993.
6. Sehgal VN, Wagh SA: The history of cutaneous tuberculosis. Int J Dermatol, 29: 666-668,
1990.
7. Sehgal VN. Cutaneous tuberculosis. Dermatologic Clinics, 12: 645-653, 1994.
8. Tan SH, Tan HH, Sun YJ, Goh CL. Clinical utility of polymerase chain reaction in the detection of Mycobacterium tuberculosis in different types of cutaneous tuberculosis and tuberculids. Ann Acad Med Singapore. 2001 Jan;30(1):3-10.
9. Tigoulet F, Fournier V, Caumes E. Clinical forms of the cutaneous tuberculosis
Bull Soc Pathol Exot. 2003 Jan;96(5):362-7.
Micobacterium ulcerans infection
1. Trott KA, Stacy BA, Lifland BD, et al. Characterization of a Mycobacterium ulcerans-like
infection in a colony of African tropical clawed frogs (Xenopus tropicalis). Comp Med. 2004
Jun;54(3):309-17.
2. Darie H. Mycobacterium ulcerans infection: epidemiological, clinical and therapeutical aspects Bull Soc Pathol Exot. 2003 Jan;96(5):368-71.
3. Pszolla N, Sarkar MR, Strecker W, et al. Buruli ulcer: a systemic disease. Clin Infect Dis.
2003 Sep 15;37(6):e78-82.
4. James K, Attipou KK, James YE, et al. Buruli ulcer in Togo: a hospital study Sante. 2003
Jan-Mar;13(1):43-7.
5. Guarner J, Bartlett J, Whitney EA, et al. Histopathologic features of Mycobacterium ulcerans infection. Emerg Infect Dis. 2003 Jun;9(6):651-656.
6. WHO Buruli ulcer disease. Wkly Epidemiol Rec. 2004 May 14;79(20):194-9.
2.2 Pyococcal infections
1. Brown J, Shriner DL, Schwartz RA, Janniger CK. Impetigo: an update. Int J Dermatol.
2003 Apr;42(4):251-5.
2. George A, Rubin G. A systematic review and meta-analysis of treatments for impetigo.
Br J Gen Pract. 2003 Jun;53(491):480-7. Review.
3. Gniadecki R, Jemec GB. Lipid raft-enriched stem cell-like keratinocytes in the epidermis,
hair follicles and sinus tracts in hidradenitis suppurativa. Exp Dermatol. 2004
Jun;13(6):361-3.
4. Jemec GB. Medical treatment of hidradenitis suppurativa. Expert Opin Pharmacother.
2004 Aug;5(8):1767-1770.
5. Mahe E, Girszin N, Descamps V, Crickx B. Furunculosis and IgG subclass deficiency.
Dermatology. 2004;208(1):84-5.
6. Plewig G, Jansen T. Acneiform dermatoses. Dermatology. 1998;196(1):102-7.
7. Slade DE, Powell BW, Mortimer PS. Hidradenitis suppurativa: pathogenesis and management. Br J Plast Surg. 2003 Jul;56(5):451-61.
8. Wiseman MC. Hidradenitis suppurativa: a review. Dermatol Ther. 2004;17(1):50-4.
9. Zirn JR, Scott RA, Hambrick GW. Chronic acneiform eruption with crateriform scars.
Acne necrotica (varioliformis) (necrotizing lymphocytic folliculitis). Arch Dermatol. 1996
Nov;132(11):1367, 1370.
204
2.3 Non-pyococcal infections
Pseudofilliculitis Barbae
1. Bridgeman-Shah S. The medical and surgical therapy of pseudofolliculitis barbae.
Dermatol Ther. 2004;17(2):158-63.
2. Cook-Bolden FE, Barba A, Halder R, Taylor S. Twice-daily applications of benzoyl peroxide 5%/clindamycin 1% gel versus vehicle in the treatment of pseudofolliculitis barbae.
Cutis. 2004 Jun;73(6 Suppl):18-24.
3. Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae. Dermatol Clin. 2003
Oct;21(4):645-53. Review.
4. Leyden JJ. Topical treatment for the inflamed lesion in acne, rosacea, and pseudofolliculitis
barbae. Cutis. 2004 Jun;73(6 Suppl):4-5.
5. Perry PK, Cook-Bolden FE, Rahman Z, Jones E, Taylor SC. Defining pseudofolliculitis
barbae in 2001: a review of the literature and current trends. J Am Acad Dermatol. 2002
Feb;46(2 Suppl Understanding):S113-9.
6. Roberts WE. Chemical peeling in ethnic/dark skin. Dermatol Ther. 2004;17(2):196-205.
7. Scheinfeld NS. Pseudofolliculitis barbae. Skinmed. 2004 May-Jun;3(3):165-6.
Erythrasma
1. Bielan B. What’s your assessment? Erythrasma. Dermatol Nurs. 2001 Feb;13(1):41, 4
2. Holdiness MR. Erythrasma and common bacterial skin infections. Am Fam Physician.
2003 Jan 15;67(2):254.
3. Holdiness MR. Management of cutaneous erythrasma. Drugs. 2002;62(8):1131-41.
4. Dermatoes due to viruses
205
4. DERMATOSES DUE TO VIRUSES
Aldo Morrone, Margherita Terranova
Three main groups of viral cutaneous infections may be distinguished according to the micro-organism responsible:
Poxvirus DNA 250-300 nm
• Molluscum contagiosum
Herpesvirus DNA 90-170 nm
• Varicella
• Herpes zoster
• Herpes simplex
Papillomavirus DNA 46-52 nm
• Common warts (verruca vulgaris)
• Flat warts (verruca plana)
• Anogenital warts (condylomata acuminata, described in the sexually
transmitted diseases section)
In the following chapter we will also examine:
• HIV cutaneous manifestations
2.1 Molluscum Contagiosum
Synonymous with: molluscum sebaceum, dellwarzen
Definition: the molluscum contagiosum is a cutis infectious disease, caused
by a DNA virus of the Poxvirus group, characterized clinically by a papular
umbilicated lesion.
Distribution: ubiquitous infection, very frequent in children as well as in
HIV infected patients. In the latter case it can assume very diffused and largedimensioned clinical characteristics.
Incubation period: varies from 2 to 8 weeks. In some cases it can reach 3-4
months.
Clinical Features: the lesion manifests itself with small hemispherical reliefs,
umbilicated in the centre, of milky white colour, sometimes pink, with a
smooth surface and well delimited borders, of variable dimensions from a
pinhead to a pea; some forms can reach greater dimensions, longer or pedunculated (in the giant forms). The umbilicated centre is the characteristic that
can be observed particularly in the bigger elements. It can manifest itself with
206
only one element, but more often we can observe multiple elements, up to
more than ten. Preferred zones are the face, torso and, in adults, the genitals.
Figure 2.1.4. Molluscum contagiosum of
the genital area in a child.
Diagnosis: the clinical aspect of the lesion is characteristic and indicative for
the diagnosis. If needed, histological examination may be performed.
Differential diagnosis: must be made in confrontation with colloid milia,
syringoma, the keratoacanthoma, verruca vulgaris and granuloma pyogenicum.
Histopathology: included intracytoplasmic bodies (Patterson corpuscles).
Therapy: In many cases lesions resolve spontaneously within 8 months without scarring. Nevertheless, even if molluscum contagiosum is self-limiting
and asymptomatic in healthy individuals, the correct therapeutic decision is
crucial, in order to prevent autoinoculation or transmission of the virus via
close contact, to relieve symptoms and, sometimes, for cosmetic considerations. The single elements can be removed with the use of a surgical spoon,
or by producing an epidermal injury and subsequent desquamation of the
molluscum and surrounding uninvolved skin. The treatment should be chosen considering the age and immunocompetence of the patient, and the extent of the areas involved as well. Patients should be advised to avoid swimming pools, communal baths, shared towels, etc., until cleared. Sexual partners should be examined and treated to prevent reinoculation.
207
2.2 Varicella
Synonyms: chickenpox, varicelle, petite vérole volante, windpocken
Definition: a generalized acute viral infection, with sudden onset, caused by
the varicella-zoster virus, accompanied by a light general symptomatology
and a generalized eruption of cutaneous lesions in different evolutionary
phases: blisters, papules, crusts and scars.
Distribution: the disease is universally distributed, very common in childhood, but not rare in adults from the tropical regions.
Incubation period: varies between 14 and 18 days, up to a maximum of 34 weeks.
Clinical features: the general symptomatology is usually light, there can be
fever associated with a transitory maculated rash, asthenia, headache. The cutaneous lesion appears progressively as a papule, and a blister that can be umbilicated and thus leading to a pustule.
At early stages it is possible to observe crusty lesions as well. The oral mucosa,
the cunnus and the conjunctiva can be affected very early on in the disease;
the lesions are distributed in a centripetal way. The multiform eruption of the
lesions in different sizes and in different evolutionary phases, affecting the
head and scalp, is very characteristic.
Itching is usually present and can be very severe. In tropical regions, due to
the lack of sufficient hygienic conditions, a secondary bacterial infection is
very frequent.
Diagnosis: characteristic appearance of lesions in different evolutionary
phases, smear from the floor of the blister, microscopic Giemsa staining examination; isolation of the virus, electronic microscopy, biopsy.
Differential diagnosis: has to be made in confrontation with herpes simplex,
disseminated exanthema in secondary syphilis, impetigo, epizoonosis, microbic eczema, multiform drug erythema, hidroa aestivalis and scabies.
Histopathology: intraepidermal blister, acantholysis.
Therapy: The treatment of varicella consists in symptomatic treatment
(mainly against pruritus and fever) and aetiologic (antiviral) therapy.
Itching may be alleviated by application of antipruritic lotions, e.g., calamine
alone or with 0,25% menthol and/or phenol. Cool water compresses and
tepid baking soda baths may also offer relief. Oral antihistamines may be effective in controlling generalized pruritus. Mouth and perineal regions can be
treated using saline or 1.5% hydrogen peroxide rinses or compresses. Fever
can be controlled by antipyretics, aspirin excluded because of its association
208
with Reye’s syndrome. Topical corticosteroids should be avoided in any case.
Bacterial superinfections of the skin can be treated using topical antibiotics
(mupirocin ointment or bacitracin-polymyxin), while systemic antibiotics
should be administered in case the infection is widespread (erithromycin, dicloxacillin or cephalexin). Aetiologic therapy includes several chemotherapeutic agents, mostly nucleoside analogues, that interfere with viral replication thus exerting a virostatic effect but not eradicating viral latency. In cases
of disseminated or complicated varicella acyclovir (ACV), a guanosine analogue, is the drug of choice. ACV must be initiated within 24-48 hours of the
outbreak of the rash. It may be administered orally (20mg/kg, maximum
800mg, 4 times a day for 5 days in children, or 800mg, 5 times daily for 5
days in adults), or intravenously (500mg/m2 or 10mg/kg every 8 hours for
8-10 days or until no new lesions have appeared for 48 hours) . Resistance to
ACV is very rare among immunocompetent individuals. In case of drug resistance or in immunocompromised patients, the use of Foscarnet (40mg/kg
i.v. every 8 hours) is indicated.
Another antiviral drug, Vidarabine, represents a valid but far more toxic alternative to ACV in case of severe varicella (10mg/kg i.v. over 12 hours for 5
days). Human interferon-a (3.5 C 105 U/kg daily for 2 days, followed by
1,75C 105 U/kg daily for 3 days), or infusion of irradiated lymphocytes from
healthy donors recovering from VZV infection, have been used with satisfactory results.
Several new antiviral agents have been developed lately, but are still under
evaluation. Oral penciclovir (and its prodrug famciclovir ) and oral valacyclovir have not been approved yet, while oral sorivudune has proved to be superior to ACV and is administered daily at a dose of 40 mg for 5 days.
2.3 Herpes Zoster
Synonyms: zona, shingles, zoster, gurtelrose.
Definition: herpes zoster is a neuro-cutaneous disease, generated by the varicella-zoster virus (VZV), with an acute inflammation course characterized by
a ganglioneuritis, by a vesicular manifestation with a metameric distribution,
and by regional adenopathy and neuritic pains. It is believed to be caused by
a violent virulence of the silent virus located in the ganglia (back root) after
chickenpox.
Distribution: the disease is generally diffused, more frequent in the elderly
209
population, but not rare in childhood. It is generally sporadic, but can present a greater incidence in spring and autumn.
Incubation period: varies from 1 to 3 weeks.
Clinical features: the cutaneous manifestations appear in an acute form and
can be preceded by a slight fever, asthenia, indisposition. Initially erythematous patches appear, disposed along the route of a nervous trunk; after a few
hours on these patches appear big hemispheric pearly blisters, with a limpid
content, disposed in clusters, that in some points are confluent with big
phlyctenas. The blisters vary in number from few to many; after a few days,
such blisters become dark, and desiccate and turn into yellow-brown crusts.
Regional early reactive adenopathy is present, causing slight sore. The zosterian neuritis is characterized by two principal forms of pain: a deep severe pain,
involving muscles and ligaments, and a superficial burning pain with great hyperaesthesia of the affected areas. The dermatosis topography coincides with a
nervous metamere; the most frequent locations are in the intercostal, loingroin-femoral, cervical and cephalic regions. Particular interest arises from the
cephalic zosters due to the possible serious complications they can provoke,
particularly when the ophthalmic area is involved. Different variations of the
zoster eruption exist: absence of exanthema (zoster sine herpete), with haematic content (haemorrhagic zoster) and necrotic forms (gangrenous zoster).
Recovery can be observed after 3-4 weeks, usually without scars, which can
be present in the necrotic-haemorrhagic forms, in dark-skinned subjects, and
particularly in the regions of Central-Africa. In immunodepressed subjects
generalized dissemination is possible.
Diagnosis: the pattern is quite characteristic, with the classical symptomatological triad: blistery eruptive lesions, segmental and radicular disposition,
neuritic pains; electron microscope observation of the virus, biopsy, and virus
cultivation.
Differential diagnosis: has to be made in confrontation with herpes simplex,
chickenpox, and in the initial phase, with erysipelas
Histopathology: presence of giant epithelial cells, multinucleated, located at
the blister.
Therapy: Symptomatic therapy aims at alleviating acute pain and itching
and at promoting healing. Cool compresses with tap water, saline solution or
Burow’s solution several times a day may have a soothing, drying effect.
Flexible collodion tincture, lotions containing alcohol, menthol and/or phenol, baking soda solutions and calamine lotion may also be beneficial. Olive
oil may help in the case of crusted lesions. Warm soaks and topical antibiotics
210
should be applied in the case of secondary infected lesions. Oral antihistamines, e.g. hydroxyzine, may relieve pruritus. Analgesics (e.g. oxycodone
with acetaminophen) are often necessary to relieve pain. Topical corticosteroids are contraindicated.
In immunocompetent individuals under 50, only symptomatic measures are
necessary. In elderly immunocompetent individuals, oral antivirals should be
administered (Acyclovir 800mg 5 times a day for 5-10 days).
Immunocompetent and immunocompromised patients of any age with cutaneous dissemination or evidence of visceral or CNS involvement, should receive
with no delay antiviral therapy with intravenous ACV (500mg/m2 or 10mg/kg
every 8 hours for 7 days or until there is no evidence of VZV replication).
Antiviral therapy should also be considered in ophthalmic herpes zoster, due to
the increased risk for ocular or CNS complications. Resistance to ACV is very
rare; Foscarnet (40mg/kg i.v. every 8 hours) is the drug of choice in this case.
Recently new antiviral drugs have been approved for the treatment of herpes
zoster, such as Valacyclovir (1g 3 times a day for 7 days), Famciclovir (500mg
3 times a day for 7 days, starting within 72 hours of the onset of the rash),
with satisfactory results and minor side effects. Experimental treatments with
Vidarabine (10mg/kg over 12 hours for 7 days), human interferon-? (1,7or
1,5 U/kg per day for 7 days) and Soriduvine have shown good results but
high toxicity. One of the major problems in patients with herpes zoster is the
management of the postherpetic
neuralgia (PHN). Once instituted,
PHN is refractory to treatment.
Emotional support and various therapeutic modalities with encouraging
results are crucial for improving the
patient’s
quality
of
life.
Carbamazepine, an antiepileptic
drug, is particularky effective for
shooting pain. Neurosurgical intervention (rhizotomy or surgical separation of pain fibers) should be considered for patients with intolerable
pain.
Figure 2.3.1 Herpes zoster in HIV.
211
2.4 Herpes simplex
Synonyms: Herpes febrilis, herpetic fever, fever blister, cold sore, herpes,
fieberblashen.
Definition: herpes simplex is an erythemato-vesicular dermatitis, with an
acute course, and with a characteristic cluster formation of the blister lesion.
It is caused by the herpes virus, of which two varieties are known: type 1 that
causes lip herpes, and type 2 that causes genital herpes.
Distribution: universal; genital herpes is more common in adolescents and
young adults, while lip herpes is diffused in all age groups.
Incubation period: can vary from 2 to 8 days, but most frequently between
3 and 5 days.
Clinical features: initial contact with the organism leads to the appearance
of acute lesions, (gingivostomatitis, balanoposthitis, vulvovaginitis). The
virus is located in the sensitive ganglia from where, as a result of immunodepression and consequent virulence episodes, it transfers to the cutis and mucous membranes. The appearance of the eruption is usually preceded by a
burning or localized painful feeling, subsequently a turgid, erythemato-oedematous patch appears, on which blisters with a serous content, in variable dimensions and number, rapidly come up in clusters. The lip and genital regions are the most frequently affected areas, but any body part can be involved. Predisposing factors may include: fever, sun exposure, mechanical irritation, and gastrointestinal problems. The type 1 virus is responsible for
eruptions in the mouth, on the lips, and on the top part of the body; type 2
causes genital lesions, lesions in the gluteal region, and, by inoculation, on
the hands and feet. Herpes can be episodic, but more often is recurrent, with
differently distanced crises, but always localized in the same areas (herpes recidivans in loco). Lip herpes is the most frequent and commonly recurrent
clinical form. When the blisters are localized to the mouth, to the face, mucous linings, lips, gums and tongue, the herpetic stomatitis clinical pattern
manifests itself. In patients with atopic eczema, often recurrent in the first
year of life, the herpes simplex virus can determine a blister-pustulous dermatitis with severe evolution, better known as varicelliform Kaposi eruption.
In genital herpes, because of the fast breaking of the blisters, we can observe
small round superficial erosions, isolated and confluent, with a tendency to
form clusters with polycyclic borders.
212
Figure 1 herpes simplex of the lips
Diagnosis: anamnesis and characteristic clinical manifestations, isolation of
the virus, and serology for Ig G and Ig M, biopsy.
Differential diagnosis: herpes zoster, chickenpox, herpetiform dermatitis,
gingivostomatitis, medicine polymorph erythema.
Histopathology: intraepidermic blister, “ballooning degeneration”, numerous leucocytes, and some giant cells at the basis of the lesion.
Therapy: Primary HSV-1 and 2 infection in immunocompetent adults
should be treated with oral aciclovir, 400mg, 5 times a day for 7 days. Any
serious disseminated complications, eczema herpeticum included, should be
treated in hospital. Initial administration of aciclovir (5mg/kg 3 times a day
for 5-7 days), must be followed by oral administration of the new antiviral
drugs valaciclovir or famciclovir, until new lesion formation ceases. Local application of acyclovir or 5-ioduridina can be useful, if performed in the initial stages of symptomatology, in case of HSV-1 recurrent disease.
Nevertheless systemic treatment seems to be so far the most effective, being
suitable for treating multifocal external, as well as intraoral lesions, avoiding
viral shedding and virus transmission by saliva. Treatment must be initiated
by the patient no later than 1-2 hours after the first prodromal warning sign.
The recovery takes usually 5-7 days, without scars. The first episode of HSV2 infection needs to be promptly treated with oral aciclovir, 200mg, 5 times
a day for 10 days. In recurent infections, oral aciclovir offers relative benefit
(200mg a day for 5 days), only if taken no later than 48 hours after the onset of symptoms. Because of the increasing resistance to aciclovir, two new
213
antiviral drugs have been introduced (valaciclovir and famciclovir) which are
absorbed better and have longer bioavailability.
In HIV-positive subjects we can observe ulcer lesions, with scars. The
Kaposi’s varicelliform eruption requires hospitalization for the numerous ocular, lung and meningeal complications, and the treatment with systemic antiviral drugs.
2.5 Flat Warts
Synonyms: verruca plana juvenilis, flat warts, verrugas planas, verrues planes
juveniles, Flachwarzen.
Definition: benign papules, autoinoculable, that develop especially in children and young adults. The aetiologic agent belongs to the papillomavirus
group, HPV (serotype 3, 10).
Distribution: the dermatosis is diffused all over the world, without any kind
of predilection of place.
Incubation period: extremely variable, from a few weeks to many months.
Pattern: the papules can appear isolated or unified. Sometimes they are disposed along cutaneous linear or punctiform excoriations of traumatic origin,
revealing an isomorphic irritation effect phenomenon (Koebner’s phenomenon). Flat warts usually affect children, but can be observed as well in adults,
particularly in females. Clinically they appear as papular flat elements, 3-4
mm in diameter, slightly elevated and thus made visible on the surrounding
skin, but neatly delimited, with a smooth surface, of pinky or yellow-brownish colour. They are usually rounded, oval or irregular polygons.
The papules, very numerous (up to hundreds of elements), can be isolated or
disseminated. The papules appear in relief, small, of the same colour as the
skin, localized principally on the face, particularly on the cheeks, on the forehead, in the areas around the mouth, the chin, and on the back of the hands;
rarely they are localized on the wrists and on the knees. Generally they are
not accompanied by subjective disturbance, the onset is slow (although we
can occasionally observe a sudden appearance) and the course is chronic, often with spontaneous regression. Occasionally they can be disseminated on
the extremities. The lesions can appear isolated, unified, or follow a linear direction mainly caused by scratching, like the isomorphic irritation effect phenomenon (Koebner’s phenomenon). In general subjective symptoms such as
itching and pain are absent.
214
Diagnosis: clinical manifestations are sufficiently typical to perform diagnosis; biopsy and histological examination.
Differential diagnosis: the differential diagnosis has to be made in confrontation with lichen ruber planus, in which the papules are localized on the
flexor surface of the wrist and forearms, on the trunk and on the oral mucous
membrane: they have polygonal forms, reddish-purple colour, neater margins
and a tougher consistency.
Sometimes the flat wart has to be differentiated from the epidermic cyst, or
from the Pringle adenoma sebaceum or the tuberous sclerosis. Flat warts also have to be distinguished from lichen nitidus, colloid milia and syringoma.
Histopathology: numerous vacuolated (koilocytes) cells can be seen in the
prickle cell layer.
Therapy: often a spontaneous resolution of the pattern is observed.
Cryotherapy or a slight localized electrocoagulation can provide good results.
Topical retinoids are also often used for flat warts. An excessively destructive
method should be avoided as it may be a risk, particularly in the darkskinned population, for hypertrophic or keloid scars. Hypnosis and autosuggestion have also been proposed.
2.6 Common wart (verruca vulgaris)
Synonyms: hard wart, verrugas vulgares, skin papilloma, verrues vulgaires.
Definition: warts are papular epidermic reliefs, moderately contagious, benign, autoinoculable. The aetiologic agent is a virus of the papillomavirus
group, HPV (serotypes most frequently 2, 6).
Distribution. The dermatosis is ubiquitous and very common.
Incubation period: extremely variable, from a few weeks to many months.
Clinical features: at the beginning, warts manifest themselves as small
smooth papular reliefs, pink, irregularly rounded or oval, that appear on normal skin. After a few weeks they grow progressively until reaching the size of
a small nut, making new epidermic formations salient and well localized,
with a variable colour from greyish-pink to yellowish-brown, and of hard
consistency. The dermatosis remains isolated, even for several months.
However, often enough, because of autoinoculation of the virus, the warts
multiply to dozens or, less commonly, to hundreds. Because of the unifications of viral colonies, sometimes we can observe the formation of large verrucous plaques, with typical characteristics difficult to diagnose at a superfi-
215
cial observation. The areas most frequently involved are the dorsum of the
hands and fingers, more rarely the palm and subungual surface. Also the face,
scalp, lips, legs and eyelids can be involved, and more often in children elbows and knees. Usually they are not accompanied by a subjective relevant
symptomatology. The course is chronic and recurrent; occasionally, especially in the case of only one or just a few viral units, we can observe a spontaneous regression. In other cases, we observe continuous recurrences, in spite
of repeated abscissions. Complications are very rare. There can be pyogenic
superimposition, with the formation of small abscess groups. In the periungual region, very painful fissures can be formed.
Diagnosis: usually the diagnosis is not difficult; a biopsy can be useful in unclear cases.
Differential diagnosis: in the lesion localized on the palms, differential diagnosis must exclude papular secondary syphilis and keratotic elements. The
palm and plantar keratoma in small elements (keratoma dissipatum) is distinguished from the verruca vulgaris because it is hereditary and appears in childhood. In the single lesions, which are large and inflamed, present with secondary pyogenic infection, differential diagnosis needs to be made with wart
tuberculosis. Finally, it has to be differentiated from Darier’s disease, molluscum contagiosum, keratoacanthoma, verrucous lichen and cutaneous corns.
Histopathology: We can observe slight parakeratosis, acanthosis, koilocytosis, papillomatosis.
Therapy: spontaneous resolution is possible. Cryotherapy and electrocoagulation are the methods of choice. Podophyllin, phenol and silver nitrate can
be used for small lesions. For multiple warts, a topical treatment (keratolytic, vescicant or cytotoxic agent) can be used, sometimes in association with
an oral immunomodulatory agent. Cimetidine has been reported to be an effective monotherapy in children. An excessively destructive method must be
absolutely avoided given the
risk, frequent in dark-skinned
people, of hypertrophic or
keloid scars formation.
Figure 2.6.1 multiple viral warts.
Particular.
216
2.7 Plantar warts
Synonyms: papilloma of the sole, verrugas plantares, verrues plantarires,
Dornwaezen.
Definition: plantar warts are lesions of viral aetiology. Unlike other forms of
warts, they can cause considerable pain. The aetiologic agent is the papillomavirus, HPV (prevalently serotype 1).
Distribution: very common with generalized distribution.
Clinical features: A particular morphological aspect can be observed depending on the exact location. On the sole of the foot, in fact, they are under continuous pressure and, instead of proliferating on the surface, they proliferate internally. In this way they can determine plug formations that are
able to reach plantar aponeurosis (endophytic development). They are usually located, in particular, on the calcaneum, on the first toe, and in correspondence of the fourth and fifth metatarsus.
Clinically they appear like keratotic flat lesions, of variable dimensions, with
a rounded centre part, grey, rough, disseminated with small black dots. The
surrounding skin has a normal appearance. They can appear as single or as
several units.
The fusion of more plantar warts can lead to the formation of large-sized verrucous plaques (mosaic warts). The pressure on the centre of the wart generates low or intense pain, and can lead to walking difficulties. The plantar
warts generally involve adult subjects, but can also be observed in children.
Spontaneous regression, although rare, is possible.
Diagnosis: clinical manifestations are very suggestive for the diagnosis; biopsy can be performed in unclear cases.
Differential diagnosis: must be made in confrontation with the plantar keratoderma (corn), from which the warts are differentiated by a hyperkeratotic
edge, and an irregular surface, often disseminated with little black dots. Also
it is necessary to differentiate the dystrophic lesion from compression or systemic pathologies (diabetes and vasculopathies), and from the foreign body
granuloma, particularly the ones generated by sea urchins.
Therapy: cryotherapy with liquid nitrogen or electrocoagulation are the chosen treatments. The application of salicylic creams at 10-20 per cent can be
useful too.
217
2.8 Cutaneous manifestations from HIV infections.
Synonyms: Acquired immunodeficiency syndrome, AIDS, syndrome de immunodeficencia adquerida, syndrome de l’immunodeficience acquise, SIDA,
erworbene Immunscheache durch, HIV infection.
Definition: AIDS is a multisystemic disease with a high mortality rate. The
aetiologic agent is the human immunodeficiency virus (HIV).
The immunodepression state in AIDS causes the onset of opportunistic infectious agents of viral, bacterial, protozoan and fungal nature, and in particular of tumours such as Kaposi’s sarcoma and the non-Hodgkin’s lymphomas.
Distribution: the infection and the disease are generalized with a dramatic
spread in the less developed countries, particularly in the sub-Sahara region,
where the number of people infected is more than 20 million. At the end of
1998, according to WHO data, at least 30 million people were infected with
HIV or had developed AIDS; in Botswana and Zimbabwe one person out of
every four is infected. The infection affects drug addicts, in particular those
who have acquired the virus via needle sharing, and is also transmitted
through sexual intercourse. According to the WHO and UNAIDS, 16,000
new HIV-infected cases are registered in the world every day.
Incubation period: very variable, from months to years.
Clinical features: cutaneous
manifestations from HIV infection are very varied; we can observe opportunistic or infectious
diseases, malignant cutaneous
neoplasias, vascular and non malignant hyperproliferative dermatoses, cutaneous dystrophiccarential manifestations.
The dermatosis in HIV-positive
subjects appears to be usually
more diffused and resistant to
therapy.
Figure 3 Typical scars of herpes zoster,
tinea corporis of the neck and multiple molluscum contagiosum of the
face in HIV patient.
218
Diagnosis: diagnosis is determined when HIV test is performed.
Differential diagnosis: non-HIV positive cutaneous infections, such as
atopic dermatitis, seborrhoeic dermatitis, herpes, and epidermomycosis, have
to be taken into consideration.
Therapy: the new anti-retroviral and protease inhibitor drugs seem to improve the course and the prognosis of the infection. The nucleoside reversetranscriptase inhibitors (NRTI), such as zidovudine (AZT, ZDV), were the
first drugs approved for treating HIV-infected individuals. Nevertheless,
ZDV monotherapy demonstrated modest clinical benefits because of the creation of more virulent HIV strains (due to incomplete viral suppression), and
the development of resistance. For that reason, it is commonly used in combination with another antiretroviral agent, i.e. proteinase inhibitors
(saquinavir, ritonavir, indinavir) or non-nucleoside reverse transcriptase inhibitors (nevirapine, delavirdine, loviride). The combination of antiretroviral
drugs offers a better clinical benefit but implies various toxic effects including CNS toxicity, diabetes mellitus, drug reactions (including the StevenJohnson syndrome if the drug is not discontinued). These observations underline the necessity for careful monitoring of all patients undergoing multiple antiretroviral therapy. For cutaneous lesions the treatment is similar to the
non-HIV manifestations.
219
Suggested Readings
Molluscum Contagiosum
1. Bayerl C, Feller G, Goerdt S. Experience in treating molluscum contagiosum in children
with imiquimod 5% cream. Br J Dermatol. 2003 Nov;149 Suppl 66:25-9.
2. Bikowski JB Jr .Molluscum contagiosum: the need for physician intervention and new treatment options. Cutis. 2004 Mar;73(3):202-6.
3. Burke BE, Baillie JE, Olson RD. Essential oil of Australian lemon myrtle (Backhousia citriodora) in the treatment of molluscum contagiosum in children. Biomed Pharmacother.
2004 May;58(4):245-7.
4. Laxmisha C, Thappa DM, Jaisankar TJ. Clinical profile of molluscum contagiosum in children versus adults. Dermatol Online J. 2003 Dec;9(5):1.
5. Lerbaek A, Agner T. Facial eruption of molluscum contagiosum during topical treatment of
atopic dermatitis with tacrolimus.Br J Dermatol. 2004 Jun;150(6):1210-1.
6. Michel JL. Eur J Dermatol. Treatment of molluscum contagiosum with 585 nm collagen
remodeling pulsed dye laser. 2004 Mar-Apr;14(2):103-6.
7. Ross GL, Orchard DC. Combination topical treatment of molluscum contagiosum with
cantharidin and imiquimod 5% in children: a case series of 16 patients. Australas J
Dermatol. 2004 May;45(2):100-2.
8. Sladden MJ, Johnston GA.Common skin infections in children. 2004 Jul
10;329(7457):95-9.
9. Ting PT, Dytoc MT. Therapy of external anogenital warts and molluscum contagiosum: a
literature review. Dermatol Ther. 2004;17(1):68-101. Review.
Varicella
1. Abelardo J. C. Campos, MD Varicella Zoster Virus (VZV) (Chicken pox – Shingles)
http://hopkins-heic.org/infectious_diseases/vzv.htm
2. Bhave SY. Controversies in chicken-pox immunization. Indian J Pediatr. 2003
Jun;70(6):503-7
3. Braun-aflco O., Plewing G., Wolff H.H., Burgdorf W.H.C., Dermatologia, Volume 1
Springer 2002.
4. Core information for the development of immunization policy 2002 update
(WHO/V&B/02.28)
5. Diez-Domingo J, Aristegui J, Calbo F, Gonzalez-Hachero J, Moraga F, Pena GuitianJ,
Ruiz Contreras J, Torrellas A Epidemiology and economic impact of varicella in immunocompetent children in Spain. A nation-wide study.. Vaccine. 2003 Jul 4;21(23):3236-9.
6. Gatchalian S, Tabora C, Bermal N, Leboulleux D, Desauziers E. Immunogenicity and
safety of a varicella vaccine (Okavax) and a trivalent measles, mumps, and rubella vaccine
(Trimovax) administered concomitantly in healthy Filipino children 12-24 months old. Am
J Trop Med Hyg. 2004 Mar;70(3):273-7.
7. Gross G, Schofer H, Wassilew S, Friese K, Timm A, Guthoff R, Pau HW, Malin JP,
Wutzler P, Doerr HW. Herpes zoster guideline of the German Dermatology Society (DDG).
J Clin Virol. 2003 Apr;26(3):277-89; discussion 291-3. Comment in: J Clin Virol.
2003 Aug;27(3):308-9.
8. Ho BC, Tai DY. Severe adult chickenpox infection requiring intensive care. Ann Acad Med
Singapore. 2004 Jan;33(1):84-8.
9. Kuter B, Matthews H, Shinefield H, Black S, Dennehy P, Watson B, Reisinger K, Kim
220
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
LL, Lupinacci L, Hartzel J, Chan I; Ten year follow-up of healthy children who received
one or two injections of varicella vaccine Pediatr Infect Dis J. 2004 Feb;23(2):132-7. Study
Group for Varivax.
Litt J, Burgess M. Varicella and varicella vaccination. An update. Aust Fam Physician.
2003 Aug;32(8):583-7.
Mullooly JP, Maher JE, Drew L, Schuler R, Hu W. Evaluation of the impact of an HMO’s
varicella vaccination program on incidence Vaccine. 2004 Mar 29;22(11-12):1480-5.
Russman AN, Lederman RJ, Calabrese LH, Embi PJ, Forghani B, Gilden DH.
Multifocal varicella-zoster virus vasculopathy without rash. Arch Neurol. 2003
Nov;60(11):1607-9.
S.A. Uduman, A.M. Tahira, R. Al-Wash, M.A. Usmani and A. Bener Varicella susceptibility among children and healthy adults in the United Arab Emirates Eastern
Mediterranean Health Journal vol 7, Nos 4/5, July- September 2001, 604-608.
Salmaso S, Tomba GS, Mandolini D, Esposito N. Assessment of the potential impact in
Italy of extensive varicella vaccination programs based on a mathematical model Epidemiol
Prev. 2003 May-Jun;27(3):154-60.
The WHO Position Paper on Varicella Vaccines
http://www.who.int/vaccines/en/varicella.shtml
Vazquez M, LaRussa PS, Gershon AA, Niccolai LM, Muehlenbein CE, Steinberg SP,
Shapiro ED. Effectiveness over time of varicella vaccine JAMA. 2004 Feb 18;291(7):851-5.
Villarreal EC. Current and potential therapies for the treatment of herpes-virus
infections.Prog Drug Res. 2003;60:263-307.
WHO 1998 Weekly Epidemiological Record N 32 1998, 73, 241-48
Yu HR, Huang YC, Yang KD. Neonatal varicella frequently associated with visceral complications: a retrospective analysis.Acta Paediatr Taiwan. 2003 Jan-Feb;44(1):25-8.
Herpes Zoster
1. Baiker A, Fabel K, Cozzio A, Zerboni L, Fabel K, Sommer M, Uchida N, He D,
Weissman I, Arvin AM.Varicella-zoster virus infection of human neural cells in vivo. Proc
Natl Acad Sci U S A. 2004 Jul 20;101(29):10792-7. Epub 2004 Jul 09.
2. Baron R. Post-herpetic neuralgia case study: optimizing pain control. Eur J Neurol. 2004
Apr;11 Suppl 1:3-11. Review.
3. Berry JD, Rowbotham MC, Petersen KL. Complex regional pain syndrome-like symptoms
during herpes zoster. Pain. 2004 Jul;110(1-2):8-9.
4. Bruggemann BR, Machleidt W. Coenaesthesia after infection with Varicella zoster virus
The psychodynamic meaning of suffering a children’s disease at adult age Nervenarzt. 2004
Jul;75(7):688-90.
5. Casanova Roman G, Reyna Figueroa J, Figueroa Damian R, Ortiz Ibarra J.Herpes zoster
in immunocompetent pregnant women and their perinatal outcome Ginecol Obstet Mex.
2004 Feb;72:63-7.
6. Devulder JE.Postherpetic ophthalmic neuralgia. Bull Soc Belge Ophtalmol.
2002;(285):19-23. Review.
7. Fardon D.From the dermatology clinic...postherpetic neuralgia, in which the source of
radiculopathy is revealed by examination of the skin. Spine J. 2002 Jan-Feb;2(1):85.
8. Johnson RW.Herpes zoster in the immunocompetent patient: management of post-herpetic
neuralgia. Herpes. 2003 Aug;10(2):38-45. Review.
221
9. Katz J, Cooper EM, Walther RR, Sweeney EW, Dworkin RH. Acute pain in herpes zoster
and its impact on health-related quality of life. Clin Infect Dis. 2004 Aug 1;39(3):342-8.
Epub 2004 Jul 19.
10. LeSueur BW, Abraham RJ, DiCaudo DJ, O’Connor WJ. Zosteriform skin metastases.
Int J Dermatol. 2004 Feb;43(2):126-8.
11. Loparev VN, Gonzalez A, Deleon-Carnes M, Tipples G, Fickenscher H, Torfason EG,
Schmid DS. Global identification of three major genotypes of varicella-zoster virus: longitudinal clustering and strategies for genotyping. J Virol. 2004 Aug;78(15):8349-58.
11. Park HH, Lee MH.Concurrent reactivation of varicella zoster virus and herpes simplex
virus in an immunocompetent child. J Korean Med Sci. 2004 Aug;19(4):598-600.
13. Sato-Takeda M, Ihn H, Ohashi J, Tsuchiya N, Satake M, Arita H, Tamaki K, Hanaoka
K, Tokunaga K, Yabe T.The human histocompatibility leukocyte antigen (HLA) haplotype
is associated with the onset of postherpetic neuralgia after herpes zoster. Pain. 2004
Jul;110(1-2):329-36.
14. Shann F. Povidone-iodine for herpes zoster. Lancet. 2004 Aug 7;364(9433):502.
Herpes Simplex
1. Edmiston N, O’Sullivan M, Charters D, Chuah J, Pallis L. Study of knowledge of genital herpes infection and attitudes to testing for genital herpes among antenatal clinic attendees. Aust N Z J Obstet Gynaecol. 2003 Oct;43(5):351-3.
2. Feldman PA, Steinberg J, Madeb R, Bar G, Nativ O, Tal J, Srugo I. Herpes simplex virus
type 2 seropositivity in a sexually transmitted disease clinic in Israel. Isr Med Assoc J. 2003
Sep;5(9):626-8.
3. Manavi K, McMillan A, Ogilvie M.Herpes simplex virus type 1 remains the principal cause
of initial anogenital herpes in Edinburgh, Scotland. Sex Transm Dis. 2004
May;31(5):322-4.
4. Solomon L, Cannon MJ, Reyes M, Graber JM, Wetherall NT, Reeves WC; Task Force
on Herpes Simplex Virus Resistance. Epidemiology of recurrent genital herpes simplex virus
types 1 and 2. Sex Transm Infect. 2003 Dec;79(6):456-9.
5. Song B, Dwyer DE, Mindel A.HSV type specific serology in sexual health clinics: use, benefits, and who gets tested. Sex Transm Infect. 2004 Apr;80(2):113-7.
6. Sulak PJ. Sexually transmitted diseases. Semin Reprod Med. 2003 Nov;21(4):399-413.
7. Theng TS, Chan RK.Genital herpes in a sexually-transmitted infection clinic in Singapore:
a 1-year retrospective study. Ann Acad Med Singapore. 2004 Mar;33(2):200-3.
8. Uuskula A, Raukas E. Atypical genital herpes: report of five cases. Scand J Infect Dis.
2004;36(1):37-9.
9. Weiss H.Epidemiology of herpes simplex virus type 2 infection in the developing world.
Herpes. 2004 Apr;11 Suppl 1:24A-35A.
Verrucae Planae
1. Ciconte A, Campbell J, Tabrizi S, Garland S, Marks R. Warts are not merely blemishes on
the skin: A study on the morbidity associated with having viral cutaneous warts. Australas J
Dermatol. 2003 Aug;44(3):169-73.
2. Gustafsson L, Leijonhufvud I, Aronsson A, Mossberg AK, Svanborg C. Treatment of skin
papillomas with topical alpha-lactalbumin-oleic acid. N Engl J Med. 2004 Jun
24;350(26):2663-72.
222
3. Stulberg DL, Hutchinson AG. Molluscum contagiosum and warts. Am Fam Physician.
2003 Mar 15;67(6):1233-40. Review.
4. Stulberg DL, Hutchinson AG.Oster-Schmidt C. Imiquimod: a new possibility for treatment-resistant verrucae planae. Arch Dermatol. 2001 May;137(5):666-7.
Verrucae Vulgares
1. Andrews MD. Cryosurgery for common skin conditions. Am Fam Physician. 2004 May
15;69(10):2365-72.
2. Sidbury R. What’s new in pediatric dermatology: update for the pediatrician.
Curr Opin Pediatr. 2004 Aug;16(4):410-414.
3. Sladden MJ, Johnston GA. Common skin infections in children. BMJ. 2004 Jul
10;329(7457):95-9. Review.
4. Weisshaar E, Gollnick H. Potentiating effect of imiquimod in the treatment of verrucae vulgares in immunocompromised patients. Acta Derm Venereol. 2000 Jul-Aug;80(4):306-7.
Verrucae Plantares
1. Rigo MV, Martinez-Campillo F, Verdu M, Cilleruelo S, Roda J. Risk factors linked to the
transmission of papilloma virus in the school environment. Alicante, 1999 Aten Primaria.
2003 Apr 30;31(7):415-20.
2. Soroko YT, Repking MC, Clemment JA, Mitchell PL, Berg L. Treatment of plantar verrucae using 2% sodium salicylate iontophoresis. Phys Ther. 2002 Dec;82(12):1184-91.
3. Tucker SB, Ali A, Ransdell BL. Plantar wart treatment with combination imiquimod and
salicylic acid pads. J Drugs Dermatol. 2003 Jan;2(1):70-2. Corrected and republished in:
J Drugs Dermatol. 2003 Apr;2(2):124-6.
4. Yesudian PD, Parslew RA. Treatment of recalcitrant plantar warts with imiquimod.
J Dermatolog Treat. 2002 Mar;13(1):31-3.
Signs of HIV Infection on the skin
1. Baniandres Rodriguez O, Nieto Perea O, Moya Alonso L, Carrillo Gijon R, Harto
Castano A. Nodular secondary syphilis in a HIV patient mimicking cutaneous lymphoma a
An Med Interna. 2004 May;21(5):241-3.
2. Dezube BJ, Pantanowitz L, Aboulafia DM. Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment. AIDS Read. 2004 May;14(5):236-8, 2434, 251-3. Review.
3. Liguori G, Trombetta C, Bucci S, De Seta F, De Santo D, Siracusano S, Belgrano E.
Condylomata acuminata of the neovagina in a HIV-seropositive male-to-female transsexual.
Urol Int. 2004;73(1):87-8.
4. Morrison C, Eliezri Y, Magro C, Nuovo GJ. The histologic spectrum of epidermodysplasia
verruciformis in transplant and AIDS patients. J Cutan Pathol. 2002 Sep;29(8):480-9.
5. Onyango JF, Njiru A. Kaposis sarcoma in a Nairobi hospital. East Afr Med J. 2004
Mar;81(3):120-3.
