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Malaysian Journal of Medicine and Health Sciences
Vol. 7 (1) January 2011
Editorial
1
Original Papers
Prevalence of Needle Stick Injuries and Compliance to Infection Control Guidelines Among Health Care
Workers in a Teaching Hospital, Malaysia
MZA Hamid, NA Aziz, WB Lim, SLM Salleh, SNS Rahman, R Anita & O Norlijah
3
The Impact of Preventive Fogging on Entomological Parameters in a University Campus in Malaysia
A Ruhil Amal, O Malina, AH Rukman, U Ngah Zasmy, AWan Omar & M Norhafizah
9
Prevalence of Urban Poor and Its Health Related Factors in the State of Selangor, Malaysia
MS Sherina, L Rampal, AR Hejar, A Rozali & A Mohd Yunus
17
Diphtheria Anti-toxoid Antibody Levels Among Pre-clinical Students and Staff in an Institute of Higher
Learning in Malaysia: Are They Protected?
RA Hamat, O Malina, YJ Chua, KL Seng, M Zubaidah, K Norhanim, SS Chong, PL Weng, & J Farida
27
Method Optimization on the Process of Iontophoresis with Laser Doppler Fluximetry in the Assessment
of Microvascular Endothelial Function
AT Belqes Abdullah, TGB Yvonne, SH Ahmad, ASI Abdul Aziz & HGR Aida
35
Nutritional Status of Rohingya Children in Kuala Lumpur
T Sok Teng & MS Zalilah
41
Review with Case Report
Monoclonal Gammopathy with Systemic Amyloidosis: An Evaluation of Diagnostic Elements
C. T Subashini, E. George & U Nor Aini
51
Aggressive Variant Large Granular Lymphocytic Leukaemia: A Case Report
MN Sabariah, S Zainina, I Faridah & CF Leong
57
Synchronous Mucoepidermoid Carcinoma of the Right Upper Eyelid and Right Parotid Gland in a Young
Patient
M Irfan, CY Wong, H Nik Fariza, K Maha & O Nor Hayati
61
Depression and Quality of Life among Patients with Hematological Cancer in a Malaysian Hospital
D Priscilla, A Hamidin, MZ Azhar, KON Noorjan, MS Salmiah & K Bahariah
65
The Beck Anxiety Inventory for Malays (BAI-Malay): A Preliminary Study on Psychometric Properties
M Firdaus & Z Nor Sheereen
75
Physical Activity and Sedentary Behaviour among Adolescents in Petaling District, Selangor, Malaysia
CC Kee, KH Lim, MG Sumarni, MN Ismail, BK Poh, NM Amal
83
Letter to Editor
95
Acknowledgements
97
Malaysian Journal of Medicine and Health Sciences Vol. 7 (1) January 2011
Malaysian Journal of Medicine and Health Sciences Vol. 7 (1) January 2011: 1-2
EDITORIAL
Physician and Former-Patient Sexual Contact: Ethical Issues
MZ Azhar
Faculty Of Medicine and Health Sciences,
Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor. Malaysia.
Sexual relationships between doctors and patients have been the subject of discussion, writings and perhaps legislation
but there has been scarce research on this area. And with the sprouting of Family Physicians and General Practitioners,
more attention ought to be paid to such issues among these colleagues of ours. As Malaysia is producing abundance of
doctors every year, more ethical issues will sprout. I believe as editor I need to remind lecturers and future doctors who
read this medical and health science journal some possible ethical issues that have been cropping up and may crop up
more in the future. There are many issues of course but the one I would like to focus in this editorial is about doctors
and former patients which are not clearly stated in our ethics. What is clear is regarding doctors and relationship with
current patients.
In USA, it is estimated that 11% of Family Physicians have had sexual contact with at least one of their patients.
The American Medical Association as well as our Malaysian Medical Association has ethical guidelines addressing
this issue. However there are grey areas. Are there conditions under which a doctor may become involved with a former
patient? Sexual involvement with patients appears to exist on an ethical continuum; it however results in reduced
patient autonomy. In USA, sexual contacts between patients and Mental Health Professionals are now explicitly
illegal, but there are no clear guidelines for non-psychiatric doctors. There is some research evidence that when sexual
contact occurs between a doctor and patient, it is the patient who suffers long-term psychological consequences.
In this paper, I am trying to present some views from the perspective of a psychiatrist why even non-psychiatrist
should be disallowed to have sexual relationships with their former patients. My views are stronger after reading an
article by a General Practitioner in New Zealand in the Journal Family Practice[1]. According to her, such relationships
are almost always unethical due to the persistence of transference, the unequal power distribution in the original
doctor-patient relationship and the ethical implications that arise from both these factors especially with respect to the
patient’s autonomy and ability to consent even when a former patient.
Some doctors are at risk of violating boundaries. These are doctors who cannot identify transference and counter
transference in the doctor-patient relationship of every encounter. Transference is defined as the unconscious
assignment to others of feelings and attitudes that were originally associated with important figures by the patient
onto the doctor. Counter-transference is the doctor’s reaction to this process and this can include erotic feelings.
Doctors can make mistake of that feelings of love that arise in a therapeutic relationship as being the same as love
that arises elsewhere; it is not. This love is not based on reality and is based on unequal power structure. Even skilled
and experienced doctors are not immune to rationalizing their behaviour and convincing themselves that a patient is
very special. The risk increases when the doctor is responding to particular triggers such as marital discord, loss of
important relationships and a professional crisis in their own lives. The risk seems to increase with age by a ratio of
1.44 with every increasing decade[2]. To avoid such mishaps, doctors must ensure ethical-doctor patient relationships at
all times. That relationship depends upon the doctor creating an environment of mutual respect and trust in which the
patient can have confidence and safety. Trust is a crucial aspect of that relationship together with providing confidence
that one is having good conscience and is therefore bound to act in good faith. To build that relationship, the unequal
power distribution between doctor and patient has to be acknowledged and contained in an ethically correct manner.
The onus lies in the person with the most power, i.e. the doctor.
What is the relevance of this analysis to relationships with former, non-current patients? First, any privileged
knowledge gained under the conditions of the original power imbalance of doctor-patient cannot be “unlearnt” or
forgotten and this can continue as an unfair advantage for the doctor. Information gained in such power imbalance can
be artificially intimate; for example one will not normally discuss details of sexual function within a few minutes of
meeting a stranger but this happens in a general practice consultation. Secondly, based on the above example, it is hard
to see how a relationship of equals could develop from such unequal beginnings.
How can a claim be judged that a former patient gave his or her consent before entering into the relationship?
There is no disagreement that a current patient cannot validly consent, but a former patient? This is more debatable.
Evidence is beginning to show that transferences can persist indefinitely and with it the perpetuation of potential or
*Corresponding Author: [email protected]
2
MZ Azhar
real incompetence of the patient to recognize these feelings for their true nature (for Psychiatrist at least, the view is
generally held “once a patient, always a patient”). This is held so strongly that the American Psychiatric Association
has stated categorically that “sexual activity with a current or former patient is unethical” with no qualifications[3].
In California, legally there is a two year gap period with no patient contact that will make it possible to have a
relationship. But there is no empirical research to show that transference disappears for the patient or even decreases
with cessation of the doctor-patient relationship. The concept of a supposed ‘waiting period’ after termination before
sexual intimacies is naive because it does not take into account the timeless nature of the subconscious. There has
been no published reports demonstrating or suggesting that therapist-patient sexual involvement becomes safe at a
point 6 months or 6 years after termination. Even the Council of Ethical and Judicial Affairs of the American Medical
Association has stated “sexual or romantic relationships with former patients are unethical if the physician uses or
exploits trust, knowledge, emotions, or influence derived from the previous professional relationship”[4].
The other issue is one of consent. It can be argued that for any relationship, there must be autonomous choice,
i.e. the choice where all relevant information has been provided, with the person having the necessary capacities to
comprehend that information whilst not acting under any form of coercion. Coercion can arise from imposed restraints
on any or all of three types of autonomy; autonomy of thought or the ability to think for oneself, autonomy of will
or the freedom to make a choice based on one’s deliberations, and autonomy of action or the freedom to enact one’s
choice physically. The persistence of transference can exert a coercive effect on one’s autonomy of thought and will.
It would then be only a very minority of consultations, especially in general practice, where the above situations
of persistent transference and power imbalance did not exist. So if there is a disciplinary hearing, the onus of proof
would lie with the doctor to demonstrate how these ethical issues were of minimal impact in the subsequent sexualized
relationship. It would be wise I think to consider relationships with former patients to be considered as ethically not
permissible.
REFERENCES
[1]
Hall KH. Sexualisation of the doctor-patient relationship: Is it ever ethically permissible? Family Practice 2001;
18: 511-515.
[2]
Dehlendorf CE, Wolfe SM. Physicians disciplined for sex-related offences. J Am Med Assoc 1998; 279: 18831888.
[3]
American Psychiatric Association. The principles of medical ethics with annotations especially applicable to
psychiatry. Washington (DC): APA 1993.
[4]
Council on Ethical and Judiciary Affairs. American Medical Association. Sexual misconduct in the practice of
medicine. J Am Med Assoc 1991; 266: 2741-2745.
Prevalence of Needle Stick Injuries and Compliance to Infection Control Guidelines
Among Health Care Workers in a Teaching Hospital, Malaysia
1
MZA Hamid*, 2 NA Aziz, 3 WB Lim, 4 SLM Salleh, 4 SNS Rahman, 3 R Anita & 1 O Norlijah
1
Department of Pediatrics, Faculty of Medicine and Health Sciences, University Putra Malaysia
University Kebangsaan Malaysia Medical Centre, Faculty of Medicine, University Kebangsaan Malaysia
3
Department of Community Medicine, Faculty of Medicine and Health Sciences, University Putra Malaysia
4
Faculty of Medicine and Health Sciences, University Putra Malaysia
2
ABSTRACT
Introduction: Health care workers (HCW) are constantly exposed to blood-borne illnesses through
needle stick injuries (NSI). Despite the increasing trend of NSI, evidence regarding the actual practice
of universal precautions among these HCWs is lacking. This study assessed the practice of universal
precautions towards prevention of NSI among HCWs in a teaching hospital setting. Methods: This
cross-sectional survey involved a newly-designed self-completed questionnaire assessing demographic
data, exposure to NSI and practice of universal precautions. Questionnaires were distributed to every
ward and completed questionnaires were collected after a period of 7 days. Results: A total of 215
HCWs responded to the survey. 35.8% were exposed to bodily fluid, with 22.3% had NSI in the last
12 months. Blood taking was the commonest procedure associated with NSI. Of practices of universal
precautions, recapping needle and removing needle from syringe were still wrongly practiced by the
HCWs assessed. Conclusion: NSI among HCW are still common despite the introduction of universal
precautions in our hospital. Incorrect practices in handling sharps should be looked into in order to
reduce the incidence of blood-borne illnesses through NSI in the hospital.
Keywords:
Needle stick injury, health care workers, infection control guideline
INTRODUCTION
Needle stick injury (NSI) is defined as ‘any wound caused by a needle (either suture or hollow-bore), which puncture
the skin accidentally.[1] It is known as a main cause of work-related injuries and illnesses among health-care workers
(HCW) worldwide.[2] The World Health Organization (WHO) estimated that of the 12 billion injections administered by
HCWs yearly, approximately one million cases of NSI cases are reported involving various levels of HCWs including
doctors, nurses and paramedics.[3] This trend is reflected in our health care system, where the Ministry of Health has
reported an increase in the incidence of NSI among HCW in the government hospitals from 498 in year 2000 to 746
in six years, with medical officers and nurses forming the most number of cases [4].
One of the occupational hazards of NSI is the transmission of blood-borne illnesses such as HIV, Hepatitis B
and Hepatitis C. Studies have shown that the transmission of these blood-borne illnesses could occur at any stage of
needle usage, commonly associated with factors such as nature of the procedures, manner of the work performed and
years of experience of the staff involved.[4,5,6,7]. Ismail et al. reported that the prevalence of NSI amongst health care
workers in Malaysia was 24.9%, in which the needle recapping was identified as the main procedure involved. For the
past two decades, hospitals in Malaysia have been following the CDC guidelines for the universal precautions of NSI
which aim to prevent transmission of HIV, HBV and other blood pathogens when providing first aid or health care.[1]
The universal precautions guidelines apply to all bodily fluids; it also includes standard isolation precautions when
outbreaks occur in a hospital setting.
Despite the increasing emphasis given to the health-care workers about the hazards of NSIs, the prevalence of NSI
among these workers in government hospitals shows increasing trend [8]. Little is known about the actual practice of
universal precautions among health care workers in Malaysia. Therefore this study was done to assess the practice
of universal precautions towards prevention of needle stick injuries among health care workers in a teaching hospital
setting.
MATERIALS AND METHODS
Subject enrolment: This was a cross-sectional survey study conducted among various levels of health care workers
in Serdang Hospital, the teaching hospital for the Medical and Health Sciences Faculty, University Putra Malaysia. It
*Corresponding author: [email protected]
4
was carried out over a period of four weeks (31st March to 30th April 2008) as part of the students’ research project.
Universal sampling method was used to recruit subjects in this study. All health care workers working in the hospital
and exposed to the use of needles in their daily works were invited to participate in the survey.
Study instrument: A newly-designed questionnaire was constructed from triangulation of resources via literature
review, clinical practice guidelines and expert opinions from the field of infectious diseases and occupational health.
The questionnaire was designed in both English and Malay languages which had been translated and cross-translated
to maintain the content validity of the questionnaire. Parameters tested in the questionnaire were demographic data,
exposure to NSI and practices of universal precautions in daily works. The 33-questions questionnaire was designed
as True/False question, with one (1) point given for true answer and zero (0) point given to wrong or unsure answer.
Data collection: A total of 240 questionnaires were distributed to all wards, clinics and laboratory units in Hospital
Serdang. The questionnaires were placed at the general area in the wards or units which were easily accessible to
all the potential respondents. Envelopes were placed at the same area for the respondents to return the completed
questionnaires. This was to maintain the confidentiality of the respondents. A period of seven days was given for
the respondents to return the questionnaire. Those who failed to return the questionnaires were considered as nonrespondents.
Statistical analysis: Data was summarized and analyzed with the Statistical Package for Social Sciences (SPSS)
version 16.0. Descriptive analysis was used for categorical variables such as age, sex, years of service etc. Comparison
of categorical data was performed with Chi-square analysis. Fisher’s exact test was used for small expected values less
than 5. A p value < 0.05 was considered as significant. Ethical clearance was obtained from Medical Research Ethics
Committee of Faculty of Medicine and Health Sciences, UPM and Ministry of Health , Malaysia ethical committee.
RESULTS
Demographic data
Of the total 240 sets of questionnaire that were distributed, a total of 215 HCW responded to the survey (response rate
of 89.6%). The demographic characteristics of the respondents are as in Table 1. The mean age was 30.0 + 6.0 years,
with the youngest respondent was 20 years and the oldest was 54 years old. The mean years of working experience
for our cohort of HCW was 6.77 + 5.58 years. Of the vaccination status, 198/215 (92.1%) of the HCW had been
vaccinated with Hepatitis B vaccine.
Table 1.
Demographic characteristics of respondents
Variable
N = 215
Percentage
Job category
Doctors
Staff nurses
Medical Assistant
41
136
38
19.1
63.3
17.6
Male
Female
48
167
22.3
77.7
Ethnic group
Malay
Chinese
Indian
173
16
20
81.1
7.5
9.4
Working experience
Up to 4 years
5 – 9 years
10 – 14 years
15 – 19 years
More than 19 years
84
79
27
9
9
40.4
38.0
13.0
4.3
4.3
5
Exposure and prevalence of NSI among HCW
In the 12 months period, 76/215 (35.8%) of the HCW have been exposed to blood and bodily fluids during the course
of their works. 89.3% had handled hollow-bore needle, while 60.9% had handled suture needles in their daily work.
Our survey demonstrated that 48 respondents (22.3%) had needle stick injuries in the 12 months preceding the survey.
Of those who have had NSI, 83.3% experienced up to two episodes of NSI and 16.7% had 3 – 4 episodes of NSI. Out
of these, only 29/48 (60.4%) reported the incident to the higher authorities. Looking into the job categories, doctors
were the most affected with the NSI (34.9%) followed by staff nurses (19.1%) and medical assistants (7.9%). Our
survey demonstrated that 11/48 (23.3%) HCW did not wear protective gloves when they experienced the NSI. Table 2
shows the procedures commonly associated with NSI.
Table 2.
Factors associated with NSIs
Number of the
respondents
Percentages of the
respondents
Types of procedures performed when experienced NSI
Blood taking
Using suture needles
Parenteral injection
Setting drip
Assisting in operation theatre
Performing in operation theatre
( N= 48 )
35 /48
17 / 48
18 /48
4 /48
4 /48
3 /47
(%)
72.9
35.4
37.5
8.3
8.3
6.2
Reasons for not wearing gloves when NSI occurred
Feeling uncomfortable
In a hurry
Feeling lazy
Allergy to latex
Insufficient gloves
Unsuitable size
( N = 11 )
2 / 11
7 / 11
1 / 11
2 / 11
1 /11
1 / 11
18.2
63.6
9.1
18.2
9.1
9.1
Reasons for not reporting the case of NSI
Source thought not to be infectious
Incident thought was not important
Worried about future consequences
Did not know how to report
Too complicated to report
Embarrassed to report
Did not know that the incidence needs reporting
(N = 19 )
17 / 19
1 / 19
17 / 19
17 / 19
10 / 19
17 /19
17 /19
89.5
5.3
89.5
89.5
52.6
89.5
89.5
Variables
Blood-taking procedure was the most frequent procedure involved with NSI (35/48, 72.9%), followed by giving
of parenteral injection (18/35, 37.5%), procedures involving suture needles (17/48, 35.4%) and performing/assisting
in minor operation (7/48, 14.6%). Assisting in major operation was not associated with NSI (3/48, 6.2%). Setting up
intravenous line was also the least source for NSI with only 4/48 (8.3%) HCW that have had NSI reported it as the
cause. Our survey demonstrated that medical officers/ specialists were the most affected with NSI (34.9%) followed
by the staff nurses (19.1%). Our survey also showed that 23.4% of those who have had NSI, did not wear any glove
during the incident.
Practices of Universal Precautions among respondents
Of the total 215 respondents, more than three quarter of respondents adhered to 10 correct practices tested in this
section. 98.6% washed their hands after contact with patients or bodily fluid, whereas 96.7% of the HCW wore
gloves during handling of the blood and bodily fluids. However there is lower compliance with washing hands after
6
changing gloves, where only 180/215 (84.9%) admitted to adhering to this washing guideline. We also found that
30.0 % respondents still recapped needles after use and threw the used-needles into the domestic dustbin. Removal
of needle from the syringe after blood-taking was practiced by 67.9 % respondents. Finally, the practice of removing
the needle from syringe and placing them into the corresponding disposal container were practiced only by 66.0% of
HCW in this survey.
DISCUSSION
The objective of this survey was to determine the prevalence of NSI and the actual practices of universal precautions
among HCW in a tertiary teaching hospital in Malaysia. Our cohorts of respondents were relatively young; with less
than 10 years of experience post-training. Nurses formed the majority of the respondents. As universal precautions
guidelines were introduced in Malaysian hospitals in the 90s, we postulated that most of the respondents would
be knowledgeable with the practices of universal precautions in their daily practices. However, our study reported
the prevalence of NSI was 22.3%, with 83.3% reported having two episodes of NSI over the last 12 months. Our
prevalence is in concordance with earlier local studies5,8 which reported prevalence of 20.9% and 22.4% of reported
single exposure of NSI respectively. Our study concurs with the findings of earlier studies, in which procedures
involving hollow-bore needles accounted for the highest proportion of NSI among the HCW.5,8 This is important
as this type of needle has the potential of retaining bodily fluid (i.e. blood) therefore most often associated with the
blood-borne pathogen infections such as hepatitis and HIV.
Following a NSI, a health care worker must report the incident to the Head of Department or the Infection Control
Team within 24 hours for record and for blood investigations. However, the reporting itself is voluntary; hence many
of the cases were left unreported and probably untreated. Our survey revealed that nearly 30.0% of the HCW who
have had NSI failed to report the incident to their superiors. One of the major reasons given by the respondents was
the perception that NSI were non-contagious.[9] Lee KH et all[5] in a similar study quoted the main reason being
the amount of blood transmitted through NSI was regarded as insignificant hence considered ‘not infectious’. This
perception need to be corrected based on two factors. Firstly, as there is no compulsory screening for HIV and hepatitis
for patients admitted hence HCW could be unknowingly exposed to asymptomatic HIV or Hepatitis B virus carriers
through NSI. Secondly, the concept of universal precaution states that all patients should be considered infectious.
Therefore all procures involving bodily contact should follow appropriate infection control procedures10 due to the
fact that infected patients cannot always be identified.
Other causes for non-reporting include ‘not informed that NSI needs to be reported and did not how to report the
incident’. It is commonly assumed that all the HCW are aware of the existing guidelines pertaining to reporting of
a NSI incident in the workplace. However, our results seemed to contradict this assumption. These findings are in
accord with previous studies by Gershon et al[11] and Alam et al[12] who also documented of respondents cited ‘did not
know how to report’ as the main reason for not reporting. These results emphasize the needs for review of the current
implementation of universal precautions in our hospitals. Although the guidelines are available in many of the wards,
there is no apparent substantiation that the documents are read by the HCW. Efforts may be needed to overcome these
problems. Apart from ensuring that the guidelines are always available in the wards and other units in the hospital,
it should be made compulsory for any new HCW to read the guidelines upon joining the wards/ units. In addition,
compulsory annual refresher course could be implemented for the senior staffs in the wards/units to ensure that the
HCW are constantly updated and made aware of the importance of adhering to universal precautions in their daily
work. Finally, every wards/units in the hospital should have the guidelines on how to report a NSI incident readily
accessible to all HCW via posters, manual or pamphlets.
Our study reported almost 30% of the HCW were still practicing recapping needles after use and removing the
needle from the syringe after blood-taking procedures. This finding is much higher than those reported by Lee KH
in 2005.[5] This is an alarming finding as the practice of recapping of needle is not only unsafe but prohibited in most
hospitals. HCW should be made aware that these practices put them at risk to highly dangerous blood-borne infections.
The administrators should identify staffs with risk taking tendencies (e.g. those with multiple exposures) so that strong
supervisory support, counseling and guidance could be given to improve their attitude in their daily practice.[11]
Although these findings provide direction and focus for possible intervention to improve the practice of universal
precautions among our HCW, cautions must be applied in generalizing these data. One of our limitations is the manner
of the data collection. As data were collected using a self- answered questionnaire, respondents might be limited by
recall bias. In addition, there was the tendency for the respondents to give socially accepted responses especially when
these questionnaires were confidential in nature. As these data were cross-sectional, we were unable to establish the
cause and event of the NSI prevalence of our study cohorts.
CONCLUSION
This study showed that health care workers are exposed to needle stick injuries in their daily work despite working
7
in a teaching hospital. Efforts should be taken in order to overcome these problems, especially concerning lack of
existing guidelines in reporting a NSI and incorrect practices of handling needles after injections and blood-taking.
Interventions such as compulsory refresher course for all staffs should be implemented in order to increase the
awareness of the danger of needle stick injuries to the HCW and cross- infections to patients.
ACKNOWLEDGEMENT
This paper is the product of the Year Two medical students of Universiti Putra Malaysia (WB Lim, SLM Salleh & SNS
Rahman) for the partial fulfillment of their Degree. This work would not have been possible without the cooperation
of the study participants and the management of Serdang Hospital which is the training centre for Universiti Putra
Malaysia.
REFERENCES
[1]
Canadian Centre for Occupational Health and Safety 2005-[cited 2007 Dec 21]. Available from : http://www.
ccohs.ca/oshanswers/diseses/needle_injury.html
[2]
International Perspectives ICN, WHO lead effort to reduce needle-stick injury. International Nursing Review.
2005; 52: 89-90.
[3]
Feldman RH. Hospital injuries. Occupational Health Safety. 1986; 55: 12-13.
[4]
Ministry of Health, Malaysia. Clinical Practice Guidelines, Liver Update 2007.
[5]
Lee KH, Noor Hassim I. Implication of the prevalence of needle stick injuries in a general hospital in Malaysia
and its risk in clinical practice. Environmental Health and Preventive Medicine. 2005; 10: 33-41.
[6]
Jahan S. Epidemiology of needle sticks injury among health care workers in a secondary care hospital in Saudi
Arabia. Annals of Saudi Medicine. 2005; 25(3): 233-238.
[7]
Hamid MZA, Aziz NA , Anita AR, Norlijah O. Knowledge of blood borne infectious disease and the practice
of universal precautions amongst health-care workers in a tertiary hospital in Malaysia. Southeast Asian J Trop
Med Public Health. 2010; Vol (41): 1192-1199.
[8]
Mohamad Yaakob N, Hassim IN. Study of incidence of needle stick injury and factors associated with these
problems among medical students. J Occup Health. 2003; 45: 172-178.