6. Trent JT, Kirsner RS. Cutaneous manifestations of HIV: a primer. Adv Skin Wound Care.
2004 Apr;17(3):116-27; quiz 128-9. Review.
Tzung TY, Yang CY, Chao SC, Lee JY. Cutaneous manifestations of human immunodeficiency virus infection in Taiwan. Kaohsiung J Med Sci. 2004 May;20(5):216-24.
5. Sexually transmitted infections
223
5. SEXUALLY TRANSMITTED INFECTIONS
Aldo Morrone, Luigi Toma
In this chapter, in addition to the condyloma acuminatum (veneraal warts),
the five classical venereal diseases will be taken into consideration:
• Syphilis
• Gonococcal urethritis
• Venereal ulcer
• Venereal Lymphogranuloma
• Granuloma genito-inguinale (granuloma pudenda chronicum) or
donovaniosis
11.1 Syphilis
Synonyms: lues venereal, great pox, morbus gallicus, sifilis, lustseuche.
Definition: chronic treponematosis, transmitted by sexual contact, caused by
treponema pallidum. The disease is characterized by some well-defined stages:
primary and secondary syphilis, highly contagious; latent syphilis that accompanies different destructive lesions; tertiary syphilis, very rare nowadays.
In the early and late forms we can observe congenital syphilis.
Distribution: universal, involves principally youngsters between 15 and 30
years old. The disease is more frequent in the urban than in the rural areas,
and greater in men than in women, with a particular frequency in the harbour zones.
Incubation period: about 3 weeks for acquired primary syphilis.
Clinical features: The primary lesion, the syphiloma, appears at the inoculation site in the form of an eroded papule, non-painful, reddish, with a hard
base and well-defined margins, often with raised borders and associated wiht
lymphadenopathy.
After about 6–8 weeks from the onset of the primary lesion, the disease progresses into the second stage, with very variable clinical manifestations. Often
general symptoms are present. Macular lesions, roseola syphilitica, are symmetrically distributed, almost always located on the trunk; they are nonitchy, pale pink, indistinguishable on dark skin. In very dark skinned women
the roseola syphilitica can emerge following discovery of a leukoderma on the
neck (Venus collar or leukoderma colli).
224
Secondary syphilis is similar to many dermatoses., Eruption can be macular,
maculous-papulous, papulous-squamous, varioliform, herpetiform, varicelliform or condylomatous. We can observe alopecia at scalp level.
Lymphadenopathy is common.
The latent period of acquired syphilis lasts less than 4 years in latent early
syphilis, and more than 4 years in latent late syphilis.
Tertiary syphilis appears between 5 and 30 years after the initial infection.
This involves cardiovascular, nervous and cutaneous system alterations.
Lesions are of a nodular type, nodulo-ulcerative, or gummous. Characteristic
is an arch form configuration of the lesion with a scarring result. Joint nodules are rare and identical to the yaws and endemic syphilis ones.
Congenital early syphilis develops before 2 years of age and resembles secondary syphilis. Late congenital syphilis can be observed around the second year
of age, and involves destructive lesions such as Hutchinson’s triad, sabre tibia or saddle nose.
Fig. 3.1.3. Secondary
syphilis. Plantar
syphiloderma
Diagnosis: dark background examination is essential for primary seronegative syphilis. Primary and secondary syphilis are confirmed by dark background examination or during the exudates contrast phase of the lesion or of
the lymph nodes aspirate. The most common serological tests become positive 4–8 weeks later with respect to the initial exposure to the infection. Tests
225
without treponemal antigens have to be supported by tests that use treponemal antibodies, such as TPHA (Treponema pallidum haemagglutination test)
or FTA-ABS test (fluoroscent treponemal antibody absorption).
Differential diagnosis: syphilis can resemble many dermatoses. Primary
syphilis has to be differentiated from herpes progenitalis; venereal ulcer, scabies, venereal lymphogranuloma, granuloma genito-inguinale, lichen planus,
psoriasis, Bechet’s syndrome, Reiter’s syndrome. Secondary syphilis has to be
differentiated from measles, pytiriasis rosea, psoriasis guttata, lichen planus,
yaws, seborrhoeic dermatitis, circinate tinea, erythema multiforme, chickenpox, impetigo. Tertiary syphilis can be confused with tuberculosis, leprosy,
deep mycosis, carcinoma. Early congenital syphilis has to be differentiated
from napkin erosive dermatitis, bullous impetigo, toxic epidermic necrolysis
and Stevenson-Johnson’s syndrome.
Histopathology: histopathological venereal syphilis alterations are the same
as those observed in endemic syphilis.
Therapy: Intramuscular penicillin remains the antimicrobial treatment of
choice for all patients who are not hypersensitive to it. The aim is to maintain a prolonged low and continuous concentration of the drug in the tissues.
There is no evidence of development of resistance by T. pallidum to penicillin. It is advisable to apply, for each single region, the therapeutic protocols
suggested by the WHO and by the respective national health services, summarized as follows:
P.S.,S.S., E.L.S.
L.L.S., cardiovascular
Syphilis
N.S., ocular syphilis
Procaine
penicillin
1 200 000 U i.m.
Number
of days
Alternative
treatment
10
1.200 000 U i.m. +
probenecid 500mg
4 times/day
15
2 400 000 U i.m. +
probenecid 500mg
4 times/day
20
Number
of days
! Doxycycline 100mg ! Doxycycline 100mg ! Doxycycline 100mg
twice/day
twice/day
twice/day
! Tetracycline 500mg ! Tetracycline 500mg ! Tetracycline
3 times/day
4 times/day
4 times/day
! Erythromycin 500mg ! Erythromycin 500mg ! Erythromycin 500mg
4 times/day
4 times/day
4 times/day
15
15
28
P.S.= primary syphilis, S.S= secondary syphilis, E.L.S= early latent syphilis, L,L,S,= late latent syphilis, N.S.= neurosyphilis
226
A recent, but controversial study, demonstrated the potential benefit of
azithromycin. Cephalosporins may show cross-reactivity with penicillin in allergic patients. Additionally, it must be taken into consideration that:
a) Doxycicline and tetracycline cannot be used during pregnancy and lactation.
b) Steroid cover with Prednisolone 30mg daily is recommended to prevent
Jarish Herxheimer reaction in the treatment of cardiovascular, ocular and
neurosyphilis.
c) Babies delivered by women with syphilis should be treated with Procaine
Penicillin 50.000 units/kg i.m. daily for 15 days in cases where the mother had not been treated with penicillin during gestation.
d) Some authors sustain that Benzathine Penicillin 2 400 000 U i.m. weekly for 3 weeks is a less ideal regimen, because it does not achieve levels sufficient to prevent CNS involvement. Nevertheless, its administration is
most useful, especially in those cases when it is doubt ful that the patient
will return for follow up.
e) It is necessary to educate patients with regard to preventive behaviour, encouraging the use of condoms and advising treatment to partners of infected individuals.
3.2 Gonorrhea
Synonyms: blenmorrhoea, gonococcia, blenorrhagie, tripper, gonoccoccal
utethritis, blennorrhagia.
Definition: acute or chronic infection due to the Neisseria gonorrhoeae, usually sexually transmitted. It usually concerns the mucous membrane of the
genital and anal areas.
Distribution: general, more frequent in subjects with promiscuous sexual
habits.
Incubation period: usually varies between 2 and 6 days after sexual intercourse, sometimes longer.
Clinical features: after a slightly painful burning sensation, a urethral purulent secretion appears.
In women, the disease is often asymptomatic. Rectal infections are not rare and
provoke an inflammatory swelling of the mucosa, with a mucopurulent secretion. Neonatal gonococcal ophthalmia is caused by infection contracted during birth and manifests itself with a purulent secretion located on the eyelids.
227
Cutaneous manifestations
are rare and can manifest
themselves as papular erythematous lesions, urticated, bullous or purpuric.
Balanitis and balanoposthitis are rarely observed.
Ulceration is extremely
rare. Systemic complications such as gonococcal
gastritis are more frequent
in women. In young girls it
is possible to observe a
painful
vulvovaginitits,
with the presence of a purulent grey secretion.
Figure 3.2.1 gonococcal urethritis: acute form with purulent secretion
Diagnosis: Gram’s stain of the secretion is sufficient for diagnosis (Neisseria
is Gram negative); confirmation derives from culture examination.
Differential diagnosis: has to be made in confrontation with the other urethral secretions present in aspecific urethritis, trichomoniasis, Reiter’s syndrome, venereal lymphogranuloma and syphilis.
Therapy: in penicillin sensitive patients, the following drugs can be used: spiramycin, in single 2.5g dose, or 4–12g divided in 2 days; kanamycin in single dose of 2g i.m.; rifampin single dose 900–1200 mg i.m.; tetracycline, oxytetracycline and erythromycin, 2g the first day, followed by 0.5g 4 times a
day for 5 days; gentamycin sulphate single dose 200mg i.m; spectinomycin
single dose, 4mg i.m.
228
3.3 Chancroid
Synonyms: soft chancre, ulcus molle, Ducrey’s disease, chancro blando, chancrelle, weicher schanker.
Definition: acute autoinoculative venereal infection, caused by the
Haemophilus Ducreyi, characterized by ulceration and a painful inflammatory oedema. The disease is accompanied by regional suppurative adenopathy.
Distribution: worldwide, with high frequency in tropical and sub-tropical
regions, especially in harbours and big cities.
Incubation period: from between 2-5 days to 2-3 weeks; in traumatized mucous linings incubation period is reduced to 24 hours.
Clinical features: a macular lesion that rapidly evolves to pustule is observed.
Its rupture leads to the formation of a shallow ulcer, on an erythematous base.
Multiple ulcerative lesions can be formed through autoinoculation. A frequent complication is represented by suppurative inguinal adenitis called
bubo, which appears 1-2 weeks following the initial lesion. The disease becomes chronic if not treated, and healing leaves a scar at the site of the ulcer
or at the suppurative inguinal adenitis sites.
Diagnosis: chancroid is distinguished by the characteristic rapid onset of
shallow ulcers followed by suppurative inguinal adenitis. Pain is a diagnostic
sign. Isolation of Haemophilus Ducreyi from the secretions and the intradermal test with Ducreyi’s serum are specific.
Differential diagnosis: has to be differentiated from numerous dermatoses:
syphilis, pyoderma, herpes progenitalis, venereal lymphogranuloma and cutaneous amoebiasis.
Therapy: rapid action sulpha drugs such as sulpho-diazine 1g 4 times daily
for 7-14 days, in any case until complete recovery. In the case of secondary
infections with fuso-spirochetal micro organisms, penicillin or other antibiotics are indicated. Patients allergic to sulpha drugs can be treated with tertracyclines, oxytetracyclines and erythromycin, 500mg 4 times daily until
complete recovery. Repeated serological syphilis tests are indispensable.
229
3.4 Lymphogranuloma venereum
Synonyms: Nicolas-Favre’s disease, lymphogranuloma inguinale, venereal
lymphopathy, climatic bubo, enfermedad de Nicolas y Favre, maladie de
Nicolas-Favre, poradenitis, vierte geschlechtskrankheit.
Definition: sexually transmitted disease, with acute or chronic manifestations, of the inguinal and ano-rectal lymphatic vessels or other tissues, caused
by specific Chlamidia trachomatis serotypes.
Distribution: world-wide, but can be observed especially in the tropical and
sub-tropical regions, with a higher frequency in cities and harbours, particularly in subjects with promiscuous sexual habits.
Incubation period: for the primary lesion, 5-21 days; inguinal suppurative
adenitis appears 2-3 weeks later.
Clinical features: primary lesion is represented, usually, by an erosion located in the genitals or in the anal region, or inside the urethra, where it can produce a gonorrhoea-like secretion. Primary lesion disappears before the inguinal adenitis develops.
The inguinal adenopathy is often unilateral; femoral and iliac glands can be
involved. Frequently we can observe suppurative phenomena.
Recovery can be achieved only after several months; the disease if not treated
is self-limited. The ano-recto-genital syndrome is the chronic manifestation
of the disease. We can observe also elephantiasis of penis and vulva.
Diagnosis: direct search or cultural examination for Chlamydia.
Differential diagnosis: primary lesion has to be differentiated from herpes
simplex, syphilis, chancroid and pyoderma; the inguinal adenopathic syndrome has to be differentiated from tuberculosis, syphilis South American
blastomycosis, inguinal actinomycosis, carcinoma, cat scratch disease, inguinal granuloma, amoebiasis, haemorrhoids, filariasis, ulcerative colitis, and
tuberculosis.
Therapy: Recommended treatment is with doxycycline (100mg PO bid) or
erythromycin (500mg qid). Continue treatment for 3 weeks, combined with
aspiration of the lymph nodes if needed. Incision and drainage may result in
non-healing fistula formation, which can be minimized by draining involved
lymph nodes from above the inguinal ligament. Symptomatic treatment with
nonsteroid anti-inflammatory drugs (NSAIDs) and local heat for pain relief
may be useful adjuncts. Surgery is ofte necessary for repair of late
230
3.5 Donovanosis
Synonyms: Granuloma inguinale, granuloma venereum, granuloma pudenda chronicum, granulome vénérien, veneriches granulom.
Definition: skin and mucous membrane disease of the anal and genital regions, moderately chronic, infectious and autoinoculable, caused by the
Calymmatobacterium granulomatis and probably transmitted by direct contact with active lesions during sexual intercourse.
Distribution: primarily observed in the tropical and sub-tropical countries,
more common in men than in women.
Incubation period: not known with precision, it is presumed to be between
a few days and 2-3 months.
Clinical features: in many cases the initial lesion is located on the genitals
and appears as a blister, an erosion or a papule. Subsequently it transforms into a nodule, with a granulomatous
easy bleeding surface. The diffusion of
the lesions is very slow, but in the
space of a few years can cover a vast
area. The dermatosis is preferably located on hot-humid surfaces. The
lymph glands system is never involved. If not treated the lesions can
expand considerably, producing destruction of the genital organs and formation of destructive scars, which can
irreversibly compromise the anal region. The disease is frequently associated with cellulo-squamous carcinoma
of the penis.
Figure 1 Ulcerative lesions of the penis in
donovanosis
Diagnosis: the typical granulomatous reddish-brown coloured lesions in the
genital and moist zones, the absence of swollen lymph glands and the chronic course of the infection allow for an easy diagnosis. Giemsa’s stain of
Donovan’s bodies in the granulomatous lesions is a specific, but not always
simple, demonstration. Complement-fixation test can be useful.
231
Differential diagnosis: in the early lesions we have to exclude syphilis. In the
more advanced cases, the disease has to be differentiated from lupus vulgaris,
blastomycosis, lymphogranuloma venereum (esthioméne), cutaneous amoebiasis, genital schistosomiasis and inguinal carcinoma.
Therapy: the chosen therapy is represented by wide-spectrum antibiotics, especially tetracycline, oxytetracyclyne, chlortetracycline, doxicycline. Preferred
dosage: for tetracycline, 500mg 4 times daily 2–3 weeks, and for doxicycline,
100mg twice daily for 4 weeks. In the rare relapsing cases, treatment has to
be repeated for a much longer period. Formation of scars and the eventual
formation of fistulas may require surgery.
3.6 Condylomata acuminata (anogenital warts)
Synonyms: acuminate warts, venereal warts, moist warts, verrugas acuminata, vegetations vènèrienne, cretes de coq, Feigwarzen, venerische Warzen.
Definition: common warts modified by moistness on the flexing surfaces,
particularly in the anogenital regions. It is caused by the papillomavirus
agent, prevalent serotypes HPV 6, 11, 16, 18.
Distribution: worldwide; more common in young adults of both sexes.
Incubation period: from some weeks to many months.
Clinical features: anogenital warts are usually multiple and evolve progressively, with a cauliflower-like growth. The colour varies from pink to grey.
Infection is usually accompanied by a characteristic smell. Children are rarely
concerned; in these cases it is necessary to investigate eventual sexual abuses.
The lesions can be often associated with gonorrhoea, but the term “venereal
warts” is not correct.
Diagnosis: clinical manifestations are pathognomonic, in non-clear cases
biopsy can be useful.
Differential diagnosis: have to be differentiated by the pemphigus vegetans,
limphogranuloma venereum, carcinoma penis et vulva, hidradenoma papillarum.
Histopathology: reduced layer corneum, acanthosis, papillomatosis.
Therapy:
A) Common
1) Caustics/acids: Salicylic acid, lactic acid, monochloroacetic acid,
bichloroacetic acid, trichloroacetic acid, nitric acid, and others.
232
2) Cantharidin
3) Podophyllin resin: Especially in anogenital HPV. A purified form of
this resin containing podofilox as 0.5% solution is available.
4) Tretinoin
5) Bleomycin: Intralesional
6) 5-Fluorouracil: Topical
B) Less common
1) Oral etretinate or vitamin A
2) X-ray: Not in laryngeal papillomatosis or epidermodysplasia verruciformis
3) Heat and tape occlusion
C) Evolving treatments
a) Photodynamic therapy
b) Pulsed dye, Q-switched, and copper vapour lasers, which are directed
at the vascular component of the wart, may be useful.
c) Induction of delayed-type hypersensitivity (e.g., squaric acid
dibutylester, topical Rhus, intralesional tuberculin, dinitrochlorobenzene)
d) Colchicine, cimetidine
e) Interferon alfa: Intralesional or intramuscular
D) Surgical treatment
The listed treatments may be used alone, in combination with each other, or in combination with other non-surgical modalities.
a) Common
(1) Cryosurgery
(2) Carbon dioxide slush (dry ice and acetone)
(3) Electrosurgery & curettage
(4) Blunt dissection
(5) Carbon dioxide laser may be used for the treatment of extensive,
recurrent, or resistant warts. It may be used in conjunction with
other modalities including electrosurgical debulking, interferon,
and/or postoperative 5-fluorouracil.
b) Less common
233
Suggested Readings
Sexually transmitted Diseases
1. Baldwin HE. STD update: screening and therapeutic options. Int J Fertil Womens Med.
2001 Mar-Apr;46(2):79-88.
2. Ballard RC, Fehler HG, Htun Y, Radebe F, Jensen JS, Taylor-Robinson D. Coexistence
of urethritis with genital ulcer disease in South Africa: influence on provision of syndromic
management. Sex Transm Infect. 2002 Aug;78(4):274-7.
3. Cachay E, Mar-Tang M, Mathews WC. Screening for Potentially Transmitting Sexual Risk
Behaviors, Urethral Sexually Transmitted Infection, and Sildenafil Use Among Males
Entering Care for HIV Infection. AIDS Patient Care STDS. 2004 Jun;18(6):349-54.
4. Calmet M, Dominguez A, Barrabeig I, Sanz B, Armengol P, Boronat J. Sexually transmitted diseases. Evaluation of the objectives of the Health Plan for Catalonia for the year
2000. Med Clin (Barc). 2003;121 Suppl 1:87-93.
5. Connell P, McKevitt C, Low N. Investigating ethnic differences in sexual health: focus
groups with young people. Sex Transm Infect. 2004 Aug;80(4):300-5.
6. Hollier LM, Workowski K. Treatment of sexually transmitted diseases in women.
Obstet Gynecol Clin North Am. 2003 Dec;30(4):751-75.
7. Law DC, Serre ML, Christakos G, Leone PA, Miller WC. Spatial analysis and mapping
of sexually transmitted diseases to optimise intervention and prevention strategies. Sex
Transm Infect. 2004 Aug;80(4):294-9.
8. Lowndes CM, Fenton KA. Surveillance systems for STIs in the European Union: facing a
changing epidemiology. Sex Transm Infect. 2004 Aug;80(4):264-71.
9. Ly F, Mahe A. Fighting principles against sexually transmitted infections in tropical areas
10. Richens J. Main presentations of sexually transmitted infections in men. BMJ. 2004 May
22;328(7450):1251-3. Review.
11. Schippers EF, van Dam AP, Lavrijsen AP. Sharp increase in the number of syphilis cases in
The Netherlands: early recognition and treatment is of great importance Ned Tijdschr
Geneeskd. 2004 Jun 19;148(25):1221-6.
12. Schneede P, Tenke P, Hofstetter AG. Urinary Tract Infection Working Group of the Health
Care Office of the European Association of Urology. Sexually transmitted diseases (STDs -a
synoptic overview for urologists. Eur Urol. 2003 Jul;44(1):1-7.
13. Takahashi S, Takeyama K, Kunishima Y, Shimizu T, Nishiyama N, Hotta H, Matsukawa
M, Minowa M, Tanihata T, Kumamoto Y, Tsukamoto T. Incidence of sexually transmitted
diseases in Hokkaido, Japan, 1998 to 2001. J Infect Chemother. 2004 Jun;10(3):163-7.
14. White C. Sexually transmitted diseases continue to rise. BMJ. 2004 Jul 31;329(7460):249.
15. Wimberly YH, Hogben M. Physicians’ STD diagnosis and screening practices in the South.
South Med J. 2004 Jul;97(7):624-30.
Syphilis
1. Bonnetblanc JM. Syphilis Ann Dermatol Venereol. 2004 May;131(5):513-5.
2. Centers for Disease Control and Prevention (CDC) Congenital syphilis-United States,
2002. MMWR Morb Mortal Wkly Rep. 2004 Aug 13;53(31):716-9.
3. Centers for Disease Control and Prevention (CDC). Trends in primary and secondary
234
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
syphilis and HIV infections in men who have sex with men-San Francisco and Los Angeles,
California, 1998-2002. MMWR Morb Mortal Wkly Rep. 2004 Jul 9;53(26):575-8.
Dobson S.Congenital syphilis resurgent. Adv Exp Med Biol. 2004;549:35-40.
Dupin N. The return of syphilis. Ann Dermatol Venereol 2002; 129:849-51.
Funnye AS, Akhtar AJ. Syphilis and human immunodeficiency virus co-infection. J Natl
Med Assoc. 2003; 95:363-82
Hook EW 3rd, Peeling RW. Syphilis control-a continuing challenge. N Engl J Med. 2004
Jul 8;351(2):122-4.
Ibarra V, Oteo JA. Syphilis again? Med Clin. 2003; (8) 120:295-6.
Kalb C. An old enemy is back. Newsweek, 2003; 141:60.
Knell RJ. Syphilis in renaissance Europe: rapid evolution of an introduced sexually transmitted disease? Proc R Soc Lond B Biol Sci. 2004 May 7;271 Suppl 4:S174-6.
Krug EG et al. The global buden of inijuries. Am J Public Health 2000; 90:523-6.
Lukehart SA, Godornes C, Molini BJ, Sonnett P, Hopkins S, Mulcahy F, Engelman J,
Mitchell SJ, Rompalo AM, Marra CM, Klausner JD. Macrolide resistance in Treponema
pallidum in the United States and Ireland. N Engl J Med. 2004 Jul 8;351(2):154-8.
St. Louis ME, Wasserheit JN. Elimination of syphilis in the United States. Science 1998;
281:353
Stephenson J. Syphilis outbreak sparks concerns. JAMA 2003; 289:974.
Gonorrhea
1. Berglund T, Colucci B, Lund B, Qvarnstrom I, Sandstrom E. Increasing incidence of
ciprofloxacin resistant gonorrhea in Sweden. Choose a correct antibiotic and follow up the
treatment! Lakartidningen. 2004 Jul 8;101(28-29):2332-5.
2. De P, Singh AE, Wong T, Yacoub W, Jolly AM. Sexual network analysis of a gonorrhoea
outbreak. Sex Transm Infect. 2004 Aug;80(4):280-5.
3. Eickhoff M, Laue T, Ruckes T, Cramer SO, Krupp G, Tiemann C. Ultra-rapid detection
of Chlamydia trachomatis by real-time PCR in the LightCycler using SYBR green technology
or 5’-nuclease probes. Clin Lab. 2003;49(5-6):217-25.
4. Howie F, Young H, McMillan A. The diversity of the opa gene in gonococcal isolates from
men who have sex with men. Sex Transm Infect. 2004 Aug;80(4):286-8.
5. Manhart LE, Aral SO, Holmes KK, Critchlow CW, Hughes JP, Whittington WL,
Foxman B. Influence of Study Population on the Identification of Risk Factors for Sexually
Transmitted Diseases using a Case-Control Design: The Example of Gonorrhea. Am J
Epidemiol. 2004 Aug 15;160(4):393-402.
Conddyloma
1. Dunne EF, Burstein GR, Stone KM. Anogenital human papillomavirus infection in males.
Adolesc Med. 2003 Oct;14(3):613-32. Review.
2. Georgala S, Katoulis AC, Georgala C, Bozi E, Mortakis A. Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the cervix: a randomised placebo controlled
trial. Sex Transm Infect. 2004 Jun;80(3):216-8.
3. Kameoka H, Kojima Y, Okuni T. Intraurethral condyloma acuminatum: a case report
Hinyokika Kiyo. 2004 Jun;50(6):409-11.
235
4. Myhre AK, Dalen A, Berntzen K, Bratlid D. Anogenital human papillomavirus in nonabused preschool children. Acta Paediatr. 2003 Dec;92(12):1445-52.
5. Parise P, Sarzo G, Finco C, Marino F, Savastano S, Merigliano S. Giant condyloma acuminatum of the anorectum (Buschke-Lowenstein tumour): a case report of conservative surgery.
Chir Ital. 2004 Jan-Feb;56(1):157-61.
6. Richens J. Main presentations of sexually transmitted infections in men. BMJ. 2004 May
22;328(7450):1251-3.
Chancroid
1. Bruisten SM. Genital ulcers in women. Curr Womens Health Rep. 2003 Aug;3(4):28898. Review.
2. Kulkarni K, Lewis DA, Ison CA. Expression of the cytolethal distending toxin in a geographically diverse collection of Haemophilus ducreyi clinical isolates. Sex Transm Infect. 2003
Aug;79(4):294-7.
3. Kyriakis KP, Hadjivassiliou M, Paparizos VA, Flemetakis A, Stavrianeas N, Katsambas A.
Incidence determinants of gonorrhea, chlamydial genital infection, syphilis and chancroid in
attendees at a sexually transmitted disease clinic in Athens, Greece. Int J Dermatol. 2003
Nov;42(11):876-81.
4. Mbwana J, Ahmed HJ, Ahlman K, Sundaeus V, Dahlen G, Lyamuya E, Lagergard T.
Specificity of antibodies directed against the cytolethal distending toxin of Haemophilus
ducreyi in patients with chancroid. Microb Pathog. 2003 Sep;35(3):133-7.
5. Nikkels AF, Arrese JE, Pierard GE. Image of the month. Chancroid Rev Med Liege. 2003
Feb;58(2):64-6.
Lynphogranuloma Venereum
1. Gotz HM, Ossewaarde JM, Nieuwenhuis RF, van der Meijden WI, Dees J, Thio B, de
Zwart O, van de Laar MJ. A cluster of lymphogranuloma venereum among homosexual men
in Rotterdam with implications for other countries in Western Europe. Ned Tijdschr
Geneeskd. 2004 Feb 28;148(9):441-2.
2. Jutras I, Abrami L, Dautry-Varsat A. Entry of the lymphogranuloma venereum strain of
Chlamydia trachomatis into host cells involves cholesterol-rich membrane domains. Infect
Immun. 2003 Jan;71(1):260-6.
3. Ly F, Mahe A, Samb N. Lymphogranuloma venereum Ann Dermatol Venereol. 2002 AugSep;129(8-9):1082-3.
4. Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect. 2002
Apr;78(2):90-2. Review.
5. Nieuwenhuis RF, Ossewaarde JM, van der Meijden WI, Neumann HA. Unusual presentation of early lymphogranuloma venereum in an HIV-1 infected patient: effective treatment
with 1 g azithromycin. Sex Transm Infect. 2003 Dec;79(6):453-5.
Granuloma Inguinale
1. Bernal Ruiz AI, Gonzalez Ruiz A, Gutierrez Rodriguez C, Garcia Munoz M.
Donovanosis: increased incidence in our setting as a result of imported cases from endemic areas. An Med Interna. 2002 Feb;19(2):103-4.
236
2. Birley H, Duerden B, Hart CA, Curless E, Hay PE, Ison CA, Renton AM, Richens J,
Wyatt GB. Sexually transmitted diseases: microbiology and management. J Med Microbiol.
2002 Oct;51(10):793-807. Review.
3. CDC. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control
and Prevention. MMWR Recomm Rep. 2002 May 10;51(RR-6):1-78.
4. Morrone A, Franco G, Toma L. Latini O. Donovanosis in developed countries: neglected or misdiagnosed disease? Int J STD AIDS. 2003 Apr;14(4):288-9.
5. National guideline for the management of donovanosis (granuloma inguinale).
Clinical Effectiveness Group (Association of Genitourinary Medicine and the
Medical Society for the Study of Venereal Diseases). Sex Transm Infect. 1999 Aug;75
Suppl 1:S38-9.
6. O’Farrell N. Donovanosis. Sex Transm Infect. 2002 Dec;78(6):452-7. Review.
7. O’Farrell N. Donovanosis: an update. Int J STD AIDS. 2001 Jul;12(7):423-7.
6. Tropical treponematoses
237
6. TROPICAL TREPONEMATOSES
Aldo Morrone, Gennaro Franco
Endemic treponematosis (pinta, yaws, endemic syphilis) have in common
some characteristic aspects: they are all caused by spirochetes and can all be
observed in rural regions of countries with very hot climates countries. The
transmissions of these diseases is non-venereal and by direct contact.
Children and adolescents are more frequently affectedinterested. Lesions occur in extra-genital localizations.
They are chronic diseases and evolve in successive clinical stages. There are no
congenital manifestations. Treponematosis are seroresistant in advanced
stages. Concerning geographic distribution, we can observe important differences: yaws is present in all the hot-humid tropical countries; pinta is endemic in the hot-humid areas between Mexico and Amazonia; endemic syphilis
is usually present in small areas with arid climate in Africa and Asia, while it
has been completely eradicated from Europe and Australia.
10.1 Yaws
Synonyms: Framboesia, buba, parangi, epian, gangosa, rynopharyngitis mutilans, pian, frambosie.
Definition: chronic contagious treponematosis, endemic, caused by the epidermotropic agent Treponema pertenue. It is characterized by three stages:
primary, with an ulcer or an initial granuloma (mother yaws); secondary,
with hypertrophic granulomatous lesions; tertiary or late stage, with destructive lesions.
Distribution: frequent in all the tropical humid regions; it i’s considered a
childhood disease.
Incubation period: about 3-4 weeks; initial lesions occur in correspondence
of the site of infection.
Clinical features: Pprimary yaws is characterized by an erythematous, papillomatous, vegetant lesion, covered by a thin yellow crust, and accompanied
by regional adenopathy, with low general symptomatology (mother yaws).
The lesion persists for several months and heals spontaneously.
Secondary stage develops about 6-12 weeks later after the initial lesion has
appeared, with a generalized cluster eruption and systemic symptomatology.
238
The number and characteristic of clinical lesions are very variable. Lesions
can be macular, papular, papillomatous, papulo-quamous or rupioid; generally they are symmetrically distributed. The mucocutaneous regions of the
mouth, of the nose, of the anogenital areas, are also very frequently involved.
Lesions localized on the plantar surface are very painful (crab yaws).
Secondary stage bone lesions, are very common in children: osteoperiostitis
with tibial deformation and polydactylia. The hypertrophy of the nasal bone
is the cause of goundou. Contractures of fifth, fourth, and later of the third
finger of the hand are to be attributed to secondary yaws.
The third stage concerns the skin, bones and joints. Cutaneous lesions can be
nodular, tubercular or, in proximity of the extremities, gummatous.
Palmoplantar keratodermia is a very frequent clinical feature. The most frequent osteo-articular alterations are: periostitis, osteitis, and osteoperiostitis
gummatous. Gangosa or mutilant rhinopharyngitis, that which causes the
destruction of the central part of the face, are today rarely observed. We can
observe also, Aarticular lesions characterized by infiltrated nodular lesions,
localized in the elbow and knees, may also be observed.
Diagnosis: endemic area, dark background examination of the lesion’s exudates, serological tests for syphilis and, eventually, biopsy, give an easy diagnosis.
Differential diagnosis: has to be made in confrontation with vegetant pyoderma, tropical phagedaena ulcer, cutaneous carcinoma tuberculosis,
sporotrichosis, leishmaniasis, tungiasis, pytiriasis rosae, psoriasis, leprosy, palmoplantar keratoma and Dupuytren’s disease.
Histopathology: the primary form shows acanthosis and papillomatosis. The
epidermis is oedematous with neutrophil exocytosis. The derma presents a
plasma-cellular infiltrate of leukocytes, lymphocytes, histiocytes, fibroblasts.
The secondary form has substantially equal alterations.
The third form is characterized by ulcer lesions similar to the tertiary syphilis.
The early bone lesions show an inflammatory reaction. The articular nodules
have a central necrotic zone, an intermediate tissue granulation zone, and a
peripheral fibrotic layer.
Therapy: Identical to the endemic syphilis. People with yaws generally are
treated with penicillin G, given in various doses depending on the stage of
the disease and the age of the patient. In case of allergy to penicillin treatment, may be effected either with tetracycline hydrochloride or erythromycin can be used as alternatives, as these, which also have also proven to be effective.
239
10.2 Pinta
Synonyms: azul, carate, cative, cute, lota, mal de pinto, piquite, purù-purù,
quiriqua, tina, tinna, tinta.
Definition: endemic non-venereal treponematosis, chronic, contagious,
caused by the epidermotropic agent Treponema carateum. It is’s characterized
by three stages: an early pinta, with initial lesions and secondary manifestations; a late pinta, that which presents a partial or complete pigment loss, hyperkeratosis and atrophy.
Distribution: it’s a childhood endemic disease typical of the New World, between Mexico and the Amazons, particularly in rural areas with hot-humid
climates.
Incubation period: after contagion it varies between 1 and 3 months, experimentally about 3 weeks.
Clinical features: the primary lesion appears like a small papule that in a few
months, it will grow into a psoriasis- form plaque, rounded or oval; this is followed by a lichenification process and by pigment alterations, that in the end
leave a leukoderma patch. Usually the face, the extremities and the abdomen
are affectedinterested.
The secondary lesions – -pintid- – appear in variable number, after two
months 2 or more months. At first they appear erythematous and later become dyschromic with hyperpigmentation and leukoderma areas, forming a
pattern of polychromatic patches and of keratotic lesions, especially on the
knees and elbows.
The late pinta (third stage) is characterized by multicoloured and atrophic lesions. Adenopathy is present in the early and late stages of the dermatosis.
Diagnosis: the dark background examination, serological tests for syphilis
and an eventual biopsy allow an easy diagnosis.
Differential diagnosis: has to be made in confrontation with tinea corporis,
psoriasis, eczema, erythema discromicus perstans, leprosy, pityriasis alba,
yaws, vitiligo, pellagra and onchocerciasis.
Histopathology: the early pinta presents a moderate hyperkeratosis, acanthosis
and exocytosis of lymphocytes and neutrophils. In the older lesions we can notice quantitative alterations of the melanin content in the cells of the basal layer.
In the late pinta it i’s possible to observe irregular acanthosis atrophy of the
epidermis. In the hyperchromic lesions we can observe malanophores may be
observed in the epidermis and derma; in the achromic patches it i’s possible
to notice a melanin deficiency in the cells of the basal layer.
240
The epidermis in the early pinta appears rich in treponemata, while those
they are scarce or absent in the late form. Enlarged lymph nodes show a
chronic aspecific inflammationory situation.
Therapy: Pinta is treated with benzathine penicillin G (Bicillin), given as a
single injection. After penicillin therapy, lesions become non-infectious within 24 hours. After penicillin therapy, lesions become noninfectious in 24
hours. Primary and secondary lesions usually heal slowly within 6- – 12
months.
10.3 Endemic syphilis
Synonyms: bejel, dichuchwa, njovera, skerljevo, rewan, syphilis endémique,
endemische syphilis.
Definition: Endemic syphilis, non-venereal, chronic, contagious treponematosis, caused by the epidermotropic agent Treponema pallidum, principally acquired during childhood. Generally, Usually we can distinguish three
stages of the disease, although in the absence of the primary lesion is almost
absent. The secondary phase is usually located in the mucocutaneous regions
and the tertiary phase presents destructive lesions.
Distribution: localized especially in some small arid climate zones, in Africa
and Asia. It has already been eradicated in Europe and Australia.
Incubation period: many weeks; secondary lesions appear 2-3 months after
contagion.
Clinical features: the initial ulcer is usually a papular mucocutaneous lesion,
located on the lips, on the oral mucous lining of the cheeks and on the
tongue.
The secondary lesions appear generally on the mouth, in small number, or in
the perianal and genital regions. They can manifest themselves as papules
with papillomatous or condylomatous aspect; in the intertriginous areas they
assume a papular hypertrophic or circinate plaque characteristicss aspect. The
dry skin lesions are rare and can be represented by macular, papular or papulo-scaly manifestations. The “moth-like” alopecia can be is observed occasionally. Lymphadenopathy is common.
Latency period can last between 5 and 10 years. The lLate endemic syphilis
lesions can may be observed on the non treated patient’s skin, and appear as
tuberous , tubero-squamous or ulcerative of third syphilis type. Gummous lesions evolve towards necrosis and form perforating ulcers. Joint’ nodules can
241
be especially observed on the elbows. Pigment alterations can develop has
leukomelanodermic lesions.
Diagnosis: the dark background examination, clinical manifestations, complete serology for the syphilis and eventual biopsy, suggest diagnosis.
Differential diagnosis: there are many dermatoses with which endemic
syphilis needs to be confronted: yaws, syphilis, pityriasis rosea, psoriasis,
lichen planus, keratotic eczema, epidermomycosis, impetigo, pèrlèche,
condyloma acuminatum, bromoderma, lupus volgaris, Bowen disease,
rosacea, lupus erithematosus, mycosis fungoides.
Histopathology: primary lesions show epidermis atrophy with perivascular
plasmacells and lymphocytes infiltrate. Treponema pallidum is present. In the
secondary endemic syphilis, the derma contains dense perivascular plasmocytes infiltrates. Numerous spirochetes are present in the late condyloma. The
lLate endemic syphilis (third stage) is characterized by granulomatous infiltrates of lymphocytes, histiocytes and plasmacytes, fibroblasts, epithelial cells,
giant foreign body cells. Articulations’ nNodules of the articulations present
the same aspect of the yaws case.
Therapy: the chosen drug for all the three endemic treponematosis, is penicillin: injection of 2. 400 .000 units of penicillin G procain, or benzathine
penicillin for adults; for children under 12 we use half of the adult dose. In
the general campaign for the eradication of the endemic treponematosis the
WHO recommends 1 .200 .000 units for adults and 600. 000 for children
under 12. In the general campaigns it i’s not possible to perform more than one injection.
Penicillin-hypersensitive patients can be treated with appropriate doses of tetracyclines and
erythromycin.
Figure 10.3.1 Endemic syphilis: secondary lesions, located on the forehead region, in a child from Eritrea. A
hypochromatic lesion on the neck is
evident.
242
Suggested Readings
Endemic Treponematoses
1. Antal GM, Lukehart SA, Meheus AZ. The endemic treponematoses. Microbes Infect.
2002 Jan;4(1):83-94. Review.
2. Hackett CJ. On the origin of the human treponematoses. Boll. WHO 29: 7-41, 1963.
3. Koff AB and Rosen T. Nonvenereal treponematoses: Yaws, endemic syphilis, and pinta. J
Am Acad Dermatol 1993; 29: 519-35.
4. Musher DM. Treponemes: microbiology. In: Gorbach SL, Barlett SG, Blacklow NR (eds).
Infectious diseases. Philadelphia: WB Saunders, 1992: 1596-9.
Yaws
1. de Noray G, Capuano C, Abel M. Campaign to eradicate yaws on Santo Island, Vanuatu
in 2001 Med Trop (Mars). 2003;63(2):159-62.
2. Mafart B. Goundou. Nasal bone yaws Med Trop (Mars). 2000;60(4):322.
3. Manning LA, Ogle GD. Yaws in the periurban settlements of Port Moresby, Papua New
Guinea. P N G Med J. 2002 Sep-Dec;45(3-4):206-12.
4. Parish JL. Treponemal infections in the pediatric population. Clin Dermatol. 2000 NovDec;18(6):687-700.
5. Scolnik D, Aronson L, Lovinsky R, Toledano K, Glazier R, Eisenstadt J, Eisenberg P,
Wilcox L, Rowsell R, Silverman M. Efficacy of a targeted, oral penicillin-based yaws control program among children living in rural South America. Clin Infect Dis. 2003 May
15;36(10):1232-8. Epub 2003 May 09.
Pinta
1. Engelkens HJ, Vuzevski VD, Stolz E. Nonvenereal treponematoses in tropical countries.
Clin Dermatol. 1999 Mar-Apr;17(2):143-52.
2. Falabella R. Nonvenereal treponematoses: yaws, endemic syphilis, and pinta. J Am Acad
Dermatol. 1994 Dec;31(6):1075.
3. Quijano-Pitman F. Pinta disease. Treponema herrejoni Gac Med Mex. 1999 MayJun;135(3):329-30.
7. Tropical deep fungal infections
243
7. TROPICAL DEEP FUNGAL INFECTIONS
Aldo Morrone, Dagnachew Shibeshi
Deep mycoses are commonly observed in the tropical and sub tropical regions.
The following forms are described:
• Mycetoma
• Sporotrichosis
• Chromomycosis
• Lobo’s disease
• Paracoccidioidomycosis
• North American blastomycosis
• Coccidiodomycosis
6.1 Mycetoma
Synonyms: Madura foot, maduromycois, mycétome, Myzetom, MadurauB.
Definition: granulomatous chronic skin and subcutaneous tissue disease,
that can be caused by Eumycetes or by Actinomycetes. These microorganisms
can be observed like soil and plant saphrophytes, and are inoculated under
the skin through trauma; they localize especially on the foot and rarely on
other body parts, such as groin, gluteus, back, legs and hands. The principal
microorganisms are:
Eumycetes
Exophilia jeanselmi, Madurella mycetomatis, Madurella grisea, Leptophaeria
senegalensis, Pyrenochaeta romeroi, Curvularia lunata, Pseudoallescheria
boydii, Neutestudina rosatii, Acremonium spp, Fusarium spp.
Actinomycetes
Actinomadura madurae, Actinomadura pelletieri, Streptomycessomaliensis,
Nocardia brasiliensis, Nocardia asteroids.
Distribution: very common in the rural areas of the tropical and sub tropical regions; not rare, though, in the temperate zones of the Mediterranean
(north Africa, Greece, Italy), in Mexico, Central and South America,
Caribbean Islands.
Incubation period: not known exactly, but can be quite variable (some
months).
244
Clinical features: the disease affects adult men most frequently, especially
those who work in rural areas, and walk barefoot.
It begins generally with the formation of papules, nodules, pustules, and micro abscesses. According to the variety of the mycete concerned the granules
can be yellow, white, black or red. The draining of the fistulous tracts is never complete and the process can extend deeply into the subcutaneous tissue,
eventually involving the bone and causing increase in volume and foot deformation, and leg atrophy. Usually the mycetoma is a localized and asymptomatic lesion, not accompanied by a systemic involvement, not painful, unless
complicated by a secondary bacterial infection or involvement of the bones.
This is why very often the doctor intervenes only when the disease reaches an
advanced state with extended bone-destructive phenomena.
Diagnosis: based on the pus microscopic examination and the cultural examination of the granular exudates.
Immuno-diagnostic methods have been also developed, based on the use of
the immunodiffusion and contraimmunoelectrophoretic techniques, but
they are not used on a regular basis.
Differential diagnosis: has to be made in confrontation with furuncoloid lesions, chronic osteomyelitis, sporotrichosis, bone syphilis, vegetant pyodermitis, tuberculosis, chromomycosis.
Histopathology: The characteristic lesion is a granulomatous inflammation,
with granules formed by microorganisms surrounded by a polymorphonuclear
infiltrate, giant cells and external bodies. The granules are compact fungus
colonies, under the form of a mycelium with great hyphae closed and ramified.
At times the granules permit a primitive identification of the aetiologic agent.
Therapy: in the maduromycotic mycetoma, antifungus drugs like clotrimazole, ketoconazole (300-400 mg daily), itraconazole (400 mg daily), fluconazole and terbinafine, are the drugs of choice, even though some species appear to be totally insensitive.