[9]
Resnic FS, Noerdlinger MA. Job occupation exposure among medical students and house staff at a New York
City Medical Centre. Arch Internal Med. 1995; 155: 75-80.
[10] CDC (Centres for Disease Control and Prevention). Immunization of health care workers: recommendations
of the Advisory Committee on Immunization Practices (ACIP) abnd the Hospital Infection Control Practices
Advisory Committee (HICPAC). MMWR. 1997; 46: 1-42.
[11] Gershon RRM, Vlahov D. Occupationally acquired human immunodeficiency virus-1 infection in health care
workers: a review. In: Cundy K, Kleger B, Hinks E, Miller L,eds. Infection control: dilemmas and practical
solution: New York: Plenum. 1990: 131-46.
[12] Alam M. Knowledge, attitude and practices among health care workers on needle stick injuries. Annals of Saudi
Medicine. 2002: 2 (5-6): 396-99.
The Impact of Preventive Fogging on Entomological Parameters in a University
Campus in Malaysia
1
A Ruhil Amal, 1O Malina*, 1AH Rukman, 1U Ngah Zasmy, 1A Wan Omar & 2M Norhafizah
Department of Medical Parasitology and Entomology, Faculty of Medicine & Health Sciences,
Universiti Putra Malaysia, 43400 Serdang, Selangor
2
Department of Pathology, Faculty of Medicine and Health Sciences,
Universiti Putra Malaysia, 43400 Serdang, Selangor
1
ABSTRACT
Introduction: Preventive fogging is defined as space spraying of insecticide against mosquitoes in
order to prevent outbreak of mosquito borne infection. Despite provision of various preventive and
control activities against dengue and chikungunya infection by Ministry of Health Guideline, the detail
on preventive fogging has not yet specified. However, this has been adopted by certain institutions as
part of the routine strategies against dengue outbreak. A study on preventive fogging was conducted
in one of the hostels in Universiti Putra Malaysia. The research was done for 16 weeks in which one
routine fogging activity was done at the mid period of study. The main objectives of this study were to
determine the effectiveness of preventive fogging activities against Aedes mosquitoes and to identify
the distribution and abundance of Aedes mosquitoes in the area. Method: The fogging activity was
carried out by the management staff as part of their preventive measures in the student hostels. Ovitrap
was used as an indicator to monitor the impact of fogging activity and its continuous surveillance was
monitored weekly. The ovitraps were placed indoors and outdoors. Species identification was carried
out in the laboratory. The SPSS program was used to analyse the statistical data on the effectiveness of
fogging activity. Larval count (indoors and outdoors) and ovitrap index (OI) readings were identified
as ovitrap surveillance data for statistical analysis. Results: The results showed that Aedes albopictus
was the only species of the genus Aedes found in this hostel. The area had been highly infested by Ae.
Albopictus as indicated by high Ovitrap Index ranging between 48.33% to 90.00%. The mean (SD) of
Ovitrap Index was reduced from 71.67% (12.73%) (before the preventive fogging), to 69.42% (14.40%)
(after the fogging). Overall reduction in mosquito and larval density was also observed between pre
and post fogging activity in this study. Conclusion: The implementation of preventive fogging has
favourably reduced the dengue vector population up to 5 weeks after the introduction of preventive
fogging. However, sole dependency on preventive fogging may lead to insecticide resistance. Revisiting
the policy on preventive fogging; and identifying it as an additional tool for preventing dengue infection
in higher learning institutions are recommended.
Keywords:
Preventive fogging, Aedes, dengue fever
INTRODUCTION
Dengue fever (DF) and dengue haemorrhagic fever (DHF) have remained the most important arthropod-borne viral
diseases of human worldwide with an estimation of 2.5 billion worldwide are at risk of being infected yearly [1]. It is
also an endemic disease in more than 100 countries including Malaysia, which has reported cases of dengue outbreaks
in all states [1, 2, 3].
There are basically four main approaches to control and prevent dengue i.e. through biological control, chemical
control, environmental management and integrated vector management [2, 4]. Despite the comprehensive review of
epidemiological data on these four approaches, space spray (fogging) has been used as the most acceptable method
particularly during outbreak in South East Asian countries [5]. The fogging activities are carried out to rapidly eliminate
adult Aedes mosquitoes in the outbreak areas. Recent development has prompted controversy on the effectiveness of
fogging itself. Available studies have shown that space spraying has minimal impact on disease incidence even though
the peak of the epidemic may be delayed [2, 6]. The evidence of resistance against pyrethroids, a chemicals which are
currently used as main insecticide in fogging activities has further raised the doubt on the effectiveness of the fogging
activity [7].
In Malaysia, the trend of the diseases was consistently in an upward pattern with fluctuations in between (Figure
10
1). As there is still no vaccine and definitive treatment for dengue, vector control through several approaches has
been implemented as the single main strategy. Dengue control in our setting has been done primarily based on case
surveillance of suspected cases by doctors and vector control units by space spraying of insecticides (fogging) [8].
Vector surveillance is usually done regularly by larval surveys of Aedes mosquitoes and enforcement of DDBIA
(Destruction of Disease Bearing Insect Act 1975) by the health authorities [9].
Practice of preventive fogging as a preventive measure has not been listed as one of the recommended strategies.
Preventive fogging is defined as space spraying of insecticide against mosquitoes in order to prevent occurrence of
outbreak due to mosquito borne infection [10]. However in practice, since there is no clause provided in legislative
documentations, the implementation has been mandated to the management of any institution/ organization as part
of fulfilling the public or managerial request [10]. In Universiti Putra Malaysia, we observed several occasions where
fogging had been carried out as part of an effort to curb dengue outbreak particularly before the starting of new
academic session and before the examination week. This has been confirmed based on subsequent interviews with the
doctor in-charge at the University Health Centre who mentioned that beside a fogging activity, source reduction by
eliminating the potential breeding areas as well as putting the larvicide in the potential water containers [11] have also
been carried out. The procedure of fogging usually follows the recommendation by the Ministry of Health. However,
for the formality and administrative purposes, to date, no available written guideline for conducting this procedure is
available so far. This study was conducted to evaluate the usefulness of preventive fogging as part of integral efforts to
curb dengue infection in the campus.
Figure 1.
Total of dengue cases in Malaysia 1973-2008 (Source:
Ministry of Health, 2009)
Study area
One of the hostels in Universiti Putra Malaysia was selected as a study area. The hostel consists of five blocks and each
block has four floors. Several student utilities are located at the hostel compound such as commercial bank, Post Office
and fast food cafeteria. Sparse vegetations can be found at the surrounding campus. There were abundance of breeding
sites for Aedes mosquitoes found in this area especially around the big trees, fish pond, peacock aviary, various types
of artificial containers, drains and unused toilet.
Climate
During the period of study, the hostel area experienced a tropical climate with an average temperature of 25oC to 35oC
and the relative humidity of 75% to 95%. The total annual rainfall in all study sites exceeded 2200 mm.
Local dengue control strategy (at the study area)
Fogging activity in the hostel is done in two modes i.e. as a compulsory measure as well as a preventive measure. A
compulsory measure is conducted following any reported (suspected/confirmed) case of dengue. In response to any
dengue case notification, the activity is usually conducted in collaboration with the nearest District Health Office in
11
Petaling Jaya.
As for prevention, the fogging activity is carried out twice per semester and it usually is carried out in the late
evening by using hand-fogger machine. Pyrethroid (Aqua-Resigen ® which consisted of S-biollatherin 0.14% w/
w, permethrin 10.11 % w/w, piperonyl butoxide 9.96% w/w, inactive base 79.79% w/w) was used as the common
chemical insecticide for the fogging activity [11]. Apart from preventive fogging, there was also source reduction and
larvicide activity using temephos (Abate ®).
Ovitrap surveillance
Continuous ovitrap surveillance [12] was monitored for 16 weeks, which were 8 weeks before and 8 weeks after the
preventive fogging activity i.e. from January 2007 until April 2007. In each cycle, the number of immature mosquitoes
was collected from the designated areas and species identification was done in the laboratory. Favourable breeding
conditions were provided such as dark, water holding containers which were placed in close proximity to a human
population upon which the mosquitoes can feed. It has been recommended that breeding sites should be in clean water,
possibly with a small amount of organic matter as larval food supply [13]. The creation of the ovitraps followed the
Aedes mosquitoes preference i.e. to lay eggs on the rough, moist surfaces, just above the water line [14].
The ovitrap consisted of black paint coated plastic container (300 ml), slightly tapered sides. The diameter of the
opening measures 7.8 cm with the base (diameter) was 5.7 cm and 11.5 cm in height. An oviposition paddle (substrate)
was made from plywood cardboard (13.5 cm x 4 cm x 0.3 cm) and was placed diagonally into each ovitrap.
Sixty-six (66) ovitraps were set indoors and outdoors [10]. “Indoor” is referred to the interior of the house, while
“outdoor” is referred to outside of the house but confined to the immediate vicinity of the buildingas proposed by Lee
1992 [12]. In this study context, house is referred to the student hostels. The ovitraps were placed randomly (fixed to
identified area throughout the study period), approximately 25 - 30 meters apart.
Data analysis
For the evaluation of the effectiveness of preventive fogging activities, the larval count used for the analysis as the
followings.
1. The mean number of Aedes mosquitoes larvae (before and after introducing the control measures)
=
The total larvae count for pre/post control measures
Duration of study for pre/post control measures
----------------------------------------------------------------------------------------------------------2. Ovitrap Index (01), the percentage of positive ovitrap against the total number of ovitraps recovered for each study
sites.
3. The comparison between mean number of larvae count and also mean ovitrap index pre and post introduction of
control measures.
The paired t-test was used for the comparison of larval count before and after the fogging activities. The comparison
was made in 8th week i.e. before routine fogging and a few weeks after the routine procedures. The level of statistical
significance was determined at p< 0.05 by using SPSS (Statistical Package for Social Science) version 16.
RESULTS
In general, preventive dengue control activities in the hostels will be done in response to administrative circular from
University Health Center. The circular basically reminds the management of the hostels to carry out the dengue control
activities to prepare the hostels for new academic session as well as before the examination weeks. However, the
observation in the field during the study period however showed that despite the circular, there were only preventive
fogging and removal/ discard of the rubbish or potential breeding containers in the hostel areas. The removal of
the potential breeding areas however was done throughout the semester. There were no larvicidal activities (using
temephos or any other recommended larvicides in the market) during the observation.
Based on the Aedes mosquito identification, only Aedes albopictus was found, both in outdoor and indoor areas.
Apart from Aedes mosquitoes, Culex mosquitoes were also found in ovitrap with other insects.
According to the larval count and identification, most Ae.albopictus was found near the peacock’s aviary, fish
pond, below the staircase and adjacent to big trees areas. The ground floor level of the hostel also showed the highest
number for larval count compared to other floors.
The fogging activity
In this study, one preventive fogging activity was carried out at the hostel. It was done at 8th week of the study period.
12
The result showed that this area was highly infested with Ae. albopictus populations as shown by high Ovitrap Index
which ranged from 48.33% to 90.00%. The mean (SD) number of larvae collected before the fogging activity was
745.00 (259.97), while post-fogging was 678.50 (337.45). The mean (SD) of Ovitrap Index was reduced from 71.67%
(12.73%) before the fogging to 69.42% (14.40%) after the fogging activity (Table 1). The number of positive ovitrap
collected at this area was decreased from 344 (before fogging) to 332 (after fogging),which recorded a reduction of
3.5%.
Table 1.
The mean larval count (LSD) and Ovitrap Index before and after the implementation
of preventive fogging activity at the study area
Timing for the
control measure
Indoor
Before – preventive
Fogging activity
After - preventive
fogging activity
Figure 2.
Table 2.
Mean Larval count (SD)
Both (Indoors
Outdoor
and Outdoors)
Ovitrap Index
(%)(SD)
37.50 (22.63)
707.50 (245.09)
745.00 (259.97)
71.67 (12.73)
31.50 (22.87)
647.00 (320.83)
678.50 (337.45)
69.42 (14.40)
The graph of Ovitrap Index and larval count before and
after the implementation of routine fogging activity at
Kolej Mohamad Rashid
Paired t-test for comparison between mean larval count (per ovitrap) at 8th week and
subsequent week (weekly) after preventive fogging
Comparison of
larval count at week
Mean (SD)
95% Confidence
Interval
t
Sig. (2-tailed)
8th and 9th
8th and 10th
8th and 11th
8th and 12th
8th and 13th
8th and 14th
8th and 15th
8th and 16th
12.22 (19.37)
11.63 (19.90)
7.28 (19.00)
10.65 (18.87)
8.02 (23.74)
0.55 (24.57)
1.70 (24.62)
-5.78 (25.97)
6.77-17.66
6.03-17.22
1.93-12.62
5.34-15.95
1.34-14.69
-6.36 -7.46
-5.22-8.63
-13.09 - 1.52
4.504
4.172
2.734
4.029
2.413
.160
.495
-1.591
0.000*
0.000*
0.009*
0.000*
0.020*
0.874
0.623
0.118
* p < 0.05
13
In general, the larval counts (indoors and outdoors) and Ovitrap Index in this area showed a decreasing trend after
fogging activity. The paired t test for specific comparison before and after the routine procedures showed that there
were significant difference (p< 0.05) of the reduction of the larval counts i.e. between 8th week and 9th week, 8th week
and 10th week, 11th week and 11th week; 8th week 12th week; and 8th week and 13th week. Detailed observation showed
that the number of larval counts was steadily increased every week after the fogging was done. Surprisingly, it was
found that the larval counts were almost similar or higher after 8th week of fogging (Table 2).
DISCUSSION
In this study, only Aedes albopictus was found during the larval surveillance. It was quite different from the previous
surveillance in the campus area where both Aedes aegypti and Aedes albopictus were identified as the major dengue
vectors in Universiti Putra Malaysia [15] . The ecological background of the campus and the surrounding areas of active
development in Putrajaya and Cyberjaya are conducive for the habitats of the mosquitoes. The study area chosen
was the oldest student hostels in the campus with its landscape full of scattered vegetation; trees, fencing plants and
flowers. There were also a peacock’s aviary and a fish pond in the area. This area had several artificial habitats such
as uncovered toilet tanks, discarded rubbish in the drains. As it is known that larval breeding sites are very broad and
range from natural sites (e.g. bamboo stumps, bromeliads and tree holes) to artificial containers, findings from this
study would further support the features of its ecological preferences [16, 17]. Aedes albopictus has a strong ecological
plasticity that enables it for rapid adaptation to a variety of habitats. Its adaptation to human environments and in
suburban environments is well known. However, Aedes albopictus has been identified in highly dense urban areas [15].
Furthermore, previous studies reported that only Aedes albopictus was found or identified as the dominant vector in
major epidemics in regions [18].
The main activities of dengue control and preventive measures conducted by the Health District Office would
follow the guidelines of Ministry of Health [9]. In Malaysia and many other South East Asian countries, fogging has
still been used as the main control measure during dengue outbreak [5]. Due to the use of fogging as a major approach to
curb dengue infection, the public and the authorities are very dependent on the use of chemical control for adult Aedes
mosquitoes18. Previous study by Chua et al. in 2005 [6] documented that, efforts to break the reproductive lifecycle
through elimination of the gravid female Aedes mosquitoes by application of chemical fogging in natural environment
was ineffective.
Standard ovitrap index set by the Vector Control Unit, Ministry of Health recommended that the Ovitrap Index
should be less than 5% to classify any place as a low risk area. The Ovitrap Index in this study showed a high percentage
readings i.e. ranging from 48.33% to 90.00% throughout the study. Similar findings were also documented in study at
other places in Kuala Lumpur and Penang where the OI recorded in the study areas ranged from 40% - 99% [19].
In this study, there was a significant difference in larval count during before and after fogging activities. The
differences however only lasted up to 5 weeks after the fogging was done. However, the larval mosquito population in
the study area showed a constant upward trend after 5th week of fogging. However, previous studies by Lofgren et al
1970 [20], Pant et al., 1971 [21], Uribe et al., 1984 [22] and Mani et al., 2005 [5] pointed the ineffectiveness of the fogging
activity. The possible explanation for this is probably due to the re-emergence of the vector population after the
fogging activity is completed [23]. Re-emergence of mosquitoes did occur in this study, but it appeared after 5th week
of the preventive fogging, which would indicate that preventive fogging could contribute to the reduction of dengue
transmission for 5 weeks. The effort, however, maybe more effective if it is integrated with other approaches i.e.
environmental friendly strategies namely by the use of biolarvicide (Bacillus thurigiensis israelensis) spray, mosquito
light traps and continuous effort on search and destroy activities.
Moreover, future research is needed to study the cost analysis of fogging activity and other sensitive parameters to
identify the impending dengue outbreak.
ACKNOWLEDGEMENT
Special thanks to the Manager of Kolej Mohamad Rashid for the permission given to carry out this research, University
Health Centre (UPM), Dr.Salmiah Mohd.Said from Community Health Department, Faculty of Medicine & Health
Sciences, UPM for special assistance in data analysis and to the staff of Unit Medical Parasitology & Entomology,
Faculty of Medicine & Health Sciences, UPM for their assistance in the field work.
REFERENCES
[1]
World Health Organization. (2009). http://www.who.int/mediacentre/factsheets/ fs117/en/2009. Accessed on 5th
June 2009.
[2]
Ministry of Health. (2009). http://www.moh.gov.my/MohPortal/healthfact.jsp. Accessed on 7 January 2009.
14
[3]
Halstead S.B. 2008. Dengue.Tropical Medicine: Science and Practice. Imperial College Press. Singapore.
[4]
Erlanger, TE, Keiser J, and Utzinger J. (2008) Effect of Dengue control on entomological parameters in developing
countries: a systematic review and meta analysis. Medical and Veterinary Entomology 22 (3): 203-221.
[5]
Mani TR, Arunachalam N, Rajendran R, Satyanarayana K, Dash P. (2005). Efficay of thermal fog application of
deltacide, a synergized mixture of pyrethroids against Aedes aegypti, the vector of dengue. Tropical Medicine
and International Health 10 (12): 1298-1304.
[6]
Chua KB, Chua LL, Chua IE, Chua KH. (2005). Effect of chemical fogging on immature Aedes mosquitoes in
natural field conditions. Singapore Med J46(11): 639-644.
[7]
Marcombe S, Carronn A, Darriet F, Etienne M, Agnew P et al (2009). Reduced efficacy of pyrethroid space
sprays for dengue control in an area of Martinique with pyrethroid resistance. The American Journal of Tropical
Medicine and Hygiene 80 (5): 745-51.
[8]
Kumurasamy V. (2006). Dengue fever in Malaysia: Time for review. Med J Malaysia Vol 61 (1): 1-3.
[9]
Ministry of Health. (1986). Guidelines for prevention and control of dengue fever and dengue haemorrhagic
fever.
[10] Zailiza S. (2009). Vector Control Unit, Pejabat Pengarah Kesihatan Negeri Sembilan. 19th August 2009; Personal
Communication.
[11] Adithiya A. (2009) Medical Officer in-charge of Dengue Preventive activities at University Health Center UPM.
5th June 2009; Personal Communication.
[12] Lee HL. (1992). Sequential sampling: its application in ovitrap surveillance of Aedes (Diptera: Culicidae) in
Selangor, Malaysia. Tropical Biomedicine 9: 29-34.
[13] Christophers SR. (1960) Aedes aegypti, the Yellow fever Mosquito: Its life history, bionomics and structure.
Cambridge University Press, Cambridge.
[14] Maria G, Gustavo K. (2002) Dengue: an update. The Lancet Infectious Disease Vol, 1: 33-42.
[15] Wan Omar A, Mohd Yunus A, Malina O, Ngah Zasmy U, Roslaini AM, Mohd Nawawi D. (2003). The seasonal
abundance of Aedes mosquitoes (dengue vectors) in the Serdang main campus of Universiti Putra Malaysia.
Malaysian Journal of Public Health Medicine, 3 (Suppl): 57.
[16] Sucharit S, Tumrasvin W, Vutikes S, Viraboonchai S. (1978). Interactions between larvae of Aei aegypti and Ae.
albopictus in mixed experimental populations. Southeast Asian Journal of Tropical Medicine and Public Health
9: 93-97.
[17] World Health Organization. (1999). Prevention and control of dengue and dengue haemorrhagic fever. WHO
Regional Publication, SEARO. No. 29: 1-135.
[18] World Health Organization. (2008). Asia-Pacific Dengue Program Managers Meeting, 5th to 9th May in Singapore
2008. 1-289.
[19] Rozilawati H, Zairi J, Adanan CR. (2007). Seasonal abundance of Aedes albopictus in selected urban and
suburban areas in Penang Malaysia. Tropical Biomedicine 24 (1): 83-94.
[20] Lofgren CS, Ford HR, Tonn RJ, Bang YH, Siribodhi P. (1970). The effectiveness of ultra low volume applications
of malathion at a rate of 3 US fluid ounces per acre in controlling Aedes aegypti in Thailand. Bulletin of World
Health Organization 42: 27-35.
[21] Pant CP, Mount GA, Jatanasen S, Mathis SL. (1971). Ultra low volume aerosols of technical malathion for the
15
control of Aedes aegypti. Bulletin of the World Health Organization 45: 805-817.
[22] Uribe LJ, Garrido G, Nelson M, Tinker ME, Moquillaza J. (1984). Experimental aerial spraying with ultra low
volume malathion to control Aedes aegypti in Buga, Colombia. Bulletin of the Pan American Health Organization
18: 43-57.
[23] Lo EKC, Narimah A. (1984). Epidemiology of dengue disease in Malaysia, 1973 - 1982. Journal of Malaysian
Society of Health 4(1): 27-35.
Prevalence of Urban Poor and Its Health Related Factors
in the State of Selangor, Malaysia
1
MS Sherina*, 1L Rampal, 1AR Hejar, 2A Rozali & 1A Mohd Yunus
Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.
2
Health Services Division, Ministry of Defense Malaysia
1
ABSTRACT
The objectives of this study were to determine the prevalence of the urban poor and its health related
factors in Selangor. This cross-sectional study was conducted in the community of Selangor. Data
was collected from January 2006 to June 2006. Three out of nine districts were selected to be involved
in the study, which were Klang, Kuala Langat and Petaling. A Multistage Stratified Proportionate
Systematic Random Sampling was used for this study. The sampling was carried out by the Statistics
Department of Malaysia. The survey frame was based on the information gathered from the Population
and Housing Census in year 2000. The respondents were interviewed by trained research assistants
using a structured pre-tested standardized questionnaire prepared in Malay and English languages.
A monthly income of RM706 and less was used to define urban poor based on the guidelines given
by the Economy Planning Unit of Malaysia (2004). SPSS 16.0 version was used to analyze the data.
Out of 2535 respondents interviewed in this study, 2491 respondents answered the questionnaire
completely (response rate 98.3%). Out of 2491 respondents, 202 (8.1%) had a monthly income of
RM706 and less. Analysis of the urban poor respondents found that majority were aged between 18 to
40 years old (55.9%), and 29.7% had diagnosed medical illnesses, where hypertension, diabetes and
asthma were the most common illnesses at 12.4%, 10.9% and 5.0% respectively. About 10% of the
urban poor respondents had physical disabilities such as blurring of vision (7.9%), hearing problems
(1.0%) and other disabilities (1.0%).
Keywords:
Urban poor, prevalence, health-related-factors, Selangor
INTRODUCTION
Malaysia has been facing rapid urbanization and population growth. The increasing trend of urbanization in Malaysia
is accompanied by the concentration of people in the metropolitan as well as large urban areas.[1] The process of such
urbanization has produced many negative impacts on the socioeconomic and environmental well-being of the urban
poor; particularly those who are living in squatters accommodation and low-cost flats.[2]
In Malaysia, the prevalence of absolute poverty has traditionally been determined by reference to a threshold
poverty line income (PLI). This PLI is based on what is considered to be the minimum consumption requirements of a
household for food, clothing, and other non-food items, such as rent, fuel, and power. The proportion of all households
living below this threshold is the proportion living in poverty – that is the poverty rate. The PLI for Selangor was
RM529 in 2002 and was increased to RM706 in 2004.[3]
Although the overall prevalence of urban poverty in Malaysia is low compared with that of rural poverty, it must be
noted that the PLI used in measuring poverty prevalence in urban areas is similar to that of rural areas, i.e. RM529 per
month in Peninsular Malaysia, RM690 in Sabah and RM600 in Sarawak.[3] Thus, if one uses different PLI for urban
areas, say 20-30 per cent higher from that of rural areas, reflecting the higher cost of living in the urban areas, one will
find higher incidence of urban poverty. Consequently, if we consider other socioeconomic variables such as housing
conditions, amenities, in measuring the incidence of urban poverty in addition to income, the extent and magnitude of
urban poverty may be more serious.[1]
According to World Bank, poverty is defined in terms of a person’s income or the amount of goods they are able to
consume. The World Bank has set the international poverty line at an expenditure level of $1 for every person a day.
Another standard definition of absolute poverty is “a condition of life so characterized by malnutrition, illiteracy, and
disease as to be beneath any reasonable definition of human decency”.[4] This definition concentrates on what it means
to be in a state of poverty – to lack food, to be uneducated, and to lack access to basic health care. Poverty and health
are inextricably linked, where more illnesses (both communicable and non-communicable) are associated with poverty.
There is in fact a two way relationship between poverty and ill-health, with illness often further impoverishing the
18
poor. Illness prevents people from working, affects their productivity and lowers their income. The costs of obtaining
health care can also be substantial, both in terms of time off from work and in terms of money spent on services.[5]
It was estimated that between 1990 and 1994, 21% of previously non-poor households in Bangladesh slipped into
poverty as a result of health-related causes.[6]
Even though PLI is usually based on households and not individuals [3], this study presents its results for both
individuals and households. This is because the objectives of this study were to determine the prevalence of urban
poor, and also the health factors of the urban poor in Selangor, which need to be identified individually. The
findings of this study can be used to improve the lives of the poverty groups in terms of health related factors in the
urban areas.
METHODOLOGY
This was a cross-sectional study conducted in the community of Selangor. Data was collected from January 2006 to
June 2006. Out of the nine districts in Selangor, three districts Klang, Kuala Langat and Petaling were selected in the
study.
A Multistage Stratified Proportionate Systematic Random Sampling was used for this study. The sampling was
carried out by the Statistics Department of Malaysia. The survey frame was based on the information gathered
from the Population and Housing Census in year 2000. The state was stratified into the following four sub-stratums
namely, metropolitan areas (75,000 population and above), urban large (10,000 to 74,999), urban small (1,000
to 9,999) and rural (the rest of the areas). Further selection was made based on artificially created, contiguous
geographical areas called Enumeration Blocks (EBs). An EB consists of 80-120 households and has specified
boundaries. Only population residing in non-institutional households was covered, and only Malaysian citizens
were included in this study.
For the purpose of this study, only EBs in urban areas of Selangor were identified. Both urban large and urban
small areas were included, but not metropolitan and rural areas. There was no difference in PLI levels between the
urban small and urban large areas, as the definition for urban poor is the same for all areas in Selangor (based on the
Economy Planning Unit’s definition for PLI in 2004).[3] Selection of sample within the EBs was based on the number
of households in the stratum. The sample size calculated for this study was 823 households (based on the EPI INFO
STATCALC calculation at 99.9% confidence interval and 5% expected prevalence of urban poor households). Based
on an estimate that the response rate of households might only be 70%, an additional 247 (30%) households were
sampled. A total of 1070 households were selected using a table of random numbers, with each household estimated
to have at least 1 to 2 adult respondents. All adults aged 18 years and above of the selected households were included
in the study.
The respondents were interviewed by trained research assistants using a structured pre-tested standardized
questionnaire in both Malay and English languages. The interviewer obtained verbal consent before administering
the interview and the information was immediately and directly transcribed into the questionnaire. The questionnaire
included questions on socio-demography such as age, sex, race, religion, marital status, school attendance, education
level, employment status and total monthly income. Questions assessing health related factors included questions on
health problems, medically diagnosed chronic and mental illnesses (personal and family), history of smoking, and
physical disabilities. Questions on utilization of health services included questions on types of health services utilized,
usage of government clinics or hospital in the last 6 months, knowledge on the services of the nearest government
clinic and expenditure on medical treatment for the past 6 months.
This study was approved by the Ethical Committees of the Malaysian Ministry of Health, and the Faculty of
Medicine and Health Sciences, University Putra Malaysia. Statistical Package for Social Sciences (SPSS 16.0) was
used to analyze the data.
RESULTS
Out of the 1070 households sampled, 1056 had respondents fulfilling the selection criteria (Malaysian citizens aged 18
years and above) who were willing to participate in the study. A total of 2535 respondents from the 1056 households
were identified to be interviewed in this study. However, only 2491 respondents who were interviewed answered the
questionnaires completely, while 44 of the respondents did not complete the interview section giving a response rate
of 98.3%. The reasons given for not completing the interview were having to go to work and too busy with housework.
Each household had one to three respondents who participated in the study.
Table 1 shows the household monthly income of the respondents. Out of 2491 respondents, 202 (8.1%) had a
monthly income of RM706 and less, and 1238 (49.7%) had a monthly household income of RM1500 and less. The
202 respondents were from 88 households which were all located in urban small areas of Selangor.
Table 2 shows the sociodemographic profile of the urban poor respondents with PLI RM706 and below. Majority
of the respondents were in the age category of 18 to 40 years old (55.9%). About 41.6% of the respondents were males,
19
whereas others were females (58.4%). Most of the respondents were Malays (55.9%), Muslims (55.9%), and married
(65.8%), attended school (91.1%) and had secondary education (57.1%), with the highest certificate in SPM/SPMV/
MCE (28.7%). However, half of the respondents were unemployed (50.0%).
Table 1.
Household monthly income by respondents (n = 2491) and households
(n=1056)
Characteristics
Respondents (%)
Households (%)
2289 (91.9)
202 (8.1)
968 (91.7)
88 (8.3)
1253 (50.3)
1238 (49.7)
644 (61.0)
412 (39.0)
By PLI RM706/month
Above RM706
RM706 and below
By PLI RM1500/month
Above RM1500
RM1500 and below
Table 2.
Socio demographic profile of the urban poor respondents (n = 202)
Profile of the respondents
n
%
Age (years)
18-40
41-59
60 and above
113
71
18
56.0
35.1
8.9
Gender
Female
Male
118
84
58.4
41.6
Race
Malay
Indian
Others
Chinese
113
74
8
7
55.9
36.6
4.0
3.5
Religion
Muslim
Hindu
Buddha
None
Christian
113
76
6
4
3
55.9
37.6
3.0
2.0
1.5
20
Continuation
Table 2.
Socio demographic profile of the urban poor respondents (n = 202)
n
%
Marital Status
Married
Single
Widowed
Divorced
133
52
15
2
65.9
25.7
7.4
1.0
Attended School
Yes
No
184
18
91.1
8.9
Education Level (n=184)
Primary
Secondary
Tertiary
64
105
15
34.8
57.1
8.1
Highest Certificate (n=173)
UPSR
PMR/SRP/LCE
SPM/SPMV/MCE
STPM/HSC
Certificate/Diploma
Bachelor Degree
56
44
58
5
6
4
27.7
21.8
28.7
2.5
3.0
2.0
Employment
Unemployed
Non-Government
Government
Self Employed
Others (Labourer)
101
59
19
18
5
50.0
29.2
9.4
8.9
2.5
Table 3 shows the health related factors of the urban poor respondents. About 29.7% of them had health problems,
where hypertension, diabetes and asthma were the most common chronic medical illnesses at 12.4%, 10.9% and 5.0%
respectively. As for the family members of the respondents, hypertension was also the commonest chronic illness
(21.8%), followed by diabetes (18.8%), asthma (7.9%) and ischaemic heart disease (7.9%). Most of the respondents
in this study did not smoke (74.9%), and did not have any diagnosed mental illness (91.6%). Almost 10% of the
respondents had physical disabilities such as blurring of vision (7.9%), hearing problems (1.0%) and other disabilities
(1.0%).
Table 4 shows the utilization of health services among the urban poor respondents. A majority of the respondents
sought treatment at government clinics (88.6%), and 62.4% sought treatment at these government clinics during the
past 6 months. Most respondents had knowledge about the services of the nearest government clinic to their houses
(95.0%), and received either free medical treatment or at a nominal fee of RM 1 (43.6%). However, most respondents
had never received treatment at any Hospital Emergency Unit during the last 6 months (96.5%).
Table 3.
Health related factors of the urban poor respondents (n = 202)
n
%
Diagnosed Health Problem
No
Yes
Don’t know
138
60
4
68.3
29.7
2.0
Medically Diagnosed Chronic Illness
(can tick more than one answer)
Hypertension
Diabetes
Asthma
Ischaemic Heart Disease
Arthritis
Cancer
Stroke
25
22
10
7
5
4
1
12.4
10.9
5.0
3.5
2.5
2.0
0.5
Known Family Chronic Illness
Hypertension
Diabetes
Asthma
Ischaemic Heart Disease
Stroke
Cancer
Arthritis
44
38
16
16
8
4
3
21.8
18.8
7.9
7.9
4.0
2.0
1.5
Smoking
No
Yes
Quit
140
40
7
74.9
21.4
3.7
Diagnosed Mental Illness
No
Do not know
Yes
185
15
2
91.6
7.4
1.0
Known Family Mental Illness
No
Do not know
Yes
183
15
4
90.6
7.4
2.0
21
22
Continuation
Table 3.
Health related factors of the urban poor respondents (n = 202)
n
%
Physical Disability
Blurring of vision
Hearing Problems
Other Disabilities
Blind
Deaf
Mute (unable to speak)
Paralysis (upper and / or lower limbs)
Mental Retardation
Congenital Diseases
16
2
2
0
0
0
0
0
0
7.9
1.0
1.0
0.0
0.0
0.0
0.0
0.0
0.0
Table 4.
Utilization of health services among the urban poor respondents (n = 202)
n
%
Health Services utilized
Government Clinic
Private Clinic
Government Hospital
Self Treatment
Private Hospital
Traditional
179
64
59
4
1
0
88.6
31.7
29.2
2.0
0.5
0.0
Received treatment at the government clinic past 6
months
Yes
No
126
76
62.4
37.6
Knowledge on services provided by the nearest
government clinic to house.
Do know
Do not know
192
10
95.0
5.0
Medical treatment expenditure for the past 6 months
Free / nominal fee of RM 1
Do not know
Do know
88
84
30
43.6
41.6
14.9
Received treatment at Hospital Emergency Unit past
6 months
No
Yes
195
7
96.5
3.5
23
DISCUSSION
Prevalence of urban poor
Urban poverty is a multidimensional phenomenon, and the poor suffer from various deprivations, e.g., lack of
opportunities to employment, inadequate housing and social protection, and lack of access to health, education and
personal security.[6]
This study found that the prevalence of urban poor was 8.1% for individuals and 8.3% for households. In comparing
this figure to other figures worldwide, it must be kept in mind that there are various estimates of the proportion of
urban poor populations and also, different definitions have been used. One global estimate suggested that 27.7 per
cent of the developing world’s urban population lived below official poverty lines. Regional variation for urban poor
was also considerable: sub-Saharan Africa, 41.6 per cent; Asia, 23 per cent; Latin America, 26.5 per cent; and the
Middle East and North Africa, 34.2 per cent. According to the state of world population series, urban poverty has been
increasing faster than rural poverty.[6]
Malaysia’s poverty rate has declined dramatically over the past three and a half decades. About half of Malaysian
households lived below the poverty line in 1970, falling to 16.5 per cent in 1990 and to just 5.1 per cent in 2002. The
prevalence of urban poverty declined from 3.3 per cent in 1999 to 2.5 per cent in 2004. Although the urban poverty
rate is very low, rapid urbanization that has occurred over the decades means that the number of the urban poor is now
considered significant.[3] The redefinition of urban areas in 1991, whereby about 6 per cent of the total poor in built-up
areas that were previously defined as rural were classified as urban, has contributed to the rise in urban poor. As such,
the number of poor households in urban areas in Malaysia rose significantly from about 77,900 in 1993 to 99,300 in
1995 primarily due to this redefinition.[7]
However, even this may be an underestimate: official poverty lines are often set unrealistically low, below the
levels required to meet basic needs, and standard income-based definitions do not usually take into account the higher
cost of living in the cities. In this study, if an alternative measure of household income of RM1500/month was used
as the PLI, the prevalence of urban poor for households would have been much higher (39.0%) as compared to the
national PLI of RM 706/month (8.3%) found in this study.
Socio demographic profile of the urban poor
A person’s age and gender have remarkable influence on their likelihood of experiencing poverty. In this study, 55.9%
of the respondents who were found to be poor were from the age of 18 to 40 years. This study also found that 58.4% of
the urban poor respondents were females. A study in Canada reported that the young and the elderly were more likely
to experience poverty. As well, women in every age group were more likely to live in poverty than men.[8]
There are three main ethnic communities in Malaysia, which are Malays, Chinese and Indians. In this study, the
prevalence of urban poor was highest among Malays (55.9%) compared to Indians (36.6%) and Chinese (3.5%).
Previous studies in Sabah and Sarawak have showed that Bumiputera (Malays and other indigenous groups) were
experiencing higher levels of poverty than the Chinese since 1990.[9] The report by the Economic Planning Unit in 2003
also stated that the poverty rates for the Bumiputera, Chinese and Indians were 7.3%, 1.5% and 1.9% respectively.[3]
It showed that poverty was higher among the Bumiputera than the other communities. Meanwhile, a national survey
in America on poverty by race and ethnicity showed that Blacks, Hispanics and Native Americans, each have poverty
rates almost twice as high as Asians and almost three times as high as Whites.[10]
Majority of the urban poor respondents in this study were married (65.8%). This finding defers with the national
survey in America, where families with a female head of household had a poverty rate of 29.9% and comprised the
majority of the poor families. Poverty rates were also higher among families with female households with no husbands
present (26.5%), followed by male households with no wives present (12.1%).[10]
This study also found that most of the respondents (57.1%) had secondary education, 34.8% had primary education
and 8.9% had never attended school. Half of the respondents in this study were also unemployed (50.0%). Poverty in
urban areas has been strongly linked to the low levels of education and unemployment. High poverty rates have been
linked to low levels of educational attainment. Low levels of formal education have been linked to employment in
low wage earning jobs. Low wages have been linked to subsistence living. Education - especially basic (primary and
lower-secondary) education - helps reduce poverty by increasing the productivity of the poor, by reducing fertility and
improving health, and by equipping people with the skills they need to participate fully in economy and society.[10]
A variety of studies in diverse settings have shown that unemployment is two to three times greater among the
poor than among the middle or higher income groups and correspondingly higher among the very poor compared to
the relatively poor.[11] It is not merely that employment prevents poverty, but that poverty restricts access to skills,
attitudes and opportunities for further advancement. A study by Johari and Kiong (1991) of urban poor in Sabah found
the following: urban poor were found in all ethnic groups; the urban poor were wage earners and concentrated in low
wage sectors, they had low levels of education, as well as limited access to employment opportunities, social facilities
and services.[9]
24
Health related factors of the urban poor
It should also be noted that many of the population groups, which suffer a heavy load of ill health, disease and
malnutrition, are poverty groups. This study found that most of the respondents suffered from two major chronic
illnesses; hypertension (12.4%) and diabetes (10.9%). Diabetes is recognized as one of the most common disease in
Malaysia. The National Health Morbidity Surveys showed that the prevalence of diabetes in Malaysia increased from
6.3% in 1986 to 8.3% in 1996,[12] and further increased to 11.6% in 2006.[13]
A recent study by Anand et al conducted in 2003 to 2004 in urban slums of Faridabad district, Haryana found that
there was a high prevalence of hypertension (blood pressure ≥ 149 / 90, or on an antihypertensive drug) among the
urban poor; 17.2% in men and 15.8% in women.[14]
Another important illness among the urban poor in this study was asthma (5.0%). Mielck et al (1996) found that
poverty and severe asthma were associated in Germany. The authors concluded that the lack of basic sanitation and
inadequate housing among the poor and low socioeconomic class probably contributed to respiratory problems such
as asthma.[15]
This study also found that 21.4% of the respondents were currently smoking. The study by Anand et al found that
the prevalence of smoking among men was 36.5% and 7% among women in their study among respondents in urban
slums. This study concluded that there was a high prevalence of risk factors, such as smoking for non-communicable
diseases among the urban poor community. The authors expressed concern that there was a likelihood of a high future
burden of non-communicable diseases such as hypertension and diabetes among the urban poor.[14]
Utilization of health services among the urban poor
Preliminary studies have shown that among the urban poor, there are increased health problems and increased need for
health care services.[8, 16, 17] This study found that majority of the urban poor preferred to seek treatment at government
clinics (88.6%) as compared to private clinics. One of the reasons was that a majority of them received free treatment
or were only asked to pay a nominal fee of RM 1 at these government clinics (43.6%). Almost all respondents in this
study had knowledge on the services provided by the nearest government clinic to their house (95.0%).
Health professionals have a key part to play in eradicating poverty. Firstly, they need to make sure that interventions
within the health sector benefit the poor; such as ensuring government health expenditure proportionately serves the
poor in both urban and rural areas, and ensuring that there is no prejudice among the health professionals in treating
the poor. One of the commonest complaints from poor people using health services was that health professionals
treated them with disrespect and offered them substandard treatment.[5]
The fact that the Malaysian government provides free treatment or just a nominal fee of RM 1 in government clinics
is a good factor in promoting the use of health services in the government sector among the urban poor. A study by
Russell and Gilson among the urban poor in Sri Lanka found that free health care services in Sri Lanka protected the
majority of poor households against high out of pocket payments for treatment at the time of illness. This protection
against even relatively low fees was an important poverty reduction measure because, even a small direct cost could
cause impoverishment among the poor.[18]
CONCLUSION
The prevalence of urban poor in Selangor was 8.1% for individuals and 8.3% for households. The prevalence of urban
poor was highest among the Malays, those who were married, with secondary education and unemployed. Among the
major chronic illness, there was a high prevalence of hypertension and diabetes among the urban poor population and
a very high percentage of them sought treatment at government clinics.
The findings of this study show that there are many areas to be explored among the urban poor population, such as
unemployment and management of chronic illnesses. These people need adequate support to help them improve their
lives in our community.
ACKNOWLEDGEMENT
This study was funded by the Intensified Research Prioritized Area – Experimental and Applied Research (IRPAEAR) Grant “Assessment of Physical, Mental and Social Well-being of Urban Poor in Selangor” (06-02-04-10048
EAR) awarded by the Ministry of Science and Technology (MOSTE) to Associate Professor Dr Sherina Mohd Sidik.
REFERENCES
[1]
Chamhuri S, Mohd Yusof K. Urban Development and urban poverty in Malaysia. International Journal of Social
Economics 1997; 24(12): 1524-1535.
[2]
Chamhuri S, Md Wahid M, Md Elias H. Socioeconomic and environmental landscapes of the urban poor in
25
Kuala Lumpur city, Malaysia. Abstracts of Annual Conference of the Norwegian Association for Development
Research (NFU), 2005.
[3]
The Economic Planning Unit. Mid-Term Review of the Eighth Malaysia Plan, 2001–2005. Kuala Lumpur:
Percetakan Nasional Malaysia Berhad, 2003.
[4]
World Bank. What is urban poverty? The World Bank: Working for a world free of poverty. www.worldbank.
org/urban/poverty/defining.html Assessed 27 September 2008.
[5]
Rowson M. Poverty and health. Student British Medical Journal 2001; 9: 180-182.
[6]
World Health Organization. Nations for Mental Health: An initiative for mental health in underserved populations.
WHO/MSA/NAM/97.4. Geneva: World Health Report, 1997.
[7]
Statistics Department of Malaysia. Population and housing census of Malaysia, 2000. Kuala Lumpur: Percetakan
Nasional Berhad, 2001.
[8]
Reutter LI. Lay understandings of the effects of poverty: Canadian perspective. Health and Social Care in the
Community 2005; 13(6): 514-530.
[9]
Johari MY, Kiong CS. An overview of urban poverty in Sabah. In Johari MY (ed.). Urban poverty in Malaysia.
Institute for Development Studies (Sabah). Kota Kinabalu, 1991.
[10] World Bank. Development in practice: priorities and strategies for education. Washington DC: World Bank,
1995.
[11] Oberai AS. Population growth, employment and poverty in third world mega-cities. Geneva: International Labour
Organization, 1993.
[12] The Second National Health and Morbidity Survey 1996 (NHMS II), Institute for Public Health, National
Institutes of Health. Ministry of Health Malaysia, 1999.
[13] The Third National Health and Morbidity Survey 2006 (NHMS III), Institute for Public Health, National
Institutes of Health. Ministry of Health Malaysia, 2008.
[14] Anand K, Shah B, Yadav K, Singh R, Mathur P, Paul E, Kapoor SK. Are the urban poor vulnerable to noncommunicable diseases? A survey of risk factors for non-communicable diseases in urban slums in Faridabad.
Nati Med J India 2007; 20(3): 115-120.
[15] Mielck A, Reitmeir P, Wjst M. Severity of childhood asthma by socioeconomic status. International Journal of
Epidemiology 1996; 25(2): 388-393.
[16] Kasim MY. Urban development and urban poverty: current thinking. In Johari MY (ed.). Urban poverty in
Malaysia. Institute for Development Studies (Sabah). Kota Kinabalu, 1991.
[17] Macintyre S, McKay L, Ellaway A. Are rich people or poor people more likely to be ill? Lay perceptions, by
social class and neighbourhood, of inequalities in health. Social Science & Medicine 2005; 60: 313-317.
[18] Russell S, Gilson L. Are health services protecting the livelihoods of the urban poor in Sri Lanka? Findings from
two low-income areas of Colombo. Social Science & Medicine 2006; 63 (7): 1732-1744.
Diphtheria Anti-toxoid Antibody Levels Among Pre-clinical Students and Staff in an
Institute of Higher Learning in Malaysia: Are They Protected?
RA Hamat*, O Malina, YJ Chua, KL Seng, M Zubaidah, K Norhanim, SS Chong,
PL Weng & J Farida
Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences,
Universiti Putra Malaysia, Serdang, Selangor, Malaysia
ABSTRACT
Introduction: Little is known about the sero-prevalence of diphtheria anti-toxoid antibody levels
among medical students in Malaysia. They too, just like other health care workers (HCWs) are at
risk of contracting and transmitting diphtheria. Fortunately, this can be prevented by giving a specific
vaccine: the diphtheria, tetanus and pertussis (DTP) vaccine. Nonetheless, data from local or regional
surveys are needed before any decision is made by the respective authorities. General objective: We
studied the epidemiology of diphtheria anti-toxoid antibody levels and vaccination history amongst
medical students and staff in Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.
Specific objectives: We determined the level of diphtheria anti-toxoid antibodies amongst pre-clinical
students and staff. Methodology: A total of 152 sera were collected from subjects aged 19 to 63, and
diphtheria anti-toxoid levels were measured by an enzyme-linked immunosorbent assay. Results: One
hundred and fifty-two (94.4%) blood samples out of 161 participants were successfully withdrawn,
which comprised 105 (69.1%) and 47 (30.9%) medical students and staff, respectively. A total of 77.6%
and the other 22.4% of the subjects had full and basic protection, respectively. Higher levels were
predominant amongst males and they were 1.3 times more protected than females in 20-29 year-old
group (85.1% vs 66.2%; odd ratios 1.25 [95% CI 1.03-1.50]; P=0.03). No significant difference in the
levels of immunity among subjects for ethnicity and academic position (P>0.05). Recommendations:
Level of full protection against diphtheria toxin should be clearly defined by broad population based
studies using several comparable detection methods. Medical students and staff with basic protection
should be closely monitored or should be given a booster dose for those who are at high risk of acquiring
the disease. Thus, a standard degree of coverage should be clearly determined for health workers to
prevent a potential outbreak. Conclusion: Students and staff possess immunity towards diptheria toxin
however the level of full protective antibody is yet to be determined in future.
Keywords:
Diphtheria, diphtheria anti-toxoid antibody, full protection, basic protection,
medical students, staff
INTRODUCTION
Greatest concerns on the re-emergence of diphtheria epidemics came from a large-scale outbreak in the Newly
Independent States (NIS) of the former Soviet Union, which involved 140 000 cases and 400 deaths during 19901995. [1] This was further stigmatized by subsequent outbreaks of varying degrees in other parts of Western Europe
and other countries through out the world. [2, 3] Recommendations and control strategies proposed by World Health
Organization (WHO) have been successful for some countries in combating the disease. One of them was to asses
diphtheria immunity levels among adults worldwide. [4, 5] However, data reported from the South East Asia region
are very much lacking. As a result, our knowledge on the epidemiology of diphtheria is still inadequate. In a similar
context, knowledge on the immunization policies of “high-risk” occupational groups in diphtheria outbreaks is also
hampered by limited available data. In addition, critical issues on vaccine-preventable diseases in health-care workers
(HCWs) and other high-risk groups have been extensively discussed. Recently, major improvements have been made
by Centers for Disease Control and Prevention (CDC) and Advisory Committee on Immunization Practices (ACIP)
in promoting tetanus, diphtheria and pertussis vaccine and other types of vaccines to all categories of health care
workers.[6]
However, teachers, medical students or other important high-risk groups in health-related fields have been
mistakenly underemphasized; and often marginalized because they are not considered hospital staff. [7, 8, 9] Furthermore,
only a small number of systematic immunization programs exist for medical students and staff in medical institutions
28
worldwide. Special consideration is needed for these target groups as they are often exposed to infectious diseases
directly or indirectly during clinical training. Now, it is recommended a one-time dose of Tdap for all HCWs including
physicians and other primary-care providers such as nurses, aides, respiratory therapists, radiology technicians,
students (e.g., medical, nursing, and other) that have direct contact with patient. This was supported by Healthcare
Infection Control Practices Advisory Committee (HICPAC). [10]
However, experts propose that groups at risk should be clearly defined and evidence-based before any decision
is made by the respective authorities. [2, 3] Thus, our aim in this study was to evaluate the immune status of medical
students and staff members towards diphtheria in relation to the selected socio-demographical variables. We do hope
that our findings would at least, in part, complement our national immunization coverage reports that have been
submitted annually to WHO/UNICEF. Also, to provide additional input for policy-makers before embarking on new
immunization programs for students who enter medical school.