In actinomycetoma, combined drug therapy is always preferred to a single
drug therapy in order to overcome drug resistance and to eradicate residual
infection. The common drugs in use include a combination of streptomycin
sulphate (14 mg/kg daily), diaminodiphenyl sulphone (dapsone) (1.5 mg/kg
twice daily). If there is no response after a few months or if there are persistent side effects, then dapsone is replaced by Co-trimoxazole (14 mg/kg twice
daily). An excellent therapeutic response to amikacin sulphate alone or in
combination with Co-trimoxazole has been reported. In the advanced cases,
though, radical surgery such as amputation seems to be necessary.
245
Figure 6.1.4 actinomycetoma of the
dorsum. Multiple nodular lesions
with granuli inside
6.2 Sporotrichosis
omycetoma of the dorsum. Multiple n
Synonyms: Beurmann and Gougerot’s diseases, esporotrichosis, esporotrichose, Sporotrichose.
Definition: deep subcutaneous tissue mycosis, due to the dimorph
Sporothrix schenkii mycete.
Sporotrichum lives as saprophyte in the external environment, particularly in
soil, plants and woods, and can cause spontaneous infections in some animals. In humans it penetrates the skin after a trauma, small cuts or thorn
stings, involving mainly the lymphatic vessels of the extremities.
Distribution: although it can be observed worldwide, sporotrichosis is endemic in the rural areas of tropical and subtropical regions.
Sporothrix schenkii penetrates the body even through very small cutaneous
lesions. Age, ethnic group, and sex seem to have no specific role to play.
Incubation period: variable, can be up to several months.
Clinical features: the classical form is characterized by gum chains that develop along the course of the lymphatic vessels, principally in the limbs, with
a characteristic torpid evolution. Regional lymphangitic sporotrichosis is the
most common form. At the inoculation site, after a variable incubation peri-
246
od, a nodular lesion with ulcerative evolution forms. Subsequently a “stab”
lymphangitis may be observed, along which are produced other sporotrichotic nodules that evolve towards suppuration. On the top of the nodule a characteristic flabby surface forms. Subsequently the gum tends towards ulceration. Rarely it is possible to observe numerous nodules distributed on all the
cutaneous surface (disseminated sporotrichosis) in which internal organs are
also involved, generally with a severe evolution (visceral sporotrichosis).
Diagnosis: often difficult; an orientation can be clinically given by the mode
examination of the pus collected with an injection in the ulcerated nodule. In the space of
of onset, and by the characteristic non-painful and torpid lesions. Diagnosis
10–15 days we obtain the characteristic chocolate-brown or black coloured colonies.
is confirmed by the cultural examination of the pus collected with an injection in the ulcerated nodule. In the space of 10-15 days we obtain the charDifferential diagnosis: has to be made in confrontation with sporotrichoid lesions of the
acteristic chocolate-brown or black coloured colonies.
atypical mycosis, with cutaneous tuberculosis, North American blastomycosis,
Differential diagnosis: has to be made in confrontation with sporotrichoid
chromomycosis, histoplasmosis, vegetant pyoderma, syphilis, leishmaniasis, Kaposi’s
lesionsand
oftularaemia.
the atypical mycosis, with cutaneous tuberculosis, North American
sarcoma
blastomycosis, chromomycosis, histoplasmosis, vegetant pyoderma, syphilis,
leishmaniasis,
Kaposi’s
sarcoma
tularaemia.
Histopathology:
in the
initial lesion,
we canand
observe
an aspecific inflammatory infiltrate, in
Histopathology:
in theepithelium
initial lesion,
we giant
can observe
aspecific
which
numerous plasmacells,
cells, and
cells are an
present.
In theinflammasubcutaneous
nodulesin
thewhich
infiltrate numerous
is instead veryplasmacells,
characteristic, disposed
in threecells,
zones: and giant
tory infiltrate,
epithelium
central
nodular
zone,
with
numerous
neutrophils,
few
lymphocytes
and
histocytes,
cells are present. In the subcutaneous nodules the infiltrate is instead very
(suppurative
zone);an
intermediate
withzones:
epithelioid
cells and
giant cells
of Langhans
characteristic,
disposed
inzone
three
central
nodular
zone,
with numerous
type (tubercolid zone); a periphery with an infiltrate made of various plasmacells,
neutrophils, few lymphocytes and histocytes, (suppurative zone); an intermelymphocytes and fibrocytes (syphiloid zone).
diate zone with epithelioid cells and giant cells of Langhans type (tubercolid
zone); a periphery with an infiltrate made of various plasmacells, lymphoTherapy: the therapy of choice is represented by iodine, which is administered in strong
cytes and fibrocytes (syphiloid zone).
doses of potassium iodide : initially 2 grams a day and proceeding with 5 grams for a
Therapy: the therapy of choice is represented by iodine, which is adminisperiod of 2–3 months. In the disseminated form and for iodine sensitive patients it is
tered in strong doses of potassium iodide: initially 2 grams a day and proceedpossible to use amphotericin B.
ing with 5 grams for a
period of 2-3 months.
In the disseminated
form and for iodine
sensitive patients it is
possible to use amphotericin B.
Fig. 6.2.1. Sporotrichosis.
fig. 6.2.1. Sporotrichosis.
247
6.3 Chromomycosis
Synonyms: chromoblastomycocsis, cromomycosis, Chromomykose.
Definition: deep skin and subcutaneous tissue mycosis, due to the species
Fonsecaea (Phialophora) fungi.
Distribution: can be observed especially in tropical and subtropical countries, and concerns particularly rural workers. The fungal elements can be
found on soil and organic materials. Males are more affected than women
and children.
Incubation period: not known precisely, but appears to be quite long.
Clinical features: manifests itself with localized infiltrative hard, nodular lesions, with a warty surface, with a tendency to form big dark brown plaques
because of the pigments produced by the fungi.
Extremities are more frequently affected, particularly foot and leg, where often an elephantoid state can be observed. In contrast to the mycetoma, there
is no bone or deep structure involvement, the general conditions are not
compromised and quoad vitam prognosis is benign.
Diagnosis: microscopic and cultural examinations for mycetes are necessary
for diagnosis.
Differential diagnosis: the following must be taken into consideration: the
warty cutaneous tuberculosis, other mycotic, bacterial and parasitic cutaneous infections, such as sporotrichosis, mycetoma and leishamaniasis.
Histopathology: the microorganism causes a deep dermal and subcutaneous
granulomatous inflammatory reaction. Inflammation is usually accompanied
by a reactive hyperplasia of the upper epidermis. Mycetes appear under the
form of brown-coloured spores, with thick walls and granular cytoplasm,
usually disposed in groups.
Therapy: small lesions can be surgically excised or treated with cryotherapy
or electro-coagulation. Itraconazole is the most effective antifungal drug, although not all patients respond. Flucytosine is sometimes useful for ancillary
therapy, because some lesions may respond rapidly but generally relapse.
Fluconazole seldom causes lesions to regress, and amphotericin B is ineffective. As in the case of sporotrichosis, it is possible to administer potassium iodide.
248
6.4 Lobo’s Disease (Lobomycosis)
Synonyms: keloidal blastomycosis, micosis de Lobo, chéloid blastomycose,
Lobo’s Mikose, Lobo-Krankheit.
Definition: described for the first time by Lobo in 1931 in Recife, the disease is a chronic cutaneous mycosis, with disseminated lesions on all the cutaneous surface, particularly in the ears, with a characteristic keloidal evolution. Caused by the Loboa loboi mycete.
Distribution: very rare, can be observed in the following countries:
Suriname, Amazon areas of Brazil, Central America, Venezuela and
Colombia.
Incubation period: unknown.
Clinical features: primitive lesions are represented by keloidal nodules that appear first of all on exposed body parts such as the face, legs or arms, usually associated with previous traumas. Later the lesions become warty and at times ulcerated. Secondary lesions can manifest themselves through autoinoculation.
Occasionally the disease can extend to the localised lymph nodes. General
conditions appear always to be good.
Diagnosis: the history, clinical features, biopsy and the demonstration of the
characteristic loboa loboi cells in the tissues permit the diagnosis. The fungus
has not yet been isolated in culture.
Differential diagnosis:must be made with chromomycosis and keloids.
Histopathology: granuloma is present with numerous loboa loboi cells, of
about 6-8 mm in diameter, spherical and oval, with thick walls, big giant cells
and histiocytes. Fibrosis is not present.
Therapy: While there have been a few case reports of success with oral clofazimine, definitive treatment is surgical excision. Although it is not uncommon for the disease to recur at the excision site, if the disease is caught early
enough, surgical excision may be curative. The major indication for removal
is cosmetic disfigurement.
6.5 Paracoccidioidomycosis
Synonyms: South American blastomycosis, Lutz-Splendore’s disease,
Brazilian balstomycosis, paracoccidioidal granuloma, Lutz-SplendoreAlmeida’s disease, blastomycose sud américaine, sudamerikanische blastomykose.
249
Definition: mucous and skin chronic infection, caused by the
Paracoccidioides brasiliensis fungus. This is a dimorphic mycete that develops under the form of a yeast, but can be cultivated either as a yeast or a
mould, and identified through micro and macroscopic characters.
Resemblance with Blastomyces dermatididis can lead to incorrect diagnosis.
Contagion of the disease is thought to occur through inhalation of spores,
but the natural reservoir still remains unknown.
Distribution: the infection is localized in Central and South America, particularly Mexico and Brazil, but patients can be diagnosed even several years
after they have left endemic areas.
Clinical features: in nearly all cases, the onset is localized with few symptoms
in the lungs, while dissemination towards mouth and nose mucous membranes, lymph nodes and other sites catches the doctor’s attention.
The mucocutaneous form usually begins on the oral mucous membrane with
infiltrative red-vermilion lesions, and a granular surface with the characteristic haemorrhagic punctuation.
The process localizes on the lips, the tongue, the palate and/or the tonsils,
and tends to extend progressively, causing destructive ulcerations. The lymphatic form manifests itself with a very extended cervical adenopathy which
can simulate Hodgkin’s disease. The visceral form, caused by haematogenous
dissemination of the morbid process, involves lungs, liver, kidneys and the
gastroenteric tube, and usually has a very severe or fatal course.
Diagnosis: the endemic area, clinical manifestations, the history, biopsy and
identification through microbiological examinations of the aetiologic agent
allow for the diagnosis.
Antibodies against P. brasiliensis can be demonstrated with a complement fixation technique in almost all patients. Serology can be useful to prospect the
diagnosis and to monitor therapy. Chest X-ray can often highlight bilateral
lung foci.
Differential diagnosis: tuberculosis, leishmaniasis and granulomatous candidiasis have to be taken into consideration.
Histopathology: a granulomatous reaction can be observed, with necrotic
and micro-abscessed foci, acanthosis and papillomatosis. P. brasiliensis appears with capsulated formations of 10-60 µm in diameter.
Therapy: clinically apparent infections are generally chronic and progressive
but not usually fatal. Azoles are highly effective. The less severe cases can be
treated with ketaconazole, 200-400 mg daily dose, for at least a year.
Itraconazole and terbinafine seem to give similar results, while in the worst
250
cases intravenous amphotericin B is administered, followed by imidazole derivates. Sulphonamides, which are widely used in some countries because
they are inexpensive, can suppress growth and improve lesions but are not
curative.
6.6 North American blastomycosis
Synonyms: Gilchrist’s disease, blastomycetic dermatitis, blastomycosis
norteamericana, blastomycose nord-americain, nordamerikanisce
Blastomycose.
Definition: systemic infection caused by the Blastomyces dermatitidis,
which is found especially in North America.
B. dermatitidis is a dimorphic fungus that grows at room temperature under
the form of white or pale-brown mould. At 37 C°, though, it develops under
the form of yeast-like rounded cells. The mycete is identified by morphological features, dimorphism and by the appearance of small spores on the
mould hyphae. The infection seems to be contracted through inhalation of
fungus deriving from the soil, by decomposed vegetation and rotten wood.
Several group cases have been verified during recreational activities in wooded areas along water courses. The infection cannot be transmitted through
humans.
Distribution: the infection is limited in geographical distribution, manifesting itself only prevalently in the south-east, central and mid-Atlantic regions
of the United States, with sporadic cases in other parts of North America. It
has been found as well in Africa, Central America, and rarely in South
America. The majority of the patients are between 20 and 60 years old. There
is no predisposition due to work conditions.
Incubation period: initial lesions, primarily of the lungs, develop 1–3 weeks
after inoculation; while for the cutaneous lesions incubation period is generally longer.
Clinical features: the disease can begin in the lung, imitating a pneumonic
tuberculosis. The initial cutaneous lesion is represented by a papule or a pustule.
The lesion gradually extends, with warty edges and scar manifestations at the
centre, even of great intensity. Various lesions can be simultaneously present.
The infecting process can involve the deep tissues, determining an osteomyelitic pattern.
251
Diagnosis: clinical manifestations, anamnesis, x-ray and microbial and histological examinations confirm the diagnosis.
Differential diagnosis: the following must be taken into consideration: tuberculosis, vegetant pyoderma, halogenodermis, leishmaniasis, other deep
fungal infections, such as sporotrichosis, chromomycosis, paracoccidioidomycosis.
Histopathology: the mycete determines a granulomatous reaction, with micro-abscesses and giant cell formations. The latter can contain numerous B.
dermatitidis spores.
Therapy: If untreated, blastomycosis is usually slowly progressive and ultimately fatal. Oral itraconazole is used for mild to moderate blastomycosis.
Fluconazole appears to be less effective. The optimum dose is undefined, but
400 to 800 mg/day may be tried to treat itraconazole-intolerant patients with
mild cases of blastomycosis. IV amphotericin B is the treatment of choice for
those with severe, life-threatening infections and is usually effective. The
dosage and the therapeutic protocol depend on the different cases according
to the diffusion of the infection to the lungs and other internal organs.
6.7 Coccidioidomycosis
Synonyms: San Joaquin valley fever, desert fever, coccidioidomycosis,
Wustenrheumatismus, Kokzidioidomykose.
Definition: coccidioidomycosis is primarily a lung infection caused by the
Coccidioide emmitis dimorph fungus, with a secondary involvement of other organs, such as the skin.
Distribution: the infection is limited to the dry and arid regions of the
southern United States, and to the northern part of Mexico. A few cases have
been reported in Venezuela, Honduras and Grand Chaco. The fungus lives as
a saprophyte in organic materials.
Incubation period: variable, at times as short as 1-2 weeks.
Clinical features: on the skin two forms of coccidioidomycosis may be observed. The rarer form may be observed after primary infection, as a consequence of accidental microorganism inoculation in the skin during laboratory activities . A plaque or a nodule, together with lymphadenopathy and lymphangitis, develops; later complete recovery may be observed. The more severe form of disseminated coccidioidomycosis is a consequence of the
haematogenous fungus diffusion of the primary lung infection. The clinical
252
feature is characterized by exophytic formations of the granulomatous tissue
and by subcutaneous abscesses with fistulous tracts. Plaques and pustules can
also develop. Nodular erythema is present at the time.
Diagnosis: anamnesis, endemic conditions, clinical manifestations and the
demonstration of pus in the fungus, biopsy, serology, lung x-ray and skin test
with coccidioidin permit the diagnosis.
Differential diagnosis: has to be made in confrontation with tuberculosis,
sporotrichosis, chromomycosis, vegetant pyodermis, tertiary syphilis, sarcoidiosis and halogenoderma.
Histopathology: it is possible to observe granuloma with epithelioid giant
cells, spherules, and endospores.
Therapy: Treatment for primary coccidioidomycosis is unnecessary in lowrisk patients. High complement fixation titre indicate spread, which requires
treatment. Mild to moderate non-meningeal extrapulmonary involvement
should be treated with 400 mg/day fluconazole or 400 mg/day itraconazole.
Amphotericin B is preferable for severely ill patients and is continued until
total dose reaches 1 to 3 grams depending on the degree of infection. Patients
with AIDS-associated coccidioidomycosis require maintenance therapy to
prevent relapse; 200 mg/day of an azole usually is sufficient, and weekly IV
amphotericin B may suffice for azole-intolerant patients.
253
Suggested Readings
Deep Mycoses
1. Beer Romero P, Rodriguez-Ochoa G, Angulo R e coll., Sporotrichosis in the Orinoco river basin Venezuela and Colombia, Mycopathologia. 1989 Jan;105(1):19-23.
2. Castrejon OV, Robles M, Zubieta Arroyo OE, Fatal fungaemia due to Sporothrix schenkii,
Mycoses. 1995 Sep-Oct;38(9-10):373-6.
3. Hay RJ, Baran R. Deep dermatophytosis: rare infections or common, but unrecognised, complications of lymphatic spread? Curr Opin Infect Dis. 2004 Apr;17(2):77-9.
4. Kohno S. New strategy of treatment for deep-seated mycosis Jpn J Antibiot. 2004
Apr;57(2):149-56.
5. Pappas P.G., Sprotrichosis in Peru: description of an area of hyperendemicity, Clin Infect
Dis, 2000, Jan, 30 (1),65-70.
6. Tsuta K. Et al., Analysis of deep mycoses in autopsy cases, Nippon Rinsho, 2000,Apr, 58
(4),969-76.
Micetoma
1. Abd Bagi ME, Fahal AH, Sheik HE, Abdul Wahab O, Taifoor MK, Osmanr EM.
Pathological fractures in mycetoma. Trans R Soc Trop Med Hyg. 2003 SepOct;97(5):582-4.
2. Abd El-Bagi ME, Abdul Wahab O, Al-Thagafi MA, et al. Mycetoma of the hand. Saudi
Med J. 2004 Mar;25(3):352-4.
3. Develoux M, Dieng MT, Kane A, Ndiaye B. Management of mycetoma in West-Africa
Sporotricosi
1. Bhattacharjee P, Brodell RT. A lesion with lymphangitic spread in a gardener. Exposure to
soil increases risk of sporotrichosis. Postgrad Med. 2004 May;115(5):21-3
2. Shinogi T, Misago N, Narisawa Y. Cutaneous sporotrichosis with refractory and reinfectious
lesions in a healthy female. J Dermatol. 2004 Jun;31(6):492-6.
Cromomicosi
1. Bonifaz A, Paredes-Solis V, Saul A. Treating chromoblastomycosis with systemic antifungals.
Expert Opin Pharmacother. 2004 Feb;5(2):247-54
2. Castro LG, Pimentel ER, Lacaz CS. Treatment of chromomycosis by cryosurgery with
liquid nitrogen: 15 years’ experience. Int J Dermatol. 2003 May;42(5):408-12
Lobomicosi
1. Elsayed S, Kuhn SM, Barber D, Church DL, Adams S, Kasper R. Human case of lobomycosis.
2. Emerg Infect Dis. 2004 Apr;10(4):715-8.
3. Saint-Blancard P, Maccari F, Le Guyadec T, Lanternier G, Le Vagueresse R. Lobomycosis:
a mycosis seldom observed in metropolitan France Ann Pathol. 2000 May;20(3):241-4
254
Paracoccidioidomicosi
1. Kalmar EM, Alencar FE, Alves FP, Pang LW, et al. Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from the brazilian amazon using skin tests. Am J Trop
Med Hyg. 2004 Jul;71(1):82-86
2. Pereira RM, Bucaretchi F, Barison Ede M, Hessel G, Tresoldi AT. Paracoccidioidomycosis
in children: clinical presentation, follow-up and outcome. Rev Inst Med Trop Sao Paulo.
2004 May-Jun;46(3):127-31. Epub 2004 Jul 20.
Blastomicosi
1. Balasaraswathy P, Theerthanath. Cutaneous blastomycosis presenting as non-healing ulcer
and responding to oral ketoconazole. Dermatol Online J. 2003 Dec;9(5):19
2. Su O, Demirkesen C, Onsun N. Localized blastomycosis-like pyoderma with good response
to cotrimoxazol and cryotherapy. Int J Dermatol. 2004 May;43(5):388-90.
8. Dermatoses caused by arthropos
255
8. DERMATOSES CAUSED BY ARTHROPODS
Aldo Morrone, Valeska Padovese, Margherita Terranova
Dermatoses caused by arthropods are very frequent in the tropical zones.
Scabies and pediculosis can be frequently observed in the immigrant population too.
In this chapter we examine:
• Scabies
• Pediculosis
• Tungiasis
• Dermomyiasis
7.1 Scabies
Synonyms: the itch, human scabies, Norwegian scabies, escabiasis, la gale
Norvégienne, Kratze.
Definition: scabies (from the Latin scabere = to scratch) is a parasitic contagious dermatosis, caused by a mite, the Sarcoptes scabiei, characterized by intense itching and by a pathognomonic lesion: the scabious tunnel. It is the S.
scabiei pregnant female that determines the disease. The mite digs a tunnel in
the corneum layer of the epidermis, leaving eggs behind.
The evolutionary cycle of the parasite is completed in six weeks; the mites are
fertilized at the 28 day and the males live about two months, the females
three months.
Distribution: Worldwide, though more frequent in the tropical and subtropical zones. A very frequent disease among poor people living in poor hygienic conditions and in overcrowded environments.
Incubation period: coincides with the development period of the parasite;
the duration varies according to the relation between the subject’s hygiene
and cutaneous sensitivity. It can vary between many days and a few weeks after the contact.
Clinical features: the scabious tunnel appears on the cutaneous surface like
a small grey relief, slightly lifted, straight or not, 2-3 mm long. The tunnel is
formed by a cephalic extremity which is the entry site of the mite and by a
caudal extremity where it is possible to observe a pearl blister, the parasite’s
den. The itching is very intense and it is the main symptom of the dermatoTH
256
sis; especially severe at bedtime, it can persist all night long, possibly causing
insomnia and anxiety states. Because of the itching and the consequent
scratching, secondary lesions appear on the skin, formed by linear and punctiform excoriations, crusty formations, itchy red swellings, follicular papules
and secondary eczema manifestations. The preferred sites for scabies are
hands, wrists, elbows, anterior armpits areas, gluteal regions (especially the
subgluteal folds), and the abdomen. The face is consistently spared. Lesions
can also take place frequently on male genitals, particularly on the prepuce
and on the glans, where they can assume an erosive-papular aspect, while on
the scrotal region they appear like papulo-nodular lesions. The nipple and the
mammary areola are frequently involved in adult women. In babies they can
be found as well on the palmar, plantar and scalp areas. The Norwegian scabies characterized by skin hyperkeratosis on the part invaded by the mite is
relatively rare, although recently it has been observed frequently in homeless
people, and is on the rise, especially in large metropolitan areas.
Diagnosis: based especially on nocturnal itching, on evidence of the tunnels
and pearly blisters, on the dermatosis topography and on the possible presence of other cases in the family. Microscopic examination will allow observation of the mite and eggs, but this is not always easy.
Differential diagnosis: must be made in confrontation with pyogenic dermatosis, insect bite dermatitis, papular urticaria, primary syphilis, onchocercosis and neurodermitis.
Histopathology: the tunnel is situated in the layer corneum, with the exception of the caudal blind part (where the parasite lives), which penetrates into
the mucous membrane.
Therapy: Treatment with topical medications (scabicide) is usually effective,
and the medication must be applied thoroughly to the whole skin from the
neck down, particularly the finger webs, genitalia, perianal areas and toe
webs. Medication should remain on the skin for more than 12 hours, preferably 24, and then washed off. Improvement is slow, despite rapid eradication
of mites. It is important to proceed with treatment of the patient and simultaneously with people of the same family context. Prednisone 40 mg/day for
7 to 10 days provides prompt relief and prevents over-treatment dermatitis
caused by repeated applications of scabicide by a patient who believes that the
infection persists. The topical medication of choice is permethrin cream 5%
because it is safe for all age groups. Lindane cream or lotion is mainly of historical interest because it is irritating and potentially neurotoxic and should
be avoided in infants and small children. Benzyl benzoate emulsions (20%)
257
.
are also administered with
very good results. A 5-10%
sulphur ointment is also
mainly of historical interest.
In patients affected with scabies since a long period, a
nervous itching may remain
(acarophobia); this may be
cured with antihistamines.
Figure 7.1.3 scabies in Ethiopian
child: typical plantar manifestations.
Figure 7.1.3 scabies in Ethiopian child: typical plantar manifestations.
7.2 Pediculosis
Synonyms: phthiriasis, pediculosis pubis, pediculosis capitis, pediculosis corporis, pediculiasis, lousiness, infestationis por piojos, pèdiculose, Lausebefall.
Definition: lice can infest humans provoking three types of pediculosis:
Pediculus humanus capitis, which only invades the scalp, and determines
pediculosis capitis; pediculus vestimenti seu corporis, which invades skin and
clothes and causes pediculosis corporis; Phthirius inguinalis or pubic, which
lives preferably on the genital hairs, causing phthiriasis or pubis pediculosis.
Lice have a life cycle of 6-8 weeks; eggs hatch after 6 days.
Distribution: ubiquitous.The principal causes for infestation are overcrowded areas, poor hygiene, and the wearing of dirty clothes. Phthiriasis, because
of the pubic localization, is considered an accessory sexually transmitted disease, while pediculosis capitis is very frequent in schools, especially among
children who attend schools in developing countries.
Incubation period: variable, between hours and a few days; in the pediculosis capitis, the life of an adult parasite lasts about 30 days; females lay 15-20
eggs a day.
Clinical features: the head louse is a long grey insect with a black spotted
back which lays eggs on the hair shaft in the form of nits; intense itching, excoriations, crusty formations and subsequent pyodermic lesions, which can
extend to the head, face and auricles, may be observed. In tropical countries,
lymphangitis with chronic inflammatory adenopathy of the head and mastoid region is frequent. The Pediculosis corporis, rare in the western world, is
Formatta
Inglese (R
258
regularly present in the peripheral areas of the cities in tropical and subtropical countries, where many people live in precarious conditions. The disease
manifests itself with localized itching especially in the covered regions and
particularly in correspondence of the posterior parts of the arms, at the wrist
level, and on the scapular and lumbar areas, where it is possible to observe
papulous-urticated pruriginous lesions. The itching is the cause of scratching
lesions and of super-infections. The skin of subjects infected for a long period of time becomes thickened, dry and presents a characteristic leucomelanodermia.
In particular countries and circumstances, body lice can transmit to humans
Rickettsia prowazekii, aetiologic agent of the classical typhus, R. Quintana, responsible for trenches fever, and Borrelia recurrentis, agent of recurrent fever.
Pubic pedicolsis is an ectoparasitosis due to Phthirius pubis that preferably locates on the perigenital areas covered by hair. The adult insect lives attached
to the base of the hair, next to the follicular ostium, where it can appear like
a small grey or brown mass. The eggs are laid along the hair shafts. The infection can extend to the chest hair, armpits, eyelashes, eyebrows and vibrissae. Clinically it is possible to observe more or less intense itching, with excoriated pink papules at the bite site.
Diagnosis: based on clinical examination and on egg and lice examination.
Differential diagnosis: eczema capitis, contagious impetigo, pseudotinea
amiantacea, psoriasis capitis, herpetiform dermatitis, prurigo and eczematous
dermatitis.
Therapy: Pediculosis capitis: it is essential to kill not only the lice but also the
embryos within the nits. The drug of choice is benzene hexachloride (lindane) as an emulsion or gel (1%). Pyrethrin has also been shown to be useful. Permethrin (1%) is generally the treatment of choice for head lice.
Shampoos are usually the most convenient to use in children.
Pediculosis corporis: Treatment consists in changing hygiene (if appropriate)
and clothes, and use of ectoparasiticidal agents. Dry heat is also effective in
killing lice and their ova.
Phthiriasis pubis: The drugs normally used are yellow mercuric oxide ointment (0.1grams in 10 grams of white petrolatum) or white petrolatum alone.
Malathione, lindone or permethrin are also effective.
259
7.3 Tungiasis
Synonyms: Chigoe infestation, chigger, sand flea infestation, picadura de
nigua, Sandflohbefall.
Definition: caused by the penetration in the epidermis of a small,
haematophagus female flea (about 1 mm), denominated Tunga penetrans,
which causes inflammatory lesions accompanied by an intense itching and
burning sensation.
Distribution: originally described at the beginning of the XVI century, it is
possible that it was so diffuse at the time as to oblige the population of entire
cities to flee.
At the present moment it is largely localized to the tropical and subtropical
regions of America and Africa. The sandy and warm soil of the desert, or of
the beaches, represents its natural habitat, although it can live in stables, in
breeding areas and in farm areas.
Incubation period: after the flea’s skin penetration, a small black stain may
be observed that reaches its maximum dimension in about 2 weeks.
Clinical features: after 4-5 days of skin penetration, a nodular tumefaction
may be observed which is hard and centred around a small dark spot that corresponds to the orifice where the female lays the eggs. Penetration of Tunga
does not cause subjective symptoms. The plantar and periungual regions of
the toes represent the sites of choice for the parasite. Lesions can vary in number in different people. It must be emphasized how extremely skilful the populations living in endemic areas are at extracting the Tunga from the skin.
Usually a painful and pruriginous symptomatology is present only when the
parasite increases in size. At times it is possible to note a necrotic tissue leak,
with subsequent formation of small ulcerations. In some cases it is possible
to observe a secondary infection, with the formation of abscess and lymphadenitis. Septicaemia, tetanus and gas gangrene have rarely been the most
serious complications.
Diagnosis: clinical manifestations, parasite demonstration and regional endemia provide the diagnosis.
Therapy: accurate extraction of the Tunga, after having removed the epidermal ring that surrounds the orifice where eggs are deposited. The residual
cavity should then be surgically cleaned to remove its entire contents.
Afterwards, an antibiotic ointment may be applied to prevent secondary infections. Certain chemicals have also proven to be effective, including 4 percent formaldehyde solution, chlorophenothane (DDT), chloroform, turpentine, and niridazole. These treatments do not physically remove the flea from
260
the skin however, and therefore do not result in quick relief. They also carry
their own risk of morbidity.
Anti-tetanus vaccination is strongly recommended; antibiotics are reserved to
super-infected and diffused forms. The best prophylaxis is to avoid walking
barefooted on beaches in endemic regions.
7.4 Dermamyiasis
Synonyms: dipteram larvae dermatitis, dermal myiasis, myasis dermatosa,
misis, myiases cutaneé et sous cutaneé, Fliegenmadenbefall.
Definition: caused by the active penetration in the skin, particularly at the
pilosebaceous follicules level, of diptera larvae. Different varieties of lesions
may be observed. More than 50 different species of diptera may be involved.
The insect’s eggs come into contact with the skin, where they rapidly hatch.
Distribution: ubiquitous, very common in the tropical and subtropical regions. The most important species involved are, for Africa: Cordylobia anthropophaga (ver de Cayor, Tumbu fly) and Chrysomya; for America:
Dermatobia hominis (ver macaque) and Cochliomya; for Asia: Chrysomya
and Wohlfahrtia; Gasterophilus and Hypoderma species are largely diffused.
The observation of Cordylobia myiasis is frequent in tourists and workers
who visit Africa.
Incubation period: can vary between a few days and a week.
Clinical features: penetration and maturation produce, in the space of 5-6
days, an inflammatory tumefaction that resembles a furuncle. Careful examination of the centre, which mimics a necrotic core, shows in reality that what
we are observing is the caudal extremity of the larva, because of the presence
of two small spots corresponding to the respiratory siphons orifices: the respiratory plate, with its stigmas.
The furunculoid myiasis is characterized by the presence of erythematous and
pruriginous papules, which tend towards the formation of furuncles. Eye,
nose, external ear-canal, mouth and vaginal infestations may be observed.
Diagnosis: determined by the presence of the larvae in the cutaneous lesions.
Differential diagnosis: must be made in confrontation with cutaneous dirofilariasis, which is transmitted by mosquitoes and causes a furunculoid lesion
through which a dirofilaria is expelled; must also be distinguished from onchocerciasis, furunculosis, tropical ulcer, tungiasis, creeping eruption caused
by nematodes larvae.
Therapy: consists in extraction of larvae followed by simple local disinfection. Anti-tetanus prophylaxis is useful in zones at risk.
261
Suggested Readings
Scabies
1. Consigny S, Chosidow O. Huynh TH, Norman RA. Scabies and pediculosis. Dermatol
Clin. 2004 Jan;22(1):7-11.
2. Downs AM. Seasonal variation in scabies. Br J Dermatol. 2004 Mar;150(3):602-3
3. Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004 Jan
15;69(2):341-8.
4. Heukelbach J, Feldmeier H. Ectoparasites-the underestimated realm. Lancet. 2004 Mar
13;363(9412):889-91.
5. Laube S. Skin infections and ageing. Ageing Res Rev. 2004 Jan;3(1):69-89.
6. McCarthy JS, Kemp DJ, Walton SF, Currie BJ. Scabies: more than just an irritation.
Postgrad Med J. 2004 Jul;80(945):382-7.
7. McCarthy JS, Kemp DJ, Walton SF, Currie BJ. Scabies: more than just an irritation.
Postgrad Med J. 2004 Jul;80(945):382-7.
8. Prins C, Stucki L, French L, Saurat JH, Braun RP. Dermoscopy for the in vivo detection
of sarcoptes scabiei. Dermatology. 2004;208(3):241-3.
9. Richardson M. Causes and effective management of insect bites in the UK. Nurs Times.
2004 Jun 1-7;100(22):63-5, 67.
Pediculosis
1. Buczek A, Markowska-Gosik D, Widomska D, Kawa IM. Pediculosis capitis among
schoolchildren in urban and rural areas of eastern Poland. Eur J Epidemiol.
2004;19(5):491-5.
2. Consigny S, Chosidow O. Cutaneous infections in the homeless. Rev Prat. 2003 Nov
30;53(18):1977-81.
3. Consigny S, Chosidow O. Huynh TH, Norman RA. Scabies and pediculosis. Dermatol
Clin. 2004 Jan;22(1):7-11.
4. Flinders DC, De Schweinitz P. Pediculosis and scabies. Am Fam Physician. 2004 Jan
15;69(2):341-8.
5. Garcia Sanchon C. Human pediculosis, or how to treat lice infestations? Rev Enferm. 2004
May;27(5):60-4.
6. Pierard-Franchimont C, Pierard GE. Paroxismal reactions of the scalp Rev Med Liege.
2004 Apr;59(4):180-5.
7. Steen CJ, Carbonaro PA, Schwartz RA. Arthropods in dermatology. J Am Acad Dermatol.
2004 Jun;50(6):819-42, quiz 842-4.
Tungiasis
1. Bauer J, Forschner A, Garbe C, Rocken M. Dermoscopy of tungiasis. Arch Dermatol.
2004 Jun;140(6):761-3.
2. Heukelbach J, Eisele M, Jackson A, Feldmeier H.Topical treatment of tungiasis: a randomized, controlled trial. AnnTrop Med Parasitol. 2003 Oct;97(7):743-9.
3. Heukelbach J, Feldmeier H. Ectoparasites-the underestimated realm. Lancet. 2004 Mar
13;363(9412):889-91
4. Heukelbach J, Franck S, Feldmeier H. High attack rate of Tunga penetrans (Linnaeus
262
1758) infestation in an impoverished Brazilian community. Trans R Soc Trop Med Hyg.
2004 Jul;98(7):431-4.
5. Romano C, Albanese G, Gianni C. Emerging imported parasitoses in Italy. Eur J
Dermatol. 2004 Jan-Feb;14(1):58-60.
6. Wilson ME, Chen LH. Dermatologic Infectious Diseases in International Travelers. Curr
Infect Dis Rep. 2004 Feb;6(1):54-62.
Dermomyiasis
1. Buchwald A. Occupational dermal myiasis. J Occup Med. 1992 Sep;34(9):872-3.
2. Contreras-Ruiz J, Arenas-Guzman R, Vega-Memije ME, Castillo-Diaz M. Furunculoid
myasis due to Dermatobia hominis. A case imported to the Mexican capital’s Federal District
from Costa Rica Gac Med Mex. 2004 Jan-Feb;140(1):81-3
3. Greco JB, Sacramento E, Tavares-Neto J. Chronic ulcers and myasis as ports of entry for
Clostridium tetani. Braz J Infect Dis. 2001 Dec;5(6):319-23
4. Rubel DM, Walder BK, Jopp-McKay A, Rosen R. Dermal myiasis in an Australian traveller. Australas J Dermatol. 1993;34(2):45-7.
5. Tamir J, Haik J, Schwartz E. Myiasis with Lund’s fly (Cordylobia rodhaini) in travelers. J
Travel Med. 2003 Sep-Oct;10(5):293-5.
9. Protozoan dermatoses
263
9. PROTOZOAN DERMATOSES
Aldo Morrone, Margherita Terranova, Valeska Padovese
A brief history of the disease
Although cutaneous leishmaniasis can be traced back many hundreds of
years, one of the first and most important clinical descriptions was made in
1756 by Alexander Russell following an examination of a Turkish patient.
The disease, then commonly known as “Aleppo boil”, was described in terms
which are relevant: “After it is cicatrised, it leaves an ugly scar, which remains
through life, and for many months has a livid colour. When they are not irritated, they seldom give much pain.”
It affects the natives when they are children, and generally appears in the face,
though they also have some lesions on their extremities. In strangers, it commonly appears some months after their arrival in an endemic area; very few
escape having lesions, but they seldom affect the same person above once.
Representations of skin lesions and facial deformities have been found on
pre-Inca potteries from Ecuador and Peru dating back to the first century
AD. They are evidence that cutaneous and mucocutaneous forms of leishmaniasis prevailed in the New World as early as this period. Texts from the Inca
period in the 15th and 16th centuries, and then during the Spanish colonization, mention the risk run by seasonal agricultural workers who returned
from the Andes with skin ulcers which, in those times, were attributed to
“valley sickness” or “Andean sickness”. Later, disfigurements of the nose and
mouth become known as “white leprosy” because of their strong resemblance
to the lesions caused by leprosy. In the Old World, Indian physicians applied
the Sanskrit term kala azar (meaning “black fever” ) to an ancient disease later defined as visceral leishmaniasis.
In 1901, Leishman identified certain organisms in smears taken from the
spleen of a patient who had died from “dum-dum fever” . At the time “Dumdum”, a town not far from Calcutta, was considered to be particularly unhealthy. The disease was characterized by general debility, irregular and repetitive bouts of fever, severe anaemia, muscular atrophy and excessive swelling
of the spleen. Initially, these organisms were considered to be trypanosomes,
but in 1903 Captain Donovan described them as being new.
The link between these organisms and kala azar was eventually discovered by
Major Ross, who named them Leishmania donovani. The Leishmania genus
had been discovered.
Ross,
who
named
them
Leishmania
The Leishmania
genus
The link
between
these
organisms
and kala donovani.
azar was eventually
discovered by
Majo
discovered.
Ross, who named them Leishmania
donovani. The Leishmania genus had bee
264
discovered.
The
Thevector
vector
The
leishmaniases
are caused
by 20
speciesforpathogenic
for humans belon
The
are caused
by 20 species
pathogenic
humans belonging
The leishmaniases
vector
genus
Leishmania,
a protozoa
transmitted
by
thebite
biteoffor
of
ahumans
tiny
3 millimetre
a protozoa
transmitted
the
a tiny
2 to2 3to
to
theleishmaniases
genus Leishmania,
The
are
caused
by
20 speciesby
pathogenic
belonging
to th
vector,
the
phlebotomine
sandfly.
millimetre-long
insect
vector,
the
phlebotomine
sandfly.
genus Leishmania, a protozoa transmitted by the bite of a tiny 2 to 3 millimetre-long inse
Of 500 known phlebotomine species, only
vector, the phlebotomine sandfly.
Of 500
phlebotomine
species,
some
30 ofknown
them have
been positively
identi- only some 3
Of
500
known
phlebotomine
species,
only
some 30 of
of the
themd
have
been
positively
identified
as
vectors
fied as vectors of the disease. Only the female
have
positively
as
vectors
of the disease.
On
thebeen
female
sandfly
transmits
the itself
protozoa,
infectin
sandfly
transmits
the identified
protozoa,
infecting
the
female
sandfly
transmits
the
protozoa,
infecting
itself
with
thethe
Leishmania
parasites
contained
Leishmania parasites
contained
in thein the blood it
with
theits
Leishmania
parasites
contained
in
the
bloodto
it sucks
or mammalian
in order
obtainfrom
th
bloodhuman
it sucks from
its human orhost
mammalian
its human or mammalian host in order to obtain the protein
necessary
develop
its eggs.
host
in order totoobtain
the protein
necessary
necessary to develop its eggs.
to develop its eggs.
During a period of 4 to 25 days,
the aparasite
continues
in-parasite
During
a period
to development
25the
days,
the
During
period
of 4 toof254 its
days,
parasite
continues conti
its
side
the
sandfly
where
it
undergoes
a
major
transformation.
development
inside
the
sandfly
where
it
undergoes
a
major
transformation.
development inside the sandfly where it undergoes a major transformation.
When the now infectious female sandfly feeds on a fresh source of blood, its
When
now
infectious
female
sandfly
onand
asource
fresh
source
pa
Whenthe
the
now
infectious
sandfly
on a fresh
of blood,of
itsblood,
painful its
sting
painful
sting
inoculates
its female
new
victim
withfeeds
thefeeds
parasite,
the transmission
inoculates
its new
thethe
parasite,
and the
cycle is completed.
cycle
is completed.
inoculates
its
newvictim
victimwith
with
parasite,
andtransmission
the transmission
cycle is compl
The insect vector of leishmaniasis, the phleThe
insect
vector
ofisleishmaniasis,
the phlebotomine
sandfly
The
insect
vector
of leishmaniasis,
the phlebotom
the
botomine
sandfly,
found
throughout
is found
throughout
the world's
inter-tropical
and
is found
throughout
the temperate
world's
inter-tropical
an
world’s
inter-tropical
and
retemperate regions.
temperate regions.
gions.
The female
female sandfly
ininthe
The
sandfly lays
laysitsitseggs
eggs
theburrows
burrows of certain
of
certain
rodents,
in
the
bark
of
old
trees,
in
The
female
sandfly
lays
its
eggs
inbuildings,
the burrows
of
rodents, in the bark of old trees, in ruined
in cracks
ruined
buildings,
in bark
cracks
house
in
rodents,
in in
the
ofinold
trees,
ruined building
in
house
walls,
animal
shelters
andwalls,
in in
household
rubbish,
animal
shelters
and
in
household
rubbish,
as
itwillin
in animal
and
househo
as in
it ishouse
in suchwalls,
environments
thatshelters
the larvae
find
the
is
in
such
environments
that
the
larvae
will
find
the
organic
matter,
heat
and
aswhich
it is inaresuch
environments
that the larvae will fin
organic matter, heat and humidity
necessary
for their development.
humidity
which heat
are necessary
for their which
development.
organic
matter,
and humidity
are necessary for their development.
In
its search
search for
In its
forblood
blood (usually
(usuallyinin the
theevening
eveningand
andatatnight),
night),the
thefemale
femalesandsandfly covers a
fly
covers
a
radius
of
a
few
to
several
hundred
metres
around
its
habitat.
radius
of
a
few
to
several
hundred
metres
around
its
habitat.
In its search for blood (usually in the evening and at night), the female sandfly c
radius of a few to several hundred metres around its habitat.
The leishmaniases and Leishmania/HIV co-infections
Transmitted by the bite of the infected female phlebotomine sandfly, the
leishmaniases are a globally widespread group of parasitic diseases. The sandfly vector is usually infected with one species of flagellate protozoa belonging
to the genus Leishmania.
About 30 species of sandflies can become infected when taking a blood meal
from
a reservoir host.and
Hosts
are infected humans,
wild animals, such as roThe leishmaniases
Leishmania/HIV
co-infections
dents, and domestic animals, such as dogs. Most leishmaniases are zoonotic
Transmitted by the bite of the infected female phlebotomine sandfly, the leishmaniases ar
The leishmaniases and Leishmania/HIV co-infections
a globally widespread group of parasitic diseases. The sandfly vector is usually infecte
Transmitted by the bite of the infected female phlebotomine sandfly, the leishm
with one species of flagellate protozoa belonging to the genus Leishmania .
265
(transmitted to humans from animals), and humans become infected only
when accidentally exposed to the natural transmission cycle. However, in the
anthroponotic forms (those transmitted from human to human through the
sandfly vector), humans are the sole reservoir host.
Leishmaniasis presents itself in humans in four different forms with a broad
range of clinical manifestations. All forms can have devastating consequences.
Visceral leishmaniasis (VL), also known as kala azar, is the most severe form
of the disease, which, if untreated, has a mortality rate of almost 100%. It is
characterized by irregular bouts of fever, substantial weight loss, swelling of
the spleen and liver, and anaemia.