Study population
The cross-sectional study was conducted from January 2008 to July 2008 at the Faculty of Medicine and Health
Sciences, University Putra Malaysia (UPM)—a public university in Peninsular Malaysia, approximately 30 kilometres
from Kuala Lumpur. The participants consisted of pre-clinical (medical) students, and staff members. Informed
consent was obtained and the following data was recorded in the standard Pro Forma: age, sex and ethnicity. Students
and staff were ensured that the results would be kept confidential, and would be personally informed; advice about
the risks and benefits of immunization were also provided. A standard questionnaire was also given to obtain the data
on the history of DPT vaccination. The protocol and consent procedures were approved by the Ethical Committee of
Universiti Putra Malaysia.
Serological method
Three millilitres of venous blood samples were obtained from the participants. The samples were allowed to clot
naturally at room temperature, and the sera were collected and stored at –80°C for analyses. Measurement of specific
IgG antibody against diphtheria toxoid levels in International Unit (IU/ml) was performed by using ELISA (enzymelinked immunosorbent assay, VaccZymeTM Diphtheria Toxoid IgG, The Binding Site Ltd., United Kingdom). The
relative sensitivity and specificity of this kit as compared with the gold standard Vero Cell Assay (VCA) are 93.06%
and 91.82%, respectively.
All procedures and interpretations were done according to the manufacturer’s guidelines. Briefly, 100 µl of each
calibrator, control and 1: 100 diluted sample were added to the appropriate wells, all of which were coated with
diphtheria toxoid antigen derived from Corynebacterium diphtheriae. Following incubation for 30 minutes; all
unbound proteins in the wells were discarded by washing three times. One hundred (100) µl of purified peroxidaselabeled rabbit anti-human IgG used as conjugate were added and again re-incubated for another 30 minutes. The
wells were washed three times to remove excess unbound conjugate. Finally, 100 µl of tetramethylbenzidine (TMB)
were added as substrate and subsequently incubated in a dark room for 30 minutes to give blue reaction product. The
intensity of the reaction was determined by using DYNATEX Microplate Reader (USA) at optical density (OD) of
450 nm. The measurement was done within 30 minutes of stopping the reaction using 100 µl of phosphoric acid. All
procedures were carried out at room temperature.
The results were interpreted as follows based on the manufacturer’s guideline:
Diphtheria immunity status:
< 0.01 IU/ml:
No protection
0.01 to 0.1 IU/ml:
Basic protection
> 0.1 IU/ml:
Full protection
Statistical analysis
Data analysis was carried out by using SPSS version 16.0 software (SPSS Inc., Chicago, IL, USA). Pearson chi square
and Fisher’s exact tests were used to analyze the association of the various socio-demographical variables with the
prevalence of diphtheria antitoxins. P values < 0.05 were considered to be statistically significant.
RESULTS
One hundred and fifty-two (94.4%) blood samples out of 161 participants were successfully withdrawn, of whom
100 (65.8%) and 52 (34.2%) were females and males, respectively. Their ages ranged from 19 to 63 years (median
21.0 years, standard deviation [SD] 6.2 years). The remaining 9 participants were excluded, as their blood could not
Diphtheria Anti-toxoid Antibody Levels Among Pre-clinical Students and Staff in an Institute of Higher Learning in Malaysia
29
be taken for various reasons. Of 152, 105 (69.1%) comprised medical students and 47 (30.9%) staff. The ethnicity
distribution was as follows: 99 (65.1%) Malays, 44 (28.9%) Chinese, 6 (3.9%) Indians and the remainder, 3 (2.0%)
were of other ethnic groups. Overall, 147 (97.2%) received diphtheria, tetanus and pertussis (DTP) vaccine as primary
immunization and a booster dose at school entry. All of the participants (100%) were serologically immune. One
hundred and eighteen (77.6%) and 34 (22.4%) of them had full and basic protection, respectively. The prevalence of
diphtheria immunity status according to socio-demographic characteristics is shown in Table 1. The median diphtheria
anti-toxoid antibody concentration reached 0.21 IU/ml (quartiles Q25–Q75; 0.1 to 0.37; Table 2).
Table 1.
Diphtheria immunity status of participants according to socio-demographic
characteristics
Socio-demographic profiles
Diphtheria immunity status
Basic protection
Full protection
(0.01–0.1 IU/ml)
(> 0.1 IU/ml)
No. (%)
No. (%)
P-value
Age-group ( in years)
< 20
20–29
30–39
>39
0 (0.0)
34 (25.8)
0 (0.0)
0 (0.0)
3 (100.0)
98 (74.2)
14 (100.0)
3 (100.0)
0.084
Gender
Male
Female
7 (13.5)
27 (27.0)
45 (86.5)
73 (73.0)
0.057
Ethnicity
Malay
Chinese
Indian
Others
22 (22.2)
11 (25.0)
0 (0.0)
1 (33.3)
77 (77.8)
33 (75.0)
6 (100.0)
2 (66.7)
0.549
Academic position
Medical lecturer
Tutor
Science officer
Laboratory personnel
Administrative staff
Medical student
0 (0.0)
0 (0.0)
1 (33.3)
7 (31.8)
3 (37.5)
23 (21.9)
10 (100.0)
4 (100.0)
2 (66.7)
15 (68.2)
5 (62.5)
82 (78.1)
0.266
Vaccination among subjectsa
Completed
Not sure
34 (23.1)
0 (0.0)
113 (76.9)
5(100.0)
0.446
History of diphtheria vaccination was considered completed if three doses of toxoid given at 3, 4, and 5
months of age as primary immunization in combined vaccine against DPT, followed by a fourth dose at
18 months, and a booster dose at school entry, between 6 and 7 years of age were documented.
a
In general, 86.5% of the males had full protective diphtheria anti-toxoid levels whereas; only 73.0% of the females
were fully protected. The difference was not statistically significant (P=0.06; Table 1). The median diphtheria antitoxoid antibody concentration in males was 0.18 IU/ml (0.12–0.32) compared with 0.22 IU/ml (0.09–0.39) in females
(Table 2). However, when gender in the 20–29 year-old category was analyzed on those with full protective diphtheria
anti-toxoid levels (Figure 1), significant difference was observed (P =0.03, data is not shown). Males (85.1%) had
higher percentages of full protective diphtheria anti-toxoid levels than females (66.2%) among this group, and males
30
were the most predominant and 1.3 times more protected than females in 20-29 year-old group (odd ratios 1.25 [95%
CI 1.03-1.50]).
Table 2.
Diphtheria anti-toxoid antibody concentration (IU/ml) according
to academic position, gender and ethnicity
Diphtheria anti-toxoid concentration (IU/ml):
median (Q25–Q75)
Characteristics
Total
0.21 (0.10–0.37)
Academic position
Staff
Medical student
0.31 (0.10–0.44)
0.18 (0.10–0.38)
Gender
Male
Female
0.18 (0.12–0.32)
0.22 (0.09–0.39)
Ethnicity
Malay
Non-Malay
0.22 (0.10–0.39)
0.17 (0.10–0.32)
Figure 1.
Distribution of full protective diphtheria anti-toxoid
levels in 98 participants of 20 to 29-year-old age group
according to gender
With reference to ethnicity, levels of full protection were found in 77 (77.8%), 33 (75%), 6 (100%) and 2 (66.7%)
of Malays, Chinese, Indians and others, respectively. However, neither ethnicity nor academic position had statistically
significant difference (Table 1; P >0.05). In general, the median diphtheria anti-toxoid antibody concentration in
Malays (0.22 IU/ml; quartiles Q25–Q75; 0.10–0.39) was slightly higher than non-Malays (0.17 IU/ml; quartiles Q25–
Q75; 0.10–0.32; Table 2). Overall, medical students and staff seemed to have equal percentages of full protective
diphtheria anti-toxoid levels, i.e., 82 (78.1%) and 36 (76.6%) of students and staff, respectively (Figure 2). However,
median diphtheria anti-toxoid antibody concentration in staff members (0.31 IU/ml; quartiles Q25–Q75; 0.10–0.44)
31
was higher than medical students (0.18 IU/ml; quartiles Q25–Q75; 0.10–0.38; Table 2). Nevertheless, small number
of subjects (staff) may contribute to this finding.
Figure 2.
Distribution of diphtheria immunity status according to
academic position (basic protection: 0.09–0.1 IU/ml; full
protection: > 0.1 IU/ml)
DISCUSSION
In our present study, we documented that 78.1% of medical students had full protective diphtheria anti-toxoid levels (>
0.1 IU/ml). The remaining 21.9% had basic protective levels (0.01—0.1 IU/ml). Importantly, all of them (100%) had
immunity to diphtheria. This is not surprising, as most of them were born after the year of commencement of Extended
Program on Immunization (EPI) [11], which was started in 1989. And also, this probably reflects highly sustainable
immunization coverage of diphtheria, tetanus and pertussis (DTP) of more than 90% in our country since 1990. [12] Our
findings are also comparable to previous studies, which reported 68.3 % and 78.4% of medical students in London [13]
and Poland [14] respectively, were fully protected. As high protective levels are vital in this group, a booster dose might
be required in those who had basic protection. Several studies have reported that high immunity levels were required
for full protection. [15] In a different scenario, it is well documented that at least 70% of children must be immunized in
order to prevent major outbreaks of diphtheria in the community. [16] However, so far, no general consensus has been
proposed for HCWs, including medical students and staff as to what percentage to be achieved in order to prevent
nosocomial or institutional outbreaks.
As for staff members, 76.6% were fully protected and 23.4% had basic protection. Again, all of them (100%)
were immune to diphtheria toxin. Surprisingly, higher concentration of anti-toxoid antibody was found in our staff
(0.31 IU/ml) than medical students (0.18 IU/ml; Table 2) in general. As for comparison, our prevalence rate of full
protection is very much higher than reported in other studies. Lower prevalence rates of 26%, 51% and 57% were
reported in Germany [17], United Kingdom [18] and Australia [19], respectively. Recently, only 36.3% of infection control
staff in Japan was reported to have full protective levels against diphtheria antitoxin. [20] However, different values of
these percentages were attributed to the different study designs and methodologies, vaccination programs and types
of serological test used. Our result may also probably signify the effectiveness of vaccine surveillance networks and
good public health infrastructures. These are very important and possibly explain lower levels of full protection in
underprivileged and minority populations in Thailand despite persistently high immunization coverage, which was
more than 90% reported annually in that country. [21]
In addition, for adults in highly developed countries, a booster dose is given to them before they are recruited into
the army, which might probably explain high levels of protective immunity. [22,23] As for our case, it may be related to
our national immunization policy. In Malaysia, the national policy of diphtheria immunization includes three doses
of toxoid given at 3, 4, and 5 months of age as primary immunization in combined vaccine against DPT, followed
by a fourth dose at 18 months, and a booster dose at school entry, between 6 and 7 years of age. [24] Because of the
boostering effects, this may probably contribute to higher prevalence of full protection in our study. It is well known
32
that booster effects can be maintained for up to 30 years. [25] One study reported 90% of respondents produced more
than or equal to 1 IU/ml of antitoxins following a booster after one-month period. [26] Also, the acquisition rate of fully
protective level was higher among young adults as reported in Japan. [20] This was also supported by a study in Israel
that reported adults acquired higher protective antitoxin levels following a booster dose injection given to them at 18
years of age. [27]
However, experts postulated that other factors rather than vaccination alone could possibly play a role. Changes
in socioeconomic and lifestyle would give different epidemiological patterns of the disease. [20] Based on these
observations, higher percentages of full protection found in both medical students and staff may also be related to
these factors. Malaysia is now recognized as a rapidly industrialized country with high standard of living. Also, our
socio-economic stability might have provided equal opportunities of vaccination among our participants. However,
local data on age-related difference in diphtheria cases was not available for further analyzes. The limitation of this
study is that we did not conduct a population based randomized study, and therefore a recruitment bias is possible.
However, as immunity levels in HCWs are of the main priority, this can be accepted.
In this present study, males (86.5%) had significantly higher percentage of full protection than females (73%) in
general (Table 1). However, the difference was not statistically significant (P=0.06). Interestingly, in the 20-29-year-old
group, males were 1.2 times more likely to have full protective antibodies than females (odd ratios 1.25 [95% CI 1.031.50]). Forty (85.1%) out of 47 males in this group, were fully protected as compared to females (68.2%); (data not
shown). The difference was statistically significant (P=0.03; Figure 2). With regard to gender-related difference, many
conflicting results were documented; and multiple contributing factors were proposed. [27] Some of them remained
poorly understood. [28, 29] In several studies, routine administration of Tetanus-Diphtheria toxoids vaccine (Td) for
injury cases—men were more prone, was responsible for higher protection rates in males [3, 30, 31], as well as, a booster
dose given prior to army’s recruitment (mostly males). [2] Different immunization responses in females following
vaccination were also responsible for the finding. Lower antibody titres and shorter period in maintaining immunity
levels in females were reported in several studies. [22, 29] In our case, the concentrations of anti-toxoid in males (0.18
IU/ml) and females (0.22 IU/ml) were almost equal (Table 2). In contradiction, few studies reported that males had
lower protection rates than females. [32, 33] Nevertheless, neither Td vaccination nor booster dose is recommended for
such occasions in Malaysia. In our study, ethnicity of different origin was not statistically associated with diphtheria
immunity status. This was in accordance with previous studies conducted in Israel. [27]
CONCLUSION
In summary, our study revealed that medical students and staff members possess immunity to diphtheria toxin. Hence,
the risk for contracting and transmitting the disease is relatively minimal. For this reason, it might not be necessary
to institute a specific vaccination program for diphtheria in our medical school and institution. However, our findings
will not be similar to medical schools in other developing countries and the full protective immunity is yet to be further
determined. Each country should analyze data gathered from its local and national surveys before formulating specific
recommendations on diphtheria vaccination.
ACKNOWLEDGEMENTS
The authors would like to thank the Dean of the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
for permission to conduct the study. Special thanks are extended to Dr Androulla Efstratiou and Professor Farida Jamal
for their support and encouragement. We are also indebted to our medical students: Chua Yi Jiang, Seng Kit Leng,
Zubaidah Mohamad for performing the serum antibody analyses and technical assistance and also to all anonymous
reviewers for their valuable comments. This work was funded by the Research University Grant Scheme (RUGS)
Project No. 04-02-07-0340RU and was supported by the Department of Medical Microbiology and Parasitology,
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia.
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diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned. J Infect Dis 2000;
181: S10-22.
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Galazka A, Robertson SE, Oblapenko GP. Resurgence of diphtheria. Eur J Epidemiol 1995; 11: 95-105.
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Galazka AM, Robertson SE. Immunization against diphtheria with special emphasis on immunization of adults.
Vaccine 1996; 14: 845-57.
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ICP/EPI 024 5582 r.
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Dittmann S, Roure C. Diphtheria Plan of Action for the Prevention and Control of Diphtheria in the European
Region (1994–1995). The Expanded Programme on Immunization in the European Region of WHO, ICP: EPI
038(A). Copenhagen: WHO 1994.
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Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of Advisory
Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee
(HICPAC). Morb Mortal Wkly Rep 1997; 46(RR-18): 1-42.
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Lane NE, Paul RI, Bratcher DF, Stover BH. A survey of policies at children’s hospitals regarding immunity of
healthcare workers: are physicians protected? Infect Control Hosp Epidemiol 1997; 18: 400-40.
[8]
Murray DL, Lynch MA. Determination of immune status to measles, rubella, and varicella-zoster viruses among
medical students. Assessment of historical information. Am J Public Health 1988; 78: 836-38.
[9]
McRae AT 3rd, Stephens JL. Hepatitis B virus vaccination of medical students: a call for rigorous standards.
JAMA 1995; 274: 1081.
[10] Centers for Disease Control and Prevention. Preventing tetanus, diphtheria, and pertussis among adults: use of
tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. Morb Mortal Wkly Rep 2006; 55(RR17): 1-33.
[11] World Health Organization 1984. Expanded program on immunization. Feasibility of elimination of vaccinepreventable disease. Wkly Epidemiol Rec 1984; 59: 143-5.
[12] WHO and UNICEF, WHO UNICEF review of national immunization coverage, 1980–2007 http://www.who.
int/immunization_monitoring/en/globalsummary/wucoveragecountrylist.cfm (accessed December 16, 2008).
[13] Sheffield FW, Ironside AG, Abbott JD. Immunization of adults against diphtheria. BM J 1978; 2: 249-50.
[14] Expanded Programme on Immunization. Immunization of adults against diphtheria. Wkly Epidemiol Rec 1995;
8; 56-9.
[15] Baer G, Bonhoeffer J, Schaad UB, Heininger U. Seroprevalence and immunization history of selected vaccine
preventable diseases in medical students. Vaccine 2004; 23(16): 2016-20.
[16] Mortimer EA. Diphtheria toxoid. In: Plotkin SA and Mortimer EA (ed): Vaccines. W. B. Saunders, Philadelphia,
1994, p. 41-56.
[17] John C, Selzer G, Preiser W, Zielen S. Diphtheria immunity in health staff. Lancet 1996; 347: 969.
[18] Maple PA, George RC, Miller E, Morgan-Capner P, Hayward P. Diphtheria immunity in adults. Lancet 1996;
348: 964.
[19] Hanlon M, Isaacs D, Kakakios A. Diphtheria immunity in health staff. Lancet 1996; 347: 1839-40.
[20] Nakajima H, Kariya H, Ohata R, Ogura H. Investigation of immunity level against diphtheria and reinforcement
of immunity by booster vaccination for infection control staff in Okayama Prefecture. Jpn J Infect Dis 2008; 61:
104-6.
[21] Tharmaphornpilas P, Yoocharoan P, Prempree P, Youngpairoj S, Sriprasert P et al. Diphtheria in Thailand in the
1990s. J Infect Dis 2001; 184: 1035-40.
[22] Simonsen O. Vaccination against tetanus and diphtheria: evaluation of immunity in the Danish population,
guidelines for revaccination, and the methods for control of vaccination programs. Dan Med Bull 1989; 36: 2447.
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[23] World Health Organization. Diphtheria immunity in the adult French population. Wkly Epidemiol Rec 1995; 70:
252-5.
[24] Ministry of Health Malaysia. Clinical Practice Guidelines on Childhood Immunization. 2002.http://www.moh.
gov.my (accessed May 20, 2009).
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[26] World Health Organization 1995. Expanded program on immunization. Immunization of adults against diphtheria.
Wkly Epidemiol Rec 1995; 70: 53-60.
[27] Valinsky L, Simhoni S, Bassal R et al. Prevalence and correlates of diphtheria toxoid antibodies in children and
adults in Israel. ESCMID 2006; 12(10): 968-73.
[28] Galazka AM. Changing epidemiology of diphtheria in the vaccine era. J Infect Dis 2000; 118(Suppl 1): S2-9.
[29] Galazka AM, Robertson SE. Diphtheria: changing patterns in the developing world and the industrialized world.
Euro J Epidemiol 1995; 11: 107-17.
[30] Ruben FL, Nagel J, Fireman P. Antitoxin responses in the elderly to tetanus-diphtheria (Td) immunization. Am
J Epidemiol 1978; 108: 145-9.
[31] Kjeldsen K, Simonsen O, Heron I. Immunity against diphtheria 25-30 years after primary vaccination in
childhood. Lancet 1985; i: 900-2.
[32] Jenum PA, Skogen V, Danilova E, Eskild A, Sjursen H. Immunity to diphtheria in northern Norway and northwestern Russia. Eur J Clin Microbiol Infect Dis 1995; 14: 794-8.
[33] de Melker HE, Berbers GA, Nagelkerke NJ, Conyn-van Spaendonck MA. Diphtheria antitoxin levels in the
Netherlands: a population-based study. Emerg Infect Dis 1999; 5: 694-700.
Method Optimization on the Process of Iontophoresis with Laser Doppler
Fluximetry in the Assessment of Microvascular Endothelial Function
1
AT Belqes Abdullah*, 2TGB Yvonne, 3SH Ahmad, 4ASI Abdul Aziz & 1HGR Aida*
Pharmacology Vascular Laboratory, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
3
Reconstructive Sciences Unit, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
4
Community Medicine Department, School of Medical Sciences,
Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
2
School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kota Bharu, Malaysia
1
ABSTRACT
Introduction: Iontophoresis of vasoactive substances such as acetylcholine (ACh) and sodium
nitroprusside (SNP) combined with Laser Doppler fluximetry (LDF) is a non-invasive tool used to
determine microvascular endothelial function. This study aims to test the effect of sodium chloride on
non-specific vasodilatation when used as a vehicle in the process of iontophoresis. This study also aims
to define the number of current pulses needed to get the maximum effect during iontophoresis with ACh
and SNP using low current strength. Methods: The experiment was conducted in five healthy females.
Baseline skin perfusion was taken before administration of seven current pulses. Current strength of
0.007 mA and current density of 0.01 mA/cm2 were used. Acetylcholine was used to assess endothelial
dependent vasodilatation, while SNP was used to assess endothelial independent vasodilatation. The
mean skin perfusion (AU) responses to the iontophoresis of ACh at the anodal and SNP at the cathode
leads were recorded. Sodium chloride (0.9%) was used as a vehicle to obtain concentration of 1%
for both ACh and SNP. Iontophoresis of pure vehicle (NaCl) was conducted on a separate day to
observe the effect of vehicle only on the iontophoresis process at both anode and cathode. Results:
Iontophoresis of NaCl showed no significant increase in perfusion compared to baseline at both anode
and cathode. Significant increases in skin perfusion were observed with SNP and ACh; a plateau of
ACh was reached from the 3rd pulse onwards; while the plateau of SNP was reached from the 4th pulse
onwards. Conclusion: NaCl could be used as a vehicle for Ach and SNP during iontophoresis as it did
not cause non-specific vasodilatation. Using five current pulses are adequate for iontophoresis of ACh
and SNP to assess microvascular endothelial function.
Keywords:
Microvascular endothelial function; iontophoresis; Laser Doppler Fluximetry; nonspecific vasodilatation
INTRODUCTION
Endothelial dysfunction is considered to be the earliest sign of atherosclerosis [1, 2] leading to the development of
cardiovascular diseases such as myocardial infarction and angina [3]. Thus, assessment of endothelial function can be
used as a tool to detect early vascular changes that may occur due to medical conditions and diseases, or to monitor
response to pharmacological interventions.
Skin can provide a good model to measure microcirculation as in diabetes; for example, measurable changes
in the skin have been found to pre-date the symptoms of microvascular disease in other organs by many years [4].
Different methods to assess cutaneous endothelial function have been developed; non-invasive method using laser
Doppler fluximetry (LDF) combined with the iontophoresis technique is used in the present study. LDF is a device
that permits real-time continuous measurement of microvascular blood perfusion [5, 6]. Iontophoresis is a non-invasive
method of introducing charged substances across the skin by means of a small electric current. When iontophoresis is
combined with LDF, this method enables the detection of alterations in skin perfusion in response to time-controlled
delivery of the vasoactive drug. Iontophoresis of acetylcholine (ACh) is often used to test endothelial dependent
vasodilatation, while iontophoresis of sodium nitroprusside (SNP) is used to test ‘endothelium-independent’
vasodilatation [7].
A major disadvantage with drug administration via iontophoresis is the possibility of non-specific vasodilatation
due to the influence of electric current on the blood flow. This is called galvanic response and is believed to be related
to the voltage required to establish the iontophoretic current that stimulates the local sensory nerves. The resistance of
*Corresponding author: [email protected] / [email protected]
36
the drug in its diluting solution might therefore be an important factor, and investigators have attempted to limit this
by using sodium chloride instead of water as the vehicle [8].
Another extremely important issue is the charge density used for iontophoresis; the higher the charge density, the
higher the chance to get non-specific vasodilatation. Use of larger chamber sizes and lower currents has been reported
to lower the charge density and prevent current induced non-specific vasodilatation [9]. Recently, Droog et al (2004)
suggested that it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, by limiting the current
density (≈0.01 mA/cm2) and charge density (<7.8 mC/cm2). The study also suggested adjusting the concentrations of
iontophoresis drugs to 1% and using sodium chloride 0.9% as a vehicle [10]. However, Droog et al (2004) employed
the laser Doppler imager (LDI).