Mucocutaneous leishmaniasis (MCL), or espundia , produces lesions which
can lead to extensive and disfiguring destruction of mucous membranes of
the nose, mouth and throat cavities.
Cutaneous leishmaniasis (CL) can produce large numbers of skin ulcers - as
many as 200 in some cases - on the exposed parts of the body, such as the
face, arms and legs, causingserious disability and leaving the patient permanently scarred. Diffuse cutaneous leishmaniasis (DCL) never heals spontaneously and tends to relapse after treatment. The cutaneous forms of leishmaniasis are the most common and represent 50-75% of all new cases.
Increased prevalence
• Since 1993, regions that are Leishmania-endemic have expanded significantly, accompanied by a sharp increase in the number of recorded cases
of the disease.
• The geographic spread is due to factors related mostly to development.
These include massive rural-urban migration and agro-industrial projects
that bring non-immune urban dwellers into endemic rural areas. Man-made
projects with environmental impact, like dams, irrigation systems and wells,
as well as deforestation, also contribute to the spread of leishmaniasis.
• AIDS and other immunosuppressive conditions increase the risk of
Leishmania-infected people developing visceral illness. In certain areas of
the world the risk of co-infection with HIV is rising due to epidemiological changes.
Geographic distribution
• The leishmaniases are now endemic in 88 countries on five continents Africa, Asia, Europe, North America and South America - with a total of
350 million people at risk.
266
• It is believed that worldwide 12 million people are affected by leishmaniasis; this figure includes cases with overt disease and those with no apparent symptoms. Of the 1.5-2 million new cases of leishmaniasis estimated
to occur annually, only 600 000 are officially declared.
• Of the 500 000 new cases of VL which occur annually, 90% are in five
countries: Bangladesh, Brazil, India, Nepal and Sudan.
• 90% of all cases of MCL occur in Bolivia, Brazil and Peru.
• 90% of all cases of CL occur in Afghanistan, Brazil, Iran, Peru, Saudi
Arabia and Syria, with 1-1.5 million new cases reported annually worldwide.
• The geographical distribution of leishmaniasis is limited by the distribution of the sandfly, its susceptibility to cold climates, its tendency to take
blood from humans or animals only and its capacity to support the internal development of specific species of Leishmania.
Leishmania/HIV co-infection
Leishmania /HIV co-infection is emerging as an extremely serious, new disease and it is increasingly frequent. There are important clinical, diagnostic,
chemotherapeutic, epidemiological and economic implications of this trend.
• Although people are often bitten by sandflies infected with Leishmania
protozoa, most do not develop the disease. However, among persons who
are immunosuppressed (e.g. as a result of advanced HIV infections, immunosuppressive treatment for organ transplants, haematological malignancy, auto-immune diseases), cases quickly evolve to a full clinical presentation of severe leishmaniasis.
• AIDS and VL are locked in a vicious circle of mutual reinforcement. On
the one hand, VL quickly accelerates the onset of AIDS (with opportunistic diseases such as tuberculosis or pneumonia) and shortens the life expectancy of HIV-infected people. On the other hand, HIV spurs the
spread of VL. AIDS increases the risk of VL by 100-1000 times in endemic areas.
This duo of diseases produces cumulative deficiency of the immune response
since Leishmania parasites and HIV destroy the same cells, exponentially increasing disease severity and consequences. VL is considered a major contributor to a fatal outcome in co-infected patients. Lately, however, use of tritherapy, where it is available, has improved the prognosis for Leishmania /HIV
cases.
• Leishmaniasis can be transmitted directly person to person through the
267
sharing of needles, as is often the case among intravenous drug users. This
group is the main population at risk for co-infection.
Areas of co-infection
• Cases of Leishmania /HIV co-infections are being reported more frequently in various parts of the world. It is anticipated that the number of
Leishmania /HIV co-infections will continue to rise in the coming years
and there are indications that cases are no longer restricted to endemic
Leishmania/HIV co-infections are considered a real threat, especially in
south-western Europe. Of the first 1700 cases of co-infection which have
been reported to the World Health Organization (WHO) from 33 countries worldwide up to 1998, 1 440 cases were from the region: Spain
(835); Italy (229); France (259); and Portugal (117). Of 965 cases retrospectively analyzed, 83.2% were males, 85.7% were young adults (20-40
years old) and 71.1% were intravenous drug users.
• Most co-infections in the Americas are reported in Brazil, where the incidence of AIDS has risen from 0.8 cases per 100 000 inhabitants in 1986
to 10.5 cases per 100 000 inhabitants in 1997. As HIV transmission has
spread into rural areas, VL has simultaneously become more urbanized especially in north-eastern Brazil - increasing the risk of overlapping infection.
• The number of cases of Leishmania/HIV co-infection is expected to rise
in Africa owing to the simultaneous spread of the two infectious diseases
and their increasingly overlapping geographical distribution, complicated
by mass migration, displacement, civil unrest, and war.
• In general, the reported cases of Leishmania/HIV co-infection in Africa
are a very modest estimation and would substantially increase if active surveillance were implemented throughout the continent. Ethiopia has a
well-organized system of detection, management and reporting of co-infection. Kenya and Sudan began surveillance in 1998 and Morocco has also established a surveillance centre.
In East Africa, cases of Leishmania/HIV co-infections have been reported in
Djibouti (10), Ethiopia (74), Kenya (15), Malawi (1) and Sudan (3). West
Africa has no official surveillance system yet, but several cases have been reported: Cameroon (1), Guinea Bissau (1), Mali (4) and Senegal (2). In North
Africa, cases have been reported in Algeria (20) and Morocco (4). areas.
The overlapping geographical distribution of VL and AIDS is increasing due
to two main factors: the spread of the AIDS pandemic in suburban and ru-
268
ral areas of the world, and the simultaneous spread of VL from rural to suburban areas.
The protozoan infections of dermatological interest, consist of different diseases in the tropical and sub tropical regions. In this chapter we consider:
• Cutaneous Leishmaniasis
• Mucocutaneous Leishmaniasis
8.1 Cutaneous Leishmaniasis
Synonyms: Mediterranean cutaneous leishmaniasis, Biskra button, Aleppo
button or Delhi boil, Siskra button, Baghdad sore, leishmaniasis cutanea,
leishmaniose cutaneé, bouton d’Orient, Orientbeule.
Definition: cutaneous leishmaniasis is a granulomatous infection caused by
protozoa of the genus Leishmania (L. tropica, L. maior or L. aethiopica),
transmitted to man by diptera of the genus Phlebotomus (Old World) and
Leutzomya (New World). These parasites are usually transmitted to the human host by animal reservoirs through the sting of sandflies of the genus
Phlebotomus. The most classical form is the Biskra button. Because of the
different types of leishmania and immunology response of the host, clinical
features can be very polymorphous.
The disease affects only the skin, and is characterized by single or multiple
ulcerative lesions. The different types of Leishmania appear morphologically
identical and are distinguished, generally, by clinical and geographical characteristics. Traditionally the identification of the species requires the isoenzyme characterization, the flotation density of the kinetoplast DNA, or the
identification of the specific phlebotomine vector. Monoclonal antibodies,
DNA hybridization, the analysis of DNA fragments obtained after restriction
with endonuclease, and the determination of chromosomal karyotypes using
discontinuous polyacrilamide gel electrophoresis are new and effective methods for the identification of these parasites.
Distribution: cutaneous leishmaniases are endemic in many geographic regions: the Mediterranean basin, Sahel, Middle East for the complex L. tropica; Ethiopia, East Africa for L. aethiopica; Central America and Amazonians
for L. mexicana and L. brasiliensis. Regions of northwest India, Pakistan, and
South Russia are also affected.
Geographical distribution is important for diagnosis of travellers or immigrants coming from leishmaniasis endemic areas and manifesting cutaneous
269
lesions. Leishmaniasis is a zoonosis that affects rodents and dog species of all
continents, with the exception of Australia. Infection is transmitted to man
by the sting of the female sandfly (of the genus Phlebotomus or Leutzomaya)
on the infected animal. The sandfly becomes infected by stinging an infected animal and ingesting amastigotes together with the blood; these transform
inside the insect’s intestine into promastigotes, migrate into the “trunk” and
finally are deposited, with a new sting, on the skin of another animal or of
man.
Phlebotomes live in hot-humid micro-environments, and can be found especially in rodents’ dens and in decomposed vegetation. Humans can contract
the disease from the moment they enter the cycle. The stabilization of the infection in the dog is an important human leishmaniasis reservoir, while interhuman contamination is rare except in the Indian kala azar; even more rarely
the infection is transmitted with transfusions, by contact inoculation or by
sexual intercourse. It has been calculated that at the moment there are more
than 12 million people affected by Leishmania.
Incubation period: usually varies between 2-3 weeks and one year.
Clinical features: all age groups of people are affected by this disease, which
manifests itself usually on the cutaneous parts exposed to phlebotome bites.
It begins with a small erythematous, punctiform papule that enlarges in the
space of a few months until reaching various centimetres in diameter, and
deepens until it becomes completely nodular. The surface of the nodule is
covered with thin squamous formations and is strongly adherent, originating
in correspondence of the follicular foci; if the squamous formation is detached with a clip, it is possible to observe numerous corneous taproot extensions, expression of the follicular hyperkeratosis (nail sign). After 3-4 months
the centre part of the nodules can evolve towards ulceration and become covered by scale-crusts. After 3-4 months spontaneous recovery is possible.
The disease usually persists for about a year. Preferred sites for the lesions are
exposed body parts, particularly the forehead, zygomatic regions, temples and
nose, but the neck, back of the hands and feet can also be involved. The number of lesions is usually small, but sometimes they can be multiple due to simultaneous multiple bites on the exposed parts. The distinction between dry
urban forms (L. major) and humid rural forms (L. tropica) is based on epidemiological differences. On a clinical level this distinction is difficult.
Together with the characteristic forms, other numerous clinical varieties exist: ulcerative or ectymatous forms, erysipeloid, neoplastic forms, tubercoloid, sarcoidosic and pseudosporotrichotic forms.
270
Diagnosis: clinical diagnosis of cutaneous leishmaniasis is relatively easy,
even if the disease can present various atypical forms. Diagnostic suspect
comes from the examination of the characteristic lesions, by history (regarding possible visits to endemic regions) and by confirmed antiseptic or antibiotic treatment resistance.
Confirmation is given by May-Grunwald-Giemsa’s staining. Leishmania
Microscopic identification in culture is also possible (in Novy-NicolleMcNeal media).
The leishmanina skin test (Montenegro test), which is highly specific, is not
important for diagnostic scope, but gives a chance to better evaluate the immune reaction of the host.
Differential diagnosis: a long list of diseases has to be considered, particularly granulomatous affections: impetigo, pyogenic infections, basal cell carcinoma, keloids, keratoacanthoma, erythematous lupus, phagedenic and tropical
ulcers, yaws, lymphoma, primary and tertiary syphilis, lupus vulgaris and other cutaneous tuberculosis forms, leprosy, deep mycosis and sarcoidosis.
Histopathology: histopathologic alterations are different in relation to the
diverse phases of the disease.
In the initial phase we can observe in the dermis an inflammatory granuloma formed by histiocytes, lymphocytes, plasmacells, and polymorph nucleate leukocytes in various proportions.
Parasites, contained in the histiocytes cytoplasm, during the first months are
various. Leishmania can be present in capillary endothelia and outside cellular elements. Protozoa can be well highlighted with May-Grunwal-waldGiemsa’s staining, and appear as little oval pale-blue or pyriform bodies of 24 cm in length, with an eccentric red nucleus. After about 5-7 months they
usually disappear. In a second phase the histological pattern modifies, evolving towards a tubercoloid structure.
Therapy: to date, no ideal therapy exists for leishmaniasis. The most important measures in endemic zones are health education, early treatment of patients and elimination or control of reservoir, hosts and vectors. It is recommended not to undergo any treatment until ulceration appears and until the
state of immunity has been ascertained, except in the case of: disfiguring
and/or disabling lesions, or lesions existing for over six months. Meglumin
antimonate is the chosen drug. It can be used for intra-lesion injections, with
application of 0.2-0.4ml sodium gluconate intradermally 3 times a week for
a total of 15 injections. In case of multiple lesions intramuscular injections
are preferred (20mg/Kg/per day for 20 days). In case of unsuccessful results
injections. In case of multiple lesions intramuscular injections are preferred (20m
day for 20 days). In case of unsuccessful results with N-methyl-glutamine, pe
has been used ( 3–4mg/kg once weekly for 4 months) with equal success. T
271
Ketoconazole (600 mg) and itraconazole (7 mg/kg per day for 4-8 weeks)
encouraging, but they cannot be used as single agents. Topical therapy is used
concentrate
the drug on
specific sites of the
minimize systemic
with N-methyl-glutamine, pentamidine
has toxicity
been and
used
(3-4mg/kg
once
of
paramomycin
sulphate
(an
aminoglucoside)
twice
application
weekly for 4 months) with equal success. The use of Ketoconazole (600 mg) a day has obta
results. Cryotherapy, CO2 lasers and localized heat have been used, with variab
and itraconazole (7 mg/kg per day
for 4-8 weeks) has been encouraging, but
Alternative and experimental treatments include the use of interferon-γ, va
they cannot be used as single agents.
Topical therapy is used today to miniimmunotherapy, WR 6026, liposomal amphotericin-B.
mize systemic toxicity and concentrate the drug on specific sites of the skin.
The application of paramomycinFigures:
sulphate (an aminoglucoside) twice a day
has obtained good results.
Cryotherapy, CO2 lasers and
localized heat have been used,
with
variable
results.
Alternative and experimental
treatments include the use of
interferon-g, vaccination, immunotherapy, WR 6026, liposomal amphotericin-B.
Fig. 8.1.2 cutaneous leishmaniasis.
Multiple nodular lesions with central ulceration on the face
Fig. 8.1.2 cutaneous leishmaniasis. Multiple nodular lesions with central ulcerati
face
8.2 Mucocutaneous leishmaniasis
Synonyms: South American leishmaniasis, Brazilian leishmaniasis, Breda’s
disease, New World cutaneous leishmaniasis, American leishmaniasis, forest
yaws, espundia, chiclero ulcer, Bahuru.Bahia ulcer, uta, leishmaniasis americana, llaga brava, pian bois, Schleimhautleishmaniasis.
Definition: specific granulomatosis, caused by the Leishmania braziliensis,
and by the Leishmania mexicana, that involves the skin and, secondly, the
upper respiratory tract. It has been known since the pre-Columbian era.
Distribution: largely diffused in Central and South America, and still endemic in the hot and humid forestal regions; especially found in southern
Texas, Mexico, Costa Rica, Ecuador, Colombia, Peru, Brazil, and Argentina.
The leishmaniae responsible for the mucocutaneous disease are distinguished
in L. mexicana and L. braziliensis subspecies. Natural reservoirs of these two
subspecies can be found in various mammals living in the Central and South
American forests. The infection, which usually affects workers who regularly
272
enter the jungle for the harvest of ìchiclaî or for the massive forest destructions, is more frequent in Amazonia, but still present in all of the above mentioned geographical areas.
Incubation period: between 2-4 weeks, up to 2 or more months.
Clinical features: the mucocutaneous leishmaniasis, in contrast to the
Mediterranean form, manifests itself more severely, with mucous ulcerative
mutilating lesions, major resistance to therapy and at times with a fatal
course. The initial erythemato-papular lesion grows rapidly, assuming a papillomatous and squamous aspect. Later the lesions tend to become ulcerative and to extend. The disease usually hits the more exposed parts, most frequently the face, legs, feet, and the upper limbs, often with multiple and successive lesions. Facial nodular lesions may be observed with a tendency towards necrosis and ulceration, which can lead to severe mutilations. In many
cases the leishmaniasis invades the nasal, pharyngeal and laryngeal mucous
membranes, forming chronic ulcerative vegetation with no tendency to recovery. The course is generally long, many years in the more severe cases. The
general conditions can be compromised with fever and anorexia; death for
secondary infection or cachexia may intervene. In some cases the disease presents particular aspects. L. Mexicana Mexicana causes chiclero ulcer or “bay
ulcer”, which manifests on workers collecting latex in the forests during the
rainy season when phlebotomes are more abundant (Oreja de los Chicleros).
The lesions are papulo-nodular, with rare tendency to ulceration; they heal
spontaneously in the space of 6 months. The auricular sites lesions, though,
persist for years and can cause vast destruction of the auricle. The L. m.
venezuelensis causes nodular asymptomatic lesions; L. m. granhami causes lesions with ulcerative evolutions; L. m. amazonensis produces persistent lesions, which rarely heal spontaneously; L. braziliensis peruviana causes the
Andes uta, characterized by ulcerative facial lesions which usually heal in the
space of 4 to 12 months: it can be found on the western Andes front at altitudes of over 600 m; L. b. panamensis causes torpid ulcerative lesions; and
L.b. guyanensis is responsible for the nodular persistent lesions that metastasize via the lymphatic system (pian bois). The L. p. braziliensis causes the
Espundia form that manifests typically with one or more lesions located on
the legs, with a characteristic ulcerative evolution: they rarely heal spontaneously, but more often are followed, after months or years, by the formation
of metastatic lesions on the naso-pharyngeal area and, less frequently, on the
perineum. Obstruction and epistaxis symptoms frequently begin the clinical
pattern and are followed by massive destruction of the cartilagineous struc-
273
tures, with painful mutilating erosions (espundia); fever, anaemia, and weight
loss are associated. Death is caused by bacterial infection, malnutrition, pneumonia ab ingestis or by respiratory obstruction.
Diagnosis: based on the evolving of the initial cutaneous lesion, on ulceration characteristics, on the frequent involvement of the mucous membranes
and on the general conditions. The identification of the leishmania species is
important in order to be able to foresee the evolution of the infection, which
Histopathology: a granulomatous process on the dermis site is present, formed by
dependslymphocytes,
on the aetiologic
Cutaneous
is theblood
method
leukocytes,
histiocytesagent.
cells, rare
giant cells,biopsy
with evident
vesselsof choice
for
obtaining
a
sample
for
colouring
and
culture
examinations.
alteration that appear thrombosed and that can generate frequent necrotic and ulcerative
Differential diagnosis: syphilis, blastomycosis, paracoccidioidomycosis,
processes.
sporotrichosis, leptospirosis, carcinoma, sarcoidiosis, rhinoscleroma, onchocerciasis,
leprosy
and
mycobacterial
infections.
Therapy:
non-extended
lesions
in particular
can be treated
with local antimony injections.
granulomatous
process oninvolvement,
the dermis
site is present,
In Histopathology:
the case of disfiguring ora disabling
lesions with cartilaginous
it is necessary
byantimonial
leukocytes,
lymphocytes,
cells, rare orgiant
cells, with evto formed
perform an
systemic
therapy, withhistiocytes
sodium stibogluconate
meglumine
antimonate.
For the
ulcerative-nodular
an occlusive
medication and
is recommended
ident blood
vessels
alterationlesions,
that appear
thrombosed
that can generate
to frequent
prevent possible
further
by vectors
of the canine and human species of
necrotic
andinfection
ulcerative
processes.
parasites
vectors
infections and lesions
other dog
and can
human
Therapy:
non-extended
in species
particular
be parasite
treatedinfections.
with local antiResistant
cases
have
to
be
treated
with
amphotericin
B
and
pentamidine.
No
mony injections.
reconstructive
prosthesis need
applied before
a year
aftercartilaginous
the end of remission
In the casefacial
of disfiguring
orbedisabling
lesions
with
involvement,
without
treatment.
it is necessary to perform an antimonial systemic therapy, with sodium stibogluconate or meglumine antimonate. For the ulcerative-nodular lesions, an
occlusive medication is recommended to prevent possible further infection by vectors of the
canine and human species of parasites vectors infections and other dog species and human parasite infections. Resistant cases
have to be treated with amphotericin B and pentamidine. No
reconstructive facial prosthesis
need be applied before a year after the end of remission without
treatment.
Figure 8.2.1 mucocutaneous leishmaniasis: warty lesions on the legs, caused
by L. mexicana, in a patient from
Costa Rica.
274
Suggested Readings
Protozoan Dermatoses
1. Alcais A, Abel L, David C, Torrez ME, Flandre P, Dedet JP. Risk factors for onset of cutaneous and mucocutaneous leishmaniasis in Bolivia. Am J Trop Med Hyg. 1997
Jul;57(1):79-84
2. Ara M, Maillo C, Peon G, Clavel A, Cuesta J, Grasa MP, Carapeto FJ. Visceral leishmaniasis with cutaneous lesions in a patient infected with human immunodeficiency virus. Br
J Dermatol. 1998 Jul;139(1):114-7.
3. Belic A, Pejin D, Stefanovic N, Spasojevic J, Durkovic D. Hematologic characteristics of
leishmaniasis Med Pregl. 2000 Jan-Feb;53(1-2):89-91.
4. Berman JD. Treatment of New World cutaneous and mucosal leishmaniases. Clin
Dermatol. 1996 Sep-Oct;14(5):519-22.
5. Calza L, D’Antuono A, Marinacci G, Manfredi R, Colangeli V, Passarini B, Orioli R,
Varoli O, Chiodo F. Disseminated cutaneous leishmaniasis after visceral disease in a patient
with AIDS. J Am Acad Dermatol. 2004 Mar;50(3):461-5.
6. Davidson RN. Practical guide for the treatment of leishmaniasis. Drugs. 1998
Dec;56(6):1009-18.
7. Dedet JP, Lambert M, Pratlong F. Leishmaniasis and human immunodeficiency virus infections. Presse Med. 1995 Jun 17;24(22):1036-40.
8. El Hajj L, Thellier M, Carriere J, Bricaire F, Danis M, Caumes E. Localized cutaneous
leishmaniasis imported into Paris: a review of 39 cases. Int J Dermatol. 2004
Feb;43(2):120-5.
9. Falqueto A, Sessa PA, Ferreira AL, Vieira VP, Santos CB, Varejao JB, Cupolillo E,
Porrozzi R, Carvalho-Paes LE, Grimaldi Junior G. Epidemiological and clinical features
of Leishmania (Viannia) braziliensis American cutaneous and mucocutaneous leishmaniasis
in the State of Espirito Santo, Brazil. Mem Inst Oswaldo Cruz. 2003 Dec;98(8):1003-10.
10. Goihman-Yahr M. American mucocutaneous leishmaniasis. Dermatol Clin. 1994
Oct;12(4):703-12.
11. Kar K. Serodiagnosis of leishmaniasis. Crit Rev Microbiol. 1995;21(2):123-52.
12. Laguna F. Treatment of leishmaniasis in HIV-positive patients. Ann Trop Med Parasitol.
2003 Oct;97 Suppl 1:135-42.
13. Markle WH, Makhoul K. Cutaneous leishmaniasis: recognition and treatment. Am Fam
Physician. 2004 Mar 15;69(6):1455-60.
14. Singh S, Sivakumar R. A Therapeutic update on Cutaneous leishmaniasis. J Coll
Physicians Surg Pak. 2003 Aug;13(8):471-6.
15. Singh S, Sivakumar R. Recent advances in the diagnosis of leishmaniasis. J Postgrad Med.
2003 Jan-Mar;49(1):55-60.
16. Telles S, Abate T, Slezynger T, Henriquez DA. Trypanosoma cruzi ubiquitin as an anti-
gen in the differential diagnosis of Chagas disease and leishmaniasis. FEMS
Immunol Med Microbiol. 2003 Jun 10;37(1):23-8.
10. Helminthic dermatoses
275
10. HELMINTHIC DERMATOSES
Aldo Morrone, Ugo Fornari
Dermatoses caused by helminthic infections are particularly frequent in the
tropical and subtropical regions. The climate, the socio-economic conditions,
poor hygiene and inadequate health facilities are all elements that favour onset.
In many tropical developing countries they represent a serious public health
problem.
Of dermatological interest are:
• Creeping eruption
• Filariasis
• Onchocerciasis
• Loiasis
• Dracunculiasis
9.1 Creeping eruption (Cutaneous larva migrans)
Synonyms: migrant or linear myiasis, larbish, plumber’s itch, water dermatitis, dermatitis verminosa serpiginosa, kutane larva migrans.
Definition: the disease is a cutaneous infection caused by a cats’ and dogs’
hookworm larva, the Ancylostoma brasiliense, and other dog species of hookworms, the A. caninum and and the Uncinaria stenocephala, or human parasites, such as the Strongyloides stercoralis, and the Necator americanus.
A similar cutaneous infection is produced by the Gnathostoma spingerum larva, a nematode present in Far East countries, and the Gasterophilus, or horse
fly. Human transmission requires temperature and humidity to be conducive
to the development of the filiform-infesting larva’s eggs. Humans are infected through contact with soil polluted by animal defecation. Parasites, principally the Ancylostoma brasiliense or A. caninum and Strongyloides stercoralis,
produce under the epidermis, advancing 2-3 cm per day, sinuous filiform
tracts disposed in a curious arabesque-like style.
Distribution: worldwide, but especially diffuse in the hot-humid tropical
and sub tropical regions.
Incubation period: larva migration begins 4 days after penetration; the complete clinical pattern appears after 18 days.
Clinical features: the areas affected are those that come into contact with the
276
parasites. The lesions can localize in any part of the body that has been in
contact with contaminated soil, principally legs and gluteal region.
They begin as pruriginous papules, followed by the formation of a serpiginous cutaneous relief, inflamed and very characteristic. They assume a progressive evolution, with sinuous bizarre forms, particularly if more larvae are
active. Parasite migration varies between a few mm to 2-3 cm a day, and can
last several weeks. The larva dies, because it is not adaptable to human organisms, generating clinical recovery. In general the mucous membranes of the
anal and genital regions are not involved. Pain is associated especially at
night, and secondary pyogenic infections are often also associated. The larva
migrans does not cause eosinophilia in circulating blood. Prevention is difficult because bathing suits can be crossed by the ancylostoma larva. On the
beach it is advisable to remain on those sandy areas covered by sea water; the
salty environment is, in fact, not favourable to the larva.
Diagnosis: based on: the history of a possible trip to some endemic region
and contamination with infected soil; on the characteristic clinical aspect of
the lesions; on the effectiveness ex iuvantibus of thiabendazole used locally or
generally. Cutaneous biopsy, if the fragment doesn’t contain the larva, is often ineffective, because non-pathogmonic.
Differential diagnosis: the cutaneous migration of an adult filaria of the Loa
loa species, bacterial and fungal infections and some manifestations of contact dermatitis and scabies need to be taken into consideration
Histopathology: an inflammatory superficial dermal process is present, rich
in eosinophils.
Therapy: self-recovery after weeks or months; cryotherapy with liquid nitrogen can be used. The use of thiabendazole, local or systemic, is indicated with
optimal results.
9.2 Filariasis
Synonyms: elephantiasis arabum, wucheriasis, brugiasis, Brug’s filariasis, filariose, elephantiasis filariensis, filariasis linfatica, filarioses lymphatiques, filariose.
Definition: caused by infection with the parasitic nematodes worms of the
family filariidae. Three species are of significance, Wuchereria bancrofti,
Brugia malayi and Brugia timori. which produce deformations called elephantiasis. It is thought that the filariae that parasitize humans infect more
277
than 200 million people, producing a vast quantity of varieties of pathological manifestations that are relatively characteristic to each parasite species.
Transmission
Via the bite of bloodfeeding female mosquitos which transmit immature larval forms of the parasitic worms from human to human. W. bancrofti parasites are mainly transmitted by Culex quinquefasciatus mosquitos and some
species of Anopheles. Brugia parasites are mainly transmitted by Mansonia
mosquitos. In humans, adult worms can live for many years, producing large
numbers of larval forms (known as microfilariae) which circulate in the lymphatics and blood where they can be ingested by bloodfeeding mosquitos, so
completing the transmission cycle.
Distribution: Endemic in over 80 countries in Africa, Asia, South and
Central America and the Pacific Islands. More than 40% of all infected people live in India and one-third live in Africa. Wuchereria bancrofti is the most
largely diffused human filaria: it is present in equatorial Africa, the Indian
subcontinent, southeast Asia, the western Pacific, the eastern Mediterranean
regions and Central and South America.
The total number of people infected with W. bancrofti is estimated to be
around 80-90 million. Brugia malayi has a more confined distribution, principally interesting Southeast Asia and the western Pacific, and the
Southwestern Indian coastal region. The number of people infected is estimated at around 9–10 million. W. bancrofti is transmitted through the bite
of a female mosquito of the genus Culex and/or in urban areas, the genera
Anopheles and Aedes. B. malayi is transmitted principally by a mosquito of
the genera Anopheles and Mansonia. It is believed that animal reservoirs play
no specific role in the lymphatic filariasis epidemiology. Infection is transmitted from person to person by mosquitoes that assume microfilariae during
blood meals.
Incubation period: male and female filariae couple inside the lymphatic system, and after 6-12 months microfilariae are freed into the blood. Initial clinical manifestations may be observed after 3-4 months; the male parasites can
live for decades in the human organism.
Clinical features:characterized by fever and lymphatic obstruction; headache
and pain along the course of the lymphatic vessels may be present.
Lymphangitis is often accompanied by lymphadenitis. At the objective examination the lymphatic vessels appear to be painful, tumid, hard and flushed;
the overlying skin is painful. The chronic lymphatic obstruction generates a
hardening oedema, with skin thickening and hyperkeratosis, which becomes
278
fragile, presents abrasions easily, and is subject to bacterial and mycotic super-infections. Elephantiasis of the leg, in W. bancrofti filariasis, typically involves the whole leg, while in the case of B. malayi the part above the knee
appears normal. Scrotum elephantiasis is a characteristic feature of the
W.bancrofti form and usually is not seen in the B. malayi form.
Symptoms:
Infective larvae develop into adult worms (known as macrofilariae) in the afferent lymphatic vessels, causing
severe distortion of the lymphatic system. Adult Wuchereria are often lodged
in the lymphatics of the spermatic cord, causing scrotal damage and swelling.
Elephantiasis painful, disfiguring swelling of the limbs- is a classic sign of
late-stage disease. There are three basic disease stages:
1. Asymptomatic: patient have hidden damage to the lymphatic system and
kidneys.
2. Acute: attacks of ‘filarial fever’ (pain and inflammation of lymph nodes
and ducts, often accompanied by fever, nausea and vomiting) increase
with severity of chronic disease.
3. Chronic: may cause elephantiasis and hydrocoele (swelling of the scrotum) in males or enlarged breasts in females.
Diagnosis: clinical manifestations and geographical areas where filariasis is
endemic allow for an easy diagnosis, which can be made by demonstrating
microfilariae in the blood, or (in the case of obstructive disease), on the basis
of clinical presentation. Other data may include eosinophilia and high antifilaria antibody levels.
Differential diagnosis: bacterial lymphangitis, gonorrhoea, other filariae infections such as Onchocerca, Loaloa and Mansonella.
Therapy: the treatment of choice for lymphatic filariasis is diethylcarbamazine citrate, 5mg/kg/day in divided doses for three weeks. This treatment
rapidly eliminates all the microfilariae from the blood and is in part effective
against the adult worms. There can be some adverse effects, such as persistent headache, fever with shivers, vertigo, nausea. These side effect seem to be
related to the death of the microfilariae, and are more prevalent in the first
two days of treatment, when the use of corticosteroids may be recommended. Ivermectin, the drug of choice in the case of onchocerciasis, seems to be
effective for lymphatic filariasis as well, although it only reduces microfilariae. In chronic lymphatic obstruction surgery may be performed.
recommended. Ivermectin, the drug of choice in the case of onchocerciasis, seems to be
effective for lymphatic filariasis as well, although it only reduces microfilariae. In chronic
lymphatic obstruction surgery may be performed.
279
Forma
Figure
9.2.2.
Filariasis.
Elephantiasis of the scrotum,
with verrucous, hyperkeratotic
lesions.
Figure
9.2.2. Filariasis. Elephantiasis of the scrotum, with verrucous, hyperkeratotic
lesions.
9.3 Onchocerciasis
9.3 Onchocerciasis
Introduction
Onchocerciasis, or river blindness, has plagued millions (mostly in Africa) for
Introduction
centuries. Its common name portrays the common perception of the disease
and its public health
- ithas
causes
severe
eye problems
including
perma- Its
Onchocerciasis,
or river impact
blindness,
plagued
millions
(mostly in Africa)
for centuries.
common
name portrays
of the disease
health
nent blindness,
and the
cancommon
shortenperception
life expectancy
by upand
toits15public
years.
Butimpact
in
- it causes severe eye problems including permanent blindness, and can shorten life
1990, another
of this
disease
was brought
atten-was
expectancy
by updevastating
to 15 years. impact
But in 1990,
another
devastating
impactto
of global
this disease
brought
to
global
attention.
New
knowledge
and
awareness
was
generated
about
tion. New knowledge and awareness was generated about skin disease in on-skin
disease in onchocercal infection. Biomedical and clinical aspects of the disease were
chocercal infection. Biomedical and clinical aspects of the disease were quantified, and for the first time, the socio-cultural aspects of onchocercal skin
disease were understood.
Biomedical aspects of skin disease:
• incessant itching
• bleeding and ulceration of skin
• secondary infections
• disfiguring skin lesions
• alterations of skin pigmentation
• rashes
• bone pain
• headache
• fatigue
280
Socio-cultural aspects of skin disease (particularly relevant to women):
• people worried that skin disease would affect their ability to interact socially
• people worried that they would never marry
• they feared being ostracized
• they had low self-esteem
• they experienced social isolation
• some considered suicide
• children were more likely to be distracted in school due to constant itching
This new knowledge contributed to, and reinforced plans to eliminate onchocerciasis in West Africa based on distribution of the drug ivermectin. It
changed the perception and actions of donors and disease control personnel,
and made it easier for health workers to engage and involve communities in
treatment programmes.
Synonyms: river blindness, onchocercose, enfermedad de Robles, erispela de
la costa, onchocerse, Onchozerkose.
Definition: onchocercosis, also defined as “river blindness”, is a chronic filariasis caused by the nematode Onchocerca volvulus, which infects only humans and gorillas. It manifests itself with a nodular dermatitis and ocular alterations. Onchocercosis is one of the four main causes of blindness in the
world. Infection begins with the inoculation of infecting larvae in the skin,
through bites of the female of Diptera Simulium (black fly).
Distribution: in the world there are at least 20 million people who present
an O. volvulus infection; the great majority of them are situated in equatorial Africa, in a belt that extends for more than 6 000 km, from the extreme
coastal region of the Atlantic Ocean to the Red Sea.
In Guatemala and Mexico there are about 80 000 infected people who live
at altitudes between 500 and1000 metres, on the Pacific side of the Sierra
Madre; in Venezuela there are 30 000 infected people. Minor foci have been
reported in Colombia, Brazil, Ecuador, Yemen and Saudi Arabia. The predominant vector in the majority of the endemic areas in Africa and South
Arabia is represented by Simulium damnosum. In Central America the principal vector is Similium ochraceum.
Incubation period: microfilariae may be found in the skin one or even more
years after the infection.
Clinical features: principal manifestations are dermatitis, subcutaneous nodules (onchocercoma), lymphadenitis, and visual disorders that lead to blind-
281
ness. In Africa the nodules containing the adult worms are located in correspondence of the coccyx, of the femoral trochanter and of the antero-lateral
iliac crest. In the American onchocerciasis they tend to distribute along the
neck, head and shoulders. Usually they are not painful and present a very
slow growing process. Itching is frequent and at times unbearable, even in the
presence of very few microfilariae. After about a year people affected with onchocerciasis develop greatly atrophic and wrinkly skin. Hyperkeratosis,
desquamation and pigment alteration may also be observed. In Africans a
slight or moderate adenopathy is present. The visual disorder is the most severe effect of the onchocerciasis; punctate sclerosing keratitis anterior uveitis
and iridocyclitis may be observed. In the forest areas of Africa the corioretinal lesions are the most frequent cause of blindness, rather than the sclerosing keratitis.
Diagnosis: based on the demonstration of the microfilariae. Cutaneous biopsy, besides delivering a definitive diagnosis, allows approximate evaluation of
the intensity of the infection. Microfilariae can be found in the urine, in the
cornea, in the anterior chamber and in the corpus vitreum. Mazzotti’s test can
be useful.
Differential diagnosis: it is necessary to take
into consideration other filariTherapy: the drug of choice is currently invermectin, with a do
asis forms, sebaceous cysts, fibroma, lipoma,
tuberous
xanthoma. The
single dose. Diethylcarbamazine
actsacute
only against the mic
forms of onchocerciasis have to be differentiated
erysipelas,
lepromaabandonedfrom
because
it causes severe
adverse effects; the sam
tous reactions, atopic dermatitis, contact dermatitis,
scabies,
cercaria
The elimination
of the vectors
with dermatilarvicide substances is the b
tis, prurigo.
Therapy: the drug of choice is currently
invermectin, with a dosage of 150-200
ug/kg in a single dose.
Diethylcarbamazine acts only against the
microfilariae; and it has been abandoned
because it causes severe adverse effects;
the same is true for mebendazole. The
elimination of the vectors with larvicide
substances is the best treatment.
Figure 9.3.1. Oncocerchosis.
Figure 9.3.1. Oncocerchosis.
282
Therapy: the drug of choice is currently invermectin, with a dosage of 150–200 ug/kg in a
9.4 Loiasis
single dose. Diethylcarbamazine acts only against the microfilariae; and it has been
abandoned because it causes severe adverse effects; the same is true for mebendazole.
Synonyms: Loa loa filariasis, calabar
swelling, Kamerunshwellung.
Definition: filariasis caused by the
Loa loa nematode transmitted by female haematophagous and common
horseflies of the genus Chrysops (red
fly). It presents the characteristic
Calabar’s oedema, an angioedematous
eruption, with a fast-evolving course,
often localized on the arms and legs.
Distribution: endemic in central
Africa; prevails particularly in the
coastal zones of western Africa at the
level of Nigeria and Cameroon. In
Figure 9.3.3 Fig. 9.3.3. onchocerchosis. some villages along the Congo river,
Typical Leopard spot.
more than 90% of the population is
infected.
Incubation period: microfilariae can appear in the peripheral infected blood
6-12 months after the infection. It is possible to observe symptoms after onFigure
9.3.1. Oncocerchosis.
ly 4 months,
or after years.
Clinical features: the principal disease manifestation is a transient subcutaneous oedema (Calabar’s oedema) that typically affects the distal extremities
or the soft tissues that surround the eye. It may appear as an allergic oedema
not correlated to the filaria migration, although it appears with the migration
of adult worms across the tissues; it can be painful, but resolves in 1-2 days.
In people who live in endemic areas we can observe fever, urticaria, intense
itching and marked eosinophilia, while in the indigenous population symptomatology is more moderate. The adult filariae live and migrate in the subcutaneos tissue; the microfilariae are present in the blood with a daily frequency: the maximum concentration takes place at midday. The migration of adult
worms under the bulbar cunjunctiva is accompanied by pain and oedema.
Diagnosis: in the endemic areas the subcutaneous oedema is suggestive for
the diagnosis, the adult worms can be found in the skin and in the cunjunctiva. Microfilariae can be identified in the peripheral blood. Eosinophilia is
always present. Immuno-diagnostic tests can be useful.
Differential diagnosis: needs to be distinguished from other forms of filariThe elimination of the vectors with larvicide substances is the best treatment.
283
asis, particularly the Wuchereria bancrofti, Onchocerca volvulus or
Mansonella perstans.
All other causes of urticaria and subcutaneous oedema must be taken into
consideration.
Therapy: the treatment consists in the surgical removal of the migrant adult
worms, if reachable, or in high doses of diethylcarbamazine citrate (400-600
mg/day for 2-3 weeks). Repeated cycles may be necessary. It is useful to associate antihistamines and cortisones in order to reduce allergic reactions. It is
recommended to test for possible drug reaction, by administering 25 grams
of diethylcarbamazine citrate.
It has been demonstrated that 300 grams of diethylcarbamazine citrate, once
a week, prevents infection in the population living in endemic regions.
9.5 Dracunculiasis
Synonyms: dracontiasis, Medina worm infection, Guinea worm disease, filaire de Medine, Medinawurm.
Definition: filariasis caused by the nematode Dracunculus medinensis
known also as Guinea worm or Medina’s filaria. Humans are contaminated
by drinking well water containing a small crostaceum of the genus Cyclops
infested with D. medinensis larvae. The disease is known since ancient times
and Agaterchide from Cnido, in 11 B.C. was the first to call the parasite
drakontion, “small dragon”.
It is probably with this that we can identify the “fire worm” mentioned by the
Bible (Numbers 11:6), from which the Jews suffered during their long journey to Edom. The maturation of the parasite is a long process and the parasite can survive one year. The adult Medina’s filaria is responsible for superficial or deep phlegmons; in the case of ulceration, consequent to the formation of a phlyctena, we can observe the filaria as a white cord.
Distribution: a disease with well-defined endemic centres and with a poor
tendency to diffuse.It is conditioned by precise ecological factors: persistently dry climate for long periods of the year, and consequent concentration of
the water resources, present the ideal conditions for the development of the
Cyclops, and of the worm larvae, in wells and ponds. The population is
obliged to collect water, submerging bare feet in water. Such situations occur
in temporary basins that are formed in the arid regions during the rainy seasons, or in the stepped wells in India.
284
The regions with higher endemia are India, tropical Africa and the Middle
East; the disease is also present in Pakistan, Iran and Iraq. Human beings represent the only reservoir of infestation.
Incubation period: At least 10-12 months have to pass for the complete development of the emerging adult female parasite.
Clinical features: during the long incubation period there are no particular
signs of deteriorating health. General symptoms such as fever, vertigo, gastrointestinal problems, dyspnea, urticated erythema usually anticipate the
acute phase of the disease that is characterized by the formation of papules,
blisters and superficial ulcers. Intense itching and a burning sensation at the
parasite perforation site is present. Later a blister forms that grows until it
reaches a few centimetres in diameter, before opening after 2-3 days. With
the opening it transforms into an ulcer that soon tends to closure, leaving only a small hole from which the worm protrudes. In the majority of the cases
between one and three worms protrude, but there may be even more.
Diagnosis: clinical diagnosis is practically impossible, until the first characteristic local symptoms appear, linked to the exit of the worm. X-ray can
highlight calcified D. medinensis.
Differential diagnosis: secondary complications of the disease, such as lymphangitis, gangrene, septicaemia and allergic reactions, require careful differentiation from other similar pathological conditions prevalent in the tropical
areas.
Therapy: progressive extraction of the worm through winding remains the
most effective and economical treatment. When the worm comes out, it has
to be fixed to a small stick and winded for 2-3 cm a day; in this way it will
be eliminated in about three weeks. To avoid complications bactericide
creams may be applied on the ulcers. Chemotherapy, unknown before 1965,
today uses metronidazole (successfully used in India) and diethylcarbamazine
and thiabendazole. Individual prophylaxis requires not to drink water that
could contain infested Cyclops, unless it is eliminated through boiling and
filtrating. The general prophylaxis is based on the destruction of the Cyclops,
not always an easy task given the risks involved in using insecticides and especially because of the sources of drinking water available to these populations.
285
Suggested Readings
Filariasi
1. Bruschi F, Castagna B. The serodiagnosis of parasitic infections Parassitologia. 2004
Jun;46(1-2):141-4.
2. Cuadros J.A., Martinez R., Lizasoain M., Alos J.I., Generalized pruritus and eosinophilia in an African woman, Enferm Infecc Microbiol Clin, 1992; 10: 169-170.
3. Durrheim DN, Wynd S, Liese B, Gyapong JO. Editorial: Lymphatic filariasis endemicity - an indicator of poverty? Trop Med Int Health. 2004 Aug;9(8):843-5.
4. Garraud O., Nkenfou C., Bradley J.E. et al. Identification of recombinant filarial proteins
capable of inducing polyclonal and antigen-specific IgE and IgG4 antibodies. J Immunol
1995; 155, (3): 1316-1325.
5. Sharma DC. India expands mass chemotherapy to eradicate filariasis. Lancet Infect Dis.
2004 Aug;4(8):478
Oncocercosi
1. Adjami AG, Toe L, Bissan Y, et al. The current status of onchocerciasis in the forest/savanna transition zone of Cote d’Ivoire. Parasitology. 2004 Apr;128(Pt 4):407-14
2. Wagbatsoma VA, Okojie OH. Psychosocial effects of river blindness in a rural community
in Nigeria. J R Soc Health. 2004 May;124(3):134-6.
Dracunculiasis
1. Greenaway C. Dracunculiasis (guinea worm disease) CMAJ. 2004 Feb 17;170(4):495500
2. WHO Dracunculiasis eradication. Wkly Epidemiol Rec. 2004 Jun 18;79(25):234-5.
English, French.
Loiasis
1. Akue J.P., Hommel M., Devaney E., Markers of Loa loa infection in permanent residents
of a loiasis endemic area of Gabon, Trans Royal Soc Trop Med Hyg, 1996; 90: 115-118.
2. Carme B., Boulesteix J., Boutes H., Puruhence M.F., Five cases of encephalitis during
treatment of loiasis with diethylcarbamazine, Am J Trop Med Hyg. 1991; 44 (6): 684690.
3. Klion A.D., Horton J., Nutman T.B., Albendazole therapy for loiasis refractory to diethylcarbamazine treatment., Clin Infect Dis. 1999; 29, (3): 680-682.
4. Klion A.D., Ottesen E.A., Nutman T.B., Effectiveness of diethylcarbamazine in treating
loiasis acquired by expatriate visitors to endemic regions: long-term follow-up, J Infect Dis
1994; 169 (3): 604-610.
5. Le Guyadec T., Wolkenstein P., Ortoli J.C. et al. Granulome à corps étrangers sur filaire
Loa loa calcifiée, Ann Derm Venereol, 1992 ; 119: 127-130.
6. Martin-Prevel Y., Cosnefroy H.Y., Tshipamba P. et al. Tolerance and efficacy of single highdose ivermectin for the treatment of loiasis, Am J Trop Med Hyg, 1993; 48: 186-192.
7. Morrone A, Franco G, Toma L, Tchangmena OB, Marangi M. A case of loiasis in Rome,
J Eur Acad Dermatol Venereol. 2002 May;16(3):280-3.
8. Noireau F., Apembet J.D., Nzoulani A., Carme B., Clinical manifestation of loiasis in an
endemic area in the Congo, Trop Med Parasitol, 1990; 41: 37-39.
286
9. Pakasa N.M., Nseka N.M., Nyimi L.M., Secondary collapsing glomerulopathy associated
with Loa loa filariasis. Am J Kidney Dis 1997; 30 (6): 836-839.
10. Pisella P.J., Assaraf E., Rossaza C. et al. Conjunctivitis and ocular parasitic diseases. J Fr
Ophtalmol 1999; 22(5): 585-588.
11. Shenoy R.K., John A., Babu B.S. et al. Two-year follow-up of the microfilaraemia of
asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin,
diethylcarbamazine and albendazole, in various combinations. Ann Trop Med Parasitol.
2000; 94, (6): 607-614.
11. Tabi TE, Befidi-Mengue R, Nutman TB, et al. Human loiasis in a cameroonian village:
a double-blind, placebo-controlled, crossover clinical trial of a three-day albendazole regimen.
Am J Trop Med Hyg. 2004 Aug;71(2):211-215.
13. Thomson M.C., Obsomer V., Dunne M. et al. Satellite mapping of Loa loa prevalence in
relation to ivermectin use in west and central Africa, Lancet, 2000; 356: 1077-1078.
11. Dermatoses due to malnutrition
287
11. DERMATOSES DUE TO MALNUTRITION
Aldo Morrone, Tesfalem Hagos
In vast tropical areas of South America, Africa and Asia, more than a third of
the population lives in conditions of chronic malnutrition.
Nutritional disorders may be defined as pathological conditions caused by
qualitative or quantitative deficiency or derangement of nutrient elements essential to normal tissues.
The malnutrition diseases of a dermatological interest are principally caused
by a calorie-protein deficiency and by hypovitaminosis:
• Kwashiorkor
• Hypovitaminosis A
• Pellagra
17.1 Kwashiorkor
Synonyms: protein-energy malnutrition (PME), malignant malnutrition,
nutritional dystrophy, kwashiorkor marasmus, EiweiBmangelkrankheit.
Definition: kwashiorkor is a typical childhood pathology, which principally
involves children between 6 months and 4 years old, characterized by severe
hypoproteinaemia, responsible for oedema with facies lunare, which covers
up the lack of fat, already consumed. Together with growth retardation,
anaemia, and muscular weakness, some typical dermatological manifestations
may be observed. The name kwashiorkor derives from the Ga dialect of
Ghana and means “first child-second child.” It refers to the observation that
the first child develops PEM when the second child is born and replaces the
first child at the breast.
Distribution: the WHO states that more than 400 million children in prescholastic age suffer from malnutrition in developing countries, and a great
number of them suffer from severe protein deficiency like kwashiorkor.
Clinical features: PME clinically presents three forms: the dry form, marasmus, results from near starvation with deficiency of protein and non-protein
nutrients. The wet form is called kwashiorkor. The weaned child is fed a thin
gruel of poor nutritional quality (compared with mother’s milk) and fails to
thrive. The protein deficiency is usually more marked than the energy deficiency, and oedema results. The combined form of PEM is called marasmic
288
kwashiorkor. Children with this form have some oedema and much body fat.
Mucocutaneous alterations are the most frequent lesions. The onset in many
cases is insidious. It is possible to observe stomatitis, cheilitis, conjunctivitis,
blepharitis, and a characteristic dermatitis, erythematous and cyanotic, with
a “painted” (flaky paint dermatitis) aspect. Subsequently the cutaneous lesions assume a hyperpigmented character, with a tendency to form rhagades,
bullae and erosions with well-defined borders. The most affected areas are the
perineum, the regions under mechanical pressure, and the folds. In black
children hair assumes a characteristic large band pigmentation that varies
from lucent brown, to red and to white, and develops in successive cycles
(flag sign). General symptoms are associated such as anaemia, hepatomegalia,
marasma, and mental retardation. Secondary infections and ulcerations may
also be observed.
Diagnosis: diagnosis depends largely on the patient’s history, on the country
on origin, on the clinical oedema signs and on cutaneous manifestations.
Hypo-albuminaemia in these cases is significant.
Differential diagnosis: must be made in confrontation with childhood pellagra, with ankylostomiasis with oedema and anaemia, abdominal tuberculosis, nephritis and celiac disease.
Histopathology: hepatic biopsy shows a fat degeneration. Cutaneous alterations are variable. The epidermis can appear atrophic with hyperkeratosis or
parakeratosis.
Therapy: for children and adults who have severe protein energy malnutrition
(kwashiorkor), the first step is to correct fluid and electrolyte abnormalities and
to treat infections with antibiotics. The most common electrolyte abnormalities are hypokalemia, hypocalcemia, hypophosphatemia, and hypomagnesemia. Children with PEM should be treated with I.V. fluids. The initial rehydrating fluid is Darrow’s solution, which contains 1:2:3 parts by volume of
0.17 M lactate: normal saline:5% glucose, to which 50 ml of 50% D/W is
added to each 500 ml. This solution supplies 78 mEq/L of sodium and 55
mM/L of glucose. The water deficit should be replaced over the first 8 to 12 h
of therapy. The use of I.m. iron or high doses of oral iron (100 to 200 mg/day
of elemental iron) in children is very important. IM iron immediately increases bone marrow iron stores. For oral rehydration in adults, a solution containing 90 mEq/L sodium, 20 mEq/L potassium, 80 mEq/L chloride, 30 mEq/L
bicarbonate, and 111 mM glucose/L given in divided doses over 24 h is satisfactory. The second step, which may be delayed 24 to 48 h in children (to
avoid worsening the diarrhoea), is to supply macronutrients by dietary thera-
kcal/kg and 2 g of protein/kg for adults can be given. When diarrhoea
may be kept NPO (nothing per os) for up to 48 h. When diarrhoea su
the first 48 h), the i.v. is discontinued and oral feeding
289 begins.
py. Milk-based formulas are the
treatment of choice. The amount is
gradually increased during the first
week; after a week, the full rate of
175 kcal/kg and 4 g of protein/kg
for children and 60 kcal/kg and 2 g
of protein/kg for adults can be given. When diarrhoea is severe, the
patient may be kept NPO (nothing
per os) for up to 48 h. When diarrhoea subsides (usually during the
first 48 h), the i.v. is discontinued
and oral feeding begins.
Figure 17.1.1 kwashiorkor: erythematocianotic lesion, with a painted aspect, in a
child from Ethiopia.
Figure 17.1.1 kwashiorkor: erythemato-cianotic lesion, with a paint
from Ethiopia.
17.2 Vitamin A deficiency (Hypovitaminosis A)
Synonyms: retinal deficiency, phrynoderma, avitaminosis A, Vitamin-AMangelkrankheit.
Definition: vitamin A deficiency is associated with various ocular disorders
and with mucocutaneous characteristic manifestations. Children and young
adults are the most affected by the disease.
Distribution: ubiquitous, but particularly frequent in the tropical and sub
tropical regions.
Clinical features: skin appears dry and wrinkled, itchthyosiform, squamous
and xerotic. On the arms, head, shoulders and trunk follicular hyperkeratosis (phrynoderma) may be observed. It is possible to observe sebaceous and
sudoriparous gland atrophy. Hemeralopia and keratomalacia are the affection’s ophthalmic typical manifestations.
Diagnosis: diet history, endemia of the country of origin, cutaneous and ocular manifestations suggest the diagnosis. Vitamin A dosage is indicative.
Differential diagnosis: ichthyosis vulgaris, keratosis pilaris, follicular keratosis and Darier’s disease have to be taken into consideration.
Histopathology: It is possible to observe sebaceous and sudoriparous gland
atrophy.
290
Therapy: treatment with adequate vitamin A doses (vitamin A palmitate in
oil 60 000 IU daily for 2 days and once before discharge from the hospital
after 7 to 10 days) is usually effective. Since xerophthalmia is the major cause
of blindness among young children in most developing countries, prophylactic doses of 200 000 IU of vitamin A palmitate in oil orally once every 3 to
6 mo are advised for all children aged 1 to 4 yr; the dose is halved for those
under to 1 yr. The diet should include dark green leafy vegetables and yellow
fruits, such as mango and pawpaw. Bread, sugar, and monosodium glutamate
are fortified with vitamin A. For secondary deficiency, vitamin A supplements should be given routinely. Infants suspected of being allergic to milk
should be given adequate vitamin A in the substitute formula. It is advisable
to avoid excessive vitamin A dosage.
17.3 Pellagra
Synonyms: nicotinic acid deficiency, niacin hypovitaminosis, pellagra, pellagroid.
Definition: the complete syndrome of vitamin PP deficit includes dermatitis, diarrhoea, dementia (the “three D syndrome”), stomatitis and glossitis. It
is often observed in rural populations that are used to eating excessive quantities of corn and only assume very small quantities of animal proteins and
fresh fruit. Corn is rich in nicotinic acid, more than rice, but almost all of it
is present in a form not absorbable by the body.
Distribution: very frequent in the tropical and sub tropical regions of the developing countries, particularly in populations with a diet based exclusively
on corn. Still represents a severe problem in many African countries, in Latin
America and India. The first description of the disease, observed in Asturias
around 1835, was recorded by the Spanish doctor Gaspar Casal.
Clinical features: the clinical pattern is characterized by a triad, prevalently
cutaneous, but with a gastrointestinal and at times neurological involvement.
Cutaneous lesions are usually symmetrical and are represented by a dark red
erythema, with well defined borders, that rapidly appears on the exposed areas, accompanied by oedema. Skin appears thin and fissured; later a bullous
leak, with a sero-haemorrhagic content, may be observed, which slowly recovers leaving atrophic and pigmented skin. Diarrhoea, stomatitis and glossitis can at times precede the cutaneous manifestations. In the worst forms
apathy, depressive syndromes, sensitive disturbances and dementia are present. Pellagra is a slowly progressive process.
291
Diagnosis: the clinical aspect of the lesions, in the pellagra endemic zones,
suggests the diagnosis. A still valid diagnostic criterion is the ex-iuvantibus
test by vitamin load: after the therapy with PP vitamin, successful recovery
may be observed.
Differential diagnosis: cutaneous lesions have to be differentiated from solar dermatitis, contact dermatitis, porphyria cutanea tarda, neurodermitis,
erythematous lupus and Hartnup’s disease.
Histopathology: inflammatory infiltrates in the superior derma and in the
sub-epidermis bullae.
Later hyperkeratosis appears with parakeratosis, moderate acanthosis,
melanin growth, oedema and chronic derma inflammatory infiltrate.
Therapy: PO nicotinamide or niacin usually is effective in reversing the clinical manifestations of pellagra. Oral or preferably parenteral administration
leads to a rapid regression of the cutaneous manifestations and subsequent recovery of the neurological and gastroenterological conditions. Providing a diet high in protein and adequate in calories is very important. The addition of
meat, milk, peanuts, green leafy vegetables, whole or enriched grains, and
brewers’ yeast can enhance the niacin intake. In patients with oral dysphagia
secondary to glossitis, a liquid or a semisolid diet may be required. Long-term
inclusion of milk, meat, and eggs in the diet ensures dietary adequacy of proteins essential for recovery. Alcoholic intake must be forbidden.
292
Suggested Readings
1. Stratigos JD, Katsambas AD: Pellagra: A reappraisal. Acta Vitaminol Enzymol 1982; 4:
115-121.
2. Garcia-Albea Ristol E: Deficiency neuropathies in Madrid during the Civil War period.
Neurologia 2000; 15: 141-142.
3. Malfait P, Moren A, Dillon JC et al: An outbreak of pellagra related to changes in dietary
niacin among Mozambican refugees in Malawi. Int J Epidemiol 1993; 22: 504-511.
4. Rajakumar K: Pellagra in the United States: a historical perspective. South Med J 2000;
93: 272-277.
5. Ryan B: Severe measles in Vietnam. Med J Aust 1976; 1: 353-355.
6. Cripps DS, Peters HA, Gormen A et al: Porhyria turcica due to hexachlorobenmzene. A
20 to 30 year follow-up study of 204 patients. Br J Dermatol 1984; 111: 413-422.
Dermatosis caused by malnutrition
1. Collins S, Sadler K. Outpatient care for severely malnourished children in emergency relief
programmes: a retrospective cohort study. Lancet. 2002 Dec 7; 360 (9348):1824-30.
2. Fongwo NP, Arinola OG, Salimonu LS. Leucocyte migration inhibition factor (L-MIF)
in malnourished Nigerian children Afr J Med Med Sci. 1999 Mar-Jun; 28 (1-2):17-20.
3. Fontaine O, Beau JP, Ndiaye AM. Oral rehydration and nutritional rehabilitation of severely malnourished children. Child Trop. 1985;(158):56-63.
4. Gernaat HB, Dechering WH, Voorhoeve HW. Mortality in severe protein-energy malnutrition at Nchelenge, Zambia. J Trop Pediatr. 1998 Aug;44(4):211-7.
5. Golden MH. Oedematous malnutrition. Br Med Bull. 1998;54(2):433-44.
6. Kahn K, Tollman SM, Garenne M, et al. Who dies from what? Determining cause of death
in South Africa’s rural north-east. Trop Med Int Health. 1999 Jun;4(6):433-41.
7. Kessler L, Daley H, Malenga G, Graham S. The impact of the human immunodeficiency
virus type 1 on the management of severe malnutrition in Malawi. Ann Trop Paediatr. 2000
Mar;20(1):50-6.
8. Kuhl J, Davis MD, Kalaaji AN, Kamath PS, Hand JL, Peine CJ. Skin signs as the presenting manifestation of severe nutritional deficiency: report of 2 cases. Arch Dermatol. 2004
May;140(5):521-4.
9. McLaren DS. Skin in protein energy malnutrition. Arch Dermatol 1987; 123: 1674-6.
10. Miller SJ. Nutritional deficiency and the skin. J Am Acad Dermatol 1989; 21: 1-30
11. Oumeish OY, Oumeish I. Nutritional skin problems in children. Clin Dermatol. 2003
Jul-Aug;21(4):260-3. Review.
12. Stephen CA, Thame MM, Gray R, Barker D, Wilks R, Forrester TE, McKenzie CA.
Primary malnutrition. Can we always tell? West Indian Med J. 2002 Sep; 51(3):148-52
Kwashiorkor
1. Amadi B, Kelly P, Mwiya M, et al. Intestinal and systemic infection, HIV, and mortality
in Zambian children with persistent diarrhea and malnutrition. J Pediatr Gastroenterol
Nutr. 2001 May;32(5):550-4.
2. Ashour MN, Salem SI, El-Gadban HM, Elwan NM, Basu TK. Antioxidant status in
children with protein-energy malnutrition (PEM) living in Cairo, Egypt. Eur J Clin Nutr.
1999 Aug; 53 (8): 669-73.
293
3. Iputo JE, Sammon AM, Tindimwebwa G. Prostaglandin E2 is raised in kwashiorkor. S
Afr Med J. 2002 Apr; 92 (4):310-2.
4. Krawinkel M. Kwashiorkor is still not fully understood. Bull World Health Organ.
2003;81(12):910-1. Epub 2004 Mar 01.
5. Lenhartz H, Ndasi R, Anninos A, Botticher D, Mayatepek E, Tetanye E, Leichsenring
M. The clinical manifestation of the kwashiorkor syndrome is related to increased lipid peroxidation. J Pediatr. 1998 May;132(5):879-81.
6. Liu T, Howard RM, Mancini AJ, et al. Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance. Arch Dermatol. 2001 May; 137
(5):630-6.
7. Manary MJ, Broadhead RL, Yarasheski KE. Whole-body protein kinetics in marasmus and
kwashiorkor during acute infection. Am J Clin Nutr. 1998 Jun;67(6):1205-9.
8. Nguyen J, Cazassus F, Atallah A, Baba N, Sibille G, Coriatt D. Kwashiorkor after an exclusion diet for eczema Presse Med. 2001 Oct 20; 30 (30):1496-7.
Vitamin A deficiency
1. Haidar J, et al. Malnutrition and xerophthalmia in rural communities of Ethiopia. East Afr
Med J. 1999 Oct;76(10):5903
2. Khandait DW, et al. National Vitamin A Prophylaxis Programme: need for change in current age strategy. Indian J Pediatr. 1999 NovDec;66(6):8259.
3. Rajeshwari K. Vitamin A supplementation in early infancy. Indian Pediatr. 1999 Apr;
36(4):4202.
Pellagra
1. Cervantes-Laurean D, McElvaney NG, Moss J. Niacin. In: Shils ME, Olson JA, Shike
M, et al., Modern Nutrition in Health and Disease. 9th edn. Baltimore: William &
Wilkins Co, 1998: 401-411.
2. Hampl, J. S. and Hampl, W. S. (1997) Pellagra and the origin of a myth: evidence from
European literature and folklore. J. Roy. Soc. Med. 1997, 90; 636-639
3. Karthikeyan K, Thappa DM. Pellagra and skin. Int J Dermatol, 2002; 41 (8), 476-81.
4. Katrak SM, Desai JD, Yasha TC, Shankar SK. Dementia in tropics. In: Chopra JS,
Sawhney IMS, eds. . New Delhi: B.I. Churchill Livingstone, 1999: 594-609.
5. Murray MF. Niacina as a potential AIDS prevention factor. Medical Hypothesis. 1999;
53: 375-379.
6. Ruze P. Kava-induced dermopathy: a niacin deficiency? Lancet 1990; 335: 1142-5.
7. Stratigos JD, Katsambas A. Pellagra: a still existing disease. Br J Dermatol 1997; 96: 99106.
8. Taori GM, Iyer V. Nerulogical manifestations in nutritional deficiencies. In: Chopra JS,
Arjundas G, Prabhakar S, eds. Textbook of Neurology. New Delhi: B.I. Churchill
Livingstone, 2001: 466-484.
294
BIANCA
295
12. Ethnodermatology
12. ETHNODERMATOLOGY
Introduction
The world’s Mobile Human Population, people who temporarily or permanently cross borders for reasons of employment, politics or tourism, comprised 1,4 billion people in 2005. In particular, 200 million people travelled
in search of employment. This demonstrates increasing desperation in the
world: in the eighties the number was 70 million. Mobility has always been
a necessity for humanity and has constantly been mixing human geography
and state of health. Travelling always includes danger and the risk of illness;
the word itself possesses a relationship to illness. In fact, the Greek noun
επιδε ια and the verb επιδε εο originally meant journeying to arrive and settle in a foreign land. The profoundly rooted idea that travelling is an experience that builds character and tests the health of the traveller is seen clearly
in the German adjective bewandert that today means “shrewd” or “expert”,
but in the 15 century simply meant “well-travelled”. The English verbs to
fare and to fear have the same etymological root and have the experiential terrain in common, within the idea of travelling.
TH
Ethnomedicine
Another feature of recent history, paralleling the phenomenon of immigration, is the growing interest in ethnomedicine in the West countries. This discipline protects and reclaims the medicinal culture of developing countries.
The forms and qualities of natural or traditional therapies used by people in
tropical or “distant” countries continually stimulates anthropological and
medical curiosity and interest in Europe. The remedies used are often perceived as a mix between medicine and magic, where it is difficult to separate
one from the other. We have no difficulty in admitting that certain plants
have unanimously recognized therapeutic qualities but we view the rites, celebrations and attitudes of appeasement that often accompany therapeutic
events or are themselves viewed as therapeutic events, with healthy scepticism. But more than anthropological interest, the clinical and scientific interest that “other” cultures have raised in Europe and the US has resulted in millions of patients using remedies and therapies defined “complementary” or
“natural”. Furthermore, these disciplines are taught in many universities, and
296
many hospitals have created or are planning to open wards that incorporate
and study these new/ancient medicines.
In contrast to the past, researchers now rarely go to distant countries to study
other habits and medicines. The phenomenon of immigration means that patients, with their different cultures, rites and habits “bring” the concrete use
of “other” medicines to Italy and Europe.
In today’s multi-ethnic societies, ethnomedicine can be a useful aid for
Western physicians and health-care personnel in understanding immigrant
illness.
In fact, whether in an intercultural or intracultural context, patients present
themselves with the totality of their experiences and their knowledge and are
examined by people who are likely to have a completely different perspective.
Misunderstanding is often an obstacle to effective treatment. Knowing what
is being talked about and how to discuss it together, and knowing in what
overall scheme the patients’ comments are contextualized leads to a better understanding of how to treat their suffering and improves the effectiveness of
treatment.
We have seen a return of scientific attention to natural treatments, remedies
derived from ancient medical practices such as Ayurveda, centuries-old
Indian medicine, based on an extraordinary body of work or the long tradition of Chinese medicine and particularly acupuncture in recent years. There
are many forms of complementary medicine, and international debate between the proponents and detractors of these practices is lively. In this article, we will limit ourselves to describing certain skin conditions most frequently observed as side effects of alternative medical practices, putting aside
for the moment the debate on the usefulness of complementary or alternative medicine, as dealt with by Witkowski and Parish in 2002.
Ethnodermatology
Our service has an extremely varied patient group, coming from different and
distant geographical and cultural situations. In our out-patient clinic we see
more and more frequently people of different coloured skin, with skin lesions
that are difficult to identify. It is very important to understand the country
of origin and related cultural behaviours, which often have an effect on skin
and venereal clinical pictures. It is thus possible, after taking an accurate case
history and doing a careful medical examination, to reveal particular and
varying behaviours that may lead to the appearance of certain skin lesions.
Some of these conditions derive from peculiar cosmetic practices, such as ac-
297
quired ochronosis, alopecia and follicular-occlusive disturbances. Others are
linked to traditional medical practices such as cupping, coining, scraping,
moxibustion or to anthropological and ritual reasons, such as female genital
mutilation and keloids resulting from perforation. At the Centre for
Preventive Medicine for Migration, Tourism and Tropical Dermatology of
the San Gallicano Institute numerous dermatological disturbances related to
various common cultural practices in use in the country of origin have been
observed. The difficulty of diagnosing and doing a differential diagnosis and
follow-up due to the particular “mobility” of this population is critical.
These cultural behaviours can be subdivided into:
1. Cosmetic habits
2. Traditional medical practices
3. Anthropological and ritual motives
4. Psycho-cultural motives
1. Among traditional cosmetic practices that produce dermopathologies
we find the use of:
• depigmentation substances
• hair products
• greasy creams
The use of depigmentation products containing hydroquinone can have the
opposite effect from that intended and lead to ochronotic type hyperpigmentation of dark skin. The pathogenic mechanism lies in the inhibition of oxidase of homogentisic acid in skin, with a consequent local accumulation of
the acid in the skin and successive polymerization and production of
ochronotic fiber.
The characteristic xerosis of dark skin and particularly of the skin of immigrants from the Indian subcontinent induces them to use continually greasy
substances, with a consequent development of follicular-occlusive phenomena. The clinical picture is often that of so-called “pomade acne”, made up of
usually comedonic lesions, with few inflammatory elements, but which may
leave pigmentary results for a long time.
2. The principal traditional medical practices leading to lesions are:
• cupping
• coining
• moxibustion
• piercing
Lesions resulting from traditional medicine must often be looked at using
differential diagnosis with sexual abuse, in particular in infancy.
298
Cupping, which consists in the application of hot glass cups or suction cups
in which a vacuum has been created. In dry cupping the interior of a round
glass cup is covered with alcohol. The alcohol is then burned and the cup applied to the skin. In the wet method an incision is made on the skin and the
cup is applied in such a way as to encourage bleeding. The vacuum created
by the combustion of air creates suction on the skin within the cup, with consequent local hyperemia. There are many hypotheses for the use of cupping,
from biophysical mechanisms to magic-ritual practices. The most common
are:
– Driving evil spirits out (medicine men in primitive cultures)
– Draining of “humours” from diseased internal organs (ancient Greece)
– Theory of “counter-irritation”
– Nerve and hormone theories
– Psychosomatic theories
– Chinese theory of energy
In the humoral theory, cupping drains “humours” from the area below the
skin, therefore eliminating pathologies from internal organs damaged by an
excess of humour. The theory of counter-irritation states that irritation of the
skin, in producing local hyperemia with an increase in blood-flow to the surface, eliminates congestion in diseased internal organs. The nerve and hormone theories state that irritation of the skin causes a nervous or hormonal
reflex reaction that produces favourable circulatory or trophic effects on the
organs below.
Coining consists in vigorously rubbing a coin over the chest or back after applying hot oil or Tiger Balm, to the point of creating ecchymosis and linear
petechiae. The idea is to “liberate the breath” and has a therapeutic goal in
curing a myriad of adult disturbances but particularly fever in children.
Superficial observation often causes coining lesions (cao-gio in Cambodian)
to be mistaken for child abuse.
Moxibustion uses heated sticks, incense or herbal sticks such as artemisia
vulgaris. The material used takes the name of moxa. The artemisia is placed
inside burning cones or moxa cigars are used, which may cause burns, generally in the abdominal, neck or heel regions. It is often used as a last resort
when other methods have not been effective or for chronic respiratory illness.
Piercing (perforation of the skin) is traditionally used to distinguish the roles
of members within a tribe. It regulates the relations between individuals, both
day to day and during ceremonies, establishing with a single glance the position of the individual in relation to the group. Nowadays it is very fashion-
299
able among young people in the West. It often causes dermatitis due to contact with nickel sulphate.
3. Among anthropological-ritual dermopathologies are found:
• Female Genital Mutilation (FGM)
• Scarification (scraping, branding, cutting)
• Tattoos
• Perforation (lip plates, ear plates )
Female Genital Mutilation (FGM) is a condition that, while originating in
distant countries and regions, is frequently observable in our country due to
the continuous flow of people from the African continent, particularly Egypt,
the Horn of Africa and sub-Saharan Africa. While being frequently practiced
by people of the Islamic religion, it is also observed among Christian populations, animists and Jews (Ethiopian Falashas).
In this connection, for a clear definition of FGM, it would be appropriate to
report here the joint statement issued in April 1997 by the World Health
Organization (WHO), by the United Nations International Children’s
Emergency Fund (UNICEF), and by the United Nations Population Fund
(UNFPA): ” Female genital mutilation comprises all procedures involving
partial or total removal of the external female genitalia or other injury to the
female genital organs whether for cultural or other non-therapeutic reasons”.
The three agencies also classified the different types of FGM as follows:
Type 1. Excision of the prepuce, with removal of all or part of the clitoris.
Type 2. Excision of the clitoris, with removal of all or part of the labia minora.
Type 3. Excision of all or part of the external genitalia and narrowing of the
vaginal opening (infibulation).
Type 4. Unclassified: includes perforation, penetration or incision of the clitoris and/or labia; stretching of the clitoris and/or labia; cauterization by
burning the clitoris and surrounding tissue; scraping of the tissue surrounding the vaginal opening (angurya cuts) or incision of the vagina (gishira
cuts); introduction of corrosive substances or herbs into the vagina to cause
bleeding in order to close or tighten it; and any other procedure falling under the definition of FGM.
The complications observed are serious, both physical (haemorrhagic shock,
vaginal fistulae, keloids, dermoid cysts) and psycho-sexual. A specially created law prohibits the practice being carried out in Italy.
Scarification is the creation, through whatever technique, of one or more
permanent scars in any area of the skin. It is used in African societies for dec-
300
oration of the face or for medical reasons.
Branding is a particular form of scarification using heated metal instruments.
Cutting is carried out by incision of the skin, repeated in the same spot over
time, with the goal of obtaining a clear and visible mark. In other cases, the
wounds are temporarily kept open in order to create a pronounced scar like
a keloid.
Cutaneous perforations are common in ethnic groups from Central Africa.
One of these is the lip disk. The women of the Mursi tribes in Ethiopia use
a rounded disk made of clay and the perforated lip is continually manipulated to make it more elastic and capacious. Sometimes the lower incisors are removed to create more stability. In Sudan, Suma women use a rectangular
plate made of light Balsa wood. The lower incisors are removed for greater
stability. If the lip, freed from its plate, reaches up to the top of the woman’s
head, she will be especially prized and her dowry extremely large.
4. Among psycho-cultural motivations are found:
• Dhat Syndrome
The term “Dhat Syndrome” was coined by Wig in 1960 and describes a culture-bound syndrome common in the Indian sub-continent, related to a
Hindu theory according to which seminal fluid is rich in a particular vital
force and losing it impoverishes the physical and psychic energy of the individual.
This disorder is characterized by profound anxiety over the loss of seminal
fluid through ejaculation and wet-dreams. The term “culture-bound” means
a psychopathological entity of defined geographic prevalence determined by
the beliefs and paradigms of a specific cultural area. Clinical symptomatology
often mimics prostatitis, aspecific urethritis or epididymitis, with consistent
negative results of microbiological exams. Patients complain of anxiety, feeling unwell, burning sensations, weakness, psychic disturbance and trembling.
Most clinical studies have investigated the phenomenon of “Dhat Syndrome”
in the resident population in the country of origin. In Italy, an increasing
number of cases can be seen in immigrants. A multidisciplinary approach is
very important, with the presence of anthropologists, ethno-pyschologists
and the help of linguistic-cultural mediators.
Conclusions
In every era and in every human population, a particular vision of the world
and perception of health and illness is constructed through culture and
301
knowledge. People interpret their own situation in forms and ways based on
their culture’s knowledge, which is transmitted and used in everyday life,
through different rites and rituals.
From this knowledge, each group focuses on and develops whatever appears
most useful for their well-being and turns it into tradition. Representations
of good and evil, wisdom and foolishness, physiology and pathology are articulated through a variety of cultural models. Differing classifications are
made according to different knowledge and the meeting of complementary
and conventional medicine produces complex and fluid situations. Today we
have the fascinating task of reading and developing these, for our own future
and the future of our children. Dermatology is the medico-scientific discipline that, more than any other, may help all of us in this historical challenge.
302
References
1. Halder RM, Nootheti PK., Ethnic skin disorders overview., J Am Acad Dermatol. 2003
Jun;48 (6 Suppl):S143-8.
2. Carter EL., Race vs ethnicity in dermatology.. Arch Dermatol. 2003 Apr;139(4):539-40;
3. Ramos-E-Silva M., Ethnic hair and skin: what is the state of the science?. Chicago, IllinoisSeptember 29-30, 2001, Clin Dermatol. 2002 May-Jun;20(3):321-4.
4. Bolaffi G., Bracalenti R., Braham P, Gindro S. (edited by), Dictionary of Race, Ethnicity,
& Culture, 2003, London, Sage Publications
5. Morrone A, Hercogova J., Lotti T, Stop female genital mutilation: appeal to the international dermatologic community, Int J Dermatol. 2002 May;41(5):253-63
6. Taylor SC., Epidemiology of skin diseases in people of color.,Cutis. 2003
Apr;71(4):271-5
7. Rees JL., Two cultures?, J Am Acad Dermatol. 2002 Feb;46(2):313-6.
8. Amshel CE, Caruso DM. Vietnamese “coining”: a burn case report and literature review,
J Burn Care Rehabil 2000 Mar-Apr;21(2):112-4
9. Bhatia MS An analysis of 60 cases of culture bound syndromes. Indian J Med Sci. 1999
Apr; 53 (4): 149-152.
10. Look KM, Look RM. Skin scraping, cupping, and moxibustion that may mimic physical abuse., J Forensic Sci. 1997 Jan; 42 (1): 103-5.
11. Morrone A, Hercogova J, Lotti. Stop female genital mutilation: appeal to the international dermatologic commuty. Int. J. Dermatol. 2002 May; 41 (5): 253-63
12. Witkoski JA, Parish LC. The Other Medicine: Complementary and Alternative-Why,
Why Not? Clinics in Dermatology, 2002;20:456-460
13. Yang J. The history of cupping therapy, Zhonghua Yi Shi Za Zhi. 1999 Apr; 29(2): 82-4.
Figure
1. traditional tattoo in an Ethiopian girl
303
Figure 1. Traditional tattoo in an Ethiopian
girl
FGM Type I
Area of tissue removed - Type I FGM (Sunna)
Type
ype I I
Type
ue
rem
- pe
pe
I FGM
(Sunna)
rem
oveove
d - dTy
I FGM
• Ty
Excision
of(Sunna)
the
prepuce,
with or without
excision of part or all of the clitoris.
n of
the
prepuce,
with
without
excision
of
the
prepuce,
with
oror
without
excision
ofof
l of
the
clitoris.
of
the
clitoris.
FGM Type II
Area of tissue removed - Type II FGM (khefad or tahara)
Type
ype II• II
Type
Excision of the clitoris with partial or
total excision of the labia minora.
sue
removed
- Type
II FGM(khefad
(khefad
tahara)
ssue
ue
removed
- Type
II FGM
or or
tahara)
n of
the
clitoris
with
partial
total
excision
of
the
clitoris
with
partial
oror
total
excision
ofof
minora.
f the clitoris with partial or total excision of
nora.
304
FGM Type III
Area of tissue removed - Type III FGM
ype III
• Excision of part or all of the external
genitalia
andIIIstitching/narrowing
of the
FGM
e removed
- Type
vaginal opening (infibulation).
f part or all of the external genitalia and
arrowing of the vaginal opening
n).
Appearance of Type II after suture
Appearance of Type III after suture
13. Emerging and re-emerging infectious diseases
305
13. EMERGING AND RE-EMERGING
INFECTIOUS DISEASES
Smallpox
Bertram L. Jacobs (Arizona State University, Tempe, AZ) opened the conference with a presentation on smallpox, one of the most devastating diseases
known to humankind. Smallpox was eradicated from the wild in the 1970s,
although the potential use of Variola virus as a bioterrorism agent makes it
still of great concern. Dr. Jacobs described Vaccinia viruses deficient in E3L,
a regulator of the cellular antiviral response and noted their potential for the
production of improved vaccines. He also showed that double-stranded
(ds)RNA- and ZDNA binding proteins had a role in poxvirus pathogenesis.
In the poster section, Joanna Shisler (University of Illinois at UrbanaChampaign [UIUC], Urbana) reported that the modified virus, Ankara, activates nuclear factor kB through the mitogen-activated protein kinase, extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase
(ERK) pathway, possibly facilitating the host immune response. This virus
was used to vaccinate 100,000 people, with no reported complications, at the
end of the global smallpox vaccination campaign led by the World Health
Organization in the 1970s.
West Nile Virus and Geographic Information Systems
Since it was first detected in New York City in 1999, West Nile virus (WNV)
has spread from coast to coast and has been found in 43 states from Maine
to California. Stephen C. Guptill (U.S. Geological Survey, Reston, VA) reported that the U.S. Geological Survey is working with the Centers for
Disease Control and Prevention (CDC) to learn the current geographic extent of WNV. This will allow us to understand how it moves between birds,
mosquitoes, and humans and to better predict future outbreaks. A collaborative 3-year research project is being conducted on lands administered by the
U.S. Fish and Wildlife Service, the National Park Service, and other federal
lands, and on state, local, and private lands along the Atlantic and Mississippi
flyways. This study tests sampled migratory and local wild birds to detect
WNV and identify possible avian carriers. Over 10,000 birds of more than
150 species have been captured, sampled, and released at 20 federal sites and
306
3 other sites in 12 states during the spring and fall bird migration seasons of
2001 and 2002. A parallel study, conducted with CDC, is examining the distribution and number of mosquito species in relation to land cover, weather
conditions, and avian deaths. Systematic mosquito surveillance (weekly collections at seven sites) is being conducted year-round in St. Tammany Parish
in Louisiana, complementing avian collections at the Bogue Chitto and Big
Branch National Wildlife Refuges in the parish. Finally, WNV surveillance
data from CDC is being studied to determine the spatial and temporal relationships between disease outbreaks in birds and animals and human illness.
Information from these analyses will guide the creation of predictive models
of disease risk. These surveillance systems provide the basic information on
the “geography” of the virus. Combining these data with information about
avian migratory patterns, landscape characteristics, and weather conditions,
over space and time, will provide the foundation for developing spatial analytical and forecasting models to assess the risk for human illness. In related
work, presented at the poster session, Marylin Ruiz (UIUC, Urbana) reported the efforts of the College of Veterinary Medicine Geographic Information
System and Spatial Analysis Laboratory, in collaboration with the Illinois
Department of Public Health, and the Illinois Department of Agriculture in
the mapping and analysis of the WNV outbreak in Illinois. (Illinois was the
state hit the hardest by the epidemic in 2002.) Geographic information systems in conjunction with fine resolution satellite data and spatial statistics are
also useful to investigate the distribution of other diseases, for example, schistosomiasis (Julie A. Clennon, UIUC, Urbana).
Animal Models of Infectious Diseases
Streptococcal pathogens continue to evade concerted efforts to decipher clearcut virulence mechanisms, although numerous genes have been implicated in
pathogenesis. Melody N. Neely (Wayne State University, Detroit, MI) reported the development of a unique animal model, the zebrafish (Danio rerio), to
characterize specific virulence mechanisms used within various tissues in vivo.
Her group is using this model host to study infection by two streptococcal
species that represent two forms of streptococcal disease: a natural pathogen
of fish and humans, Streptococcus initiae, and a human-specific pathogen, S.
pyogenes. S. initiae primarily causes a fatal systemic disease in the zebrafish after intramuscular injection, with pathologic changes similar to those seen in
human infections caused by S. agalactiae and S. pneumoniae. The fatal infection by S. pyogenes causes a locally spreading necrotic disease confined to the
307
muscle with pathologic features similar to those observed in a human infection of necrotizing fasciitis. By studying pathogens that are virulent for both
fish and humans and that mediate disease states in the zebrafish identical to
those found in human streptococcal infections, common virulence strategies
shared by a number of gram-positive pathogens can be identified. Using several genetic strategies with the two streptococcal strains, Dr. Neely’s group is
currently conducting specific screens in the zebrafish to 1) identify and characterize cell membrane proteins that interact with the host in vivo to cause
specific disease states; 2) identify genes required for growth in vivo, as well as
progressive stages of infection; 3) identify genes that are only expressed while
in the host along with tissue specificity of the encoded proteins; and 4) analyze responses of the host that affect progression of disease.
Foodborne Diseases
Shigella boydii is a food pathogen that was implicated in a 1999 foodborne
outbreak involving contaminated bean salad that contained fresh parsley and
cilantro. Hans Blaschek and collaborators (UIUC, Urbana) reported the high
tolerance of this bacterium to acidic pH, and the presence and formation of
biofilms in cilantro and parsley samples treated with produce wash and water. Cells in biofilms are known to be more resistant to antibiotics and disinfectants, and biofilm formation may explain the decreased efficacy of produce
wash on parsley and cilantro samples.
Intracellular Parasites
The trypanosomatid protozoan Leishmania synthesizes a variety of glycosylphosphatidylinositol (GPI) anchored molecules on its surface. Sorting out
their individual functions has been difficult and in some cases controversial
as they share structural domains and generally have been tested outside the
context of key components such as the major glycolipid lipohosphoglycan
(LPG) and phosphoglycans (PGs); ether lipids, which constitute approximately 20% of the membrane lipids and most GPI anchors; and others.
Stephen M. Beverley and his collaborators (Washington University, St. Louis,
MO) have studied their role of GPI-anchored proteins role in the context of
parasite knockouts and “add-back” controls, probing their role in diverse aspects of parasitism such as entry, inhibition of phagolysosomal fusion and
host-signal transduction, and pathogenesis. All of these molecules play critical roles in virulence, although sometimes in unanticipated ways. PGs in particular are required for parasite persistence but not acute pathology, therefore
308
defining a new class of parasite genes important to transmission. Ted
Hackstadt (National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Hamilton, MT) reported that, unlike most intracellular
parasites, which block maturation of endosomes to lysosomes at discrete
stages and then replicate within those vacuoles, chlamydiae appear to dissociate themselves from the endocytic pathway shortly after internalization by
actively modifying the vacuole to become fusogenic with sphingomyelincontaining exocytic vesicles. Interaction with a secretory pathway appears to
provide a pathogenic mechanism that allows chlamydiae to establish themselves in a site not destined to fuse with lysosomes. Fusion with Golgi-derived
vesicles provides a likely source of cellular lipids for the growth of the inclusion membrane as it expands to accommodate the multiplying parasites.
Kasturi Haldar (Northwestern University, Chicago, IL presented studies on
the malaria parasite, focusing on protein trafficking, gene expression, and
drug development. Her group has studied vacuolar trafficking of host raft
proteins and parasite virulence determinants (by tagging genes with green
fluorescent protein and expressing them by transfection) for their consequences on malarial entry into the red blood cell, virulence secretion systems,
and apicoplast biogenesis. The apicoplast is a newly identified residual plastid acquired by secondary endosymbiosis that has attracted attention for its
evolutionary novelty and its potential as a drug target. Temporal regulation
of plasmodial genes may be important for protein- targeting in cells. In this
context, Dr. Haldar’s group is examining the role of unique promoter elements and chromatin in regulating expression of secretory determinants such
as the histidine-rich proteins and adherence antigens. Whole genome scanning approaches (microarrays and other functional approaches) are being
used in combination with informatics to develop novel lipid-linked targets
for drug development. Studies on Salmonella are currently examining effectors of the SPI-2 system (Salmonella Pathogenicity Island-2 system for their
effects on sterol recruitment, metabolism, and bacterial virulence in the
mouse model. The requirement for nonsterol precursors in protecting infected cells from death by apoptosis, necrosis, or both, is also being investigated.
Finally, microarrays are used to identify subsets of S. typhimurium virulence
determinants required for lipid-linked intracellular bacterial replication.
Toxoplasma gondii is a major cause of birth defects and infections in immunocompromised persons. Like all members of the phylum Apicomplexa, T.
gondii is an obligate intracellular organism. Micronemes and rhoptries are
specialized secretory organelles of the Apicomplexa, whose contents are
309
thought to be essential for successful invasion of host cells. Kami Kim (Albert
Einstein College of Medicine, Bronx, NY) reported identifying two subtilisin-like serine proteinases from T. gondii, TgSUB1 and TgSUB2, which are
necessary for successful invasion. Serine proteinase inhibitors have been reported to block host cell invasion by both T. gondii and the related apicomplexan parasite, P. falciparum. Disruption of TgSUB2 was unsuccessful,
which implies that TgSUB2 is an essential gene. Both TgSUB1 and TgSUB2
undergo autocatalytic processing as they traffic through the secretory pathway. TgSUB1 is a microneme protein, whereas TgSUB2 localizes to rhoptries
and associates with rhoptry protein ROP1, a potential substrate. Mutational
analysis suggests that TgSUB2 is a rhoptry protein maturase. Processing of secretory organelle contents appears to be ubiquitous among the Apicomplexa.