Therefore, this study firstly aims to test 0.9% NaCl on non specific vasodilatation when used as a diluent / vehicle
to prepare acetylcholine and sodium nitroprusside solutions for iontophoresis. Secondly, this study aims to determine
the number of current pulses needed for ACh and SNP iontophoresis to get the maximum effect using LDF and low
current density.
METHODS
Subjects
For part 1 of the study, five healthy females with mean age of 23.8 ± 0.58 years and BMI of 20 ± 0.74 kg/m2 were
included. All were non-smokers; none had received any medications or supplements for at least 7 days before the
experiments. They were fasted overnight and refrained from drinking coffee and high salted food for at least 12 hours
before the experiments. All measurements were conducted between the 2nd and 5th days of their menstrual cycle. All
subjects had normal hemoglobin (mean 12.40 ± 0.62 g/l), and hematocrit levels (mean 38.76 ± 1.17 %) and were
normocholesterolemic (mean 5.36 ± 0.19 mmol/l). The protocol of the study was fully explained to the subjects; all
subjects signed an informed consent. The study protocol was approved by the Ethical Committee of Universiti Sains
Malaysia.
Equipment
Dual-channel DRT4 laser Doppler fluximetry (Moor Instruments, Axminster, United Kingdom) was used to measure
skin perfusion during iontophoresis and a battery-powered iontophoresis controller (Moor Instruments, Axminster,
United Kingdom) was used to deliver constant direct current pulses to the skin.
Principles and technique of laser Doppler fluximetry
Dual-channel DRT4 laser Doppler fluximetry is a non-invasive device that permits real-time continuous measurement
of microvascular perfusion. In the present study, this instrument was used together with DP1T-V2 skin laser probe
(Moor Instrument), which was held stable by using a PH1-V2 probe holder (Moor Instrument). LDF generates a lowintensity beam of infrared monochromatic coherent 780-nm light. This light was delivered to the site of measurement
by a flexible fiber optic probe. The laser light usually penetrates to a depth of 1-2 mm of skin [11], and the measurement
is therefore predominantly a reflection of perfusion in arterioles, capillaries, postcapillary venules and venules of the
superficial dermal plexus [12].
Laser Doppler fluximetry uses laser Doppler shift principles to measure perfusion of blood cells, mainly
erythrocytes, in the skin. Photons of laser light scattered in moving blood cells produce a Doppler shift on the reflected
light. This reflected light is detected by a photo-detector, and the signal is processed to determine the amount of
the frequency shift. Theoretically, the blood perfusion measured by Laser Doppler fluximetry is determined by the
product of blood flow velocity and the number of moving red cell corpuscles within the surface micro-vessels of skin.
The blood perfusion recorded is generally termed as “flux” and is expressed in perfusion using arbitrary units (AU);
the DP1T-V2 probe used also monitors the skin temperature at measurement sites.
Iontophoresis operation principles
A battery-powered iontophoresis controller (Moor Instruments, Axminster, United Kingdom) was used to deliver
constant direct current pulses to the skin. The technique of iontophresis is based on the principle that an electric
potential difference will cause ions in solution to migrate according to their electrical charges. To transfer a drug into
the skin the polarity of the active electrode has to have the same charge as the active ions of the drug, for example; if
ACh is to be investigated, anodal currents are used to transfer the cation (ACh+) during iontophoresis. The quantity
of a drug delivered is directly proportional to the total charge that migrates through the skin. The charge measure in
millicoulombs (mC) unit is equal to the current measured in milliamps (mA) multiplied by the duration of current
flow in seconds.
Method Optimization on the Process of Iontophoresis with Laser Doppler Fluximetry
37
Drugs
Acetylcholine chloride (ACh) powder (Fluka Chemie Gmbh, Japan) and sodium nitroprusside dehydrate (SNP)
powder (Riedel-de Haen, C.O.O. Switzerland) were used to assess endothelial dependent and endothelial independent
vasodilatation. Sodium chloride (NaCl) 0.9% at a physiological strength of 0.154M (Excel Pharmaceutical, Selangor,
Malaysia) was used to prepare 1% ACh and 1% SNP (Droog, 2004). It was also used alone for iontophoresis to test
the effect of pure vehicle on non-specific vasodilatation. Drug solutions were freshly prepared daily before each
experiment.
Iontophoresis protocols
The experiments were conducted in a temperature – controlled room (22-23ºC). All measurements were performed
in the morning. During a 10-minutes acclimatization period, the participants lie supine comfortably with the right
forearm uncovered and supported by a hand supporter to reduce involuntary movement during measurements. The
flexor surface of the right forearm was gently cleaned with alcohol to remove dead keratinocytes. Two iontophoresis
chambers with 9.5 mm inner diameter for ACh and SNP were used simultaneously. The ACh chamber was attached
to the anodal lead while the SNP chamber was attached to the cathodal lead. The two chambers were attached to the
skin by special double adhesive discs. Skin sites with superficial veins, hair follicles and broken skin were avoided.
The SNP chamber was applied 5 cm from the wrist creases while the ACh chamber was applied 5 cm proximal to the
SNP chambers. The laser probes were fixed into the chambers. Each chamber was filled with 0.4ml of drug solution.
Iontophoresis of sodium chloride was performed on day 1 while ACh and SNP iontophoresis was performed on day 2.
The chambers were carefully washed in running water after each use.
Two minutes of baseline perfusion were recorded before each series of current pulses. Each series of current pulse
consists of 7 pulses of 2 minutes each separated by 1 minute interval of current free interval. Current strengths of 0.007
mA (current density of 0.01 mA/cm2 with chamber surface of 0.7 cm2) and charge density [current density (mA/ cm2) x
duration of current (sec)] of 8.4 mC/ cm2 were used. Current density is a measure of electric current per cross sectional
area. The skin perfusion responses to iontophoresis of ACh and SNP at anode and SNP and sodium chloride at cathode
were recorded after each current pulse (AU).
Statistical analyses were performed using Statistical Package for Social Science (SPSS) Software version 12.0 (SPSS,
Chicago, IL, USA). Data were presented as mean ± SEM. Statistical significance was sited at P<0.05. Repeated measures
ANOVA was used for analysis of perfusion response and paired t test was used to determine the maximum effect of ACh
and SNP. Multiple paired t tests with Bonferroni correction were performed to test for any elevation from baseline.
RESULTS
Anodal iontophoresis
Figure 1 showed microvascular perfusion with iontophoresis of 1% ACh (upper line) and NaCl (lower line) at the
anode. There was a strong and significant increase in mean perfusion compared to baseline from the first pulse with
iontophoresis of 1% ACh (p = 0.003). The plateau was reached from the third pulse onwards; no significant difference
in perfusion was observed between the third pulse and subsequent pulses (P = 0.267).
Figure 1.
Microvascular perfusion with iontophoresis of 1%
acetylcholine solution (ACh) and 0.9% sodium chloride
solution (NaCl) at anode (n=5)
38
For iontophoresis with sodium chloride solution only, no significant increase in perfusion over baseline was
observed (p = 0.396).
Cathodal iontophoresis
Figure 2 showed microvascular perfusion with iontophoresis of 1% SNP (upper line) and NaCl (lower line) at the
cathode. There was a gradual and significant increase in mean perfusion compared to baseline from the first pulse
with iontophoresis of 1% SNP (p = 0.029). The plateau was reached from the fourth pulse onwards; no significant
difference in perfusion was observed between the fourth and subsequent pulses (P = 0.377).
For iontophoresis with sodium chloride 0.9% solution, although there appears to be a small increase in perfusion
compared to NcCl iontophoresis at anode, the increase was not significant compared to baseline (p = 0.08).
Figure 2.
Microvascular skin perfusion with iontophoresis of 1%
sodium nitroprusside (SNP) and 0.9% sodium chloride
solution (NaCl) at cathode (n=5)
DISCUSSION
Our study used low current strength and density as the study by Droog et al. (2004) [10], however we used the laser
Doppler fluximetry as we do not have the laser Doppler imager. LDI has the advantage over LDF as it is able to
measure perfusion over a larger area compared to LDF. LDF, on the other hand gives a constant measure of perfusion,
whereas LDI gives only a snapshot of the perfusion. Our results showed that with the current strength of 0.007 mA
and current density of 0.01 mA/cm2, the maximum response of 1% ACh diluted in 0.9% sodium chloride at the anode
can be reached from a charge density of 3.6 mC/cm2 without showing non-specific vasodilatation. At the cathode, the
maximum response to 1% SNP diluted in 0.9% sodium chloride can be reached from a charge density of 4.8 mC/cm2
without significant increase in perfusion due to iontophoresis of pure vehicle. Iontophoresis of SNP measures the
maximum vasodilatation of the microvasculature, independent of endothelial function.
Non-specific vasodilatation during iontophoresis is considered a major disadvantage to the process of iontophoresis
and different approaches have been used to suppress it. One approach was to subtract the response of NaCl from the
response of the drug [6, 13]. However, this method could introduce erroneous results due to variability in perfusion
response between different sites and difficulty in assessing the two responses independently. The other approach is to
apply local anaesthesia to inhibit the stimulation of local sensory nerves [14, 15, 16]. Although this method successfully
suppress the nonspecific response, local anaesthetic agents has vasoactive properties in itself [17]. Another approach
is to use NaCl instead of water to minimize the non-specific vasodilatation as demonstrated by previous studies [8, 9,
10, 18]
that conceded with our result as iontophoresis of NaCl showed no significant increase in perfusion compared to
baseline. But this finding is in contrast to a study by Noon et al. (1998) which reported that saline (0.9%) and tap water
delivered by iontophoresis alone produced vasodilator response [19]. This can be explained by the current strength that
was used in that study which ranged between 0.1 to 0.2 mA and reached a higher charge density of 16 mC/cm2.
Our findings suggest that the important factor inducing non-specific vasodilatation was not the vehicle in itself
but the current threshold reached through current strength, density and charge density. Thus, an effective approach
is to limit the current density and total charge during iontophoresis. This was applied successfully by several studies
[4, 9, 20]
. However, applying this method may lead to incomplete response as maximum drug response may not be
reached. A study by Droog et al. (2004) had limited the current density and total charge while reaching the maximum
response using the laser Doppler imager [10]. In our study also, the maximum change in perfusion response reached
were approximately eight to nine fold increase over baseline perfusion for both ACh and SNP; this is consistent
with previous studies (Kubli et al., 2000). While ACh response in Figure 1 showed a lower value as it represented
Method Optimization on the Process of Iontophoresis with Laser Doppler Fluximetry
39
the mean skin perfusion at current free period which was affected by the maximum and minimum value at that
period. The response to ACh was not stable throughout the current free period and rapidly decline due to the effect of
acetylcholine-cholinesterase; in contrast, SNP is more stable [21].
Larger chamber size is another suggested approach by Ferrell et al (2002) to reduce non-specific vasodilatation
as it results in lower current density. However, in our study the current strength was calculated according to the inner
diameter of our chambers and this limits the effect of chamber size to non-specific vasodilatation.
As the microvascular responses depend on the current strength and duration of current applied, constant current
approach has been chosen by our study rather than a gradual increase in current over time approach. This is because
the aim of this study is to obtain maximum microvascular responses at lower charge density to avoid non-specific
vasodilatation.
In conclusion, our study showed that iontophoresis protocol using five current pulses with current strengths of 0.007
mA and current density of 0.01 mA/cm2 was sufficient to get maximum effects for both ACh and SNP iontophoresis.
0.9% sodium chloride can be used as a vehicle for iontophoresis of both ACh and SNP, as iontophoresis of NaCl alone
did not produce significant non specific vasodilatation at both anode and cathode.
ACKNOWLEDGMENTS
We would like to thank Universiti Sains Malaysia (USM) for providing a grant to support this study (304/PPSK/6131612)
and awarding USM fellowship to Dr. Belqes Al-Tahami.
REFERENCES
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Ross R. Atherosclerosis: an inflammatory disease. N. Engl. J. Med. 1999, 340: 115-126
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T Sok Teng & MS Zalilah*
Department of Nutrition and Dietetics,
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
ABSTRACT
The Rohingya is a group of refugees from Myanmar who have been residing in Malaysia since the
1980s. At present, there is no published information on health and nutritional status of refugee children
in Malaysia. This study was conducted to assess nutritional status of the Rohingya children aged
6 months to 12 years old (N=87) and to determine the associations between nutritional status with
socio-demographic, dietary diversity and health (birth weight, immunization and childhood illness)
variables. Children were measured for weight and height while their guardians were interviewed for
socio-demographic, dietary diversity and health information. About 27.5% of the Rohingya children
were underweight, 11.5% stunted, 16.1% thin and 12.6% at risk of overweight and overweight. The
percentage of children with low birth weight (< 2.5 kg) and no immunization was 17.8% and 11.5%,
respectively. Fever (67.8%) and flu (62.1%) were the most common childhood illnesses reported in
previous month with 44-75% of the children with these illnesses did not receive any medical treatment.
The mean dietary diversity score was 8.9+3.2 out of a possible 14, with a higher score indicating a
more diverse diet. There were significant correlations between frequency of immunization received
by the children with weight-for-age-z score (rs=0.27, p<0.05), height-for-age-z score (rs=0.25, p<0.05)
and BMI-for-age-Z score (rs=0.24, p<0.05). Height-for-age-z score was also positively correlated with
childhood illness score (rp=0.24, p<0.05) and dietary diversity score (rp=0.23, p<0.05) in that children
with less common childhood illnesses and variety of foods in the diets had better linear growth. As
refugees have limited access to health care services, they are at greater risk of health and nutritional
problems.
Keywords:
Nutritional status, refugee, Rohingya, immunization, dietary diversity
INTRODUCTION
A refugee is defined as “a person who owing to a well-founded fear of being persecuted for reasons of race, religion,
nationality, membership of a particular social group or political opinion, is outside the country of his nationality and
is unable or, owing to such fear, is unwilling to avail himself of the protection of that country; or who, not having a
nationality and being outside the country of his former habitual residence as a result of such events, is unable or, owing
to such fear, is unwilling to return to it” [1, 2]. Globally, the total population of refugees is about 9.9 million [3].
In Malaysia, there were 41,400 refugees and asylum seekers registered with United Nations High Commissioner
for Refugees in 2008 [4]. The majority of these refugees came from Indonesia and Myanmar with the largest ethnic
groups being Acehnese (Indonesia), Chins (Myanmar) and Rohingyas (Myanmar). Since Malaysia has not ratified
the 1951 United Nations Convention Relating to the Status of Refugees [5], the Federal Government does not have
the obligation to protect or grant any legal status to the refugees. However, the government permits the operation of
UNHCR in Malaysia and it is the responsibility of UNHCR to grant the status of refugees in Malaysia as well as to
provide protection and financial support to the refugee population.
Compared to the Rohingyas, the Acehnese and Chins have higher chances to return home or be resettled in
other countries [6]. The Rohingya is a Muslim minority ethnic group from the Rakhine state of Myanmar. In 1978,
the Rohingyas started to flee Myanmar to escape ethnic persecution by the Myanmar government. Since then, the
Rohingyas have fled to its neighboring countries, including Bangladesh, Thailand and Malaysia [7]. Subsequently, the
Rohingyas have been residing in Malaysia for more than 20 years and the estimated population in mid-year 2007 was
12708, comprising 31.1% children and 68.9% adults.
As the Rohingyas do not have work permits, many are illegal workers surviving on part time jobs with relatively
low wages [8]. The children do not have access to formal education but they attend religious or informal schools
organized by UNHCR and other non-governmental agencies. Although the identity cards issued by UNHCR allowed
the Rohingyas to have access to the government health care services at a discounted rate [3], financial and social
42
constraints may prevent them from seeking medical care. Lack of education and employment opportunities as well as
access to health care services may place the Rohingyas at risk of poor health and nutritional status.
The general health status of refugees in various countries is reported to be poor with malnutrition being the major
health problem due to lack of access to sufficient food and nutrient intakes [9, 10, 11]. Other health problems among
refugees include mental illnesses, intestinal parasites, hepatitis B, tuberculosis, sexually transmitted diseases, HIV/
AIDS, malaria and anemia [12]. Refugees may have difficulties to access health care services due to reasons such as
unaffordable medical costs, language barriers, difficulty to take work leave, lack of transportation and discrimination
or rejection by health staff due to absence of legal documentation [13]. Consequently, refugees become hesitant to seek
medical care and this may exacerbate their health problems.
At present, there is no published information on health and nutritional status of Rohingya population in Malaysia.
This study was conducted to assess nutritional status of Rohingya children and to determine its association with sociodemographic, dietary diversity and health factors.
METHODS
This study was conducted in three Rohingya concentrated areas in Ampang, Cheras and Setapak as recommended by
UNHCR (United Nations High Commissioner for Refugees) Malaysia. Rohingya informal schools (madrasah) and
community centers in these areas were visited to recruit male and female children in the age group of 6 months – 12
years. A study information sheet and an informed consent form were distributed to all children to be given to their
caregivers. Only children who met the study criteria (age 6 months-12 years, no physical deformity and free from health
problems such as asthma, diabetes mellitus and congenital diseases) and whose caregivers were willing to be interviewed
and allowed their children to be measured were accepted as study subjects. The final sample consisted of 87 children.
The weight and standing height of the children were measured without shoes using TANITA weighing scale (to the
nearest 0.1kg) and SECA body meter (to the nearest 0.1cm), respectively. Each weight and height was measured twice
and the average value was recorded as the final value for analysis. The z-scores for weight-for-age (WAZ) (aged 0 – 9
years), height-for-age (HAZ) (aged 0 – 12 years) and BMI-for-age (BMI Z) (aged 0 – 12 years) were calculated and
compared to WHO growth standard (0-60 months) [14] and WHO growth reference (5-19 years) [15].
Information on household demographic and socio-economic as well as children’s health status and dietary diversity
were obtained through an interviewer-administered questionnaire with the caregivers. Children’s birth weight and
immunization information were obtained from either caregiver’s recall or official documents such as birth certificate
and immunization card. However, as a majority of the caregivers did not have children’s immunization cards or birth
certificates at the time of the interviews, most of the information was based on recalls. Birth weight was classified as
low birth weight (less than 2.5kg) and normal birth weight (equal to or more than 2.5kg) according to WHO definitions
(1990). The caregivers were also asked whether their children had never received immunization, received only once or
received more than once since birth (excluding the immunization received immediately after birth). These categories
were used as it was difficult for the caregivers to recall the types of immunization received as well as the actual number
of times they brought the children to the clinics or hospitals for immunization.
The caregivers were also asked on the frequency of children having 6 common childhood illnesses (fever, cough,
diarrhea, vomiting, runny nose and asthma) in the previous month. A scoring system was constructed in that 1 point
was given to children having the symptoms but were not brought to the doctors, 2 points for children with symptoms
and were brought to the doctors and 3 points for children with no symptoms. The higher score indicates better health
status of the children.
The dietary diversity questions were adapted from individual dietary diversity questionnaire [16]. The instrument
consisted of 16 food groups – cereals (e.g. rice, glutinous rice, bread), vitamin A rich vegetables and tubers (e.g.
pumpkin, carrots, sweet potato), white tubers and roots (e.g. potato, cassava, yam), dark green leafy vegetables (e.g.
spinach, mustard leaves, swamp cabbage, green shoots), other vegetables (e.g. cucumber, tomato, cabbage, broccoli),
vitamin A rich fruits (e.g. mango, papaya), other fruits (e.g. apple, pineapple, banana, orange), organ meats, flesh
meat (e.g. beef, mutton, chicken), eggs, fish (e.g. fresh fish, dried fish, seafood), legumes/nuts/seeds, milk and milk
products, oils and fats, sweets, coffee and tea. The examples of foods in each food group were modified as to represent
foods commonly consumed by Malaysians. The caregivers were asked on the children’s consumption frequency of
each of the food groups in the past 7 days. One score was given to each food group if it was consumed ≥ 3 times in
the past week and 0 for the food group that was consumed less than 3 times in the past week. Dietary diversity score
(DDS) was calculated as the sum of 14 food groups, excluding sweets, coffee and tea [17].
Ethical approval for this study was obtained from the Medical Research Ethics Committee, Faculty of Medicine
and Health Sciences, Universiti Putra Malaysia. Permission to conduct the study with Rohingya communities was
granted by UNCHR Malaysia. Rohingya community leaders were also consulted for assistance to recruit children and
caregivers for the study. Anthropometric assessments of children and interview of the caregivers were conducted in the
madrasah or community centers. Incentives were given to the children upon completion of all measurements.
43
The Statistical Package for the Social Sciences (SPSS) version 15 was used for data analysis. Data were presented
descriptively and associations between variables were analyzed using Pearson correlation (continuous data) and Point
Bi-serial / Spearman Rank correlation (categorical data) tests. Significance level was set at p<0.05.
RESULTS
Socio - demographic Characteristics
Table 1 shows the socio-demographic characteristics of the study sample. The mean age of the children was 6.15
± 2.86 years ranging from 9 months to 11 years 8 months. There were almost equal numbers of male (50.6%) and
female (49.4%) children in the study. All of the caregivers were women and mothers to the children. The caregivers’
average year of education was 2.54 ± 3.90 years with more than half (63.2%) had no formal schooling. The mean year
of residence in Malaysia was 3.88 ± 1.48, with a range of 1 to 10 years. Sixty five (74.7%) of the caregivers were
unemployed and only 22 (25.3%) were employed. The mean household size and number of children was 6.16 ± 2.46
and 3.62 ± 1.78, respectively. Out of the 87 children, 9 families (10.3%) had no fixed monthly household income while
66.6% had income between RM 401 – RM 800. Families with no fixed household income depended on aids (monetary,
food and non-food items) given by various non-profit organizations. The mean income per capita was RM 113.15 ± 63
with a majority of the families (78.9%) were living below the poverty line income (PLI) of RM 155 per month.
Table 1.
Socio-demographic characteristics of children (N =87)
Variable
n (%)
Children
Sex
Male
Female
Age (years)
6 – 12 months
Male
Female
1 – 5.99
Male
Female
6 – 9.99
Male
Female
10 – 11.99
Male
Female
Caregivers
Age
Years residing in Malaysia
Education (years)
Never attended school
Primary school
Secondary school
Others
Employment status
Employed
Unemployed
Household size
Number of children per household
Monthly household income (RM)
No income
RM 1 – 600
RM 401 – 600
RM 601 – 800
RM 801 – 1400
Income per capita (RM)
< 155a
> 155
a
Mean ± SD
44 (50.6)
43 (49.4)
6.15 ± 2.86
1 (1.1)
0 (0)
19 (21.8)
18 (20.7)
20 (23.0)
21 (24.1)
4 (4.6)
4 (4.6)
32.09 ± 8.38
3.88± 1.48
2.54 ± 3.90
55 (63.2)
14 (16.1)
15 (17.2)
3 (3.4)
22 (25.3)
65 (74.7)
9 (10.3)
6 (6.9)
25 (28.7)
33 (37.9)
14 (16.1)
68 (78.2)
19 (21.8)
6.16 ± 2.46
3.62 ± 1.78
618.85 ± 305.96
113.15 ± 63.63
Poverty line income (9th Malaysian Plan)
44
Health Status
Birth weight information was only available for 45 children based on recall by the caregivers. For the other children,
the information could not be obtained as caregivers could not recall, the information was not available in the birth
certificate or several children (n=16) were born at home in Myanmar. The mean birth weight was 2.97 ± 0.69 kg with
more male (28.6%) than female (8.3%) children had low birth weight (< 2.5 kg) (Table 2). Although the majority of
male (75.0%) and female (76.7%) children were taken more than once to the clinics or hospitals for immunization
after birth, about 24% of the children were not brought or brought only once for immunization. Fever (67.8%), runny
nose or cold (62.1%) and cough (51.7%) were the most common childhood illnesses among the Rohingya children.
The percentages of children with common illnesses and were not brought to the doctors were 44% (fever), 53%
(cough), 65% (diarrhea), 62% (vomiting), runny nose (44%) and 75% (asthma). The mean total score for common
childhood illnesses was 14.4+3.1 (out of possible 18).
Table 2.
Health status of children
Variable
Male n (%)
Female n (%)
Total
Birth weight (Mean ± SD) (n=45)
< 2.5 kg
> 2.5 kg
2.92 ± 0.82
6 (28.6)
15 (71.4)
3.00 ± 0.56
2 (8.3)
22 (91.7)
2.97 ± 0.69
33 (75.0)
4 (9.1)
7 (15.9)
33 (76.7)
7 (16.3)
3 (7.0)
14.68± 3.07
14.05 ±3.05
16 (57.1)
12 (42.9)
17 (54.8)
14 (45.2)
Cold (n=54)
Brought to the doctor
Did not bring to the doctor
15 (60.0)
10 (40.0)
15 (51.7)
14 (48.3)
Cough (n=45)
12 (54.4)
10 (45.6)
9 (39.1)
14 (60.9)
Vomiting (n=26)
6 (46.1)
7 (53.9)
4 (30.8)
9 (69.2)
Diarrhea (n=17)
3 (37.5)
5 (62.5)
3 (33.3)
6 (66.7)
Asthma (n=8)
2 (50.0)
2 (50.0)
0 (0.0)
4 (100.0)
Immunization
> Once
Once
Never
Childhood illnessa (Mean ± SD)
Fever (n=59)
a
14.37 ± 3.06
Only for children with the reported symptoms in the previous month
Dietary diversity score
Table 3 shows the frequency of food groups consumed by the children in the last 7 days. Grain and cereals (94.3%),
dark green leafy vegetables (79.3%), other vegetables (81.4%), other fruits (77.0%), eggs (66.7%), fish (71.3%), milk
and milk products (67.8%), oils and fats (87.4%) and sweets (80.5%) were consumed > 3 times in the last week by
at least two third of the children. Organ meats (92%), legumes/nuts and seeds (60.9%) and coffee/tea (57.5%) were
45
consumed less frequently (< 3 times last week). The average dietary diversity score for all children was 8.90 ± 3.19
(out of possible 14), with similar mean score for male (8.90 ± 3.30) and female children (8.89 ± 3.11).