Since subtilases are found in genomes of all the Apicomplexa sequenced to
date, they may represent a novel chemotherapeutic target. Transcriptional
regulatory pathways in apicomplexan parasites are understudied and may
contain novel drug targets. William Sullivan and his collaborators (Indiana
University School of Medicine, Indianapolis, IN) identified and mapped a
gene in T. gondii that encodes a homologue of chromatin remodeling factors
that uses ATP to promote a more favorable environment for transcription.
They also described a novel histone acetyltransferase, which contains a
unique 820-amino acid N-terminal extension of unknown function.
Parasite Organelles
Acidocalcisomes are novel calcium-containing acidic organelles present in
unicellular eukaryotes. Several posters from researchers in the groups of Silvia
Moreno and Roberto Docampo (UIUC, Urbana) highlighted recent work on
these organelles. Andrea Montalvetti described a functional aquaporin (water
channel) found in the organelles of T. cruzi, the etiologic agent of Chagas disease, and Peter Rohloff showed that this protein is translocated to the contractile vacuole upon hypo-osmotic stress. Joanna Cox and Shuhong Luo
demonstrated that a Ca2+-ATPase is localized to acidocalcisomes and the
plasma membrane of Trypanosoma brucei, the etiologic agent of African sleeping sickness, and is essential for cell growth, as demonstrated by RNA interference experiments. Manfredo Seufferheld presented evidence of the presence acidocalcisomes in the bacterium Rodospirillum rubrum. Felix Ruiz
showed that acidocalcisomes of Plasmodium falciparum, one of the etiologic
agents of malaria, do not differ significantly from the organelles in other apicomplexan parasites, whereas the platelet-dense granules possess several char-
310
acteristics common to acidocalcisomes. T. brucei possesses a P-type proton
ATPase with homology to fungal and plant H+-ATPases but absent in
mammalian cells; this proton pump constitutes a formidable target for
chemotherapy (Shuhong Luo, UIUC, Urbana).
Chemotherapeutic Targets
A number of poster presentations identified novel chemotherapeutic targets
for infectious diseases. Steve Grimme (UIUC, Urbana), who received an
award for the best poster presentation, demonstrated that a GPI mannosyltransferase (CaSMP3) was essential for the human pathogenic fungus
Candida albicans and therefore was validated as a potential target for
chemotherapy. M. Laura Salto (UIUC, Urbana) showed that inositolphosphoceramide, a lipid used in anchoring several proteins to the plasma membrane of T. cruzi and absent in the host, is remodeled during the differentiation of different stages of the parasite. Novel lipid modified phosphoinositide
phospholipases C were reported in T. cruzi (Michael Okura, UIUC, Urbana)
and T. brucei (Jianmin Fang, UIUC, Urbana). The enzymes are apparently
involved in differentiation of the parasites and are different from their host
counterparts. Recently, bisphosphonates have been proposed as novel antiparasitic drugs, and Yan Ling (UIUC, Urbana) reported the cloning and
characterization of Toxoplasma gondii farnesyl pyrophosphate synthase, the
target of these compounds. Tryptophan metabolism in mosquitoes and the
separation and identification of mosquito chrorion proteins through two-dimensional electrophoresis and mass spectrometry will provide useful targets
against these vectors of several infectious diseases, as reported by Jianyong Li
and his collaborators (UIUC, Urbana).
311
References
1. Olshansky SJ, Carnes B, Rogers RG, Smith L., Infectious diseases. New and Ancient
threats to world health, Pop Bull, 1997,52,2,18-40.
2. Who, Emerging and re-emerging infectious diseases, Fact Sheet,1998,97 (available on
http://www.who.int/inf-fs/en/facto97.html).
3. Halstead SB, Human factors in emerging infectious diseases, EMHJ, 1996,2,1,21-9.
4. Manders SM, Infectious diseases update, Derm Clin, 2001,19,4,749-55.
5. Morrone A, Toma L, Franco G., Latini O, Donovanosis in developed countries: neglected
or misdiagnosed disease?, Int J STD AIDS. 2003 Apr;14(4):288-9.
6. Morrone A, Franco G., Toma L, Tchangmena OB, Marangi M., A case of loiasis in
Rome., J Eur Acad Dermatol Venereol. 2002 May;16(3):280-3.
7. Bianchini C., Marangi M., Meledandri G., Morrone A., Medicina internazionale, 2000,
Roma, Società Editrice Universo.
8. Gratz NG, Emerging and resurging vector-borne diseases, Ann Rev Entomol, 1999,14,5179
9. Goldrick BA, 21st-century emerging and reemerging infections. Am J Nurs. 2004
Jan;104(1):67-70
10. Bravo F, Sanchez MR., New and re-emerging cutaneous infectious diseases in Latin America
and other geographic areas, Dermatol Clin. 2003 Oct;21(4):655-68
312
BIANCA
313
14. Negleted diseases
14. NEGLECTED DISEASES
Aldo Morrone, Genet Fitwi
Neglected diseases – though not always neglected
Are there “neglected diseases”? If there are “neglected diseases” are there “neglected people” too?
The so-called “neglected” diseases are largely ancient infectious diseases such
as sleeping sickness, kala-azar, and Chagas disease, that have burdened humanity for centuries. In their long histories, several have acquired notoriety
as deforming and disabling diseases, often associated with intense stigma.
However they have not always been neglected. In the past, the magnitude of
their impact on health and productivity led to considerable research into
their biology and epidemiology, and effective control tools were developed
for most. In addition, as living conditions improved in many parts of the
world, opportunities for transmission were reduced. As a result, these diseases
are now rarely seen in populations that enjoy good access to health services
and a reasonable standard of living. These diseases now occur in many developing countries on the poor population with no access to socio and health
public services.
Neglect - a key feature of neglected diseases
Neglected diseases, their consequences and the cost of inaction
Today, neglected diseases can be usefully considered as a group because they are
concentrated almost exclusively in impoverished populations living in marginalized areas – the populations left behind by socioeconomic development.
Number of poor by country earning less than 1$/a day
Although medically diverse, neglected diseases share features that allow them
to persist in conditions of poverty, where they cluster and frequently overlap.
Unsafe water and poor sanitation sustain transmission cycles and favour the
proliferation of vectors. Lack of access to health services, low levels of literacy, inadequate nutrition and poor personal hygiene all help to increase vulnerability to infection and work against prevention. Where curative interventions exist, they generally fail to reach populations early enough to prevent
permanent impairments. Conditions of poverty also work to exclude affected populations from the social systems set up to safeguard health as a fundamental human right.
314
Neglect occurs at three main levels. At the community level, fear and stigma
can sometimes lead their sufferers and their families to conceal their condition. At the national level, these diseases are often hidden – out of sight,
poorly documented, and silent, as those most affected have little political
voice. As a result, neglected diseases are rarely given high priority by ministries of health or finance in endemic countries.
Neglected diseases lack visibility at the international level as well. Tied as they
are to specific geographical and environmental conditions, they are not perceived as direct threats to industrialized countries. They impair or permanently disable millions of people, but cause comparatively few deaths. This
low mortality diminishes their stature when seeking to gain international attention and funds, and they are frequently given low priority in the agendas
of development cooperation agencies.
Negligible incentives for R&D
Neglected diseases have traditionally suffered from a lack of incentives to develop drugs and vaccines for markets that cannot pay. Research for new products is not commercially viable. When inexpensive and effective drugs already
exist, demand for their delivery fails because of the inability to pay. Even
when drugs are available at no cost, they may fail to reach populations because delivery systems are rudimentary or non-existent. Inadequate operational and implementation research, as well as inadequate research to develop better and more affordable products, has contributed to this failure.
The high price of neglect
The mortality rates associated with neglected diseases are typically low, but
morbidity rates are high. Although the full impact of the neglected diseases
has thus far been inadequately documented, there is a growing recognition
that it is significant.
Like the diseases themselves, their fallout is seldom visible yet highly significant. The toll it takes on human development is reflected in lost potential
and reduced productivity due to impaired physical growth and cognitive development, missed days from school and/or work, the care of chronic disabilities, inefficient use of land, etc.. It exacerbates the abject poverty existent in
the affected areas.
Accurate assessments of socioeconomic impact that go beyond a narrow focus on health care costs could do much to raise the visibility of neglected diseases, place the low cost of interventions in perspective, and demonstrate the
315
remarkable returns on investment. Basic messages about the simplicity and
effectiveness of control measures will carry more weight when their ability to
avert significant economic costs is part of the argument. This can only change
with adequate data which permits a reassessment of the situation.Till such information is available, data for other better publicised communicable diseases
could serve as a proxy in assessing the impact of neglected diseases.
The burden of communicable diseases divides the world
Gwatkin and Guillot looked at the morbidity and mortality from 25 specific diseases found in the poorest 20% of countries and the richest 20% of
countries.
This allowed the relative importance of diseases within a specific population
group to be assessed in terms of a poverty alleviation strategy as well as enabling a comparison between the rich and the poor which could lead to an
inequality reduction strategy. They found an inverse relationship between
economic status and communicable diseases.
Based upon the situation in 1990, they estimated that communicable diseases
cause 59% of deaths and 64% of disability adjusted life years (DALYs) among
the populations living in countries with the lowest per capita incomes.
Communicable diseases are responsible for 77% of the mortality gap and 79%
of the DALY gap between the world’s poorest 20% and the richest 20%.
Although the burden is considerable, it is still considered to be an underestimate of the extent of the problem. A 92% reduction in the burden of communicable diseases in poorest countries would be required to close the mortality gap with the richest countries.
The leading causes of death in the poorest countries are respiratory infections, diarrhoeal diseases and perinatal conditions – all of which are preventable and easily curable. These illnesses are also responsible for the majority of
morbidity as expressed in DALYs. Non-communicable diseases also cause
higher rates of disability and death among the poor but these diseases accounted for less than one-fifth of the death/DALY gap between the richest
and the poorest countries. The poor-rich differences in the rate of death from
communicable diseases appear to be 4-12 times as great as they are for noncommunicable diseases.
Women and children are more vulnerable
A significant gender gap was also found in communicable diseases as women
face additional barriers to seeking, and often receiving, treatment.
316
Communicable disease morbidity and mortality were higher among poor
women than poor men, especially because of maternal health.
Children bear a heavy burden. Nearly 70% of all deaths and 75% of all
DALYs in the world from communicable disease occur in children under 14.
In the 5-14 age group the death rate from non-communicable diseases was 5
times higher among the global poor while the death rate from communicable diseases was 56.2 times higher for the poor compared to the global rich.
For poor countries whose populations are on average much younger than the
global rich, this has major implications for both the ability to participate in
education and also for future economic productivity.
Communicable disease will remain a burden for the poor
Based upon the situation in 1990, it was estimated that by 2020 deaths attributable to communicable disease would fall from 59% to 44% of all deaths
among the global poor. Deaths from non-communicable disease among the
poor would rise from 32% to 42%. DALY loss from communicable disease
would fall from 64% to 43% whilst DALY loss from non-communicable diseases would increase from 23% to 40%.
However as communicable diseases would also be declining in richer populations, they would continue to be much more important for the poor.
Indeed the estimates for 2020 of 44% of deaths and 43% of DALY loss
caused by communicable diseases among the global poor can be compared to
the 15% of deaths and 20% of DALY loss in the world as a whole and 7%
of deaths and 8% of DALY loss among the global rich.
The authors concluded that, if the aim of the global community is to improve
the health of the poor to the maximum possible extent and reduce the poorrich gap, an accelerated overall decline in communicable diseases would benefit the poor much more than the rich and would produce a life expectancy
gain of 4.1 years for the former. This would lead to a reduction in the poorrich life expectancy gap of 3.7 years. By contrast, the same accelerated decline
non-communicable diseases would actually widen the gap by 3.9 years.
Challenges posed by neglected diseases
Despite many differences, neglected diseases share a number of common features. Future initiatives should build on these features and the challenges
enumerated below in order to have a synergistic effect:
– These diseases affect the poorest in the community and efforts to address
them should form an integral part of pro-poor policies. A reduction in the
–
–
–
–
–
–
–
–
–
317
communicable disease burden will enable communities to become more
economically active thereby narrowing the gap between poor and rich.
The introduction of basic public health measures, such as access to education, clean water and sanitation, in communities would significantly reduce the burden of a number of diseases where these elements play an important role.
There is considerable overlap in the prevention and management of these
diseases, permitting useful synergies, and emphasising the need for combined programmes which are integrated into existing education and
health infrastructures, particularly primary health care.
Although the eradication of certain diseases can be achieved at minimal
cost per individual patient, the total cost at the national level can be significant in view of the large numbers affected by the diseases. Unless external support is provided, this could have significant opportunity costs
and implications for other budgets. It is thus crucial to look at the cost-effectiveness and cost-benefit impact of differing health interventions.
Even when treatment is subsidised, families can be unwilling or unable to
pay because of the burden it constitutes on their limited resources.This
needs to be considered when looking at cost-recovery schemes. Moreover
such schemes could lead to the exclusion of the poorest members of a
community, who are often the target population.
Evidence-based cost-effective strategies are the cornerstone of any successful disease intervention strategy. Unfortunately such strategies have not
yet been developed for some diseases and must be developed urgently.
While there is a reasonable body of literature available on the socio-economic implications for some diseases such as lymphatic filariasis, for many
others there has been little or no attempt to quantify the economic implications despite the considerable burden of death, ill health and disability
they cause.
These studies should look at the wider implications of the disease, and recommended intervention, for the patients, their families as well as on economic productivity instead of maintaining a narrow focus on health care
costs.
There is an urgent need in many cases for improved and integrated disease
surveillance and monitoring.
A number of successful programmes aimed at reducing the disease burdens have been provided through schools. However specific strategies
need to be developed to reach the poorest in each society as many children
318
–
–
–
–
in this category may not attend school. An additional challenge will be addressing the gender issues, in particular reaching girls in societies where it
is not common for girls to attend school.
Very little information is available on the long-term impact of such diseases on children and the extent to which their inability to attend school
or residual disability impairs their ability to find well-paid employment.
The impact of disease on women as well as gender specific barriers to
treatment have been under-researched.
There is a need to undertake more qualitative research to seek the views of
communities themselves about their perceptions and beliefs about diseases
and their attitudes to treatment. Community participation and education
are crucial for the sustainability and success of programmes.
For some diseases there has been little research in recent years into new
safer and cheaper drugs or the development of vaccines. Public-private
partnerships, particularly those involving the pharmaceutical industry,
have an enormous contribution to make in such matters.
But there is cause for optimism
Recent developments are making it possible to circumvent many of these
longstanding problems. While important constraints remain, the prospects
for controlling some of the most burdensome neglected diseases, on a large
scale and in sustainable ways, have never looked better. Major achievements
have been possible under extremely challenging conditions. As these diseases
share common determinants and must overcome similar obstacles to control,
hard-won successes against any single disease pave the way for progress
against others.
Neglected diseases – a global public goods perspective
Inge Kaul
The control of communicable disease is a global public good as it benefits all
people, in poorer and richer countries, present as well as future generations.
However the reality is that communicable diseases continue to spread relentlessly within and across borders and serve as global public “bads” in economic terms.
The persistence of the current disease burden of sub-Saharan Africa and other poor countries has serious repercussions for international peace and security, and the prosperity and well-being of industrialized countries. Despite
growing recognition of this fact, global public goods policies tend to wait for
319
the emergence of a global public bad and then respond on an emergency basis. The nature and speed of global response depends largely on the extent to
which the health of wealthy nations is at risk. Can the global public good argument be successfully used to mobilize a global response against neglected
diseases?
Neglected diseases still neglected in millennium development goals
Health is a key concern of the global agenda and features prominently on the
Millennium Development Goals (MDGs). Fighting the big killer diseases,
HIV/AIDS and malaria, are highlighted as important goals, whereas neglected diseases remain “neglected”.There is however the following reference to
neglected diseases in the road map for the MDGs.
“Many of the world’s health needs can only be met at the international level
through the provision of global public goods. Among the most critical global public goods for health are the generation and dissemination of knowledge
of research, effective health system reforms and the transfer of new technologies. Research and development of new drugs, vaccines and other technologies are desperately needed to prevent and control diseases that primarily affect poor countries.”
Public goods are available to all
In economic terms well-being is determined by the consumption of private
or public goods. Private goods are things such as food, clothing and shelter,
whose consumption can be withheld from other individuals (i.e. they are “excludable”, according to economists). Private goods usually have clear property rights attached to them and individuals are prepared to pay the market
price for them.
Public goods, by contrast, are non-excludable and are available for all to enjoy (e.g. law and order). Many public goods are also public in provision, since
they depend on the contributions of many individuals. For example, enjoying law and order often depends less on one’s own attitudes and behaviour,
than on the general level of respect that others have for social norms and institutions. Public goods almost always depend on policy choices and are not
an inherent characteristic of the good.
Global public goods are public goods that do not “respect”
national borders…
The benefits or costs of global public goods extend across countries, people
320
and generations. Many public goods cannot be achieved through domestic
policy action alone and depend on international cooperation.
…as are global public bads
The global spread of communicable diseases and the emergence of drug-resistant microbial strains are examples are global public bads.Their prevention,
rather than their production, is desirable. However policy-making is largely
organized on a country-by-country basis and as a result, global public goods
are increasingly underprovided and global public bads are increasingly overprovided.
The response to health challenges is rapidly forthcoming when the health of
wealthy nations is directly affected. This is exemplified by the rapid response
to the recent outbreak of SARS.
Available policy response options
The Millennium Declaration:
Ten Global Public Goods (GPGs) for the MDGs
1. Basic human dignity for all people, including universal access to basic education
and health care
2. Respect for national sovereignty
3. Global public health, particularly communicable disease control
4. Global security or, put differently, a global public domain free from crime and violence
5. Global peace
6. Communication and transportation systems harmonized across borders
7. Institutional infrastructure harmonized across borders to foster such goals as market efficiency, universal human rights, transparent and accountable governance,
and harmonization of technical standards
8. Concerted management of knowledge, including worldwide respect for intellectual property rights
9. Concerted management of the global natural commons to promote their sustainable use
10. Availability of international arenas for multilateral negotiations between states as
well as between state and non-state actors
There is an urgent need for enhanced policy coherence, notably between
global public goods 1 and 8 of the Millennium Declaration, namely universal access to health care and a global system for knowledge management.
Knowledge has significant private properties, because it is typically produced
by research teams and can be withheld and made excludable. Moreover, they
need to be adequately rewarded for their efforts to ensure continued invest-
321
ment in R&D usually through a system of intellectual property rights and
compliance with it worldwide. Knowledge also has important public qualities, such as being non competitive in consumption i.e. the marginal cost of
sharing knowledge is zero or relatively modest.
It would be more efficient to foster policies which find a balance between rewarding innovation and promoting greater sharing. The varying degrees of
utility that any policy has for different population groups, will inevitably lead
to differences in their preferences and priority as well as room for negotiation.
Some measures now being discussed to correct the health care imbalance include the selective use of compulsory licensing and parallel imports. Yet
durable solutions for stimulating R&D for neglected diseases, such as purchase guarantees, are still lacking.
The key challenge is to strike the right balance between government (public)
support for health-related knowledge generation and dissemination and market-based (private) provision. Examples of knowledge generation include
Medicines for Malaria Venture; Global Alliance for Vaccines and
Immunization (GAVI) to the extent that it creates the perception that there
is demand for innovation;
Drugs for Neglected Diseases Initiative; differential patenting; subsidy
schemes for pharmaceutical companies in rich countries to engage in relevant
R&D.
Incentives for knowledge dissemination include the Global Fund; the new
US AIDS policy; GAVI to the extent that bulk vaccines purchases provide incentives to increase immunization rates; differential pricing. A global regime
of knowledge management should generate positive net-benefits for all as
well as enhanced policy coherence.
Tools for control – ensuring development of new tools and refinement
of existing ones Drugs for neglected disease initiative (DNDi)
Dr Bernard Pecoul
The challenge
During the last 25 years, the gulf between the development of drugs for tropical and non-tropical diseases has grown.Tropical diseases such as chloroquine-resistant malaria, human African trypanosomiasis, visceral leishmaniasis (kala-azar), lymphatic filariasis, Chagas disease and schistosomiasis continue to cause significant morbidity and mortality. These disabling and/or life-
322
threatening diseases can be collectively called ‘neglected diseases’.These diseases are neglected by the very mechanisms that ensure research and development (R&D) of new drugs, as the patients suffering from them do not represent a significant market. Only 1 percent of the 1,393 new drugs registered
during 1975-1999 were for tropical diseases and tuberculosis, yet these diseases constitute over 10 percent of the global disease burden. A mere 10 percent of the world’s health research expenditure is spent on diseases that account for 90 percent of the global burden of disease. And neglected diseases
get an even smaller share of the pie – of the US $60-70 billion spent on
health research last year, less than 0.001 percent went towards developing
new and urgently needed treatments for this category of diseases.
Despite intense scientific scrutiny, the most neglected of these diseases have
been all but ignored by the pharmaceutical industry, which is almost the only generator of new medicines today. Most of the drugs to combat these diseases are either too expensive, difficult to administer, toxic at recommended
doses, or increasingly ineffective due to drug resistance. People affected by
these diseases cannot afford to buy the drugs and are thus off the radar screen
of drug companies.
The crisis in R&D of drugs for neglected diseases is not due to a lack of scientific knowledge, as a great deal is known and information continuously
generated, about the biology, immunology and genetics of the parasites that
cause, for example, human African trypanosomiasis, leishmaniasis, and
Chagas disease. In fact the crisis is more the result of the failure of both the
market and public policy to promote drugs for neglected diseases.
Market failure: The vast majority of R&D of new drugs is conducted in the
western world, mainly by the pharmaceutical industry whose research agendas are largely defined by the potential return on investment and reflect market prospects rather than health needs. The populations of poorer nations
have limited purchasing power and thus their diseases are ignored.
Public policy failure: In spite of visibly waning private sector interest, governments have been slow to take action against this global problem. In industrialized countries, public policy has long provided incentives such as patents,
tax credits, and health-care insurance systems to encourage private-sector investments in drug R&D, but these rarely target neglected diseases. Moreover,
in spite of these incentives, there is a bias towards ‘me-too’ and lifestyle drugs
for conditions such as impotence and baldness.
Governments in less developed countries, on the other hand, are confronted
with a combination of lack of financial resources, absence of willingness to
323
invest in long-term health development, and failure to establish public policy incentives that foster a viable domestic drug development capacity.
UNDP/World Bank/WHO’s Special Programme for Training and Research
in Tropical Diseases (TDR) was established in 1975 in response to appeals
from countries where neglected diseases were endemic. Over the past 25
years, it has successfully partnered the development of several new treatments
for tropical diseases, but significant unmet curative and preventive medical
needs remain, particularly for the most neglected diseases.
DNDi – an innovative approach to research
The not-for-profit Drugs for Neglected Diseases Initiative (DNDi) is the
brainchild of Médecins Sans Frontières (MSF) and the Drugs for Neglected
Diseases Working Group, an independent body of international health experts. DNDi seeks to address the need for research and development of new
field-adapted, effective, and affordable drugs for patients suffering from ‘neglected diseases’. The idea is simple – to harness accumulated knowledge and
cutting-edge science and technology to develop critically needed drugs for
neglected diseases, making sure they are suitable for and accessible to the
poorer patients of the world. The modus operandi will be to collaborate predominantly with developing country organizations and governments.
The vision
The DNDi vision is to improve the quality of life and the health of people
suffering from neglected diseases by using an alternative, not-for-profit model to develop drugs for these diseases and ensuring equitable access to new
and field relevant health tools. It will address unmet needs by taking on projects that others are unable or unwilling to pursue.
Although DNDi’s primary focus will be the development of drugs for the
most neglected diseases such as sleeping sickness, kala-azar, and Chagas disease, it will also consider undertaking R&D projects on other neglected diseases. As means permit, it will consider the development of diagnostics
and/or vaccines.
DNDi will not conduct research and scientific work to develop compounds
by itself; rather, it will capitalize on existing, fragmented R&D capacity, especially in the developing world, and complement it with additional expertise as needed. As a virtual drug development organization it will thus significantly lower overhead costs.
It will collaborate with partners from both the developing and developed
324
worlds (public and academic institutions, pharmaceutical and biotech companies etc.), and stringently manage legal issues (including intellectual property).The overall goal will always be to ensure the greatest accessibility to and
affordability of the results of DNDi’ work.
TDR: Critical challenges for neglected diseases research
The major challenges facing neglected diseases relate to both upstream basic
scientific research and downstream implementation-related research. For
some of the neglected diseases, new tools are needed. For others, existing
strategies and treatment protocols need to be simplified. Innovative, evidence-based solutions need to be found which are fully responsive to the field
reality.
Generation of basic knowledge
For many neglected diseases there is an urgent need to go back to the drawing board using the state-of-the-art tools of genomics or molecular biology to
understand the pathogenesis of the disease.This could help identify new avenues for research and development.
Research elucidating the pathogenic process of Chagas disease as an auto-immune process, for example, would make the further development of
chemotherapy focusing on the parasite obsolete. Elucidating the genomics of
the T. brucei genome for African trypanosomiasis or improved understanding of cell-parasite interaction in leishmaniasis have key implications for drug
development. At the other end of the spectrum, basic social research can clarify issues such as identifying obstacles to access to treatment, help seeking behaviour and adherence with treatment.
New Tools
New tools, such as drugs, vaccines, diagnostics and vector control tools, are
usually developed in close collaboration with industry.There have been some
notable successes through public private partnership activities (multi-drug
therapy for leprosy; ivermectin for onchocerciasis; eflornithine for human
African trypanosomiasis; miltefosine for leishmaniasis).
Vaccine research faces formidable scientific and technical obstacles and is in
its early days for parasitic diseases. There is growing interest in the development of new diagnostics and vector control tools, such as improved pesticides. A key challenge involves translating basic academic research into new
drugs, vaccines, diagnostics and insecticides.
325
New and Improved Methods
Effective tools exist for some neglected diseases but their geographical coverage is limited often due to complex diagnostic and treatment protocols.There
is an urgent need to simplify the control of neglected diseases so that it can
be managed by local health services with minimal support from specialized
staff.This will require refining existing methods and developing new ones.
Examples include research on a uniform multidrug therapy regimen for all
types of leprosy patients which would facilitate the further integration of leprosy control into routine health services; studies on the efficacy of increased
praziquantel dosage for treatment of schistosomiasis and short dose pentamidine for treatment of African trypanosomiasis. Establishing fixed dose combinations of existing drugs is another important research avenue as it simplifies treatment delivery, reduces the risk of parasite resistance as well as simplifies logistics.
Research on new methods can help to improve the effectiveness of disease
control.
For example, research is ongoing to develop new entomological sampling
methods for more cost-effective vector control for dengue. Research on rapid
assessment methods to determine the geographic distribution of prevalence
and intensity of infection has produced new methods that are of great practical importance for the control of onchocerciasis and lymphatic filariasis.
Often the mere proof of efficacy of new tools and methods is not enough.
Their effectiveness must be demonstrated in field conditions.This may require large scale field trials which tend to be expensive but are essential to
convince health decision makers to make a new tool or method available
through routine health services.
Gwatkin D R and Guillot M. (1999) The Burden of Disease among the Global Poor –
Current Situation, Future Trends, and Implications for Strategy. World Bank, Washington
D.C.
326
BIANCA
15. Health systems and skin infectious diseases
327
15. HEALTH SYSTEMS AND SKIN
INFECTIOUS DISEASES
Emma Pizzini, Ottavio Latini, Aldo Morrone
Introduction
In 1990, the Commission on Health Research for Development estimated that
less than 10% of the global health research resources (totalling US$30 billion/year in 1986) were being applied to the health problems of developing
countries, which accounted for over 90% of the world’s health problems, an
imbalance subsequently captured in the term the “10/90 gap”.
The commission’s report, Health Research: Essential link to equity in development1, made the observation that health research was significantly skewed towards diseases that affected the developed world. The commission estimated
that only 5% of global spending on health research in 1986 was devoted to
health problems in developing countries, where 93% of the world’s burden
of ‘preventable mortality’ occurred. Later in the 1990s, while the size of the
imbalance had become increasingly more complex and difficult to measure
quantitatively, the term ‘10/90 gap’ began to be used as a shorthand reference
to the issue. It has come to symbolise the gross mismatch between needs and
investments in health research for development.
In 1996, the WHO Ad Hoc Committee on Health Research Relating to
Future Intervention Options estimated that US$55.8 billion was expended
globally on health research in 1992 but noted that the “10/90 gap” persisted.
The world now spends considerably more on health research: our latest estimate puts the figure at US$105.9 billion for 2001, of which 44% by the public sector, 48% by the private for-profit sector and 8% by the private not-forprofit sector.
Despite these positive increases, there is still a massive under-investment in
health research relevant to the needs of low-and middle-income countries,
the imbalance of the “10/90 gap”.
The 192-member World Health Assembly adopted a resolution in May to
create a strategy to support “needs-driven” research on diseases that particularly affect developing countries. In line with the findings of the Commission
1 Commission on Health Research for Development. Health Research: Essential link to equity in development. New York, Oxford University Press, 1990 (http://www.cohred.org).
328
on Intellectual Property Rights, Innovation and Public Health, the resolution
acknowledges that although intellectual property rights provide an incentive
for innovation, this is not enough to encourage companies to develop products to fight diseases that primarily affect the poor in developing countries.
The WHO has convened a new intergovernmental working group the WHO
Secretariat on Public Health, Innovation and Intellectual Property to identify priority areas for research and development and sources of funding.
The resolution recommends these governments:
• Establish a global framework for supporting essential medical R&D based
upon the principle of an equitable contribution that all nations can make to
financial investments in R&D. This includes the promotion of incentives to
invest in useful R&D that meet patients’ needs and public health interest.
• Make global health and medicines a strategic sector. Governments must
promote action to ensure that R&D efforts address real needs, especially for
people living in resource-poor settings, by harnessing new and innovative
R&D collaborations with disease-endemic countries, and enabling progress
in basic science and biomedicine to be translated into better, safer, and affordable health products, drugs, vaccines, and diagnostics. These new essential medicines must be rapidly delivered to people, with special attention to
those living in poverty.
• Create a new global system of finance for R&D of diseases that most affect the poor, such as malaria and other neglected diseases, as well as for important projects such as new treatments, diagnostics, and preventive tools for
AIDS. Most of the 3.1 million persons who died of AIDS-related illnesses in
2005 were living in poverty. The development of health tools is a global public good, and requires a multilateral strategy for widespread success.
• Set up a Working Group of Member-States within WHO, whose task is
to deliver a final report with concrete proposals to the Executive Board in
January 2008.
Over past years, the crisis in research and development in the worldwide pharmaceutical industry, and in particular the absence of research and development for new medicines targeting diseases that mainly affect people in developing countries (neglected diseases), has become a global concern. This worrying situation is clearly shown by the number of drugs targeting neglected
tropical diseases. From 1975 to 1999, only 13 drugs from 1393 new chemical entities (NCE) marketed were indicated for a neglected disease. The 13
drugs included four for malaria and nine for the most neglected diseases.
Three more drugs could be added if tuberculosis is included in the analysis.
329
From 2000 to 2004, an additional 163 NCEs have been marketed in the
world, adding up to a total of 1556 NCEs for the 30 years from 1975 to 2004.
Not only do the poor suffer disproportionately from disease, but their out-of-pocket payments for
Not only
docare
theoften
poor
disproportionately
from disease, but their outmedical
leadsuffer
to further
impoverishment.
of-pocket∞payments
for medical
care
often population
lead to further
impoverishment.
41% of the poorest
quarter of
the world’s
are underweight
compared with 3% of the
• 41% of richest;
the poorest quarter of the world’s population are underweight
compared
with
3%
of the
richest;
∞ 114
deaths
among
children
under fi ve per 1,000 live births in the poorest quarter compared
withamong
13 per 1,000
for the richest;
• 114 deaths
children
under fi ve per 1,000 live births in the poor∞
63
maternal
deaths
per
10,000
per live
birthsfor
for the
quarter compared with 4 per 10,000
est quarter compared with 13 per
1,000
thepoorest
richest;
for
the
richest;
• 63 maternal deaths per 10,000 per live births for the poorest quarter com164 AIDS deaths per 100,000 people for the poorest compared with 31 for the richest.
pared ∞with
4 per 10,000 for the richest;
• 164 AIDS deaths per 100,000 people for the poorest compared with 31
for the richest.
Padma Shetty in “Investing in
health for equitable development: lessons from the National
Commissions of Macroeconomics
and Health” Source: Evidence
and Information for Policy,
Health
WHO
(World
Organization)
Padma Shetty in "Investing in health for equitable development: lessons from the National Commissions of
Macroeconomics and Health" Source: Evidence and Information for Policy, WHO (World Health Organization)
One of the greatest opportunities and challenges for international public health was be and is
330
One of the greatest opportunities and challenges for international public
health was be and is globalization. It live in an era where the growth of trade,
travel, and communications is spreading new cultural influences and lifestyles
faster than ever before, and the border between domestic and international
health problems is becoming insignificant. At the same time, globalization also permits the spread of risks, pathogens, and other threats. The ever-increasing movement of people everywhere increases the potential for epidemics.
Travelers, refugees, and displaced people are more vulnerable to infectious diseases, and their movement contributes to spreading pathogens into new areas.
The epidemiological and demographic profiles of many low- and middle-income countries (LMICs) and the range of available health interventions have
changed significantly.
With the year 2006, begins the 10-year countdown to the 2015 deadline for
achieving the MDGs. During the next decade, if the MDGs will be achieved,
as it pointed out in the UN Millennium Project2, more than 500 million people will be lifted out of extreme poverty. More than 300 million will no
longer suffer from hunger. The lives of 30 million children and 2 million
mothers can be spared. The spread of AIDS can be reversed3. There’s more:
350 million fewer people are without safe drinking water and 650 million
fewer people live without the benefits of basic sanitation; hundreds of millions more women and girls will go to school, access economic and political
opportunity, and have greater security and safety4.
In the course of the 20 century its saw a number of changes in the ways in
which countries interrelate, in the demands and pressures on people to move
between zones, and in the patterns of health associated with those new spatial and social interactions. All these changes have both positive and negative
features and opportunities for the countries and individuals involved.
The 20th century will can be remembered for witnessing the largest universal
increase in life expectancy in worldwide. While life expectancy is highest in
the richest countries, the upward trend is apparent in almost every society.
TH
2 UN Millennium Project. 2005a. Investing in Development: A Practical Plan to Achieve the
Millennium Development Goals, Report to the Secretary-General. London and Sterling,
Virginia: Earthscan.
3 UN Millennium Project. 2005a. Combating AIDS in the Developing World. Task Force on
HIV/AIDS, Malaria, TB, and Access to Essential Medicines, Working Group on
HIV/AIDS. New York.
4 UN Millennium Project. 2005a. Investing in Development: A Practical Plan to Achieve the
Millennium Development
331
The 20th century differed markedly from previous history in two focal
points:
• first, the rapid economic growth that had begun in the 19 century in
countries of the North of the world diffused widely around the globe
while continuing in the countries where it originated (DeLong 2000;
Maddison 1999). It is undoubted that the improved health has contributed significantly to economic welfare. Per capita GNP rose rapidly in
developing countries in the decades following 1960, and economic research suggests that health improvements led to perhaps 10% to 15% of
that GNP growth. Although GNP includes the costs of providing medical
care and reflects changes in health-related consumption, such as the quantity and quality of food, it omits altogether the value that mortality reduction represents for countries. Recent economic research has extended
measurement to a broader indicator, known as full income, that reflects
reasonable valuation of changes in mortality. For many countries, recent
mortality changes exceed in value the growth of GNP. More widespread
use of full income measures to calculate the rate of return to investments
in health and in health research will almost certainly conclude that, today,
most countries substantially undervalue those investments.
• Second, the human mortality rates decreased, and all other dimensions of
health improved dramatically. These changes, remained modest until the
20th century, during which the rate of improvement increased and spread
to most of the rest of the world. Moreover, in the past 50 years, variations
in this health indicator across and within countries have decreased.
Average life expectancy in low- and middle-income countries increased dramatically in the past half century, while cross-country health inequalities decreased, even in the presence of widening income gaps in many regions. In
the countries with the best health indicators, life expectancy increased a substantial two and one-half years per decade since 1960; low- and middle-income countries on average, with life expectancy gains of about five years per
decade, have been converging toward the countries with the longest life expectancy. This convergence of improved life expectancy and reduced variations and of worldwide gains in health can be explained by the impact. of
knowledge expansion and direct public health interventions; of improvement
in average income and education levels. Of much greater quantitative significance, however, have been the generation and diffusion of new knowledge
and of low-cost, appropriate technologies. Increased access to knowledge and
technology has accounted for perhaps as much as two-thirds of the impresTH
332
sive 2% per year rate of decline in under-five mortality rates.
Almost all developing regions are facing a transition in its epidemiological
profile from an environment with high fertility rates and high mortality from
preventable causes to one in which a combination of lower fertility rates and
changing lifestyles has led to aging populations and epidemics of tobacco addiction, obesity, cardiovascular disease, cancers, diabetes, and other chronic
diseases. The increase in life expectancy worldwide will, however, soon reach
a plateau, and a retraction has occurred in many countries. HIV/AIDS and
civil unrest in Africa, vaccine preventable diseases, alcoholism, and TB in
Eastern Europe, obesity in the United States and in the richest countries, are
reducing the years of life their populations.
It has long debated which approach to delivering health interventions is more
effective: vertical programs or horizontal programs. This is a unnecessary
dilemma, because both need to coexist like a diagonal approach, that is, the
proactive, supply-driven provision of a set of highly cost-effective interventions on a large scale that bridges health clinics and homes. This approach often starts vertically but moves toward an increasing number of interventions,
making full use of field health workers and existing infrastructure.
The health has a major impact on the economic situation and well-being of
an individual in any society. This is particularly true in the lower income
countries (where social safety nets are weak or non existent) and for the absolute poor, due to the vicious circle of poverty and ill health.
Conversely, improvements in health will boost the individual’s level of income (due to lower treatment costs, higher revenue, a longer term increase in
revenue due to better work opportunities, and overall growth in revenues due
to longer life-expectancy); increase the individual’s capacity to acquire an education; increase the family’s productive opportunities; and greatly improve
the psychological wellbeing of both the individual and the family.
The benefits of good health will be even greater for the absolute poor, as they
may transform the vicious circle of poverty into a virtuous circle, with better
nutrition, lower risks of unemployment or underemployment, better housing, better use of training opportunities, higher productivity and, overall,
better control over their life situation and that of their family.
Global health priorities have in recent years been defined through several
processes and by several actors and at various forums. In 2000 and 2001,
HIV/AIDS, tuberculosis and malaria came to be discussed in a variety of forums at the UN as well as outside the UN, and commitments to address the
three diseases were made, for example, by the G8, the World Bank, the World
333
Economic Forum and the European Commission. Millennium Development
Goals (MDGs)5 are a product of consultations between international agencies, but were also adopted by the United Nations (UN) General Assembly
in September 2001 as part of the road map for implementing the substantially broader Millennium Declaration, which it had adopted in September
20006. The MDGs have eight goals, three of which are health-focussed,
namely those on child mortality, maternal health, and HIV/AIDS, malaria
and other diseases.
Improvements in health are partly due to an increase in the standard of living
of a society. Similarly, improvements in health are due to the impressive increase in the average level of education, which has led to better understanding
by families of the importance of nutrition, hygiene and sanitation. As a result,
public officials have tended to rely on the development process to bring health
to the people and to consider health as a consequence of the development
process rather than one of its engines. In this sense, health has traditionally
mostly been valued for its social welfare and redistributive role, and considered
by officials and citizens alike more as a consumption item than an investment.
Worldwide, 57.5 million people died in 2003. One third of these deaths were
due to communicable, maternal, and perinatal conditions and nutritional deficiencies (‘Group I’ in the Global Burden of Disease, or GBD, classifi cation).
This proportion has remained almost unchanged from 1990. Among Group
I causes, HIV/AIDS accounted for 2% of deaths in 1990, but 17% in 2003,
rising from 0.3 million deaths to 3.0 million in 2003. HIV/AIDS represented 5% of total global deaths in 2003. Excluding deaths due to HIV/AIDS,
deaths due to Group I conditions fell from one-third of total deaths
in 1990 to less than one-fifth in 2003. In all, 97% of the ‘non-HIV/AIDS
Group I’ deaths occurred in low- and middle-income countries.
Impressive improvements have occurred in global health status in the past
century. Unfortunately, these improvements have not been shared equally
and health in equalities within and among countries are entrenched. The
fragility of health gains has been seen in response to economic, political, and
social changes, and civil disruption. These factors suggest that, from a global
perspective, sustainable and equitable health advancement is not yet secure,
5 United Nations: Road map towards the implementation of the United Nations Millennium
Declaration. Report of the Secretary-General A/56/326.
6 United Nations General Assembly: United Nations Millennium Declaration. Resolution
A/RES/55/2.
334
especially because the economic disparities between countries of the north
and south continue to grow.
It is well know that poverty in the world, encompasses several dimensions, including not only material deprivation but also low educational achievement,
poor health, vulnerability and exposure to environmental and occupational
risks, as well as voicelessness and powerlessness. Therefore, the poverty deprives every single individual of the freedom to satisfy hunger, to achieve sufficient nutrition, to obtain remedies for treatable illnesses or to enjoy clean
water or sanitary facilities. This lack of freedom prevents individuals from
fulfilling their potential, thus leading to a great loss for society and hampering development7.
In 2000, the Commission on Macroeconomics and Health set out to examine the links between health and poverty and to demonstrate that health investment can accelerate economic growth.
Poverty and illness create a vicious cycle.
Poverty is at the source of major health risks, such as insufficient and improper nutrition, poor sanitation and hygiene and limited access to health and education services, all of which determine almost 45% of the disease burden in
Least Developed Countries8. Moreover, the impact of poverty might be unequally distributed among the poor and it can have different impact according, for example, to gender and age group2.
Illness is a major reason that the nearly poor drop into poverty. Illness decrease people’s ability to work and moreover prevents children from obtaining the education they need.
“Disease weighs heavily on economic development. […] But economic development requires more than just healthy individuals. […] Economic development is
a multisectoral process, and the strategy for economic development must build on
a broad range of social investments as well as strategies to encourage private-sector business investments.” 9
It is widely accepted that the health, as well as the education, are among the
basic capabilities that gives value to human life6, in economic terms, health
and education are the two cornerstones of human capital, in other words, the
basis of an individual’s economic productivity and social development.
7 SEN, A. Development as freedom. New York, Oxford University Press, 2000.
8 World Health Organization World Health Report 2002: Reducing Risks, Promoting Healthy
Life. Geneva 2002.
9 World Health Organization, Macroeconomics and health: investing in health for economic
development. Report of the Commission on Macroeconomics and Health. Geneva, 2001.
335
Always, the economic growth was seen as a precondition for realistic improvements in health.
Until recently, an efficient and well-managed health care system was seen as
critical for the economic and social development of a country.
“Which are the essential global public health activities that should be carried out
in order to attain the largest impact on poverty reduction and health improvement in the world?”
The Health Care Services can widely contribute to economic development10
11 12 13 14 15
.
For the average person in a low- or middle-income country, falling sick for
any length of time seriously endangers the economic situation and well-being of both the individual and their family, in the short and long term, for
the following reasons:
• bad health will have a severe impact on the individual’s level of income
(treatment costs, immediate loss of revenue, longer term loss of revenue
due to reduced work opportunities, revenue losses due to premature
death);
• it will decrease the capacity of the individual or other family members to
acquire an education;
• it will also affect the family’s productive opportunities as some members
of the family will be called upon to help the member who has fallen ill;
• if ill health persists, the family may fall into absolute poverty (due to loss
of income and the “catastrophic payments” needed to regain health);
10 World Health Organization. The world health report 2000. Health Systems: Improving
Performance. Geneva.
11 Allin S et al. National approaches to public health in eight countries [unpublished].
London, European Observatory on Health Systems and Policies, 2003. The full report is
available at http://www.observatory.dk.
12 Maynard A, Dixon A. Voluntary health insurance and medical savings account: theory and
experience. In Funding health care: options for Europe. Mossialos A et al., eds. Buckingham,
Open University Press, 2002.
13 Sandier S et al. France. In: Dixon A, Mossialos E, eds. Health care systems in eight countries: trends and challenges. Report commissioned by the Health Trends Review, HM
Treasury. London, European Observatory on Health Care Systems, 2002.