Table 3.
Dietary diversity of children
Eat < 3 times last week Eat > 3 times last week
n (%)
n (%)
Food Group
Grain and cereal
Vitamin A rich vegetables and tubers
White tubers and roots
Dark green leafy vegetables
Other vegetables
Vitamin A rich fruits
Other fruits
Organ meats
Flesh meats
Eggs
Fish
Legumes, nuts, seeds
Milk and dairy products
Oils and fats
Sweets
Coffee and tea
Dietary Diversity scorea (Mean+SD)
Male
Female
a
5 (5.7)
43 (49.4)
43 (49.4)
18 (20.7)
16 (18.6)
41 (47.1)
20 (23.0)
80 (92.0)
35 (40.2)
29 (33.3)
25 (28.7)
53 (60.9)
28 (32.3)
11 (12.6)
17 (19.5)
50 (57.5)
8.90 ± 3.19
8.90 ± 3.30
8.89 ± 3.11
82 (94.3)
44 (50.6)
44 (50.6)
69 (79.3)
70 (81.4)
46 (52.7)
67 (77.0)
7 (8.0)
52 (59.8)
58 (66.7)
62 (71.3)
34 (39.1)
59 (67.8)
76 (87.4)
70 (80.5)
37 (42.5)
Total possible score =14 (sweets and coffee/tea are not included in the total score)
Nutritional status
About 22.5% of the children were underweight (UW), 11.5% stunted (S) and 16.1% thin (T) with more male (UW=30%;
S=13.6%; T=18.2%) than female children (UW=15%; S=9.3%; T=14.0%) were underweight, stunted and thin (Table
4). The percentages of children who were at risk of overweight and overweight were 5.7% and 6.9%, respectively.
Table 4.
Nutritional status of the children
Indicators
Male n
(%)
Female n
(%)
Weight for age (n=80)
< -2SD (underweight)
-2SD < X < 2SD (normal)
12 (30.0) 6 (15.0)
28 (70.0) 34 (85.0)
Height for age
< -2SD (stunted)
6 (13.6)
4 (9.3)
38 (86.4) 39 (90.7)
BMI for age
< -2SD (thinness)
8 (18.2) 6 (14.0)
31 (70.5) 30 (69.8)
1 SD < X < 2D (at-risk of overweight) 3 (6.8)
2 (4.6)
> 2SD (overweight)
2 (4.5)
5 (11.6)
46
Correlates of nutritional status
There was no significant correlation between growth status with any of the socio-demographic characteristic (Table
5). Table 6 shows that higher frequency of visits for immunization was significantly associated with WAZ (r=0.27,
p<0.05), HAZ (r=0.25, p<0.05) and BMI Z (r=0.24, p<0.05) while common childhood illness score (r=0.24, p<0.05)
and dietary diversity score (r=0.23, p<0.05) were significantly associated with HAZ.
Table 5.
Correlationsa between socio-demographic factors and nutritional status
Variables
Sex of children
Age of children
Age of caregivers
Years of education
Occupation
Household size
Number of children
Monthly household income
Total years residing in Malaysia
a
Height for age
(n=87)
r
BMI for age
(n=87)
r
0.15
-0.07
-0.06
-0.13
-0.03
-0.07
-0.09
0.13
0.06
0.10
-0.17
-0.14
-0.06
-0.09
-0.17
-0.17
0.20
0.04
0.06
-0.19
-0.05
0.03
0.09
0.10
-0.04
0.15
0.17
Pearson correlation
Table 6.
Correlationsa between birth weight, immunization, common childhood
illness, and dietary diversity with nutritional status
Variables
Birth weight
Immunizationb
Common childhood illness
Dietary diversity
a
Weight for age
(n=80)
r
Weight for age
(n=80)
r
Height for age
(n=87)
r
BMI for age
(n=87)
r
0.19
0.27*
0.15
0.16
0.18
0.25*
0.25*
0.23*
0.07
0.24*
0.09
0.18
Pearson correlation; bSpearman correlation; *p < 0.05
DISCUSSION
Prevention of malnutrition among the refugee populations is one of the strategic objectives of UNHCR [18]. Despite the
efforts to address malnutrition, the problem still persists especially among those residing in protracted refugee camps.
Among Myanmar refugee children living in Thailand camps, 33.7% were underweight, 36.4% stunted and 8.7%
wasted [19]. In another study on 957 Myanmar refugee children residing within camps along the Thailand/Myanmar
border, 45.7% were stunted and 64.9% had iron deficiency anemia [10]. Beri-beri, due to thiamine deficiency, was not
only reported to be prevalent among the Karen refugees settled in camps along the western border of Thailand but
also a major cause of infant mortality in this population [9]. In a cross-sectional survey of refugee adolescents in the
North Gaza Strip [11], undernutrition and overnutrition coexisted in that 17.9%, 9.7% and 49.6% of the adolescents
were overweight, stunted and anemic, respectively. Poverty, poor sanitation, availability of high energy-dense
foods, insufficient micronutrient-dense foods, physical inactivity, food beliefs and cultural practices are important
determinants of malnutrition in these refugee populations.
Although the majority of Rohingya children in this study were living in poverty, their living conditions (rented
low cost houses, flats and shop houses) were much better than that in the protracted refugee camps. However, due to
poverty, the Rohingyas may be at greater risk of household food insecurity as well as living environment associated
47
with poor sanitation which could adversely affect the health and nutritional status of the children.
In general, the Rohingya children have relatively poor growth status compared to urban Malay primary school
children [20] and preschool children from low income households in Kuala Lumpur [21]. The percentages of underweight,
stunting and wasting among 6-9 year old Malay children [20] were 14.5 %, 16.7% and 9.2%, respectively. In this present
study, 21.9% of Rohingya children aged 6-10 years were underweight, 12.2% stunted and 14.6% thin. Zalilah and Ang
[21]
reported that among preschoolers enrolled in Taman Sang Kancil preschools of City Hall Kuala Lumpur, 14.6%
were underweight, 5.8% stunted and 4.6% wasted. The percentages of underweight, stunting and thinness in Rohingya
children below 6 years of age were 17.9%, 7.6% and 12.8%, respectively. We also reported that 12.6% of the Rohingya
children were at risk of overweight and overweight. Changes in eating habits and lifestyles associated with urban living
could contribute to overweight and obesity in refugee population, not only in children but also in adults. Although the
differences in growth attainment of Rohingya and Malay children could be due to different standards and indicators
used for growth categorization, the differences could also reflect the social and economic constraints experienced by
the Rohingya communities. Rohingya families may hesitate to seek health care services due to reasons such as fear of
being detained, lack of access to health care services and high medical costs [8]. As many of the Rohingya adults have
low education level or never attended school, they may have difficulty to understand the health information conveyed
by health professionals. In addition, there may also be a language barrier that could prevent them from communicating
with the health professionals.
Poor growth status of children has been associated with being male child [22, 23], insufficient household income
[24, 25]
, low education level of caregivers [26, 27], large household size and high number of children [28]. In the present
study, growth status of the Rohingya children was not significantly associated with any of the socio-demographic
factors. Small sample size as well as homogeneity of sample socio-demographic characteristics could contribute to
these non-significant findings.
We showed that Rohingya children with higher immunization score had better growth status. Complete immunization
during childhood will reduce children’s risk of getting common childhood infections. Sickness in children is always
associated with loss of appetite and reduced food intakes which could lead to significant weight loss. Studies showed
that children who had recent fever or diarrhea were more likely to be underweight and that children with complete
immunization before age 12 months were less likely to be underweight [29, 30]. In addition, frequent and repeated
infections in children which could be prevented by childhood immunization could adversely impact long term growth
i.e stunting [24, 30].
Positive relationship between dietary diversity and child nutritional status has been consistently shown in many
studies. In contemporary African communities, dietary diversity score was consistently and positively associated with
various nutritional indicators (height-for- age, weight-for-age, weight-for-height, mid-upper arm circumference and
triceps skinfold) of children aged 12 – 36 months [31]. Arimond and Ruel [32] reported that among children aged 6
- 23 months, dietary diversity was significantly correlated with children’s height-for-age z scores, independent of
socioeconomic status. In older children, several studies have also documented that diversity in children’s diets reduced
their risks of underweight and stunting [33, 34]. In a recent study among Orang Asli communities in Selangor [35], children
with varied diets were more likely to have higher energy intake and less likely to be underweight.
This study is not without its limitations. As the categorization of immunization status of children and the scoring
of common childhood illnesses were not validated prior to the study, these measurement approaches might not be
accurate to reflect the actual health conditions of the children. Nevertheless, the significant correlations between
nutritional status with immunization status and childhood illnesses observed in this study provided some support to
the validity of these measurement approaches. The small sample size and the use of purposive sampling in this study
could limit the generalization of the study findings to the Rohingya population in this country. Finally, there might be
errors or biases related to recall information. Despite these limitations, this study is the first to report on health and
nutritional status of the Rohingya children in Malaysia.
CONCLUSION
Our study showed that the nutritional status of Rohingya children was associated with immunization status, dietary
diversity and childhood illnesses. Children with better immunization record, had variety of foods in the diets and were
less frequently sick, were more likely to have better nutritional status. Refugee population in Malaysia may hesitate to
seek health care services due to fear of being detained, unaffordable health care costs, language and cultural barriers,
lack of transportation as well as discrimination by health personnel. In addition, having no permanent jobs and low
or no education may further constraint the refugees in their health seeking behaviors and understanding of health and
nutrition information. These barriers could put the refugees, especially women and children at greater risks of health
and nutritional problems. To improve health and nutrition of refugee population in Malaysia, there should be concerted
efforts by various parties to ensure that the refugees have access to free education, affordable health care services as
well as employment opportunities.
48
[1]
UNHCR. Convention Relating to the Status of Refugees. United Nations High Commissioner for Refugees
(UNHCR), 1951.
[2]
UNHCR. Protocol Relating to the Status of Refugees. United Nations High Commissioner for Refugees
(UNHCR), 1967.
[3]
UNHCR. Statistical year book 2005 – trends in displacement, protection and solutions. United Nations High
Commissioner for Refugees (UNHCR), 2007.
[4]
UNHCR. Statistic: Malaysia. 2008. http://www.unhcr.org.my/cms/basic-facts/statistics. Accessed 2 Sept 2008.
[5]
UNHCR. States Parties to the 1951 Convention relating to the Status of Refugees and the 1967 Protocol. United
Nations High Commissioner for Refugees (UNHCR), 2007.
[6]
UNHCR. Protecting refugees – questions and answers. United Nations High Commissioner for Refugees
(UNHCR), 2007.
[7]
Amnesty International. Malaysia – Refugees and immigrants. 2003. http://www.aimalaysia.org/index.php?optio
n=com&content&task=view&id=9. Accessed 2 Aug 2007.
[8]
Human Rights Watch Malaysia. Living in limbo: Burmese Rohingyas in Malaysia. 2000. http://www.hrw.org/
reports/2000/malaysia/maybr00804.htm#P929_230961. Accessed 31 July 2007.
[9]
Luxemburger C, White NJ, ter Kuile F, Singh HM, Allier-Frachon I, Ohn M, Chongsuphajaisiddhi T, Nosten F.
Beri-beri: the major cause of infant mortality in Karen refugees. Transactions of the Royal Society of Tropical
Medicine and Hygiene 2003; 97: 251-255.
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[10] Kemmer TM, Bovill ME, Kongsomnoon W, Hansch SJ, Geisler KL, Cheney C, Shell-Ducan BK, Drewnowski
A. Iron deficiency is unacceptably high in refugee children from Burma. J Nutr 2003; 133; 4143-4149.
[11] Abudayya A, Thoresen M, Abed Y, Holmboe-Ottesen G. Overweight, stundting, and anemia are public health
problems among low socio-economic groups in school adolescents (12-15 years) in the North Gaza Strip. Nutr
Res 2007; 27: 762-771.
[12] Kemp C, Rasbridge LA. Refugee and Immigrant Health: A Handbook for Health Professionals. Cambridge
University Press, 2007.
[13] Feld P, Power B. Immigrants’ access to health care after welfare reform: findings from focus groups in four
cities. The Kaiser Commission on Medicaid and the Uninsured, 2000.
[14] WHO. The WHO child growth standard. 2006. http://www.who.int/childgrowth/ standard/techinical_report/en/
index.html. Accessed 16 Aug 2007.
[15] WHO. WHO Reference 2007: growth reference data for 5 – 19 years. 2007 http://www.who.int/growthref/en/.
Accessed 16 Aug 2007.
[16] FAO/Nutrition and Consumer Protection Division. Individual dietary diversity questionnaire. Food and
Agricultural Organization, 2007.
[17] FAO Nutrition and Consumer Protection Division. Guidelines for measuring household and individual dietary
diversity. Rome, Italy: Food and Agricultural Organization, 2007.
[18] UNHCR/WFP. Acute malnutrition in protracted refugee situations: A global strategy. United Nations High
Commissioner for Refugees (UNHCR) and World Food Programme (WFP), 2006.
[19] Banjong O, Menefee A, Sranacharoenpong K, Chitchang U, Eg-kantrong P, Boonpraderm A, Tamachotipong S.
49
Dietary assessment of refugees living in camps: acase study of Msae La Camp, Thailand. Food Nutr Bull 2003;
24(4): 360-367.
[20] Zalilah MS, Bond JT, Johson NE. Nutritional status of primary school children from low income households in
Kuala Lumpur. Mal J Nutr 2000; 6: 17-32.
[21] Zalilah MS, Ang, M. Assessment of food insecurity among low income households in Kuala Lumpur using
Radimer/Cornell Food Insecurity Instrument – a validation study. Mal J Nutr 2001; 7(1&2): 15-32.
[22] Thang NM, Popkin B. Child malnutrition in Vietnam and its transition in an era of economic growth. J Hum Nutr
Dietet 2003; 16: 233-244.
[23] Phengxay M, Ali M, Yagyu F, Soulivanh P, Kuroiwa C, Ushijima H. Risk factors for protein-energy malnutrition
in children under 5 years: study from Luangprabang province, Laos. Pediatr Int 2007; 49: 260-265.
[24] Sakisaka K, Wakai S, Kuroiwa C, Cuadra Flores L, Kai I, Mercedes Aragon M, Hanada K. Nutritional status
and associated factors in children aged 0-23 months in Granada, Nicaragua. J Royal Ins Pub Health 2006; 120:
400-411.
[25] Oldewage-Theron W, Dicks EG, Napier CE. Poverty, household food insecurity and nutrition: Coping strategies
in an informal settlement in the Vaal Triangle, South Africa. J Royal Ins Public Health 2006; 120: 795-804.
[26] Shah SM, Selwyn BJ, Lubby S, Merchant A, Bano R. Prevalence and correlates of stunting among children in
rural Pakistan. Pediatr Int 2003; 45: 49-53.
[27] Sereebutra P, Solomons N, Aliyu MH, Jolly PE. Sociodemographic and environmental predictors of childhood
stunting in rural Guatemala. Nutr Res 2006; 26: 65-70.
[28] Fotso JC, Kuate-Defo B. Socioeconomic inequalities in early childhood malnutrition and morbidity: Modification
of the household-level effects by the community SES. Health & Place 2006; 11: 205-225.
[29] Balk D, Storeygard A, Levy M, Gaskell J, Sharma M, Flor R. Child hunger in the developing world: An analysis
of environmental and social correlates. Food Policy. 2005; 30: 584-611.
[30] Casapía M, Joseph SA, Núñez C, Rahme E, Gyorkos TW. Parasite risk factors for stunting in grade 5 students in
a community of extreme poverty in Peru. Int J Parasitol 2006; 36: 741-747.
[31] Onyango AW. Dietary diversity, child nutrition and health in contemporary African communities. Comparative
Biochem Physiol 2003; 136: 61-69.
[32] Arimond M, Ruel MT. Progress in developing an infant and child feeding index: An example using the Ethiopia
demographic and health survey 2000. U.S.A: International Food Policy Research Institute, 2002.
[33] Hatloy A, Hallund J, Diarra MM, Oshaug A. Food variety scores, socio-economic status and nutritional statusin
urban and rural areas in Koutiala (Mali). Public Health Nutr 2000; 3: 57-65.
[34] Steyn NP, Nel JH, Nantel G, kennedy G, Labadarios D. Food variety and dietary dieversity scores in children:
are they good indicators of dietary adequacy? Public Health Nutr 2006; 9: 644-50.
[35] Nurfaizah S, Zalilah MS, Khor GL, Mirnalini K, Nawalyah AG, Hejar AR. Food variety score is associated with
dual burden of malnutrition in Orang Asli (Malaysian indigenous peoples) household: implications for health
promotion, Asia Pac J Clin Nutr 2009; 18(3): 412-422.
Monoclonal Gammopathy with Systemic Amyloidosis: An Evaluation of
Diagnostic Elements
1
C. T Subashini*, 1E. George & 2U Nor Aini
Department of Pathology, Faculty of Medicine and Health Sciences,
Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
2
Department of Pathology, Faculty of Medicine,
Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak,
56000 Cheras, Kuala Lumpur, Malaysia
1
ABSTRACT
Monoclonal gammopathies result from an overproduction of a single abnormal clone of plasma cell
or B lymphocyte that produce an immunologically homogenous immunoglobulin (Ig) commonly
referred to as paraprotein or monoclonal (M) protein. The circulating M-protein may consist of an
intact immunoglobulin, the light chain only, or (rarely) the heavy chain only. The heavy chain is from
one of the five immunoglobulin classes G, A, M, D or E, while the light chain is either kappa (κ) or
lambda (λ) in type. Accurate detection and quantitation of monoclonal immunoglobulins is important
for the diagnosis and management of monoclonal gammopathies. We report a case of a 71 year old lady
with a history of chronic gastritis and recurrent lower respiratory tract infection whereby no specific
diagnosis was made until a computed tomography (CT) guided lung biopsy and orogastroduodenoscopy
(OGDS) 5 years later from the onset of initial symptoms revealed pulmonary and gastric amyloidosis,
respectively.
Keywords:
Monoclonal gammopathies, paraprotein, amyloidosis, light chain immunoglobulin
(Ig), heavy chain Ig
INTRODUCTION
The monoclonal gammopathies encompass a number of diseases such as monoclonal gammopathy of undetermined
significance (MGUS), smouldering multiple myeloma (SMM), multiple myeloma (MM), Waldenstrom’s
macroglobulinaemia (WM), solitary plasmacytoma, systemic amyloid light chain type (AL type) and POEMS
(Polyneuropathy, Organomegaly, Endocrinopathy,
E
Monoclonal gammopathy, and SSkin changes) syndrome.
M
Amyloidosis is a rare systemic disorder of protein metabolism with progressive extracellular deposition of insoluble
fibrillary protein, disorganisation of tissue architecture, and subsequently organ dysfunction.[1] This case highlights
the importance of interpreting and correlating consecutive laboratory, radiological and invasive investigations in the
diagnosis of monoclonal gammopathy whereby the clinical manifestations were not stereotype of the disease.
THE CASE
A 71 year old lady initially presented to Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in early April
2001 with a history of shortness of breath, lethargy, headache, palpitations, and was treated as community acquired
pneumonia with oral antibiotics, based on the physical examination and chest X-ray (CXR) findings, which showed
bilateral patchy opacities. Past medical history revealed chronic dyspepsia, relieved by antacids but she had never been
investigated for and she had a history of passive smoking; her husband who had passed away from lung cancer was a
chronic smoker.
Despite treatment, she presented frequently with similar respiratory symptoms. As such, bronchoscopy with
bronchial and trans-bronchial biopsies was done, which ruled out lung malignancy. Culture of bronchial-alveolar
lavage for acid-fast bacilli and fungus were negative. All blood investigations were unremarkable except for a raised
erythrocyte sedimentation rate (ESR) at levels 71mm/hour and low serum creatinine between the ranges of 5762µmol/L. She was started on empirical pulmonary tuberculosis treatment even though sputum for acid-fast bacilli
and Mantoux test were negative and she had no history of contact with pulmonary tuberculosis.
Three months later, patient had clinically improved but there was still no change in CXR findings. Lung function
tests showed a restrictive pattern and high resolution CT thorax showed consolidation of right lower zone and left
lingula, suggestive of alveolar lung carcinoma. Fine needle aspiration cytology (FNAC) under CT guidance of both
52
areas of the lungs revealed non-specific chronic inflammatory process with no malignant cells or granuloma seen. The
patient was further planned for open lung biopsy but she refused.
Five years later in January 2006, she was readmitted with fever, productive cough, loss of appetite, loss of weight,
epigastric pain, lethargy, weakness, bilateral leg swelling and decreased urine output. She had been seeking alternative
treatment for the last 5 years and as such defaulted all treatment and follow-ups at UKMMC. On examination, she had
oral candidiasis, bilateral, multiple, palpable submandibular lymph nodes, gross hepatomegaly of 5 finger breadths
(fb) extending to epigastric region, pansystolic murmur, coarse crepitations and dullness of bilateral lungs. CXR
showed bilateral pleural effusion with collapse consolidation. CT guided lung biopsy showed pulmonary amyloidosis,
which was confirmed with congo red staining and apple-green bifrengence under polarised light. Immunochemistry
demonstrated lymphoplasmacytic cells negative for cytokeratin, chromogranin, neuron-specific enolase and positive
for CD20. Few cells were positive for CD3. Kappa (κ) and lambda (λ) staining were equivocal. FNAC of bilateral
submandibular lymph nodes showed scanty smears with no epithelial component and was reported as unsatisfactory
for proper cytological examination. Echocardiogram (ECHO) revealed good left ventricular function with ejection
fraction of 75%, dilated left atrium, global pericardial effusion (0.3cm), thickened mitral valve with trivial mitral
regurgitation.
Laboratory investigations showed normocytic, normochromic anaemia (haemoglobin 9.8g/dL, MCV 77fl), raised
platelet count (553 X 109/L) with normal white cell counts. Full blood picture revealed mild rouleaux formation. No
leukoerythroblastic picture was noted. Clotting times were prolonged; prothrombin time (PT) 16.1secs and activated
partial thromboplastin time (APTT) 49.8secs. Renal profile was unremarkable except for a low serum creatinine
(44µmol/L). Liver function tests revealed low albumin (28g/L) with a normal total protein. The albumin to globulin
ratio was slightly reduced (0.8-1.0). Serum calcium levels were normal. Erythrocyte sedimentation rate (ESR =
119mm/hour), C-reactive protein (CRP = 13.25mg/dL) and lactate dehydrogenase (LDH = 311U/L) were elevated.
Patient was discharged 2 weeks later with further follow up at gastroenterology clinic for chronic dyspepsia, where
she was planned for OGDS and sigmoidoscopy. OGDS showed amyloid deposits with chronic active gastritis and
sigmoidoscopy revealed chronic non-specific colitis. Rectal biopsy was negative for amyloid.
Serum and urine protein electrophoresis were done considering the high ESR, low albumin, anaemia, clinical
features of hepatomegaly, submandibular lymphadenopathy and the diagnosis of pulmonary and gastric amyloidosis.
The electrophoresis results are summarised in Figure 1. A provisional diagnosis of IgM Kappa monoclonal gammopathy
was made with complication of primary (systemic) amyloidosis.
Serum protein electrophoresis of the patient showed presence
of monoclonal band in gamma region (labelled 1S)
Urine protein electrophoresis of the patient showed
generalised proteinuria. No Bence Jones protein seen
(labelled 2U).
Immunofixation of serum showed presence of IgM Kappa
chain with paraprotein quantitation of 8.9g/L.
Immunofixation of urine showed presence of free Kappa
light chains. Paraprotein quantitation was not done.
Figure 1.
Electrophoresis gel findings
53
She was also scheduled for an excision biopsy of bilateral submandibular lymph nodes and a bone marrow study to
rule out haematological malignancy. Unfortunately, the hospital was informed by the patient’s next of kin that she had
passed away at home one week before the given date for the excision biopsy of the submandibular lymph nodes. The
exact cause of death was not ascertained, as clinical autopsy was not done. However, according to the patient’s next
of kin, she was having fever with severe respiratory symptoms such as productive cough, wheezing, and shortness of
breath over the last two days prior to her death but refused admission to hospital. Thus, the presumptive cause of death
was an acute pulmonary complication of amyloidosis with IgM Kappa monoclonal gammopathy.
DISCUSSION
This is a case of systemic amyloidosis (AL type) that developed in a patient with IgM monoclonal gammopathy. A
specific diagnosis of which type of IgM monoclonal gammopathy could not be made in this patient, as she did not
undergo bone marrow examination.
In the Second International Workshop on Waldenstrom’s macroglobulinaemia (WM) held in Athens, Greece, in
September 2002, a consensus panel of experts tried to define clear and reproducible criteria for the diagnosis of the
clinicopathologic entities recognisable within the spectrum of IgM gammopathies. It was stated WM is characterised
by “unequivocal evidence of bone marrow infiltration by lymphoplasmacytic lymphoma, irrespective of the serum
IgM concentration. Moreover, WM should be considered symptomatic (S-WM) or asymptomatic (A-WM) according
to the presence or absence of features attributable to tumour infiltration; constitutional symptoms, cytopaenia(s),
organomegaly, and/or symptoms attributable to the monoclonal protein (hyperviscosity syndrome, cryoglobulinaemia,
amyloidosis, or autoimmune phenomena such as peripheral neuropathy and cold agglutinin disease). The clinical
condition with symptoms attributable to monoclonal protein, but without evidence of lymphoma, was recognised as
a distinct entity for which the term “Ig-M related disorders” was proposed. Finally, patients with IgM monoclonal
protein but no morphologic evidence of bone marrow infiltration by lymphoma (or even equivocal marrow infiltrates
without confirmatory phenotypic studies) should be classified as having a monoclonal gammopathy of undetermined
significance (IgM-MGUS).” [2] These criteria are summarised in Table 1:
Table 1.
Criteria for IgM Monoclonal Gammopathies [2]
WM Symptomatic
WM Asymptomatic
IgM Related Disorders
MGUS
IgM
monoclonal
protein
BM
infiltration
Symptoms
attributable to
IgM
Symptoms
attributable
to tumour
infiltration
+
+
+
+
+
+
-
+
+
-
+
-
The panel did not assign a specific level of bone marrow infiltration that would be required to differentiate
IgM MGUS from WM. The diagnostic criteria given in Table 1 have been updated in an evidence-based manner
such that the diagnosis of WM requires 10% or greater lymphoplasmacytic infiltration. Presence of less than 10%
lymphoplasmacytic infiltration in the absence of end-organ damage represents IgM MGUS and not WM; such patients
have a risk of progression to symptomatic disease at a rate of only 1.5% per year.[1]
World Health Organisation (WHO) criteria for the diagnosis of multiple myeloma (MM), is as follows: requires
a minimum of one major and one minor criteria or three minor criteria which must include (1) and (2). These
criteria include the following major criteria: 1) marrow plasmacytosis ≥ 30%, 2) plasmacytoma on tissue biopsy, 3)
monoclonal protein (by densitometric scanning) – IgG > 35g/L, IgA > 20g/L and Bence Jones > 1g/24hour and minor
criteria: 1) marrow plasmacytosis (10-29%), 2) monoclonal protein present but less than in major criteria, 3) lytic
bone lesions, reduced normal Ig (< 50% normal) - IgM < 0.5g/L, IgA < 1g/L, IgG < 6g/L. These criteria must manifest
in a symptomatic patient with progressive disease.[3]
In this patient, however, the following features of IgM multiple myeloma which include presence of myeloma
cells in bone marrow, suppression of normal IgG and IgA levels, presence of osteolytic bone lesions and presence
of 14q32 translocation (IgH switch region rearrangements), were not investigated for to differentiate Waldenstrom’s
macroglobulinaemia from IgM multiple myeloma.[3]
Dimopoulos et al. mention that some individuals have presented with a complication caused by the macroglobulin,
such as peripheral neuropathy, cold agglutinin disease, cryoglobulinaemia, or amyloidosis, but the concentration
54
of monoclonal IgM is low. In these patients, there is no evidence of organomegaly or lymphadenopathy, and a
lymphoplasmacytic infiltration of the bone marrow is absent. Presumably, in such patients, the specific property of
monoclonal IgM caused symptoms several years before overt WM developed.[4]
This seems to have been the case with this patient who had considerably low levels of IgM detected on electrophoresis
(8.9g/L), no signs and symptoms of bone marrow infiltration but presented with symptoms of systemic amyloid
infiltration and immunosuppression such as oral candidiasis and recurrent respiratory infections. However, this patient
had hepatomegaly and lymphadenopathy. Again, WM cannot be totally ruled out in this patient, as bone marrow
examination which, is central to the diagnosis, was not done.
In a recent study at the Mayo clinic, amyloidosis developed in 2% of patients with monoclonal IgM and 76%
showed a λ light chain. Cardiac, renal, hepatic and pulmonary involvements predominated, and were the cause of
death more often than the underlying WM. The incidence of cardiac and pulmonary involvements seemed to be higher
in patients with IgM related amyloidosis than in patients with other cases of primary amyloidosis.[4] Amyloid is best
identified from biopsy of an involved organ. The diagnostic biopsy sites generally are the abdominal subcutaneous
fat-pad, bone marrow, or the rectum.[3]
Rectal biopsy in this patient was negative. However, pulmonary and gastric amyloid involvements were confirmed
by biopsy. She may have also had hepatic and cardiac amyloid infiltration considering she had hepatomegaly and signs
and symptoms of congestive cardiac failure. Nevertheless, the hepatomegaly could have been due to direct tumour
infiltration, which may also be the cause for her submandibular lymphadenopathy.
Anaemia is the most common finding in patients with symptomatic WM and is caused by mild decrease in red
cell survival, impaired erythropoiesis, haemolysis, moderate plasma volume expansion, and blood loss from the gut.
Blood smears are usually normocytic and normochromic, and rouleaux formation is often pronounced. In addition, the
haemoglobin estimate can be inaccurate, ie. falsely high, because of interaction between the monoclonal protein and
the diluent used in some automated analysers. Leukocyte and platelet counts are usually within the reference range at
presentation.[5]
In this case, there was normochromic, normocytic anaemia with mild rouleaux formation and white cell count was
normal as expected. Thrombocytosis, however, was observed and may be a consequence of functional hyposplenism
from possible amyloid replacement of the spleen.[5]
ESR is a non-specific test that measures the speed of sedimentation of red cells in plasma over a period of 1 hour.
The speed is mainly dependent on the plasma concentration of large proteins such as fibrinogen and immunoglobulins.
The normal range in men is 1-5mm/hour and in women 5-15mm/hour but there is progressive increase in old age.
A raised ESR is associated with marked rouleaux formation of red cells in the peripheral blood film. It is almost
constantly observed in WM and may be the first clue to the presence of the macroglobulin.[5] This seemed to have been
the only clue initially in this patient.
The clotting abnormality detected most frequently is prolongation of thrombin time, which was not done in this
patient. The prolongation of the PT and APTT in this case could be due to the macroglobulin interfering with the
coagulation factors.[1, 2]
Central to the diagnosis of WM is the demonstration of bone marrow infiltration by lymphoplasmacytic lymphoma.
This is defined as a tumour of small lymphocytes showing evidence of plasmacytoid / plasma cell differentiation
without any of the clinical, morphological or immunophenotypic features of other lymphoproliferative disorders.[2, 3]
A trephine biopsy is mandatory requirement for the assessment of patients while lymph node biopsies are encouraged
in patients with accessible nodes.[2] Unfortunately, this patient passed away before bone marrow examination and
submandibular lymph node biopsy could be done to confirm if it was WM.
Biochemical investigations done in this patient revealed normal renal profile and serum calcium levels.
Hypercalcaemia and Bence Jones proteinuria more than 1.0g/24hours occur in less than 5% of patients with WM.
The low incidence of these abnormalities explains the rarity of renal tubular cast formation in these patients.[4] Serum
creatinine level was low probably because the patient was cachectic. Liver function tests were unremarkable except
for a low albumin level. In this regard, if the ratio of albumin to globulin is low, further investigation for plasma cell
disorder should follow. It is reported that low albumin may reflect effects on the liver by interleukin (IL)-6 produced
by microenvironment of myeloma cells but it remains to be explored in WM.[4]
C-reactive protein (CRP) is a crude ‘early’ immunoglobulin, which initiates the inflammatory reaction. CRP-antigen
complexes can substitute for antibody fixation of C1q and trigger the complement cascade initiating the inflammatory
response to antigens or tissue damage. After tissue injury, an increase in CRP and other acute phase reactants may be
detected within 6-10 hours. Immunoassays of CRP are now widely used for early detection of acute inflammation or
tissue injury and for monitoring of remission, eg. response of infection to an antibiotic. IL-6 is a major plasma cell growth
factor, and elevated serum levels have been associated with short survival in multiple myeloma. IL-6 also influences
the hepatic synthesis of several acute phase proteins such as CRP. Thus, CRP represents a surrogate marker for IL-6
concentration. There is evidence that the spontaneous differentiation of the malignant B-cells in WM to monoclonal IgM-
55
secreting plasma cells in the absence of cell proliferation is dependent on autologous production of IL-6 by these cells.[1]
In this case CRP was raised but there is no current literature on the prognostic value of CRP in WM.
Lactate Dehydrogenase (LDH) activity is increased in some patients with a very aggressive form of multiple
myeloma despite intensive treatment. Although this increase occurs in only a minority of myeloma patients, it indicates
poor prognosis.1 There is an increase of LDH in this patient but, again, there is no consensus on it being a measure of
tumour burden in WM.
Serum β2microglobulin, which was not done in this patient, is used as a predictor of malignant evolution in
smoldering/asymptomatic WM and as a prognostic marker in systemic amyloidosis. A value of > 3mg/L in a patient
with monoclonal gammopathy with no renal insufficiency strongly suggest malignant disease. Serum β2microglobulin
was found to be > 3mg/L in approximately 60% of WM patients at diagnosis.[1]
Serum troponin T, a sensitive marker for ischemic cardiac injury, and N-terminal-pro brain natriuretic peptide
(NT-proBNP), which has been shown to correlate with left ventricular dilatation, dysfunction, and congestive cardiac
failure in a non-amyloidosis setting, have been shown to be powerful predictors of survival in amyloidosis, and were
feasible even in the setting of end-stage renal disease.[2]
Electrophoretic studies of serum and urine are necessary for the diagnosis, staging and serial follow-up of patients
with plasma cell disorders. A high index of suspicion is often required when symptoms are vague or inconsistent,
overt physical findings are not evident, and standard laboratory data are negative; as in this case whereby there was no
typical features of WM such as lymphocytosis (> 4 x 109/L), symptoms of hyperviscosity syndrome or severe anaemia.
Amyloidosis has often been recognised after many months of unexplained fatigability, weight loss, or peripheral
oedema; also proven to be the case in this patient.[5]
After monoclonal abnormality has been detected on serum electrophoresis, immunofixation is necessary to
confirm heavy-chain and light chain types. Once defined, a repeat immunofixation is not justified unless a new clonal
abnormality is suspected, such as after a stem cell transplant-supported treatment. The quantitation of uninvolved
immunoglobulins by nephelometry provides supplemental information. A high level for one component coupled with
low or normal levels for other components confirms the definition by immunofixation of a specific monoclonal protein
elevation.[5] The light chain is of the monoclonal IgM is κ in 75-80% of patients.[4] However, λ chains occur more
frequently in systemic amyloidosis than κ chains (λ - κ ratio 4:1).[1]
In this case, IgM κ was detected by serum electrophoresis and immunohistochemistry of amyloid deposits
showed CD20+ lymphoplasmacytic cells with equivocal κ and λ staining, consistent with a diagnosis of IgM
monoclonal gammopathy with a complication of systemic amyloidosis. Unfortunately, the patient passed away
before bone marrow examination was done to determine which type of IgM monoclonal gammopathy in order to
commence treatment.
CONCLUSION
In this patient, the clinical manifestations were not stereotype of multiple myeloma or Waldenstrom’s
macroglobulinaemia but the elevated ESR from the initial presentation 5 years ago, low albumin, recurrent infections,
constitutional symptoms such as fever, weight loss, lethargy, fatigue should have raised a suspicion of a plasma cell
disorder. Having said that, if the patient had diligently followed up and not defaulted for 5 years, the diagnosis would
have probably been made much earlier and appropriate treatment could have been commenced.
REFERENCES
[1]
Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal Gammopathy of Undetermined Significance, Waldenstrom’s
Macroglobulinemia, AL Amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clinical
Proceedings 2006; 81(5): 693-703.
[2]
Owen RG, Treon SP, Al-Katib A et al. Clinicopathological definition of Waldenstrom’s Macroglobulinemia.
Consensus panel recommendations from the Second International Workshop on Waldenstrom’s
Macroglobulinaemia. Seminars in Oncology 2003; 30(2): 110-115.
[3]
Jaffe ES, Harris NL, Stein H, Vardiman JW. WHO Classification of tumour: Pathology and genetics of tumours
of haemopoietic and lymphoid tissues. Lyon: IARC Press, 2001.
[4]
Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenstrom’s Macroglobulinemia:
Clinical features, complications, and management. Journal of Clinical Oncology 2000; 18(1): 214-226.
[5]
Gertz MA, Merlini G, Treon SP. Amyloidosis and Waldenstrom’s Macroglobulinaemia. Hematology 2004; 257282.
1
1
MN Sabariah*, 1S Zainina, 1I Faridah & 2CF Leong
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
2
Faculty of Medicine, Hospital Universiti Kebangsaan Malaysia
ABSTRACT
Clonal disorders of LGL may either be CD3+ CD56- or CD3- CD56+ phenotype and these have
been designated as T-cell leukaemia (T-LGL) or natural killer cell (NK)-LGL leukaemia respectively.
Clonality is usually demonstrated by clonal rearrangement of T-cell receptor gene rearrangement or
identified by flowcytometry analysis. Most patients with T-LGL will have an indolent course. In this
report we described an aggressiveness of disease in a patient with clonal CD3+ LGL leukaemia whose
cells also co-expressed CD56 diagnosed by flowcytometry. The patient responded well to interrupt ALL
standard risk protocol however succumbed to her disease while waiting for upfront stem cell transplant.
This case highlights on both the classical laboratory findings of rare entity of disease as well as a review
of the literature pertaining particularly on its management.
Keywords:
T-LGL, NK leukaemia, treatment of aggressive variant leukaemia
INTRODUCTION
Large granular lymphocytes (LGL) comprise 10% to 15% of normal peripheral blood mononuclear cells which
morphologically are identifiable subset of peripheral blood lymphocytes. They included natural killer (NK) cells and
cytotoxic T-cells. These cells represent in vivo antigens activated T-cells, as a response to viral or other infections.
Clonal disorder CD3+ T-LGL represents 2-3% cases of mature lymphocytic leukaemia.[1] Typically, it is a
heterogenous indolent disorder characterized by persistent (> 6 months) increase in the number of peripheral blood
(PB) large granular lymphocytes usually between 2-20 x 209/L.[1, 2] In contrast, CD3- NK-cell leukaemia is an
aggressive subtype which affect a younger group of patients. LGL NK-like leukaemia a rare described as an aggressive
CD3+, CD56+ variant of T-LGL leukaemia is illustrated here. The literature on the clinic-pathological features and
management approaches for this rare, aggressive entity are reviewed.
CASE REPORT
A 19-year-old Chinese, girl was referred for further investigation and management of pancytopaenia. She presented
with history of fever, generalized malaise, loss of appetite and significant loss of weight within few months. Her
physical examination revealed enlarged liver and massive splenomegaly with generalized lymphadenopathy.
Her complete blood profile revealed a WBC of 1.1 x 109/L (4.0-10.0 x 109/L), haemoglobin of 6 g/dl (12.0-16.0
g/dl) and platelet count of 40 x 109/L (150-400 x 109/L). Pertinent chemistries revealed: normal liver function test,
LDH of 785 U/L (211-423) U/L and total bilirubin of 32 µmo/L. Her blood culture was negative. Serology studies
showed her blood was positive for EBV IgG but negative for EBV IgM, Hepatitis C, HIV-1 and 2 and CMV IgM. Both
rheumatoid factor (RF) and antinuclear antibody (ANA) were negative. Quantitative immunoglobulins were within
normal limits.
Blood film examination showed predominantly abnormal looking, large mononuclear/ lymphoid cells that constitutes
55% of the white blood cells population. These cells were of varying sizes with abundant irregular cytoplasm, and
some having cytoplasmic granules. Subsequent bone marrow aspirate evaluation showed hypercellular marrow with
predominantly similar type of mononuclear/lymphoid cells (figure 1). Multiple aggregates of these mononuclear cells,
positive for CD3 (figure 2) were seen in her trephine biopsy. Immunophenotyping studies showed the gated cells
expressed CD3, CD7, CD8, CD16 and CD56 compatible with aggressive CD3+, CD56+ variant of LGL leukaemia or
also known as LGL NK-like leukaemia. Cytogenetic analysis showed normal cells karyotype. Unfortunately specimen
sent for TCR gene rearrangement study was unsatisfactory.
She was treated with interrupted ALL–standard risk protocol. Her disease was temporarily controlled. She had
achieved partial clinical and haematological remission after induction. Her spleen had reduced in size and repeat bone
marrow assessment showed presence of less than 10% of mononuclear/lymphoid cells. Subsequently, she was treated
with another 2 courses of combination cytarabine and mitoxantrone to further control her disease.
58
Workout for autologous peripheral blood stem cell transplant was planned. However, during an evaluation for
allogenic haemopoietic stem cell transplantation, the patient was noted to have pancytopaenia. Subsequent BMA and
flowcytometry studies showed she had relapsed with presence of similar types of cells. She succumbed to her illness
fourteen months after her initial presentation.
Figure 1.
BMA MGG X 400 . Circulating large mononuclear/
lymphoid cells, some with irregular folding nuclei,
open chromatin and distinct nucleoli. The cytoplasm is
abundant and some showed azurophilic granules (arrow)
Figure 2.
Trephine biopsy x 400: multiple aggregates of abnormal
lymphoid cells admixed with other haematopoietic
elements. These cells have vesicular nuclei with open
chromatin pattern and were positive for leukocytes
common antigen (LCA) and CD3
DISCUSSION
Recently, CD56+ entity of haematologic malignancies has attracted attention. The WHO classification of lymphoid
malignancies does not recognize an aggressive CD3+ CD56+ T-cell LGL as a subtype of LGL disorders [2]. However,
several cases with similar clinicopathological and disease progression as this case have being reported worldwide. [3,
4, 5]
We describe a rare, CD3+, CD56+ LGL leukaemia, which is a variant form of indolent T-LGL leukaemia. It is
also described as LGL NK-like leukaemia.[4] Typically, most T-LGL leukaemia have an indolent clinical course. An
59
absolute lymphocytosis of 2-20 x109/L accompanied by neutropaenia with or without anaemia and thrombocytopaenia
are frequent findings.[1] Clonality of LGL also has being reported in patients where the absolute lymphocytes count
of less than 2 x 109/L.[2] Splenomegaly was the main physical finding.[3, 4] In comparison, patients with NK-cell
leukaemia usually present with constitutional symptoms, organomegaly and leukaemic infiltration in the blood and
bone marrow.[1] As illustrated in our case, the clinical presentation of CD3+, CD56+ aggressive variant LGL leukaemia
was unlike the usual clinical course of T-LGL leukaemia, but remarkably similar to features of NK-cell leukaemia.
Macon et al., documented all patients presented with advanced stage of disease, with B symptoms.[4] An absolute
lymphocytosis (median of 4.2 x 109/L) was present in all patients at presentation which is relatively higher than values
seen in patients with typical, indolent T-LGL leukaemia.[2, 3] The marrow, spleen, liver and extranodal involvement was
seen in majority of cases.[3, 4, 5] Majority of patients (63%) were in a leukaemic phase at their presentation.[4]
The LGL cells are identified by their morphology and cell phenotype. Circulating leukaemic cells in aggressive
NK-cell leukaemia sometime are indistinguishable from the normal large granular lymphocytes. As seen in this case,
the leukaemic cells of NK-like leukaemia often exhibit marked nuclear polymorphism or have a blastic appearance.[4]
Marrow involvement is more easily established by bone marrow aspirate smears as the tissue section may only show
subtle lymphoid infiltrates as seen in this case.[4] The common phenotype in T-LGL is CD2+, CD3+, CD4-, CD8+
with variable expression of CD56.[1, 2] In comparison, neoplastic cells in aggressive NK-cell leukaemia are CD2+,
CD3- and CD56+. Our patient’s immunophenotype analysis showed the leukaemic cells expressed CD3, CD7, CD8,
CD16 and CD56 but were negative for intracellular MPO and intracellular CD22. These findings support the suspicion
of a rare entity of CD3+, CD56+ variant aggressive LGL leukaemia3 also described as LGL NK-like leukaemia.[4]
A variety of cytogenetic abnormalities are much more common in NK-like leukaemia when compared to T-LGL
leukaemia.[1] Macon et al., suggested this exercise may help to pinpoint patients with poorer prognosis as three out of
four patients studied had an abnormal karyotype which include t(2,17), isochromosome 7q and t(8,14)[4]. Our patient’s
cytogenetic analysis showed a normal cell karyotype.
Aggressive T-LGL leukaemia is not considered as a different entity by the latest WHO classification. Aleshkun et
al., suggested a diagnosis of aggressive T-LGL leukaemia can be established based upon four clinical and laboratory
features which include aggressiveness of clinical presentation (acute onset of B symptoms, hepatosplenomegaly,
peripheral cytopaenia and lympadenopathy) together with presence of an absolute large granular lymphocytes count
in blood film of more than 0.5 x 109/L (frequently > 10 x x109/L).[5] Phenotypically the leukaemic cells are positive for
CD3, CD8 and CD56 as described in this case. Demonstration of clonally rearranged TCR genes of the leukkaemic
cells also need to be established.[1, 4, 5] Unfortunately, we were unable to prove the clonality by TCR as the sample sent
was unsuitable for processing. However, our patient does fulfill the other three clinico-laboratory features as suggested
by Todd et al. Furthermore; TCR gene rearrangement is also a feature of indolent T-LGL leukaemia. Kojima et al.,
1995 reported a case with neither progressive nor aggressive clinical course CD3+, CD56+ LGL with TCR gene
rearrangement.[6]
The non-progressive nature of typical T-LGL leukaemia probably is better regarded (as clonal of uncertain
significant rather than leukaemia. Most patients usually remain asymptomatic even for more than five years.[1]
Treatment is indicated only in patients who turn aggressive and with symptomatic neutropaenia.[1, 2] In contrast, this
CD3+, CD56+ aggressive variant LGL leukaemia needed urgent treatment as most untreated cases will die within a
months of the diagnosis.[3, 4, 5]
Aggressive chemotherapy[4] and combination CHOP-like regimen[3, 4] have been tried but most patients die within a
year of treatments. Gentile et al., described a case which was temporarily controlled after being treated with childhood
ALL induction and consolidation regimen therapy. This young female was alive and awaiting for allogenic stem cell
transplant at the time of reporting.[3] Successful haematological remission was achieved in the patient treated with
hyper-CVAD (fractionated cylophosphamide with vincristine, adriamycin and dexamethasone) protocol alternating
with four cycles of high-dose methotrexate and cytarabine.[5] As seen in our case, her disease was temporarily controlled
by standard risk ALL regimen chemotherapy. She also was temporarily able to achieve clinical and haematological
remission. Unfortunately, while waiting for stem cell transplantation, she succumbed with disease relapse less than 6
months post chemotherapy.
Combination chemotherapy of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) also have
being used in treating this aggressive disease with variable outcome.[3, 4] Gentile et al., reported successful control
of disease in a patient treated with CHOP followed by high dose of oral cylophosphamide.[3] This is conflicting with
cases reported by Macon et al., where a patient died within few months of his presentation.[4] Multiple combination
chemotherapy, aggressive chemotherapy with combination of prednisolone with other chemotherapy also failed to
control the disease.[4] Combination of chlorumbucil and whole body irradiation have being tried to treat a patient
who presented with generalized maculopapular rash, however this patient also succumbed one year after his
presentation.[4]
The prognosis of this rare and aggressive disease is poor. As described in this case, recurrence of disease may
60
occur within few months even after achieving haematological remission[5]. There is no data supporting the need of
prophylactic intrathecal chemotherapy to control the disease. Studies also show that a long-term remission rarely
occurs.[3, 4, 5]. Upfront autologous haematopoietic stem cell transplantation needs to be considered in managing this
aggressive disease entity. Alekshun et al,. reported a patient who benefited by this treatment modality even after he
had recurrence of leukaemic cells within the cerebral spinal fluid.[5] Literature search shows no data on the outcome of
patients with aggressive NK-like leukaemia being treated with allogeneic haematopoietic stem cell transplantion.