14 Robinson R. User charges for health care. In: Mossialos E, et al., eds. Funding health care:
options for Europe. Buckingham, Open University Press, 2002.
15 Elias Mossialos, Anna Dixon, Josep Figueras and Joe Kutzin (ed.) Funding health care: options for Europe European Observatory on Health Care Systems Series Open University
Press 2002.
336
• finally, it will decrease substantially both their own and their family’s psychological well-being.
Bad health may make the difference between life and death, as a result of the
vicious circle of poverty and ill health, in one or more of the following ways:
disease for one member of the family means an increase in malnutrition as a
result of additional spending on treatment;
• malnutrition increases the risk of unemployment or underemployment,
further reducing family revenues;
• an already poor housing situation risks further deterioration;
• both the sick and the family members looking after them miss opportunities for education and training in the formal or informal sector;
• in the long run, the already low productivity level of the family may further decrease in the competitive environment;
• access to health care services, safe drinking water and social services in
general may become even more precarious as a result of lower revenues
and less education;
• poorer families tend to have more children, in the hope that at least one of
them will support the parents in old age (a form of long-term insurance);
• there is an elevated risk of unwanted pregnancies and substance abuse; the
sale of assets for survival may force the family to move to a more degraded environment;
• the overall impact is to reinforce the powerlessness of the family members,
putting at risk the survival of the family itself.
Conversely, the benefits of better health for the economy are also enormous.
They include an increase in production, a better trained and more productive
labour force, increased competitiveness of the economy, financially more solid enterprises, lower unemployment and a lower rate of disease transmission.
The 1990s saw a new awakening of interest in tackling global problems of
poverty, development and health that culminated, in 2000, in governments
committing to meet the Millennium Development Goals by 2015. In recent
years, exponential growth in the number of economic evaluations of health
interventions, has created a wider knowledge base for evaluating the costs and
benefits of interventions to enable better targeting of financial resources in
the health sector.
Improvements in global health status, as measured by gains in life expectancy and the reductions in preventable deaths, have been accompanied by a
widening health and poverty gap between and within countries. Investment
in health research and development remains focused largely on the health
337
problems on the 10% of the world’s richest populations, and only 10% of
funds available for health research is directed at improving the health of 90%
of the world’s population16. This disparity, referred to as the 10/90 disequilibrium, requires urgent attention17. The Global Health Forum, convened in
1997 to address this situation, is attempting to shift health research funds
from lower to higher priority projects and from projects benefiting fewer people to those benefiting the large majority18.
The WHO is also intensifying its focus on non-communicable disease and
the major common risk factors which predict them.
Health systems have two objectives:
(a) to improve the level and distribution of health outcomes in the population and
(b) to protect individuals from financial risks that are often very substantial and that are frequent causes of poverty. Financial risk results from
illness-related loss of income as well as expenditures on care; the loss
can be ameliorated by preventing illness or its progression and by using appropriate financial architecture for the system.
Two classes of resources must be available: financial resources and health system capacity. To implement an intervention in a population, the system uses
some of each resource. Just as some interventions have higher costs than others, some interventions are more demanding of system capacity than others.
In countries with limited health system capacity, it is clearly important to select interventions that require relatively little of such capacity.
In 2001, the Commission on Macroeconomics and Health, recognizing the
high rates of return on investments in health for both the individuals and the
countries concerned, recommended a massive increase in these investments
in the coming years. From an estimated level of US$ 53.5 billion in 2001,
the Commission recommends a more than doubling of investments in health
in the least-developed and other low-income countries over the 14-year period to 2015, to reach US$ 119 billion in 2015. This increase of US$ 65.5 billion would be financed by an increase in country-level commitments of US$
40 billion and an increase in donor assistance of US$ 25.5 billion (from an
16 WHO. The 10/90 Report on Health Research 1999: the Global Forum for Health
Research. Geneva: WHO, 1999.
17 10/90 Report on Health Research 2003-2004.
18 Qadeer I, Sen K. Public health debacle in South Asia: a reflection of the crisis in welfarism. J Public Health Med 1998; 20: 93-96.
338
estimated US$ 3.5 billion in 2001 to US$ 29 billion in 2015). The
Commission on Macroeconomics and Health estimated that the minimum
level of health spending needed in low-income countries to cover essential interventions is US$ 30-US$ 40 per person per year (as compared to the estimated current level of US$ 11 and US$ 25 in the least developed and the
other low-income countries respectively).
The money spent on health worldwide has reached 10% of overall global income, that amount is both
The money
spent on health worldwide has reached 10% of overall global inand poorly allocated. The World Health Organization’s Commission on Macroeconomics
come,insufficient
that amount
is both insufficient and poorly allocated. The World
and Health and several other global initiatives asked a larger investment in health. The demand should
Health Organization’s Commission on Macroeconomics and Health and several
be to reduce inequalities in health investment between and within countries: a 100-fold difference
other global initiatives asked a larger investment in health. The demand
between the rich and the poor in money spent on health services still persists in many places. There is,
should be to reduce inequalities in health investment between and within
therefore, a paradox. Clinical and public health interventions depend on the capacity of a given
countries: a 100-fold difference between the rich and the poor in money
country’s health system to deliver scarce resources, considering that some interventions are more
spent on health services still persists in many places. There is, therefore, a parcomplex than others in terms of infrastructure and human resources and the evidence-based approaches
adox. Clinical and public health interventions depend on the capacity of a
must be the foundation for allocating scarce resources. Therefore, both the costs and the likelihood of
given country’s health system to deliver scarce resources, considering that
success of the more complex interventions are a function of the health capacity in place. In addition,
some interventions are more complex than others in terms of infrastructure
decisions about which interventions should be given priority will depend on assessments of the local
and human resources and the evidence-based approaches must be the founburden of disease, local health infrastructure, and other social factors as well as on cost-effectiveness
dation for allocating scarce resources. Therefore, both the costs and the likeanalyses.
lihood of success of the more complex interventions are a function of the
The Commission on Macroeconomics and Health (CMH) at the end of the final session of the
health ndcapacity in place. In addition, decisions about which interventions
2 Consultation on Macroeconomics and Health, "Increasing Investments in Health Outcomes for the
should be given priority will depend on assessments of the local burden of
Poor"(Geneva, 2003), identified resource mobilization options, human resource constraints, and the
disease, local health infrastructure, and other
social factors as well as on costharmonization of donor funding as key issues19 and, as before, recommended global effort to scale up
effectiveness analyses.
The Commission on Macroeconomics and Health (CMH) at the end of the fiWHO
INVESTMENTS on
IN Macroeconomics
HEALTH OUTCOMES FOR
POOR“Increasing
2nd CONSULTATION ON
and THE
Health,
nal session
of INCREASING
the 2 Consultation
19
ND
MACROECONOMICS AND HEALTH-October 2003, Geneva, Switzerland
339
Investments in Health Outcomes for the Poor”(Geneva, 2003), identified resource
mobilization options, human resource constraints, and the harmonization of
donor funding as key issues19 and, as before, recommended global effort to scale
up priority health interventions20. The analytical work of the CMH was structured around working groups on key topics. Working Group 5, had the task of
elaborating “options and costs for mounting a major global effort to improve dramatically the health of the poor over the next 5 and 15 years”21.
The CMH recommended that access to and utilisation of priority health
services be dramatically expanded so that they are universally available, described as “scaling up”.
“Scaling up” can be defined as the activity of expanding an intervention or
programme from initial services that serve a small proportion of the population to services that serve a significantly larger population, such as an entire
region or country. It also means taking successful programs, policies, and
projects and expanding, adapting, and sustaining them in different places and
over time. In the last few years, increasing attention has been paid to scalingup service delivery to achieve MDGs.
The focus of problem is on understanding the constraints to scaling up, and
the options available for moderating end eliminating constraints from a
22 23 24
.
health system perspective
The costs of health expenditure, considering regional and/or national realities, regarding disease priorities, private willingness to pay for health and
public budget constraints, can be used to identify widely prevalent invest-
19 WHO INCREASING INVESTMENTS IN HEALTH OUTCOMES FOR THE POOR
2nd CONSULTATION ON MACROECONOMICS AND HEALTH-October 2003,
Geneva, Switzerland
20 Commission on Macroeconomics and Health. Macroeconomics and Health: Investing in
Health for Economic Development. 2001. Geneva, World Health Organization.
21 Commission on Macroeconomics and Health. Improving Health Outcomes of the Poor:
The Report Working Group 5 of the Commission on Macroeconomics and Health. 2002.
Geneva, World Health Organization.
22 Mills A and Hanson K (eds). Expanding access to health interventions in low and middleincome countries: constraints and opportunities for scaling up. Journal of International
Development Special Issue 15(1): 1-14, 2003.
23 Hanson K, Ranson K, Oliveira-Cruz V, Mills A: Constraints to scaling up health interventions: a conceptual framework. Journal of International Development 2003, 15:1-14.
24 Gericke CA, Kurowski C, Ranson MK and Mills A. Feasibility of scaling up interventions:
the role of intervention design.
340
ments that are not cost-effective and highly cost-effective opportunities to
improve health that policy makers are currently neglecting.The Global
Forum for Health Research has carried out a new assessment of how much
the world is spending on health research.
For 2003 the total amount spent on R&D for health was US$ 125.8 billion.
This is a substantial increase compared with the Global Forum’s estimate of
US$ 105.9 billion for 2001. The 2003 fi gure comprises three major components, with US$ 56.1 billion (45%) coming from the public sector, US$ 60.6
billion (48%) from the private for-profit sector and US$ 9.0 billion (7%)
from not-for-profit organizations. The private for-profit sector is estimated to
be the largest investor in health research globally. Pharmaceutical companies
accounted for 50% of overall funds for research for health in high-income
countries and 32% in low- and middle-income countries. The private notfor-profit sector includes private universities, foundations and charities. It
contributes approximately the same amount of funding in high-income
countries (8%) and low- and middle-income countries (9%). Official
Development Assistance (ODA) accounts for 7% of total health research
funds in low- and middleincome countries (LMICs).
Public sector contributions to global spending on health R&D are signifi
cant not only because of their size, but also because of the infl uence they
have on the directions of basic and applied research. States bear the primary
responsibility for the health and rights of their citizens and many are also signatories to international commitments on health. Governments are estimated to be the largest funders after
the private sector, accounting in 2003 for 42% of overall health research
funds in high-income countries and 59% in LMICs. Governments support
research for health through their allocations to ODA, higher education and
direct investments in R&D.
Public-private partnerships, largely funded by philanthropic foundations,
have begun creating a pipeline of potential vaccines, drugs, diagnostics and
microbicides for infectious diseases of particular importance in developing
countries, including HIV/ AIDS, tuberculosis (TB) and malaria. To ensure
that these products can be bought for use in the poorest countries, new funding channels and initiatives have been developed, including the Global Fund
to Fight AIDS, TB and Malaria, the President’s Emergency Plan for AIDS
Relief and the International Financing Facility for Immunization.
341
Measures of health status
The most useful and long-standing measure of health status continues to be
cause of death based on the death certificate. The system of classifying causes of death developed by William Farr 150 years ago still forms the basis of
the International Classification of Diseases, now in its tenth version. This
provides an invaluable source of information on causes of death and trends
over time. Unfortunately, cause-specific death data are routinely available for
only a minority of the world’s countries. Only 77 countries contributed age
and sex death statistics and cause-specific death statistics to the latest WHO
data bank. Less than one third of the world’s population is adequately covered by national vital registration systems and there is a wide regional variation ranging from 80% population coverage in the European region to less
than 5% population coverage in the Eastern Mediterranean and African regions of WHO. The ten-fold variation in infant mortality between different
regions of the world is largely due to communicable diseases, malnutrition,
and poverty. By contrast, the cause of death in adults aged between 15 years
and 60 years is due almost entirely to non-communicable diseases and injury.
Probability of death for men between
Probability of death for men between ages 15 and 60 years, 2020
ages
15 andof 60
years,
2020
Probability
death
for men
between ages 15 and 60 years, 2020
Probability of death for women
ageswomen
15 and 60 years, 2020
of between
death for
Probability of death for women between ages 15 and 60 years, Probability
2020
between ages 15 and 60 years, 2020
EME=Established market economies;
FSE=Formerly socialist economies of
Europe; IND=lndia; OAI=Other Asian
islands; SSA=sub-Saharan Africa;
LAC=Latin America and the
Caribbean; MEC=Middle Eastern
Crescent.
EME=Established market economies; FSE=Formerly socialist economies of Europe; IN
EME=Established market economies; FSE=Formerly socialist
economies of Europe;
IND=lndia; OAI=Other
islands; MEC=Middle Easte
SSA=sub-Saharan
Africa; LAC=Latin
America andAsian
the Caribbean;
SSA=sub-Saharan Africa; LAC=Latin America and the Caribbean; MEC=Middle Eastern Crescent.
Until recently, health programmes and interventions were based specific
Until recently, health programmes and interventions were based specifically on data on mortality. This
342
Until recently, health programmes and interventions were based specifically
on data on mortality. This resulted in a shift to work exclusively on diseases
which killed populations. In 1993 the World Development Report introduced the Disability Adjusted Life Year tool, which combines death, morbidity and disability in one figure. This health gap tool has been challenged
since. Additional measures to encompass these queries have been proposed,
including the HEALYs and the QALYs. Countries and international agencies
have made a qualitative leap in the funding of the global disease challenges.
The Global Fund for AIDS, TB and Malaria has received pledges totalling
over US$ 2 billion. Bilateral donors are also making important funding contributions. In this context, strengthening of health systems has become a critical issue. Research can play a major role to identify the best policies to channel massive efforts, to ensure that vertical approaches do not fragment fragile
health systems and to monitor and evaluate progress.
The extent of inequities is also a major concern. Recent analyses show that
even when interventions are provided, the poorest members of society usually have the least access to them (Gwatkin and others 2000). In many countries, gaps in child mortality between the poor and the better off widened
during the 1990s (World Bank 2004). Thus, health systems need to have the
capacity not only to deliver interventions efficiently but also to sustain high
levels of coverage, especially of the poorest and most vulnerable.
Awareness has grown that international targets, such as the Millennium
Development Goals (MDGs).
However, satisfaction must be tempered by four concerns. First, the limitations of available measures of global-health status and their coverage hinder
our ability to map health trends except in the simplest fashion. Second, the
health improvements have not been shared equally and health inequalities
among and within countries remain entrenched. Third, the fragility of health
gains has repeatedly been shown in response, for example, to economic and
social changes and civil disruption. Fourthly, the current global-health situation is a complex and challenging mixture of old and new health problems.
Cost-effectiveness ratios
The overall cost-effectiveness of a service level or package of interventions,
rather than the cost-effectiveness of individual interventions, is the appropriate indicator to determine which interventions should be used. From a planning point of view, taking the infrastructure as fixed, and then asking how it
can best be used to deliver the most cost-effective interventions might be sen-
343
sible. Where infrastructure is limited, expanding access will have to take priority. Other factors related to health system capacity and infrastructure may
play a key role in determining the adoption of interventions.
Cost-effectiveness data reflect largely what can be achieved in a reasonably
well-functioning health system. In that sense, they can be considered to represent potential cost-effectiveness and need to be supplemented with evidence and guidance on how health systems can be strengthened to provide
interventions effectively, efficiently, and equitably. This argument is given
added weight by evidence on inadequacies in the performance of health institutions in countries at all levels of development (Hensher 2001; Preker and
Harding 2003). Hensher (2001) documents the extensive inefficiencies in
low and middle-income countries.
Such inefficiencies have two main causes. First, they may occur because decision makers lack incentives to behave efficiently; for example, their promotion chances may not depend on how well they perform in managing a hospital. Second, decision makers may be constrained in their ability to make efficient choices.
Epidemiological, medical, political, ethical, and cultural factors often also
play important roles in the decision to allocate resources to a specific health
condition or intervention; however, determining how one might weigh costeffectiveness ratios alongside these other considerations when setting priorities for spending is difficult.
Cost-effectiveness ratios can be used to set health priorities in two ways. One
approach is to use a cut-off level of cost-effectiveness beyond which interventions are no longer used.
This cut-off can vary from place to place depending on the availability of
health resources, the disease burden, and the local preferences for health
spending.
The World Bank has described health interventions that cost less than
US$100 per year of life saved as highly cost-effective for poor countries, but
this benchmark is arbitrary.
An alternative approach to using cost-effectiveness data to set intervention
priorities is to interpret the cost-effectiveness ratio as the “price” of equivalent
units of health using different interventions.
Cost-effectiveness ratios can be used to set health priorities in two ways. One
approach is to use a cut off level of cost effectiveness beyond which interventions are no longer used. This cut off can vary from place to place depending
on the availability of health resources, the disease burden, and the local pref-
344
erences for health spending. The World Bank has described health interventions that cost less than US$100 per year of life saved as highly cost-effective
for poor countries, but this benchmark is arbitrary, as chapter 15 makes clear
by noting the interaction with income, budget levels, and the disease burden.
An alternative approach to using cost-effectiveness data to set intervention
priorities is to interpret the cost-effectiveness ratio as the “price” of equivalent
units of health using different interventions.
Efforts to improve health in low- and middle-income countries over the past
50 years can be divided into 3 periods: the 1950s, 1960s, and 1970s. this years
were witnessed of a number of successful disease control efforts, often termed
mass campaigns, notably smallpox eradication, but also, malaria and yaws
control (Walt 2001). The Alma Ata Declaration of 1978 was a turning point.
The challenge of scaling up services to meet the health-related MDGs and
concerns that the multiple international efforts may overwhelm countries’
fragile infrastructures have encouraged efforts to think systematically about
health system constraints on achieving the MDGs, and the extent to which
additional funding can readily and quickly improve services Weaknesses in
service delivery may stem from problems at that level, such as staff shortages,
or may be affected by factors higher up the system, such as a poor drug distribution system. Ranson and others (2003) therefore analyze constraints by
five different levels: community and household, health services delivery,
health
policy
and system.
strategic
management,
public
policies
cutting by
across
such as asector
poor drug
distribution
Ranson
and others (2003)
therefore
analyze constraints
five
sectors,
and environmental
and contextual
different levels:
community and household,
health servicescharacteristics.
delivery, health sector policy and strategic
management, public policies cutting across sectors, and environmental and contextual characteristics.
Constraints on Improving Access to Essential Health Interventions, by Level
Constraints on Improving Access to Essential Health Interventions, by Level
Health sector policy and strategic management
Public policies cutting across sectors
Environmental and contextual
characteristics
Weak and overly centralized planning and management systems
Weak drug policies and drug supply system
Inadequate regulation of pharmaceutical and private sectors and improper industry
practices
Lack of intersectoral action and partnership for health between government and civil
society
Weak incentives to use inputs efficiently and to respond to users’ needs and
preferences
Reliance on aid agency funding, which reduces flexibility and ownership
Aid agency practices that overload country management capacity
Government bureaucracy (civil service rules and remuneration, centralized management
system)
Poor availability of communications and transportation infrastructure
Governance and overall policy framework:
Corruption, weak government, weak rule of law, weak enforceability of
contracts
Political instability and insecurity
Low priority attached to social sectors
Weak structures for public accountability
Lack of a free press
Physical environment:
Climatic and geographic predisposition to disease
Physical environment unfavorable to service delivery
345
346
References
• Abraham, K. G., and C. Mackie, eds. 2005. Beyond the Market: Designing Non market
Accounts for the United States. Washington, DC: The National Academies Press.
• Arrow, K. J. 1963. “Uncertainty and the Welfare Economics of Medical Care” American
Economic Review 53 (5): 851-83.
• Arrow, K. J., C. Panosian, and H. Gelband, eds. 2004. Saving Lives, Buying Time:
Economics of Malaria Drugs in an Age of Resistance. Washington, DC: National Academies
Press.
• Arrow, K. J., H. Gelband, and D. T. Jamison. 2005. “Making Antimalarial Agents
Available in Africa” New England Journal of Medicine 353: 333-35.
• Barendregt JJ, Bonneux L, Vander Maas PJ. DALYs: the age/weight on balance. Bull
World Health Organ 1996; 74: 439-443.
• Barker C, Green A. Opening the debate on DALYs. Health Pol Planning 1996; 11:
179-183.
• Barr, N. 2001. The Welfare State as Piggy Bank: Information, Risk, Uncertainty, and the
Role of the State. Oxford: Oxford University Press.
• Becker, G. S., T. J. Philipson, and R. R. Soares. 2003. “The Quantity and Quality of Life
and the Evolution of World Inequality.” NBER Working Paper 9765, National Bureau of
Economic Research, Cambridge, MA.
• Bezanson, K. 2005. “Replenishing the Global Fund: An Independent Assessment.”
http://www.theglobalfund.org/en/files/about/replenishment/assessment_report_en.pdf.
• Bhargava, A., D. T. Jamison, L. J. Lau, and C. J. L. Murray. 2001. “Modeling the Effects
of Health on Economic Growth.” Journal of Health Economics 20 (May): 423-40.
• Bloom, D. E., D. Canning, and D. T. Jamison. 2004. “Health, Wealth and Welfare.”
Finance and Development 41 (1): 10-15.
• Bloom, D. E., D. Canning, and J. Sevilla. 2004. “The Effect of Health on Economic
Growth: A Production Function Approach.” World Development 32: 1–13.
• Bloom, D. E., D. Canning, and P. Malaney. 2000. “Demographic Change and Economic
Growth in Asia.” Supplement to Population and Development Review 26: 257-90.
• Bobadilla, J. L., J. Frenk, R. Lozano, T. Frejka, and C. Stern. 1993. “The Epidemiologic
Transition and Health Priorities.” In Disease Control Priorities in Developing Countries, ed.
D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 746. New York:
Oxford University Press.
• Boskin, M. J., and L. J. Lau. 2000. “Generalized Solow-Neutral Technical Progress and
Postwar Economic Growth.” NBER Working Paper 8023, National Bureau of Economic
Research, Cambridge, MA.
• Bourguignon, F., and C. Morrisson. 2002. “Inequality among World Citizens: 18201992.” American Economic Review 92: 727-44.
• Breman, J. G.,M. S.Alilio, and A.Mills, eds. 2004. “The Intolerable Burden of Malaria:
II. What’s New, What’s Needed.” American Journal of Hygiene and Tropical Medicine 71
(2 Suppl): 1-282.
• Burnside, C., and D. Dollar. 2000. “Aid, Policies and Growth.” American Economic
Review 90: 847-68.
• Clemens, M., S. Radelet, and R. Bhavnani. 2004. “Counting Chickens When They Hatch:
•
•
•
•
•
•
•
•
•
•
•
•
•
347
The Short-Term Effect of Aid on Growth.” Working Paper 44, Center for Global
Development,Washington, DC.
Crafts, N. 2000. “Globalization and Growth in the Twentieth Century.” IMF Working
Paper WP/00/44, International Monetary Fund, Washington, DC.
Crafts, N., and M. Haacker. 2004. “Welfare Implications of HIV/AIDS.” In The
Macroeconomics of HIV/AIDS, ed. M. Haacker, 182-97. Washington, DC: International
Monetary Fund.
de Savigny, D., H. Kasale, C. Mbuya, and G. Reid. 2004. Fixing Health Systems. Ottawa:
International Development Research Centre.
Deaton, A. 2004. “Health in an Age of Globalization.” NBER Working Paper 10669,
National Bureau of Economic Research, Cambridge, MA.
Ezzati, M., A. D. Lopez, A. Rodgers, and C. J. L. Murray, eds. 2004. Comparative
Quantification of Health Risks: Global and Regional Burden of Disease Attributable to
Selected Major Risk Factors. Vols. 1-2. Geneva:World Health Organization.
Ezzati, M., S. vander Hoorn, A. D. Lopez, G. Danaei, A. Rodgers, C. D. Mathers, and
C. J. L. Murray. 2006. “Comparative Quantification of Mortality and Burden of Disease
Attributable to Selected Major Risk Factors.” In Global Burden of Disease and Risk Factors,
ed.A. D. Lopez, C. Mathers, M. Ezzati, D. T. Jamison, and C. J. L. Murray. New York:
Fauci, A. S. 2005. “The Global Challenge of Infectious Diseases: The Evolving Role of the
National Institutes of Health in Basic and Clinical Research.” Nature Immunology 6 (8):
743-47.
Gericke, C. A., C. Kurowski, M. K. Ranson, and A. Mills. 2005. “Intervention
Complexity: A Conceptual Framework to Inform Priority-Setting in Health.” Bulletin of the
World Health Organization 83 (4): 285-93.
Gericke, C. A., C. Kurowski, M. K. Ranson, and A.Mills. 2003. “Feasibility of Scalingup Interventions: The Role of Intervention Design.” Working Paper 13, Disease Control
Priorities Project, Bethesda, MD.
Gertler, P. 2004. “Do Conditional Cash Transfers Improve Child Health? Evidence from
PROGRESA’s Control Randomized Experiment.” Health, Health Care, and Economic
Development 94 (2): 336-41.
Haacker, M., ed. 2004. The Macroeconomics of HIV/AIDS. Washington, DC:
International Monetary Fund. Institute of Medicine. 2001. Crossing the Quality
Chasm.Washington, DC: National Academies Press.
Jamison, D. T 2003. “Cost-Effectiveness Analysis: Concepts and Applications.” In The
Oxford Textbook of Public Health, ed. R. Detels, J. McEwen, R. Beaglehole, and H.
Tamaka, 2: 903-19. 2004. “External Finance of Immunization Programs: Time for a
Change in Paradigm?” In Vaccines: Preventing Disease and Protecting Health, ed. C. de
Quadros, 325-32. Scientific and Technical Publication 596.Washington, DC: Pan
American Health Organization.
Jamison, D. T., E. A. Jamison, and J. D. Sachs. 2003. “Assessing the Determinants of
Growth When Health Is Explicitly Included in the Measure of Economic Welfare.” Paper presented at the 4th World Congress of the International Health Economics Association,
San Francisco, June.
348
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Jamison, D. T., J. G. Breman, A. R.Measham, G. Alleyne, M. Claeson, D. B. Evans, P.
Jha, A. Mills and P. Musgrove, eds. 2006. Priorities in Health. Washington, DC: World
Bank.
Jamison, D. T., L. J. Lau, and J. Wang. 2005. “Health’s Contribution to Economic Growth
in an Environment of Partially Endogenous Technical Progress.” In Health and Economic
Growth: Findings and Policy Implications, ed. G. Lopez-Casasnovas, B. Rivera, and L.
Currais, 67-91. Cambridge, MA: MIT Press.
Jamison, D. T., Radelet S. 2005. “Making Aid Smarter.” Finance and Development 42
(2): 42-46.
Jamison, D. T., S. Shahid-Salles, J. S. Jamison, J. Lawn, and J. Zupan. 2006.
“Incorporating Deaths Near the Time of Birth into Estimates of the Global Burden of
Disease.” In Global Burden of Disease and Risk Factors, ed. A. D. Lopez, C. D. Mathers,
M. Ezzati, D. T. Jamison, and C. J. L.Murray. New York: Oxford University Press.
Joint Learning Initiative. 2004. Human Resources for Health: Overcoming the Crisis.
Washington, DC: Communications Development.
Kim, J. J. 2005. “Using Mathematical Modeling to Evaluate the Public Health Impact and
Cost-Effectiveness of Cervical Cancer Screening Strategies in Different World Regions.” Ph.D.
dissertation, Program in Health Policy, Harvard University, Cambridge, MA.
Kremer, M., and R. Glennerster. 2004. Strong Medicine: Creating Incentives for
Pharmaceutical Research on Neglected Diseases. Princeton, NJ: Princeton University Press.
Levine, R. and the What Works Working Group. 2004. Millions Saved: Proven Successes
in Global Health. Washington, DC: Center for Global Development.
Lindert, P. H. 2004. Growing Public: Social Spending and Economic Growth since the
Eighteenth Century. Vol. 1. Cambridge, U.K.: Cambridge University Press.
Lopez A. D., C. D. Mathers, M. Ezzati, D. T. Jamison, and C. J. L. Murray, eds. 2006.
Global Burden of Disease and Risk Factors. New York:Oxford University Press.
Lopez, A. D., C. D. Mathers, M. Ezzati, D. T. Jamison, and C. J. L. Murray, eds.
2006.“Measuring the Global Burden of Disease and Risk Factors.” In Global Burden of
Disease and Risk Factors, ed. A. D. Lopez, C. D. Mathers, M. Ezzati, D. T. Jamison, and
C. J. L. Murray. New York: Oxford University Press.
Lopez-Casasnovas, G., B. Rivera, and L. Currais, eds. 2005. Health and Economic
Growth: Findings and Policy Implications. Cambridge, MA: MIT Press.
Mathers, C. D., C. J. L. Murray, and A. D. Lopez. 2006. “The Burden of Disease and
Mortality by Condition: Data, Methods and Results for the Year 2001.” In Global Burden of
Disease and Risk Factors, ed. A. D. Lopez, C. D. Mathers, M. Ezzati, D. T. Jamison, and
C. J. L. Murray. New York: Oxford University Press.
Nordhaus, W. 2003. “The Health of Nations: The Contributions of Improved Health to
Living Standards.” In Measuring the Gains from Health Research: An Economic Approach,
ed. K. M. Murphy and R. H.
Powles, John. 2001. “Healthier Progress: Historical Perspectives on the Social and Economic
Determinants of Health.” In The Social Origins of Health and Well-Being, ed. R. Eckersly,
J. Dixon, and B. Douglas, 3-24. Cambridge, U.K.: Cambridge University Press.
Pritchard, C. 2004. “Developments in Economic Evaluation in Health Care: A Review of
HEED.” OHE Briefing 40, Office of Health Economics, London, March 2004.
•
•
•
•
•
•
•
•
•
349
Qadeer I, Sen K. Public health debacle in South Asia: a reflection of the crisis in welfarism. J Public Health Med 1998; 20: 93-96.
Radelet, S. 2003. Challenging Foreign Aid. Washington, DC: Center for Global
Development.
Roberts, M., W. Hsiao, P. Berman, and M. Reich. 2003. Getting Health Reform Right: A
Guide to Improving Performance and Equity. New York: Oxford University Press.
Sachs, J. D. 2005. The End of Poverty: Economic Possibilities for Our Time. New York: The
Penguin Press. Topel, 9-40. Chicago: University of Chicago Press.
WHO CMH (World Health Organization Commission on Macroeconomics and
Health). 2001. Macroeconomics and Health: Investing in Health for Economic Development.
Geneva: WHO.
WHO, UNICEF, UNAIDS, World Bank, UNESCO, UNFPA. Health: A Key to
Prosperity, Success Stories in Developing Countries, Geneva, 2000.
WHO. The 10/90 Report on Health Research 1999: the Global Forum for Health
Research. Geneva: WHO, 1999
World Health Organization. 1996. “Investing in Health Research and Development.”
Report of the Ad Hoc Committee on Health Researc
Monthly Progress Update - 27 July 2006. Geneva, Global Fund to Fight AIDS,
Tuberculosis and Malaria, 2006 (http://www. theglobalfund.org/en/fi
les/publications/basics/progress_update/progressupdate.pdf,).
350
BIANCA
16. Economic assessments and tropical diseases in developing countries
351
16. ECONOMIC ASSESSMENTS AND TROPICAL
DISEASES IN DEVELOPING COUNTRIES
Aldo Morrone, Lorenzo Nosotti, Ottavio Latini
Tropical diseases targeted for elimination: leprosy, Chagas disease,
lymphatic filariasis and onchocerciasis
Costs associated with leprosy control include case detection, treatment, prevention of disability, and rehabilitation. We calculate the incremental health
service cost to arrive at the average cost of curing a patient with leprosy. Our
estimates are based on the limited published cost data available, program expenditure data, and expert opinion, although costs are likely to differ substantially by country.
As case-detection rates decrease, the average cost of detecting one case increases. The previous edition of this volume estimated a cost of US$2 per case
detected based on a case-detection rate of about 300 per 100,000; however,
casedetection rates are now considerably lower in most countries
(Dharmshaktu and others 1999; Ganapati and others 2001; Smith 1999).
Many leprosy control programs now rely on voluntary case finding supported by information, education, and communication activities to raise or maintain people’s awareness of the early signs and symptoms of leprosy. We estimate the cost of this approach to be about US$1 per case detected.
Nevertheless, if active methods are still used in areas where case-detection
rates are low, the cost of case detection may be as high as US$108.
The costs of diagnosing and treating leprosy have fallen in the past decade,
and diagnosis by clinical examination only is now recommended. We therefore exclude the cost of skin smears. In addition, a shortening of the treatment regimen has lowered drug costs to about US$12 for a multibacillary
case and US$1 for a paucibacillary case. Globally, almost 40 percent of leprosy cases are classified as multibacillary cases, with the remaining 60 percent
being paucibacillary cases. Thus, we estimate the average drug cost as
US$5.40 per case.
The cost of treatment, however, is more than the cost of drugs alone. WHO
guidelines recommend that a multibacillary case receive supervised treatment
for 12 months and that a paucibacillary patient receive treatment for 6
months. Using cost data from Ethiopia and Pakistan, we estimate these treatment costs at US$20 to US$30 in low-income countries.
352
Data from studies of tuberculosis interventions show that community-supervised treatment may reduce costs by up to 50 percent (Khan and others
2002), and this approach is being advocated as part of “flexible MDT delivery” (ILA 2002) and “accompanied MDT” (WHO 2002b). Reducing the
nondrug costs of treating leprosy to about US$10 to US$20 per patient may,
therefore, be possible.We thus estimate the costs of treating a case of leprosy
with MDT to be between US$15.40 and US$35.40 per case, depending on
the strategy used.
About 10 to 20 percent of new leprosy cases are likely to suffer a reaction during or after MDT. We estimate treatment of those reactions to cost US$25
per patient. Of these patients, 1 percent may develop severe complications requiring hospitalization, at an estimated cost of US$480 per patient. In addition, 10 percent of new cases will develop neural or secondary impairments
and may require footwear and education about wound management. We estimate the lifetime cost of protective footwear at US$300 per patient
(Seboka, Saunderson, and Currie 1998) and education at US$10 per patient.
In 1 percent of cases, reconstructive surgery may be required at about
US$455 per patient. We therefore estimate the average incremental cost of
interventions for prevention of disability to be US$44.15 per new case of disability. Because about 3 percent of new patients will need rehabilitation, we
estimate the average cost at under US$1 for each new case of leprosy detected (Jagannathan and others 1993).However, a backlog of old cases exists.
Although data in this area are weak, up to a third of the 4 million people living with leprosy globally (2 million with grade 1 disability and 2 million with
grade 2 disability) could require rehabilitation.
Few data are available on the program costs associated with leprosy. A review of
expenditure in Asia found that up to 40 percent of the total costs could be classified as programmatic costs, although this amount may now be less because
leprosy programs have increasingly been integrated into general health services.
Data from Indonesia demonstrate that program costs can be reduced by up to
35 percent by integrating them with tuberculosis programs (Plag 1995). We
therefore estimate the average cost of finding, treating, and preventing disabilities and rehabilitating a new case of leprosy at US$76 to US$264.
In practice, many leprosy programs will also be providing disability prevention and rehabilitation interventions to a large backlog of patients, so the average cost per new case will be higher than here. Programs that face a high
proportion of multibacillary cases and cases presenting with high levels of disability are also likely to have higher costs.
353
Assuming a cure rate of around 85 percent, we estimate the costs of curing
one patient of leprosy to be about US$93 per new case. Using data from
India (25 percent of those with leprosy will self-cure, an average age of onset
of 27, a disability weighting of 0.152, and a life expectancy at age 25 to 29
of 44.75), we estimate the cost per DALY of detecting and treating a new case
of leprosy to be US$38.
In addition, assuming a 90 percent success rate, we calculate a cost per DALY
of US$7 for patients needing treatment for reactions and ulcers, US$75 for
those needing footwear and self-care education, and US$110 for those needing reconstructive surgery. These estimates provide only a broad indication
because data on the effectiveness of these interventions are scarce, and the application of the disability weight of 0.152 to all interventions may overestimate their benefits.
Data on the economic effect of leprosy at the national level are not available.
However, leprosy affects those who are economically active, with a peak in incidence at 10 to 20 years of age and again at 30 to 50 years of age. Studies of
the impact of leprosy on productivity show that deformity from leprosy can
reduce the probability of obtaining employment and can reduce household
income and expenditure on food (Diffey and others 2000; Kopparty 1995).
In addition, leprosy can have a significant social impact because participation
in the community may be restricted. This impact continues well beyond the
actual treatment period because leprosy-related impairments have a tendency
to get worse over time even after the infection has been arrested.
Summary
Available information indicates that interventions for the four diseases are
highly cost-effective and that the benefit-cost ratio of control is high (table 1).
Research needs and priorities
Because the diseases in this chapter are targeted for elimination as public
health problems, it is sometimes assumed that research for these diseases is no
longer necessary and that all available resources should be allocated to elimination efforts.
Summ ary
Available information indicates that interventions for the four diseases are highly cost-effective and that the benefit-cost ratio
of control is high (table 1).
354
RESEARCH NEEDS AND PRIORITIES
Because the diseases in this chapter are
targeted
for elimination
as public
health Ottavio
problems, Latini
it is sometimes assumed that
Aldo
Morrone,
Lorenzo
Nosotti,
research for these diseases is no longer necessary and that all available resources should be allocated to elimination efforts.
T a b l e 1 Cost- E f fEstimates
e c tive n ess Estima
t esMain
f or t h eInterventions
Main I n t erve n tifor
o ns Each
f or E a Disease
c h Dise ase
Table 1 Cost-Effectiveness
for the
A u t h ors: H ay R , B e n d e c s k S E , C h e n S a n d ot h ers, D i s e as e C o n t roll P rii orii tii es i n D e v e l o p i n g C o u n trii es, 2 0 0 6, Jamiso n D T a n d
o t h ers e d i SE,
t ors. Chen S and others, Disease Control Priorities in Developing
Authors: Hay R, Bendecsk
Countries, 2006, Jamison DT and others editors.
However, research remains critical to address questions pertaining to how to achieve elimination with currently available
tools and especially to how to optimize implementation in different epidemiological, sociocultural, and health system
settings.
Epidemiological questions on the required intervention coverage, frequency, and duration need to be answered to guide
elimination strategies, and research on the risk, prevention, and control of recrudescence is crucial to ensure sustained
success.
The Special Programme for Research and Training in Tropical Diseases, a joint project of the United Nations Children’s
Fund, United Nations Development Programme, World Bank, and WHO, recently undertook a systematic analysis of
research needs for each of the 10 tropical diseases in its portfolio (Remme and others 2002). This analysis involved
However, research remains critical to address questions pertaining to how to
achieve elimination with currently available tools and especially to how to optimize implementation in different epidemiological, sociocultural, and health
system settings.
Epidemiological questions on the required intervention coverage, frequency,
and duration need to be answered to guide elimination strategies, and research on the risk, prevention, and control of recrudescence is crucial to ensure sustained success.
The Special Programme for Research and Training in Tropical Diseases, a
joint project of the United Nations Children’s Fund, United Nations
Development Programme, World Bank, and WHO, recently undertook a
systematic analysis of research needs for each of the 10 tropical diseases in its
portfolio (Remme and others 2002). This analysis involved assessing the burden of disease and recent epidemiological trends, reviewing current control
strategies, and identifying the major problems and challenges for disease control and the research needed to address these challenges. Table 2 summarizes
the results of this analysis for the four diseases discussed in this chapter.
Chagas disease has two main research priorities. The first is the development
of new vector control strategies that will allow the successful elimination campaign used in the Southern Cone countries to be extended to the Central
American and Andean countries,where the vectors are often not domiciliated.
355
The second is the development of effective and affordable treatment for the
millions of people already infected and the prevention of chronic complications.
For onchocerciasis and LF, the main research priorities are similar: implementation research to improve MDA; epidemiological research to determine if,
when, and with what treatment coverage the parasite reservoir can be locally
eliminated for different vector-parasite complexes; and research to develop a
macrofilaricide and improved diagnostics that would facilitate elimination.
assessing the burden of disease and recent epidemiological trends, reviewing current control strategies, and identifying
For leprosy,
thechallenges
research
needscontrol
wereandfurther
reviewed
a Scientific
major
problems and
for disease
the research
needed to during
address these
challenges. Table 2 summari
the
results of this
analysis
for the four
diseases discussed
in
this chapter.
Working
Group
(Special
Programme
for
Research
and
Training
in
Tropical
Chagas disease has two main research priorities. The first is the development of new vector control strategies that will all
the
successful
elimination
in the at
Southern
countries to
extended
the Central American a
Diseases
2003).
Thecampaign
meetingused
arrived
a clearCone
consensus
ofbethree
toptoprioriAndean countries,where the vectors are often not domiciliated.
ties second
for leprosy
research:ofimplementation
research
sustainable
The
is the development
effective and affordable
treatment on
for the
millions of and
peopleintealready infected and
prevention
of chronicleprosy
complications.
grated
residual
control
activities,
improved
diagnosis
of
infection,
and
For onchocerciasis and LF, the main research priorities are similar: implementation research to improve MD
epidemiological
research to determine
if, when, and
and with
what treatment
the parasite reservoir can be loca
improved approaches
for preventing
managing
nervecoverage
damage.
eliminated for different vector-parasite complexes; and research to develop a macrofilaricide and improved diagnostics t
Thesefacilitate
are the
current main priorities for research in support of elimination.
would
elimination.
For
leprosy, the is
research
needs were further
reviewed during
a Scientific
Working Group
Programme for Resea
Eradication
not currently
anticipated
for any
of the diseases;
thus,(Special
research
and Training in Tropical Diseases 2003). The meeting arrived at a clear consensus of three top priorities for lepro
on better
tools andresearch
strategies
that will
a permanent
solution
for these
research:
implementation
on sustainable
andallow
integrated
residual leprosy
control activities,
improved diagnosis
infection, and improved approaches for preventing and managing nerve damage.
infectious
diseases
also needed.
currently
available
controlanticipated for any
These
are the current
main is
priorities
for research Furthermore,
in support of elimination.
Eradication
is not currently
the
diseases;
thus,
research
on betterof
tools
and strategies
thatresistance,
will allow a permanent
solutiontofordevelthese infectious diseases
tools
may
be
lost
because
factors
such
as
and
research
also needed. Furthermore, currently available control tools may be lost because of factors such as resistance, and research
op replacement
tools
is essential
develop
replacement tools
is essential
now. now.
T a bTable
l e 2 Control
Strategies,
Major Challenges,
and Research
for Each
Disease
2 Control
Strategies,
Major Challenges,
andNeeds
Research
Needs
for
Each Disease
CONCLUSION
Tropical diseases are often viewed as neglected, because the investments made to fight them appear negligible compa
with the massive amounts expended globally on the health problems of developed countries. Tropical diseases are tr
diseases of the poor, but despite the limited resources available for research and control, simple and effective interventio
have been developed and delivered to populations in need for the four tropical diseases discussed in this chapter. Th
experience with these four diseases sends a powerful message: success is possible, even for neglected tropical diseases
poor populations in developing countries. Elimination of these diseases as public health problems can be achieved, a
investments in tropical disease research and control can make a significant contribution to poverty reduction.
An important reason for the success was that the interventions were extremely cost-effective. The available costeffectiven
data, though limited, show convincingly that intervention against these diseases is a good investment, and the argument
investment gets better when other economic benefits, not reflected in DALYs, are taken into account, such as increased fo
production when fertile land along river valleys became available for agriculture after the control of onchocerciasis in W
356
Conclusion
Tropical diseases are often viewed as neglected, because the investments made
to fight them appear negligible compared with the massive amounts expended globally on the health problems of developed countries. Tropical diseases
are truly diseases of the poor, but despite the limited resources available for
research and control, simple and effective interventions have been developed
and delivered to populations in need for the four tropical diseases discussed
in this chapter. Thus, experience with these four diseases sends a powerful
message: success is possible, even for neglected tropical diseases of poor populations in developing countries. Elimination of these diseases as public
health problems can be achieved, and investments in tropical disease research
and control can make a significant contribution to poverty reduction.
An important reason for the success was that the interventions were extremely cost-effective. The available costeffectiveness data, though limited, show
convincingly that intervention against these diseases is a good investment,
and the argument for investment gets better when other economic benefits,
not reflected in DALYs, are taken into account, such as increased food production when fertile land along river valleys became available for agriculture
after the control of onchocerciasis in West Africa and increased labor productivity after effective filariasis control in India.
The pharmaceutical industry also played a major role through large drug donations, and the creation of intercountry control programs provided effective
mechanisms for implementing interventions, technical support, and coordination.
Another reason for the success was a focused research program that ensured
the development of interventions based on simple and sustainable approaches that use cheap and “appropriate” technology and that are potentially multifunctional.
Chagas disease, LF, onchocerciasis, and leprosy are now on target for elimination as public health problems from large parts of the world. However,
these diseases cannot be eradicated using current tools, and much remains to
be done to expand and sustain the control efforts and undertake the necessary research to improve the control efforts as well as to develop more definite solutions. It will be essential, therefore, that donors and ministries of
health not abandon these programs because of their success.
357
References
• Addiss, D., J. Critchley, H. Ejere, P. Garner, H. Gelband, and C. Gamble. 2004.
“Albendazole for Lymphatic Filariasis.” Cochrane Database of Systematic Reviews (1)
CD003753.
• Akhavan, D. 1998. Análise de custo-efetividade do programa de controle da doença de
Chagas no Brasil. Brasília: Pan American Health Organization.
• Amazigo, U. V., M. Obono, K. Y. Dadzie, J. Remme, J. Jiya, R. Ndyomugyenyi, and others. 2002. “Monitoring Community-Directed Treatment Programs for Sustainability:
Lessons from the African Programme for Onchocerciasis Control (APOC).” Annals of
Tropical Medicine and Parasitology 96 (Suppl. 1): S75-92.
• Basombrio, M. A., C. J. Schofield, C. L. Rojas, and E. C. del Rey. 1998. “A Cost-Benefit
Analysis of Chagas Disease Control in North-western Argentina.” Transactions of the
Royal Society of Tropical Medicine and Hygiene 92 (2): 137-43.
• Bekri, W., S. Gebre, A. Mengiste, P. R. Saunderson, and S. Zewge. 1998. “Delay in
Presentation and Start of Treatment in Leprosy Patients: A Case-Control Study of
Disabled and Non-Disabled Patients in Three Different Settings in Ethiopia.”
International Journal of Leprosy and Other Mycobacterial Diseases 66 (1): 1-9.
• Benton, B. 1998. “Economic Impact of Onchocerciasis Control through the African
Programme for Onchocerciasis Control: An Overview.” Annals of Tropical Medicine and
Parasitology 92 (Suppl. 1): S33-39.
• Borsboom, G. J. J. M., B. A. Boatin, N. J. D. Nagelkerke, H. Agoua, K. L. B. Akpoboua,
E. W. S. Alley, and others. 2003. “Impact of Ivermectin on Onchocerciasis Transmission:
Assessing the Empirical Evidence That Repeated Ivermectin Mass Treatments May Lead
to Elimination/Eradication in West-Africa.” Filaria Journal 2 (1): 8.
• Boussinesq, M., S. D. Pion, Demanga-Ngangue, and J. Kamgno. 2002. “Relationship
between Onchocerciasis and Epilepsy: A Matched Case-Control Study in the Mbam
Valley, Republic of Cameroon.” Transactions of the Royal Society of Tropical Medicine and
Hygiene 96 (5): 537-41.
• Burkot, T., and K. Ichimori. 2002. “The PacELF Program:Will Mass Drug
Administration Be Enough?” Trends in Parasitology 18 (3): 109-15.
• Dadzie, K. Y., J. Remme, A. Rolland, and B. Thylefors. 1989. “Ocular Onchocerciasis
and Intensity of Infection in the Community: II.West African Rainforest Foci of the
Vector Simulium yahense.” Tropical Medicine and Parasitology 40 (3): 348-54.
• Dharmshaktu, N. S., B. N. Barkakaty, P. K. Patnaik, and M. A. Arif. 1999. “Progress towards Elimination of Leprosy as a Public Health Problem in India and Role ofModified
Leprosy Elimination Campaign.” Leprosy Review 70 (4): 430-39.
• Dias, J. C. 1987. “Control of Chagas’ Disease in Brazil.” Parasitology Today 3 (11): 336-41.
• Diffey, B., M.Vaz, M. J. Soares, A. J. Jacob, and L. S. Piers. 2000. “The Effect of
Leprosy-Induced Deformity on the Nutritional Status of Index Cases and Their
Household Members in Rural South India: A Socioeconomic Perspective.” European
Journal of Clinical Nutrition 54 (8): 643-49.
• Dreyer, G., P. Dreyer, and J. Noroes. 2002. “Recommendations for the Treatment of
Bancroftian filariasis in Symptomless and Diseased Patients.” Revista da Sociedade
Brasileira de Medicina Tropical 35 (1): 43-50.
358
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Dreyer, G., J. Noroes, J. Figueredo-Silva, and W. F. Piessens. 2000. “Pathogenesis of
Lymphatic Disease in Bancroftian filariasis: A Clinical Perspective.” Parasitology Today 16
(12): 544-48.
Fine, P. E., and P. G. Smith. 1996. “Vaccination against Leprosy: The View from 1996.”
Leprosy Review 67 (4): 249-52.
Ganapati, R., C. R. Revankar, V. V. Pai, S. Kingsley, and S. N. Prasad. 2001. “Can Cost
of Leprosy Case Detection in Urban Areas Be Further Reduced?” International Journal
of Leprosy and Other Mycobacterial Diseases 69 (4): 349-51.
Gwatkin, D. R., M. Guillot, and P. Heuveline. 1999. “The Burden of Disease among the
Global Poor.” Lancet 354 (9178): 586-89.
Gyapong, J. O., D. Kyelem, I. Kleinschmidt, and others. 2002. “The Use ofSpatial
Analysis in Mapping the Distribution of Bancroftian filariasis in Four West African
Countries.” Annals of Tropical Medicine and Parasitology 96 (7): 695-705.
Gyapong, J. O., V. Kumaraswami, G. Biswas, and E. A. Ottesen. 2005. “Treatment
Strategies Underpinning the Global Programme to Eliminate Lymphatic Filariasis.”
Expert Opinion on Pharmacotherapy 6 (2): 179-200.
Homeida, M., E. Braide, E. Elhassan, U. V. Amazigo, B. Liese, B. Benton, and others.
2002. “APOC’s Strategy of Community-Directed Treatment with Ivermectin (CDTI)
and Its Potential for Providing Additional Health Services to the Poorest Populations:
African Programme for Onchocerciasis Control.” Annals of Tropical Medicine and
Parasitology 96 (Suppl. 1): S93-104.
ILA (International Leprosy Association). 2002. “Report of the International Leprosy
Association Technical Forum, Paris, France, 22-28 February 2002.” International Journal
of Leprosy and Other Mycobacterial Diseases 70 (Suppl. 1): S1-62.
Jagannathan, S. A., V. Ramamurthy, S. J. Jeyaraj, and S. Regina. 1993. “A Pilot Project
on Community Based Rehabilitation in South India: A Preliminary Report.” Indian
Journal of Leprosy 65 (3): 315-22.
Khan, M. A., J.D.Walley, S.N.Witter,A. Imran, and N. Safdar. 2002.“Costs and CostEffectiveness of Different DOT Strategies for the Treatment of Tuberculosis in Pakistan:
Directly Observed Treatment.” Health Policy and Planning 17 (2): 178-86.
Kim, A., and B. Benton. 1995. Cost-Benefit Analysis of the Onchocerciasis Control
Programme (OCP).Washington, DC:World Bank.
Kopparty, S. N. 1995. “Problems, Acceptance, and Social Inequality: A Study of the
Deformed Leprosy Patients and their Families.” Leprosy Review 66 (3): 239-49.
Mathers, C. D., A. Lopez, and C. J. L. Murray. 2006. “The Burden of Disease and
Mortality by Condition: Data, Methods, and Results for the Year 2001.” In Global
Burden of Disease and Risk Factors, ed. A. Lopez, C. Mathers, M. Ezzati, D. Jamison, and
C. Murray. New York: Oxford University Press.
Maxwell, C. A., C. F. Curtis, H. Haji, S. Kisumku, A. I. Thalib, and S. A. Yahya. 1990.
“Control of Bancroftian filariasis by Integrating Therapy with Vector Control Using
Polystyrene Beads in Wet Pit Latrines.” Transactions of the Royal Society of Tropical
Medicine and Hygiene 84 (5): 709-14.
Meima, A., P. R. Saunderson, S. Gebre, K. Desta, G. J. van Oortmarssen, and J. D.
Habbema. 1999. “Factors Associated with Impairments in New Leprosy Patients: The
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
359
AMFES Cohort.” Leprosy Review 70 (2): 189-203.
Molyneux, D. H. 1995. “Onchocerciasis Control in West Africa: Current Status and
Future of the Onchocerciasis Control Programme.” Parasitology Today 11: 399-402.
Murdoch, M. E., M. C. Asuzu, M. Hagan, W. H. Makunde, P. Ngoumou, K. F.
Ogbuagu, and others. 2002. “Onchocerciasis: The Clinical and Epidemiological Burden
of Skin Disease in Africa.” Annals of Tropical Medicine and Parasitology 96 (3): 283-96.
Noma, M., B. E. Nwoke, I. Nutall, P. A. Tambala, P. Enyong, A. Namsenmo, and others. 2002. “Rapid Epidemiological Mapping of Onchocerciasis (REMO): Its Application
by the African Programme for Onchocerciasis Control (APOC).” Annals of Tropical
Medicine and Parasitology 96 (Suppl. 1): S29-39.
Ottesen, E. A. 2000. “The Global Programme to Eliminate Lymphatic Filariasis.”
Tropical Medicine and International Health 5 (9): 591-94.
Ottesen, E. A., B. O. Duke,M. Karam, and K. Behbehani. 1997. “Strategies and Tools
for the Control/Elimination of Lymphatic Filariasis.” Bulletin of the World Health
Organization 75 (6): 491-503.
Peters, D. H., and T. Phillips. 2004. “Mectizan Donation Program: Evaluation of a
Public-Private Partnership.” Tropical Medicine and International Health 9 (4): A4-15.
Plag, I. 1995. Guidelines for Cost Analysis in Leprosy Control Programmes. Amsterdam:
Royal Tropical Institute.
Rajendran, R., I. P. Sunish, T. R. Mani, A. Munirathinam, S. M. Abdullah, D. J.
Augustin, and K. Satyanarayana. 2002. “The Influence of the Mass Administration of
Diethylcarbamazine, Alone or with Albendazole, on the Prevalence of Filarial
Antigenaemia.” Annals of Tropical Medicine and Parasitology 96 (6): 595-602.
Ramaiah, K. D., and P. K. Das. 2004. “Mass Drug Administration to Eliminate
Lymphatic Filariasis in India.” Trends in Parasitology 20 (11): 499-502.
Ramaiah, K.D., P. K. Das, and V. Dhanda. 1994. “Estimation of Permissible Levels of
Transmission of Bancroftian filariasis Based on Some Entomological and Parasitological
Results of a Five-Year Vector Control Program.” Acta Tropica 56 (1): 89-96.
Ramaiah, K.D., P. K. Das, E.Michael, and H.Guyatt. 2000. “The Economic Burden of
Lymphatic Filariasis in India.” Parasitology Today 16 (6): 251-53.
Ramaiah, K. D., P. K. Das, P. Vanamail, and S. P. Pani. 2003. “The Impact of Six Rounds
of Single-Dose Mass Administration of Diethylcarbamazine or Ivermectin on the
Transmission of Wuchereria bancrofti by Culex quinquefasciatus and Its Implications for
Lymphatic Filariasis Elimination Programs.” Tropical Medicine and International Health
8 (12): 1082-92.
Ramu, K., K. D. Ramaiah, H. Guyatt, and D. Evans. 1996. “Impact of Lymphatic
Filariasis on the Productivity of Male Weavers in a South Indian Village.” Transactions of
the Royal Society of Tropical Medicine and Hygiene 90 (6): 669-70.
Remme, J. H. F. 1995. “The African Programme for Onchocerciasis Control: Preparing
to Launch.” Parasitology Today 11: 403-6.
———. 2004a. “The Global Burden of Onchocerciasis in 1990.” In Global Burden of
Disease 1990. Geneva: World Health Organization. http:// www3.who.int/whosis/burden/gbd2000docs/Onchocerciasis%201990. pdf.
———. 2004b. “Research for Control: The Onchocerciasis Experience.” Tropical
360
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Medicine and International Health 9 (2): 243-54.
Remme, J. H. F., E. S. Alley, and A. P. Plaisier. 1995. “Estimation and Prediction in
Tropical Disease Control: The Example of Onchocerciasis.” In Epidemic Models: Their
Structure and Relation to Data, ed.D.Mollison, 372-92. Cambridge,U.K.: Cambridge
University Press.
Remme, J. H., F. Blas, L. Chitsulo, P.M.Desjeux, H.D. Engers, T. P. Kanyok, and others. 2002. “Strategic Emphases for Tropical Diseases Research: A TDR Perspective.”
Trends in Parasitology 18 (10): 421-26.
Reuben, R., R. Rajendran, I. P. Sunish, T. R. Mani, S. C. Tewari, J. Hiriyan, and others.
2001. “Annual Single-Dose Diethylcarbamazine plus Ivermectin for Control of
Bancroftian filariasis: Comparative Efficacywith and without Vector Control.” Annals of
Tropical Medicine and Parasitology 95 (4): 361-78.
Richards, F. O., B. Boatin, M. Sauerbrey, and A. Seketeli. 2001. “Control of
Onchocerciasis Today: Status and Challenges.” Trends in Parasitology 17 (12): 558-63.
Richards F. O., D. Pam, A. Kal, G. Gerlong, J. Oneyka, Y. Sambo, and others. 2005
“Significant Decrease in the Prevalence of Wuchereria bancrofti Infection in Anopheline
Mosquitoes Following the Addition of Albendazole to Annual, Ivermectin-Based, Mass
Treatments in Nigeria.” Annals of Tropical Medicine and Parasitology 99 (2): 155-64.
Robles, M. C. 1997. Analisis costo-efectividad de las intervenciones de salud en Bolivia. La
Paz: Unidad de Análisis de Políticas Sociales.
Salvatella, A. R., and W. Vignolo. 1996. “Una aproximación a los costos de internación
por cardiopatia Chagasica en Uruguay.” Revista da Sociedade Brasileira de Medicina
Tropical 29 (Suppl.): 114-18.
Schenone, H. 1998. “Human Infection by Trypanosoma Cruzi in Chile: Epidemiology
Estimates and Costs of Care and Treatment of the Chagasic Patient.” Boletin Chileno de
Parasitologia. 53 (1-2): 23-26.
Schmunis, G. A. 2000. “A tripanossomiase Americana e seu impacto na saude publica
das Americas.” In Trypanosoma cruzi e doença de Chagas, 2nd ed., ed. Z. Brener, Z.
Andrade, and M. Barral-Neto, 1–15. Rio de Janeiro: Guanabara-Koogan.
Schmunis, G. A., F. Zicker, J. R. Cruz, and P. Cuchi. 2001. “Safety of Blood Supply for
Infectious Diseases in Latin American Countries, 1994-1997.” American Journal of
Tropical Medicine and Hygiene 65 (6): 924-30.
Schmunis, G. A., F. Zicker, F. Pinheiro, and D. Brandling-Bennett. 1998. “Risk of
Transfusion-Transmitted Infectious Diseases in Latin America.” Emerging Infectious
Diseases 4: 5-11.
Schofield, C. J., and J. C. Dias. 1991. “A Cost-Benefit Analysis of Chagas’ Disease
Control.”Memórias do Instituto Oswaldo Cruz 86 (3): 285-95.
Seboka, G., P. Saunderson, and H. Currie. 1998. “Footwear for Farmers Affected by
Leprosy.” Leprosy Review 69 (2): 182-83.
Seketeli, A., G. Adeoye, A. Eyamba, E. Nnoruka, P. Drameh, U.V. Amazigo, and others.
2002. “The Achievements and Challenges of the African Programme for Onchocerciasis
Control (APOC).” Annals of Tropical Medicine and Parasitology 96 (Suppl. 1): 15-28.
Smith, C. M., and W. C. Smith. 2000.“Chemoprophylaxis Is Effective in the Prevention
of Leprosy in Endemic Countries: A Systematic Review and Meta-Analysis. MILEP2
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
361
Study Group—Mucosal Immunology of Leprosy.” Journal of Infection 41 (2): 137-42.
Smith,W. C. 1999. “Future Scope and Expectations:Why,When, and How LECs Should
Continue.” Leprosy Review 70 (4): 498-505.
Special Programme for Research and Training in Tropical Diseases. 2003. Report of the
Scientific Working Group Meeting on Leprosy. Geneva: World Health Organization.
Stolk, W. A., S. Swaminathan, G. J. van Oortmarssen, P. K. Das, and J. D. Habbema.
2003.“Prospects for Elimination of Bancroftian Filariasis by Mass Drug Treatment in
Pondicherry, India: A Simulation Study.” Journal of Infectious Diseases 188 (9): 1371-81.
van Beers, S. M., M. Hatta, and P. R. Klatser. 1999. “Patient Contact Is the Major
Determinant in Incident Leprosy: Implications for Future Control.” International
Journal of Leprosy and Other Mycobacterial Diseases 67 (2): 119-28.
van Brakel, W. H. 2000. “Peripheral Neuropathy in Leprosy and Its Consequences.”
Leprosy Review 71 (Suppl.): S146-53.
van Brakel, W. H., and A. M. Anderson. 1998. “A Survey of Problems in Activities of
Daily Living among Persons Affected by Leprosy.” Asia Pacific Disability and
Rehabilitation Journal 9 (2): 62-67.
Vlassoff, C., M.Weiss, E. B. Ovuga, C. Eneanya, P. T. Nwel, S. S. Babalola, and others.
2000. “Gender and the Stigma of Onchocercal Skin Disease in Africa.” Social Science and
Medicine 50 (10): 1353-68.
WHO (World Health Organization). 1991. Control of Chagas’ Disease: Report of a WHO
Expert Committee. Technical Report 811. Geneva: WHO.
———. 1995a. Onchocerciasis and Its Control: Report of a WHO Expert Committee on
Onchocerciasis Control. Technical Report 852. Geneva: WHO.
———. 1995b. World Health Report 1995: Bridging the Gaps. Geneva: WHO.
———. 2002a. Control of Chagas Disease: Second Report of the WHO Expert Committee.
Technical Report 109. Geneva: WHO.
———. 2002b. The Final Push Strategy to Eliminate Leprosy as a Public Health Problem:
Questions and Answers. Geneva: WHO.
———.2002c. Lymphatic Filariasis: The Disease and Its Control. Technical Report 71.
Geneva: WHO.
———. 2002d. The World Health Report 2002: Reducing Risks, Promoting Healthy Life.
Technical Report 248. Geneva: WHO.
———. 2004a. World Health Organization: Leprosy Elimination Project Status Report
2003. Geneva: WHO.
———. 2004b. World Health Report 2004: Changing History. Geneva: WHO.
World Bank. 1993. World Development Report 1993: Investing in Health. New York:
Zimmerman, P. A., K. Y. Dadzie, G. De Sole, J. Remme, E. S. Alley, and T. R. Unnasch.
1992. “Onchocerca volvulus DNA Probe Classification Correlates with Epidemiologic
Patterns of Blindness.” Journal of Infectious Diseases 165 (5): 964-68.
362
COSTS AND COST-EFFECTIVENESS
OF INTERVENTIONS: leishmaniasis
Leishmaniasis
Case Finding and Treatment. For leishmaniasis, diagnosis represents a small
proportion of the cost of case finding and treatment, with diagnostic tests becoming available at approximately US$1.50 for the dipstick, US$3.00 for the
direct agglutination test using freeze-dried antigen, and US$1.50 for the
urine latex agglutination text. These tests can be used in the field. A study in
Nepal (Pokhrel 1999) comparing outreach case detection using serology (the
dipstick) with parasitological diagnosis at health centers (bone marrow aspirate) concluded that the median cost per VL case detected was US$25 in the
outreach program, compared with US$145 at health centers (of which more
than 50 percent was due to absence from work).
Treatment costs increased these figures to US$131 and US$200 per patient,
respectively.
In India, an examination of the costs of drugs and hospitalization and of the
evolution of the disease under treatment (cure, relapse, failure, intolerance)
indicated that the final cost of successful treatment depends largely on the basic drug cost, which averaged US$86 per patient successfully treated with
miltefosine (using reduced pricing because of the large number of patients),
US$467 for treatment with amphotericin B, and US$1,613 for treatment
with AmBisome. Given current estimates of about 100,000 cases of VL each
year in the state of Bihar, India, the estimated total cost of treatment using
miltefosine as a first-line drug and amphotericin B as a second-line drug
would be about US$11 million, or approximately US$110 per patient (personal communication with P. Olliaro and S. Sundar on treatment options for
kalaazar [visceral leishmaniasis], 2003). By contrast, analysis of humanitarian
relief interventions by Médecins sans Frontières-Holland that combined case
finding with treatment after a VL epidemic in southern Sudan indicated total costs of US$394 per patient, or an average cost of US$595 per life saved
(Griekspoor, Sondorp, and Vos 1999). Thus, the average cost per DALY
averted was US$18.40.
Vector Control. Vector control is rarely carried out as a specific approach to
leishmaniasis control, and cost-effectiveness estimates are not available. In
general, domestic and peridomestic sandfly vectors are more susceptible to
indoor residual spraying than are other domestic vectors, such as anopheline
mosquitoes or triatomine bugs, so that transient suppression of sandfly pop-
363
ulations is seen as an additional benefit of malaria or Chagas disease vector
control in areas where these vectors coincide. However, insecticide-treated
bednets, which are becoming widely deployed against malaria transmission,
may also become cost-effective for reducing leishmaniasis in areas of domestic transmission. In Yenice, Turkey, the use of impregnated bednets reduced
the incidence of CL from 1.90 percent to 0.04 percent between 2000 and
2001 (Alten and others 2003).
References
• Attar, A. J., M. L. Chance, S. El-Safi, J. Carney, A. Azazy, M. El-Hadi, and others. 2001.
“Latex Agglutination Test for the Detection of Urinary Antigens in Visceral
Leishmaniasis.” Acta Tropica 78 (1): 11-16.
• Cref, B. J., T. C. Jones, R. Badar, D. Sampaio, R. Teixeira, and W. D. J. Johnson. 1987.
“Malnutrition as a Risk Factor for Severe Visceral Leishmaniasis.” Journal of Infectious
Diseases 156: 1030-33.
• De Raadt, P. 1985. “Trypanosomes et leishmanioses congénitales.” Archives Françaises de
Pédiatrie 42: 925-27.
• Desjeux, P. 1996. “Leishmaniasis: Public Health Aspects and Control.” Clinics in
Dermatology 14: 417-23.
• ———. 2001. “The Increase in Risk Factors for the Leishmaniases Worldwide.”
Transactions of the Royal Society of Tropical Medicine and Hygiene 95: 239-43.
• Desjeux, P., and J. Alvar. 2003. “Leishmania/HIV Co-infections: Epidemiology in
Europe.” Annals of Tropical Medicine and Parasitology 97 (Suppl. 1): S3-15.
•
Griekspoor, A., E. Sondorp, and T. Vos. 1999. “Cost-Effectiveness Analysis of
Humanitarian Relief Interventions: Visceral Leishmaniasis Treatment in the
Sudan.”Health Policy and Planning 14: 70-76.
364
ECONOMIC ASSESSMENTS AND SKIN DISEASES
IN DEVELOPING COUNTRIES
Apart from the studies mentioned here in relation to families’ costs for treating community-acquired skin diseases in Mexico (Hay and others 1994) and
costs to health posts of managing tropical ulcer in Papua New Guinea
(Morris and others 1989), no published studies are available of the economic burden of skin disease. An extensive literature search did reveal some studies related to diseases that affect the skin but discussed elsewhere in this work
(Buruli ulcer and onchocercal skin disease), as well as a paper on the direct
costs of treating scabies in Italy. These studies are shown in table 3.
Examples of drug costs (tables 3 to 4) for tinea capitis, scabies, and pyoderma can be estimated as follows:
Treatment of a single case of scalp ringworm using griseofulvin purchased
from two differently priced U.S. sources to achieve the published efficacy
rates (table 4) with a conventional therapeutic course of six weeks, assuming
a daily dose of 250 milligrams, would provide between 61 and 92 percent efficacy at a drug cost per individual of US$29 or US$53, depending on the
drug source. Alternatively, a single supervised dose of 1 gram would cost
US$1.40 or US$2.50.
With supervision of treatment, the total cost per cure using daily treatment
ranges from US$35 to US$88 per patient.
• Treatment of 100 people with scabies using sulfur ointment, assuming 500
grams per individual, would cost US$58 or US$0.58 per person. This regimen would provide a 71 percent cure rate at three months and a cost per cure
of $1.30 per patient.
• Treatment with povidone of an individual with pyoderma would cost
US$0.68, assuming that 400 milliliters would treat eight people. This regimen would provide a cure rate of 88 percent at three months and a cost per
cure of US$1.10 per patient.
These calculations have taken into account ideal community treatment conditions, where the recurrence rate is negligible.
However, if such a community-based scheme is not effectively developed,
more than 50 percent of those with scabies are likely to be reinfected. The
figures are lower for tinea capitis (15 percent) and pyoderma (10 percent).
Table 37.7 shows the costs of treating large populations.
Although little information is currently available, in particular about the effect of local pricing of medications on overall effective treatment costs, the
365
studies cited in this chapter indicate that the financial burden of skin diseases
within families may well be significant and that producing a series of robust
analyses of the cost implications of both treatment and failure to provide adequate management strategies for these common conditions is critical.
The 1990 global burden of disease study estimated that the disability weighting associated with skin disease was at least 0.02. However, the disability
weighting for severe scabies (25 percent of cases) and patients with ecthyma
(10 percent of pyoderma cases) is 0.10. If we take skin cases with the lower
disability estimates—for example, mild to moderate scabies and pyoderma—
the cost per DALY gained would be about US$1.00 to US$1.50 (table 37.7).
For tinea capitis, the cost per DALY gained using daily treatment would be
considerably higher, US$175 at the lower drug cost.
Table 3 Literature Review on the Economic Impact of Skin Diseases
366
Table 4 cost of Cure and Impact on DALYs for the Three Most Common Skin Diseases
The benefits of devising control measures for treatable skin disease are also
affected by the high prevalence figures for skin diseases in low-income countries
withof devising
total populations
oftreatable
between
40 million
and by600
million
affected,
The
benefits
control measures for
skin disease
are also affected
the high
prevalence
figures for skin
diseases
in low-income
countries withintotal
populations
of between 40 million and 600 million affected, depending on
depending
on
variations
disease
prevalence.
variations in disease prevalence.
CURRENT STATUS OF COMMUNITY CONTROL MEASURES IN DERMATOLOGY
Despite
the logic ofSTATUS
developing community-focused
services for dermatology,
such services have seldom been achieved
CURRENT
OF COMMUNITY
CONTROL
(Hay, Andersson, and Estrada 1991). Perhaps the best current example of a concerted, community-based approach is the
MEASURES
IN forDERMATOLOGY
Regional
Training Center
Dermatology in Moshi, Tanzania, which focuses on developing a primary care skills base in
African countries for the care of patients with skin and sexually transmitted diseases (Kopf 1993). The program has now
trained more than 100 medical assistants and nurses, who were placed in 15 different countries at the primary care level and
who,
in many
cases,
play of
keydeveloping
roles in developing
local health programs. A key
issue is for
that action
proportional to the
Despite
the
logic
community-focused
services
dermatology,
severity of the problem is needed. For instance, one option would be to help nonspecialized health workers significantly
such their
services
seldom
been
achieved
(Hay,
and forEstrada
improve
skills inhave
managing
common skin
diseases.
That option
would Andersson,
present a new challenge
the teaching of
dermatology. Along those lines, a recent initiative to effect change through a control and education program in Mali targeted
1991).
Perhaps
the
best
current
example
of
a
concerted,
community-based
at pyoderma, scabies, and tinea capitis is currently being evaluated. Early assessments indicate that the teaching methods
have
been effective
instilling
recognition Training
skills among primary
care for
health Dermatology
workers. The effect onin
community
levels of
approach
is inthe
Regional
Center
Moshi,
skin diseases is not yet known.
Skin
diseases remain
a low
priority for
health authorities,
despite thecare
large skills
demand base
for services.
Addressing the
Tanzania,
which
focuses
onmany
developing
a primary
in African
potential for controlling skin problems by means of simple and effective public health measures should be a realistic target
countries
for
the
care
of
patients
with
skin
and
sexually
transmitted
diseases
for alleviating a common and solvable source of ill health. An effective plan, team, and basic dermatological formulary can
do much to improve matters (Estrada and others 2000). This chapter outlines some of the challenges for such programs and
(Kopf 1993). The program has now trained more than 100 medical assistants
some of the deficiencies of current provision.
and nurses, who were placed in 15 different countries at the primary care level and who, in many cases, play key roles in developing local health programs.
REFERENCES
Abdel-Rahman, S. M., M. C. Nahata, and D. A. Powell. 1997. “Response to
A key
issueTherapy
is that
action
proportional
Initial
Griseofulvin
in Pediatric
Patients
with Tinea Capitis.” to the severity of the problem is needAnnals of Pharmacotherapy 31: 406–10.
ed. For instance, one option would be to help nonspecialized health workers
Asiedu, K., and S. Etuaful. 1998. “Socioeconomic Implications of Buruli
Ulcer in Ghana: A Three-year Review.” American Journal of Tropical
significantly
improve their skills in managing common skin diseases. That
Medicine & Hygiene 59: 1015–22.
Barton, L. L., A. D. Friedman, and M. G. Portilla. 1988. “Impetigo
option would present a new challenge for the teaching of dermatology. Along
Contagiosa: A Comparison of Erythromycin and Dicloxacillin
Therapy.”
those Pediatric
lines, Dermatology
a recent5: 88–91.
initiative to effect change through a control and educaBenton, B. 1998. “Economic Impact of Onchocerciasis Control through
the
African
Programme for
Onchocerciasis
Control: Anat
Overview.”
tion
program
in
Mali
targeted
pyoderma, scabies, and tinea capitis is curAnnals of Tropical Medicine & Parasitology 92 Suppl 1: S33–39.
Breneman,
D.
L.
1990.
“Use
of
Mupirocin
Ointment
in
the
Treatment
of indicate that the teaching methods
rently being evaluated. Early assessments
Secondarily Infected Dermatoses.” Journal of the American Academy of
Dermatology
22: 886–92.
have been
effective in instilling recognition skills among primary care health
Budimulja, U., K. Kuswadji, S. Bramono, J. Basuki, L. S. Jadanarso,
S.
Untung, and others.
1994.
“A Double-Blind,
Randomized, Stratified
workers.
The
effect
on community
levels of skin diseases is not yet known.
Controlled Study of the Treatment of Tinea Imbricata with Oral
Skin diseases remain a low priority for many health authorities, despite the
large demand for services. Addressing the potential for controlling skin
367
problems by means of simple and effective public health measures should be
a realistic target for alleviating a common and solvable source of ill health.
An effective plan, team, and basic dermatological formulary can do much to
improve matters (Estrada and others 2000). This chapter outlines some of
the challenges for such programs and some of the deficiencies of current
provision.
368
References
• Abdel-Rahman, S. M., M. C. Nahata, and D. A. Powell. 1997. “Response to Initial
Griseofulvin Therapy in Pediatric Patients with Tinea Capitis.” Annals of
Pharmacotherapy 31: 406-10.
• Asiedu, K., and S. Etuaful. 1998. “Socioeconomic Implications of Buruli Ulcer in
Ghana: A Three-year Review.” American Journal of Tropical Medicine & Hygiene 59:
1015-22.
• Barton, L. L., A. D. Friedman, and M. G. Portilla. 1988. “Impetigo Contagiosa: A
Comparison of Erythromycin and Dicloxacillin Therapy.” Pediatric Dermatology 5: 88-91.
• Benton, B. 1998. “Economic Impact of Onchocerciasis Control through the African
Programme for Onchocerciasis Control: An Overview.” Annals of Tropical Medicine &
Parasitology 92 Suppl 1: S33-39.
• Breneman, D. L. 1990. “Use of Mupirocin Ointment in the Treatment of Secondarily
Infected Dermatoses.” Journal of the American Academy of Dermatology 22: 886-92.
• Budimulja, U., K. Kuswadji, S. Bramono, J. Basuki, L. S. Jadanarso, S. Untung, and others. 1994. “A Double-Blind, Randomized, Stratified Controlled Study of the Treatment
of Tinea Imbricata with Oral Terbinafine or Itraconazole.” British Journal of Dermatology
130: 29-31.
• Bulto, T., F.H.Maskel, and G. Fisseha. 1993. “Skin Lesions in Resettled and Indigenous
Populations in Gambela, with Special Emphasis on the Epidemiology of Tropical Ulcer.”
Ethiopian Medical Journal 31: 75-82.
• Carapetis, J. R., B. J. Currie, and E. L. Kaplan. 1999. “Epidemiology and Prevention of
Group A Streptococcal Infections: Acute Respiratory Tract Infections, Skin Infections, and
Their Sequelae at the Close of the 20th Century.” Clinical Infectious Diseases 28: 205-10.
• Daroczy, J. 2002. “Antiseptic Efficacy of Local Disinfecting Povidone-Iodine (Betadine)
Therapy in Chronic Wounds of Lymphedematous Patients.” Dermatology 204: 75-78.
• Eells, L. D., P. M. Mertz, Y. Piovanetti, G. M. Pekoe, and W. H. Eaglestein. 1986.
“Topical Antibiotic Treatment of Impetigo with Mupirocin.” Archives of Dermatology
122: 1273-76.
• Elewski, B. 2000. “Tinea Capitis: A Current Perspective.” Journal of the American
Academy of Dermatology 42: 1-20.
• Estrada, R., M. Romero, G. Chavez, and G. Estrada. 2000. “Dermatologia communitaria: diez años de experiencia. Estudio epidemiológico comparativo entre población urbana y rural del estado de Guerrero.” Dermatologia Revista Mexicana 44: 268-73.
• Figueroa, J. I., L. C. Fuller, A. Abraha, and R. J. Hay. 1996. “The Prevalence of Skin
Disease among Schoolchildren in Rural Ethiopia:A Preliminary Assessment of
DermatologicNeeds.”Pediatric Dermatology 13: 378-81.
• ———. 1998. “Dermatology in Southwestern Ethiopia: Rationale for a Community
Approach.” International Journal of Dermatology 37: 752-58.
• Fuller, L. C., C. H. Smith, R. Cerio, R. A.Marsden, G.Midgley, A. L. Beard, and others.
2001. “A Randomized Comparison of Four Weeks of Terbinafine versus Eight Weeks of
Griseofulvin for the Treatment of Tinea Capitis.” British Journal of Dermatology 144:
321-27.
• Gibbs, S. 1996. “Skin Disease and Socioeconomic Conditions in Rural Africa:
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
369
Tanzania.” International Journal of Dermatology 35: 633-39.
Gupta, A. K., P. Adam, N. Dlova, C.W. Lynde, S. Hofstader, N.Morar, and others. 2001.
“Therapeutic Options for the Treatment of Tinea Capitis Caused by Trichophyton
Species: Griseofulvin versus the New Oral Antifungal Agents, Terbinafine, Itraconazole,
and Fluconazole.” Pediatric Dermatology 18: 433-38.
Hay, R. J., N. Andersson, and R. Estrada. 1991. “Mexico: Community Dermatology in
Guerrero.” Lancet 337: 906-7.
Hay, R. J., Y. M. Clayton, N. De Silva, G. Midgley, and E. Rossor. 1996. “Tinea Capitis
in Southeast London: A New Pattern of Infection with Public Health Implications.”
British Journal of Dermatology 135: 955-58.
Hay, R. J., R. Estrada, H. Alarcon, G. Chavez, L. F. Lopez, S. Paredes, and N. Andersson.
1994. “Wastage of Family Income on Skin Disease in Mexico.” British Medical Journal
309: 848.
Hay, R. J., S. Reid, E. Talwat, and K. MacNamara. 1984. “Endemic Tinea Imbricata: A
Study on Goodenough Island, PNG.” Transactions of the Royal Society of Tropical
Medicine and Hygiene 78: 246-51.
Hegazy, A. A., N. M. Darwish, I. A. Abdel-Hamid, and S. M. Hammad. 1999.
“Epidemiology and Control of Scabies in an Egyptian Village.” International Journal of
Hiletework, M. 1998. “Skin Diseases Seen in Kazanchis Health Center.” Ethiopian
Medical Journal 36: 245-54.
Koning S., L.W. van Suijlekom-Smit, J. L. Nouwen, C. M. Verduin, R. M. Bernsen, A.
P. Oranje, and others. 2002. “Fusidic Acid Cream in the Treatment of Impetigo in
General Practice: Double-Blind Randomised Placebo Controlled Trial.” British Medical
Journal 324: 203-6.
Kopf, A. W. 1993. “International Foundation for Dermatology: A Challenge to Meet the
Dermatologic Needs of Developing Countries.” Dermatologic Clinics 11: 311-14.
Leppard, B., and A. E.Naburi. 2000. “The Use of Ivermectin in Controlling an
Outbreak of Scabies in a Prison.” British Journal of Dermatology 143: 520-23.
Linder, C. W. 1978. “Treatment of Impetigo and Ecthyma.” Journal of Family Practice 7:
697-700.
Lipozencic, J., M. Skerlev, R. Orofino-Costa, V. C. Zaitz, A. Horvath, E. Chouela, and
others. 2002. “A Randomized, Double-Blind, Parallel-Group, Duration-Finding Study
of Oral Terbinafine and Open-Label, High-Dose Griseofulvin in Children with Tinea
Capitis Due to Microsporum Species.” British Journal of Dermatology 146 (5): 816-23.
Lookingbill, D. P., G. L. Lookingbill, and B. Leppard. 1995. “Actinic Damage and Skin
Cancer in Albinos in Northern Tanzania: Findings in 164 Patients Enrolled in an Outreach
Skin Care Program.” Journal of the American Academy of Dermatology 32: 653-58.
Lopez-Gomez, S., A. Del Palacio, J. Van Cutsem, M. Soledad Cuetara, L. Iglesias, and
A. Rodriguez-Noriega. 1994. “Itraconazole versus Griseofulvin in the Treatment of Tinea
Capitis: A Double-Blind Randomized Study in Children.” International Journal of
Macotela-Ruiz, E. I. C., and Q. F. B. E. N. Ramos. 1996. “Tratamiento de escabiasis con
Ivermectina por via oral en una comunidad rural cerrada: Implicaciones epidemiológi-
370
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
cas.” Dermatologia Revista Mexicana 40: 179-84.
Mahé, A., F. Ly, G. Aymard, and J. M. Dangou. 2003. “Skin Diseases Associated with
the Cosmetic Use of Bleaching Products in Women from Dakar, Senegal.” British
Journal of Dermatology 148: 493-500.
Mahé, A., H. Thiam N’Diaye, and P. Bobin. 1997. “The Proportion of Medical
Consultations Motivated by Skin Diseases in the Health Centers of Bamako (Republic
of Mali).” International Journal of Dermatology 36: 185-86.
Mallon, E., J. N. Newton, A. Klassen, S. L. Stewart-Brown, T. J. Ryan, and A. Y. Finlay.
1999. “The Quality of Life in Acne: A Comparison with General Medical Conditions
Using Generic Questionnaires.” British Journal of Dermatology 140: 672-76.
Mathers, C. D., A. D. Lopez, and C. J. L. Murray. “The Burden of Disease and Mortality
by Condition: Data, Methods, and Results for 2001.” In Global Burden of Disease and
Risk Factors, eds. A. D. Lopez, C. D. Mathers, M. Ezzati, D. T. Jamison, and C. J. L.
Murray. New York: Oxford University Press.
McLinn, S. 1988. “TopicalMupirocin versus Systemic Erythromycin Treatment for
Pyoderma.” Pediatric Infectious Disease Journal 7: 785-90.
Mirmirani, P., T. A. Maurer, T. G. Berger, L. P. Sands, and M. M. Chren. 2002. “SkinRelated Quality of Life in HIV-Infected Patients on Highly Active Antiretroviral
Therapy.” Journal of Cutaneous Medicine and Surgery 6: 10-15.
Morris, G. E., R. J. Hay, A. Srinavasa, and A. Bunat. 1989. “The Diagnosis and
Management of Tropical Ulcer in East Sepik Province of Papua New Guinea.” Journal of
Tropical Medicine and Hygiene 92: 215-20.
Oladepo, O., W. R. Brieger, S. Otusanya, O. O. Kale, S. Offiong, and M. Titiloye. 1997.
Farm Land Size and Onchocerciasis Status of Peasant Farmers in South-western Nigeria.
Tropical Medicine & International Health 2: 334-340.
Papini, M., R. Maccheroni, and P. L. Bruni. 1999. “O Tempora o Mores: The Cost of
Managing Institutional Outbreaks of Scabies.” International Journal of Dermatology 38:
638-39.
Rea, J. N., M. L. Newhouse, and T. Halil. 1976. “Skin Disease in Lambeth: A
Community Study of Prevalence and Use of Medical Care.” British Journal of Preventive
and Social Medicine 30: 107-14.
Saw, S. M.,D.Koh, M. R.Adjani,M. L.Wong, C.Y.Hong, J. Lee, and others. 2001. “A
Population-Based Prevalence Survey of Skin Diseases in Adolescents and Adults in Rural
Sumatra, Indonesia, 1999.” Transactions of the Royal Society of Tropical Medicine and
Hygiene 95: 384-88.
Schmeller, W., S. Baumgartner, and A. Dzikus. 1997. “Dermatophytomycoses in
Children in Rural Kenya: The Impact of Primary Health Care.” Mycoses 40: 55-63.
Seeberg, S., B. Brinkhoff, E. John, and I Mer. 1984. “Prevention and Control of
Neonatal Pyoderma with Chlorhexidine.” Acta Paediatrica Scandinavica 73: 498-504.
Taplin D., L. Lansdell, A. A. Allen, R. Rodriguez, and A. Corets. 1973. “Prevalence of
Streptococcal Pyoderma in Relation to Climate and Hygiene.” Lancet 1: 501-3.
Taplin, D., S. L. Porcelain, T. L. Meinking, R. L. Athey, J. A. Chen, P. M. Castillero, and
R. Sanchez. 1991. “Community Control of Scabies: A Model Based on Use of
Permethrin Cream.” Lancet 337: 1016-18.
•
•
•
•
•
•
•
371
Taylor, S. C. 1999. “Cosmetic Problems in Skin of Color.” Skin Pharmacology and
Applied Skin Physiology 12: 139-43.
Usha, V., and T. V. Gopalakrishnan Nair. 2000. “A Comparative Study of Oral
Ivermectin and Topical Permethrin Cream in the Treatment of Scabies.” Journal of the
American Academy of Dermatology 42: 236-40.
White, A. V., W. E. Hoy, and D. A. McCredie. 2001. “Childhood Post-Streptococcal
Glomerulonephritis as a Risk Factor for Chronic Renal Disease in Later Life.”Medical
Journal of Australia 174: 492-96.
Wilmington, M., R. Aly, and I. J. Frieden. 1996. “Trichophyton Tonsurans Tinea Capitis
in the San Francisco Bay Area: Increased Infection Demonstrated in a 20-Year Survey of
Fungal Infections from 1974 to 1994.” Journal of Medical and Veterinary Mycology 34:
285-87.
Workneh, W., M. Fletcher, and G. Olwit. 1993. “Onchocerciasis in Field Workers at
Baya Farm, Teppi Coffee Plantation Project, Southwestern Ethiopia: Prevalence and
Impact on Productivity.” Acta Tropica 54: 89-97.
World Bank. 2002. World Development Indicators. Washington, DC: World Bank.
Wright, S., and V. J. Robertson. 1986. “An Institutional Survey of Tinea Capitis in
Harare, Zimbabwe, and a Trial of Miconazole Cream versus Whitfield’s Ointment in Its
Treatment.” Clinical and Experimental Dermatology 11: 371-77.

Part two

Transcription

Similar documents

http://www.eo.ucar.edu/webweather/index.html

GLES CASE STUDY

Neurotic Excoriation - Physicians Practice

Ulcerations of the Oral Cavity

Hand-Reconstructive-Surgery Week and the Sunday

1-Mycobacteria 2-Chlamydia 3-Mycoplasam 4

Offered at: $100,000

Genital Dermatology Atlas

Buschke-Ollendorff syndrome accidentally diagnosed after a left