CONCLUSION
Awareness among clinician and laboratory haematologists on the existence of this aggressive entity of large granular
lymphocytic leukaemia is important in ensuring urgent and intensive treatment can be promptly initiated to control
the disease. ALL-like induction chemotherapy protocol followed by haemopoietic stem cell transplant may rescue this
rare disorder.
REFERENCES
[1]
World Health Organization, International Agency for Research on Cancer. WHO classification of tumours of
haemopoietic and lymphoid tissues. IARC Lyon 2008.
[2]
Semenzato G, Zambello R, Starkebaum G et al. The lymphoproliferative disease of granular lymphocytes:
Update criteria for diagnosis. Blood 1997; 256-60.
[3]
Gentile TC, Uner AH, Hutchison RE et al. CD3+, CD56+, Aggressive variant of large granular lymphocyte
leukaemia. Blood 1994; 84: 2315-21.
[4]
Macon WR, Williams ME, Greer GP et al. Natural Killer-Like T-Cell Lymphoma: Aggressive lymphoma of Tlarge granular lymphocytes. Blood 1996; 84: 1474-83.
[5]
Alekshun TJ, Tao J and Sokol L. Aggressive T-cell large granular lymphocytic leukaemia: A case report and
review of literature. Am J Hematol 2007; 82: 481-5.
[6]
Kojima H, Komeno T, Shinagawa A et al. CD3+, CD56+ Large granular lymphocytic leukaemia. Correspondence.
Blood 1995; 85(12): 3762
Synchronous Mucoepidermoid Carcinoma of the Right Upper Eyelid and Right
Parotid Gland in a Young Patient
1
M Irfan*, 1CY Wong, 1H Nik Fariza, 2K Maha
& 2O Nor Hayati
Department of Otorhinolaryngology-Head & Neck Surgery, School of Medical Sciences,
Universiti Sains Malaysia Health Campus, 16150 Kota Bharu, Kelantan, Malaysia
2
Department of Pathology, School of Medical Sciences,
Universiti Sains Malaysia Health Campus, 16150 Kota Bharu, Kelantan, Malaysia
1
ABSTRACT
Mucoepidermoid carcinoma and squamous cell carcinoma are tumors found predominantly in the
elderly. Most of the cases reported were from patients of more than 50 years old. In our case, it affects a
young patient, a 26 year old lady who has a history of a severely burnt and scarred face since childhood.
She represents a rare case of a high grade aggressive tumor involving her right eyelid and right parotid
gland.
Keywords:
Mucoepidermoid, carcinoma, parotid tumor, eyelid
INTRODUCTION
Mucoepidermoid carcinoma is a relatively common neoplasm that affects the major and minor salivary glands
comprising 10–30% of primary carcinomas.[1] They may involve the skin through direct extension, metastases, and
rarely, as a primary focus (adenosquamous carcinoma).[1] Our patient presented with extensive tumor of the upper eyelid,
which later was confirmed as mucoepidermoid carcinoma with areas of squamous cell carcinoma transformation. It
was difficult to determine the origin of the tumor; possibilities include upper eyelid epithelium, accessory lacrimal
gland, sweat gland or other skin appendages.
THE CASE
A 26 years old lady, with a history of burn on the face during childhood, first presented with a small ulcerative
nodule like lesion at the right upper eyelid for few weeks duration. The lesion was progressively increasing in size
and associated with pain and foul discharge with contact bleeding. An excisional biopsy was performed by a general
practitioner, and was then referred to our center for further management.
Examination at the time of presentation showed a 10 x 7cm fungating mass over the right periorbital region. The
surface was ulcerated and partly covered with exudates and foul- smelling discharge. The conjunctiva was injected
with central corneal opacity.
She was also noted to have a right parotid swelling which is hard in consistency. There was involvement of the
overlying skin which also displaced the ear lobe. There was no palpable cervical lymphadenopathy.
Computed tomography scan of the head and neck demonstrated an irregular heterogenously enhancing soft tissue
lesion involving the orbit. Medially, the mass extended to the right side of the nasal bridge, associated with soft tissue
thickening extending to the frontal sinus area. The right parotid gland was enlarged measuring 4.0 x 2.0 x 4.5 cm with
central necrosis. The deep lobe of the parotid gland was normal. Magnetic resonance imaging revealed right frontal
bone involvement with frontal lobe dura enhancement.
These clinical and radiological assessments indicate a malignancy which was further confirmed by the biopsy
result which showed squamous cell carcinoma of right upper eyelid with intraorbital extension.
Resection of right upper eyelid tumour with right total orbital exenteration, right total parotidectomy with excision
of upper branch of facial nerve were performed together with removal of right orbital rim and coagulation of tumour
attached to dura. Reconstruction was done by using free myocutaneous latissimus dorsi flap. Full histopathology
report of the right periorbital specimen confirmed the diagnosis of extensive mucoepidermoid carcinoma with
areas of transformation into squamous cell carcinoma. The right parotid showed a high grade mucoepidermoid
carcinoma.
The patient had an uneventful post-operative recovery. The patient was referred to oncology department for further
palliative radiotherapy.
62
Figure 1.
Axial MRI revealed right frontal bone
involvement with frontal lobe dura
enhancement
Figure 2.
The enhancing lesion was also seen in
the right parotid on coronal section
Figure 3.
Fungating mass on the right periorbital
region and the enlarged parotid gland
with overlying skin involvement
Synchronous Mucoepidermoid Carcinoma of the Right Upper Eyelid and Right Parotid Gland in a Young Patient
Figure 4.
Microscopy shows feature of squamous
cell carcinoma with presence of
glandular differentiation (x20)
Figure 5.
Areas of pure squamous cell carcinoma
(x40)
63
DISCUSSION
Mucoepidermoid carcinoma is a relatively common tumor involving major and minor salivary glands. It can present
as a primary focus, direct extension to skin or distant metastasis. Primary mucoepidermoid carcinoma of the skin or
sometimes refered to as cutaneous adenosquamous carcinomas has been hypothesized to be arising from the sweat
glands.[1] This is supported by the fact that salivary glands and eccrine glands in the skin are both ectodermal structures
and may express similar properties with regard to mucin production.[2] However, Landman and Farmer suggested
that primary cutaneous adenosquamous carcinoma represents a separate and distinct entity with a higher aggressive
potential.[2]
There were only few case reports of mucoepidermoid carcinoma of the upper eyelid, particularly arising from an
accessory lacrimal gland.[1, 3] In one of the cases, orbital exenteration was done due to the supratrochlear neurovascular
bundle involvement, exhibited by perineural invasion of the mucoepidermoid carcinoma.[3]
It was interesting to note that our patient was having synchronous tumours of the right parotid and right upper eyelid.
Synchronous and/or metachronous malignancies at both lacrimal and parotid gland sites are infrequent events which
frequently lead to diagnostic and clinical difficulties.[4] Klijanienko et al. observed that patients with primary parotid
lesions exhibited more aggressive behavior than those with primary lacrimal tumors; all patients with parotid primaries
died of metastatic disease, while patients with primary lacrimal had a protracted and less aggressive course.[4]
A primary parotid tumor metastasizing to the lacrimal gland would be a manifestation of hematogenous metastases;
in contrast, a lacrimal gland tumor metastasizing to the parotid gland would be a manifestation of lymphatic spread.[4]
In this case, the latter is more likely if metastatic disease is to be considered. This is because the eyelid lesion was
present few years before the right parotid mass which manifested only as a lesion near the ear lobe. The right parotid
lesion was confirmed only on MRI.
64
Apart from lacrimal gland metastases, it is also important to be aware of the fact that mucoepidermoid from
a primary tumor in the salivary gland can spread to the skin.[5] There are at least three well-documented cases of
mucoepidermoid carcinoma of salivary gland which metastasized to the skin.[6-8] In this case, the possibility of primary
mucoepidermoid carcinoma of the parotid gland which metastasized to the skin overlying the lacrimal gland should
be considered.
REFERENCES
[1]
Johnson DS, Solomon AR, Washington CV. Mucoepidermoid / Adenosquamous carcinoma of the skin:
Presentation of two cases. Dermatol Surg. 2001; 27(12): 1046-8.
[2]
Landman G, Farmer ER. Primary cutaneous mucoepidermoid carcinoma: Report of a case. J Cutan Pathol. 1991;
18(1): 56-9.
[3]
Dithmar S, Wojno TH, Washington C, Grossniklaus HE. Mucoepidermoid carcinoma of an accessory lacrimal
gland with orbital invasion. Ophthal Plast Reconstr Surg. 2000; 16(2): 162-6.
[4]
Klijanienko J, El-Naggar AK, Servois V et al. Histologically similar, synchronous or metachronous, lacrimal
salivary-type and parotid tumours: A series of 11 cases. Head Neck. 1999; 21(6): 512-6.
[5]
Riedlinger WF, Hurley MY, Dehner LP, Lind AC. Mucoepidermoid carcinoma of the skin: A distinct entity from
adenosquamous carcinoma: a case study with a review of the literature. Am J Surg Pathol. 2005; 29(1): 131-5.
[6]
Yen A, Sanchez RL, Fearneyhough P, Tschen J, Wagner RF Jr. Mucoepidermoid carcinoma with cutaneous
presentation. J Am Acad Dermatol. 1997; 37: 340-2.
[7]
Smoller BR, Narurkar V. Mucoepidermoid carcinoma metastatic to the skin: an histologic mimic of a primary
sweat gland carcinoma. J Dermatol Surg Oncol. 1992; 18: 365-8.
[8]
Locati LD, Quattrone P, Pizzin N et al. Primary high-grade mucoepidermoid carcinoma of the minor salivary
glands with cutaneous metastases at diagnosis. Oral Oncol. 2002; 38: 401-4.
Depression and Quality of Life among Patients with Hematological Cancer
in a Malaysian Hospital
1
D Priscilla*, 2A Hamidin, 2MZ Azhar, 2KON Noorjan, 1MS Salmiah & 3K Bahariah
Department of Community Health, Faculty of Medicine and Health Sciences,
2
Department of Psychiatry, Faculty of Medicine and Health Sciences,
3
Department of Medicine, Faculty of Medicine and Health Sciences,
1
ABSTRACT
Objective: To determine the prevalence of major depressive disorder (MDD) in hematological cancer
patients and to investigate MDD with quality of life. Methods: The research, which uses a cross sectional
design, has been carried out at Ampang Hospital, Kuala Lumpur. The hospital is a tertiary referral center
for cancer cases that include non-Hodgkin lymphoma, acute myelogenous leukemia, acute lymphoblastic
leukemia, Hodgkin lymphoma and other hematological cancers. In total, 105 patients with hematological
malignancies were included in the study. This study employed the MINI International Neuropsychiatric
Interview for diagnosis of MDD, the Patient Health Questionnaire (PHQ-9) for symptom severity of
depression and the European Organisation for Research and Treatment of Cancer Quality Of Life
questionnaire (EORTC QLQ-C30) to assess the quality of life of the respondents. Result: The response
rate was 83.3%. The prevalence of MDD was 24.8% (n=26) with the majority of cases classified as
moderately severe depression (38.5%). About 92.3% (n=24) of depressed hematological cancer
patients were diagnosed with a current episode of MDD. The depressed patients also had significantly
reduced quality of life in physical, role, emotional, cognitive and social domains (p<0.05). They also
had significantly more symptoms of fatigue, nausea and vomiting, dyspnea, insomnia, appetite loss,
constipation and diarrhea in addition to having financial difficulties and poor global health statuses
(p<0.05). Conclusion: The prevalence of depression among the hematological cancer patients was high
and the depressed patients had reduced qualities of life. Special attention in psychotherapy would help
to improve both depression level and the quality of life in these patients.
Keywords:
Major depressive disorder, quality of life, hematological cancer
INTRODUCTION
Patients diagnosed with cancer not only suffer from the disease itself but they also have a higher tendency to develop
psychiatric disorders. Articles have been published on psychiatric disorders of hematological cancer patients and their
qualities of life in various western countries.[1-5] However, to the best of our knowledge, the research remains minimal
in eastern countries, and there is no published research of such an article in Malaysia.
Hematological cancers such as leukemia, lymphoma and myeloma that exist in different forms[6] have serious
emotional and physical impacts on patients.[1-2, 4-5] In 2006, a total of 21,773 patients in peninsular Malaysia were
diagnosed with cancer. The hematological cancer lymphoma (3.2%) was one of the ten most frequent cancers in
peninsular Malaysia. Lymphoma (4.2%) and leukemia (3.6%) were the 8th and 9th most frequent cancers among males
in Malaysia. Among women, lymphoma (2.4%) was the 10th most frequent cancer.[7]
Psychiatric disorders such as depression are the most prevalent mental health problems that can be easily diagnosed
in cancer patients.[1] There are nine symptoms of major depressive disorder (MDD) according to the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) classification. The symptoms include depressed mood, loss of
interest, weight loss or weight gain, insomnia, psychomotor agitation, fatigue, worthless feelings, poor concentration
and frequent thoughts of death. The person must have at least five symptoms including depressed mood or loss of
interest for a two-week period of time to be diagnosed with MDD.[8]
The aim of the study was to determine the prevalence of MDD in the hematological cancer patients in Ampang
Hospital and to investigate MDD with quality of life in these patients.
66
METHODOLOGY
A hospital-based cross-sectional study was conducted in the hematological wards at Ampang Hospital Kuala
Lumpur, Malaysia between May 2009 and December 2009. The hospital is a tertiary referral center for hematological
malignancies, which include cases such as non-Hodgkin lymphoma, acute myelogenous leukemia, acute
lymphoblastic leukemia, Hodgkin lymphoma and other types of hematological cancers. Sample size estimation
calculated using the single proportion formula, n= Z2 P (1-P) / d2.[9] Based on the formula Z denoted for level of
confidence or number of standard error away from the mean.[9] The Z value was set at 1.96 with 95% confidence
interval for the result. Symbol P in the formula is the expected or anticipated proportion or prevalence.[9] Study done
by Prieto, J et al., found the proportion of major depressive disorder in hematological cancer patients was 9.0%[1]
hence, P equals to 0.09 was determined. Symbol d in the formula is denoted for precision or measures for total
percentage points of the error that will be tolerated on the either side of P. In short, symbol d is percentage points
on either side of P.[9] The d value was set at 5% or d=0.05 in the study. The formula substituted with these values,
n= 1.962 0.09 (1-0.09) / 0.052 and the sample size (n) = 126 hematological cancer patients was determined. The
Ethical Committees of the Ministry of Health and the Faculty of Medicine and Health Sciences, University Putra
Malaysia, approved the study.
All patients aged 15 years and older who were consecutively admitted to hematological wards, diagnosed with
hematological cancer, able to converse in any one of these languages: English, Malay, Mandarin or Tamil, conscious
and able to engage in an interview and give consent to participate were included in the study. Patient information
such as disease status, medication history and socio-demographic profile were obtained from the participants and
confirmed with medical records.
Many previous studies used various sets of questionnaires to screen for psychiatric disorders such as depression;[5]
however, only few studies had implemented a strict systematic clinical interview based on DSM-IV criteria to
make such diagnoses in hematological cancer patients.[10] In the present study, module A of the MINI International
Neuropsychiatric Interview (MINI), version 6.0.0, questionnaire[11] was used to diagnose MDD. The questionnaire was
developed according to DSM-IV and International Classification of Diseases (ICD-10) criteria and has 96% sensitivity
and 88% specificity.[12] The module consists of five questions with multiple sub-questions to be answered either “Yes”
or “No” within the time frame of the past two weeks or/and in a past episode.[11] The interviewer was trained to use the
MINI by senior psychiatrists who had experience and were certified in using the MINI.
The Patient Health Questionnaire, PHQ-9 questionnaire, was used to measure the severity of depression among
patients with MDD. The questionnaire is self-rated and was developed for medically ill patients based on DSM-IV
criteria. It is comprised of nine questions and it is rated according to a two week time frame of symptoms on a scale
from 0 to 3: 0 = not at all; 1 = several days; 2 = more than half the days; 3 = nearly every day. The final question is
rated for difficulties with regards to problems, i.e., 1 = not difficult at all; 2 = somewhat difficult; 3 = very difficult; 4
= extremely difficult. The PHQ 9 scores were computed and classified according to symptoms scores as follows: (0-9)
= normal to mild symptoms, (10-14) = moderate symptoms, (15-19) = moderately severe symptoms and (more than
20) = severe symptoms. The questionnaire has good internal reliability and validity.[13]
This study also used a validated[14-15] European Organisation for Research and Treatment of Cancer Quality
Of Life (EORTC QLQ-C30) questionnaire to measure quality of life among the participants. The questionnaire is
comprised of five functioning scales, three symptoms scales, a global health status scale and six single item scales.
The functioning scale is comprised of physical functioning, role functioning, cognitive functioning, emotional
functioning and social functioning. Fatigue, pain and nausea/vomiting are included in the symptom scales. Finally,
the single item scale is used to measure dyspnea, insomnia, appetite loss, constipation, diarrhea and financial
difficulties. The EORTC QLQ-C30 questionnaire consists of 30 questions with each set of questions belonging
to each scale as mentioned above. Every question has four-point scales ranging from 1 to 4 with “not at all”, “a
little”, “quite a bit” and “very much” as answer choices. The last two items, numbers 29 and 30, measure global
health status with a seven-point numbered scale ranging from 1 to 7 ranging from “very poor” to “excellent”[14].
The raw score for each scale was calculated. Then a linear transformation of a 0-100 score was computed for each
category in the scale. Thus the range of scores for each scale varies from 0 to 100. The scoring procedure was
performed according to the scoring manual of EORTC QLQ-C30. A higher score is better on the functioning scale
and indicates better global health status. Conversely, a higher score for the symptom scale and single item scale
indicate more symptoms.[16]
All data were analyzed using Statistical Package for Social Sciences (SPSS) software version 17.0. Descriptive
statistics including mean, percentages and ranges were used to describe the sample characteristics. Chi squared tests
and fisher exact tests were used to find significant difference between the presence and absence of MDD and sociodemographic or clinical variables (i.e., gender, time since diagnosis, ethnicity, and religion, marital status, children
status, highest level of formal education, highest certificate obtained and occupational status working sector and
monthly income). T-tests were applied to gender and age of respondents to determine if there is a significant difference
67
between the two variables. A Mann-Whitney U test, one tailed test for non-parametric data was performed to make
comparison of depressed and non-depressed hematological cancer patients with their quality of life. The significant
value was set at p<0.05.
RESULTS
A total of 126 patients were approached in hematological wards during the study period. Of these patients, 6 patients
refused to participate, 13 patients had non-hematological cancer diagnoses and 2 patients were unable to understand
the questionnaires. Thus, the study had a response rate of 83.3%. Table 1 shows the characteristics of the respondents.
Most of the respondents with hematological cancer (26.7%) fell into the 21-30 years age group followed by the 4150 years age group (21.9%). The mean age of the participants was 40.4 years (95% CI= 37.4, 43.5). There was a
significant difference (t = 1.991, df = 103, p=0.049) between the mean age of men (43.6 years, 95% CI = 39.0, 48.2)
and that of women (37.5 years, 95% CI = 33.4, 41.6) who participated in this study.
Table 1.
Socio-demographic characteristics of respondents
Number
Percentage
(%)
Age
15-20
21-30
31-40
41-50
51-60
61-70
>70
8
28
16
23
16
11
3
7.6
26.7
15.2
21.9
15.2
10.5
2.9
105
Gender
Female
Male
55
50
52.4
47.6
105
Ethnicity
Malay
Chinese
Indian
Others
63
26
14
2
60.0
24.8
13.3
1.9
105
Religion
Muslim
Buddhist
Hindu
Christian
Others
No religion
64
20
12
6
2
1
61.0
19.0
11.4
5.7
1.9
1.0
105
Marital status
Single
Married
Divorced
34
70
1
32.4
66.7
1.0
105
Children
Yes
No
59
46
56.2
43.8
105
Characteristics
N
68
Continuation
Table 1.
Socio-demographic characteristics of respondents
Number
Percentage
(%)
Highest level of formal education
Primary
Secondary
College/University
No education
15
57
32
1
14.3
54.3
30.5
1.0
105
Highest certificate
Primary School Evaluation Test (PSET)
Lower Certificate of Education (LCE)
Malaysian Certificate of Education (MCE)
Malaysian Higher School Certificate (HSE)
Certificate/Diploma
Degree
Master
No education
12
18
37
3
23
10
1
1
11.4
17.1
35.2
2.9
21.9
9.5
1
1
105
Occupation status
Working
Not working
House wife
Pensioner
35
56
8
6
33.3
53.3
7.6
5.7
105
Working sector
Government
Non government
Self employment
Not working
12
18
5
63
12.2
18.4
5.1
64.3
98
Total monthly income household (RM)
0-3000
3001-6000
6001-9000
>9001
60
7
1
2
85.7
10
1.4
2.9
70
Characteristics
N
In terms of ethnicity, there was preponderance of Malays (60%) followed by Chinese (24.8%). The Indians
represented a small proportion of the study population (13.3%). The majority of subjects were Muslims (61%) followed
by Buddhists (19%). Hindus accounted for 11.4% and Christians for 5.7%. The majority of patients with hematological
cancer were married (66.7%). In terms of education attainment, more than half of the patients (54.3%) were educated
up to the secondary level. Approximately 44.8% had received tertiary education (certificate/diploma: 21.9%, degree:
21.9% and masters degree: 1%), 11.4% had primary education and 1% had not received formal schooling. A majority
of the respondents were not working (53.3%). Among the working respondents, 18.4% worked in the non-government
sector, followed by 12.2% in the government sector and 5.1% were self-employed. As for total monthly household
income, most of the respondents had total household incomes of less than RM 3000.00 (85.7%).
Table 2 shows the clinical characteristics of the respondents. Nearly half of the respondents were diagnosed with
hematological cancer less than six months prior to the study (47.6%), 26.7% were diagnosed six months to one year
earlier and 25.7% were diagnosed more than one year earlier. Among the respondents, 23.8% had a diagnosis of nonHodgkin lymphoma, 22.9% had acute myelogenous leukemia, 14.3% had acute lymphoblastic leukemia, 10.5% had
Hodgkin lymphoma, and 28.5% had other hematological cancers.
Table 2.
Clinical characteristic of respondents
Number
Percentage
(%)
50
28
27
47.6
26.7
25.7
15
1
24
2
3
1
1
1
5
6
1
14.3
1
22.9
1.9
2.9
1
1
1
1
10.5
23.8
1
2.9
1.9
1
1
4.8
5.7
1
0
3
6
26
0%
2.9%
5.7%
24.8%
43.8%
3
21
2.9%
19.9%
105
Received treatment
Yes
No
104
1
99.0%
1.0%
105
Treatment
Chemotherapy
Others
97
7
93.3%
6.7%
104
Characteristics
Time since diagnosis
Less than 6 months
6 months-1 year
More than 1 year
Hematological cancer diagnosis
Acute lymphoblastic leukemia
Chronic lymphocytic leukemia
Acute myelogenous leukemia
Chronic myelogenous leukemia
Acute promyelocytic leukemia
Hairy cell leukemia
MDS-RAEB* towards leukemia
MDS-CMMOL** towards chronic leukemia
Unclassified leukemia
Hodgkin lymphoma
Non-Hodgkin lymphoma
Peripheral-T-Cell lymphoma
Natural Killer-T-Cell lymphoma
Central nervous system-lymphoma
Intravascular lymphoma
Follicular transform lymphoma
Unclassified lymphoma
Multiple myeloma
Histiocytosis
Stage
Stage I
Stage II
Stage III
Stage IV
11
25
1
3
2
1
N
105
1
1
105
Blood cell count ≥ 100
46
Blood cell count > 100
Others
* Myelodysplastic syndrome- refractory anemia with excess blasts
** Myelodysplastic syndrome-chronic myelomonocytic leukemia
69
70
The majority of the respondents (93.3%) received chemotherapy and among them 1% had received chemotherapy
and radiotherapy. The remaining (6.7%) respondents received other treatments, i.e., steroid (2%), supportive treatment
(1%), transplant (1%) and other medication (2.9%).
Hematological cancer was classified according to stages I, II, III, IV and blood cell counts. Approximately a
quarter (24.8%) of participants had stage IV hematological cancer, 5.7% had stage III, 2.9% had stage II, and none
had stage I. The majority of respondents (43.8%) had blood cell counts ≤ 100, 2.9% had a blood cell count > 100 and
19.9% had other types of blood cell counts (3% had a high blood cell count, 2% had a low blood cell count, 2% had
Ig G lambda, 1% had Ig G kappa and 11.9% had unspecified or without stage).
The prevalence of MDD in the hematological cancer patients was 24.8%. From the 105 respondents, 24.8% (n=26)
were diagnosed with MDD. Of 26 respondents, 92.3% (n=24) were diagnosed with a current episode of MDD and 3.8%
each were determined to have a current and a recurrent episode (n=1) and a current and a past episode (n=1). Among
the respondents with MDD (Table 3), the majority of them had moderately severe depression (38.5%), followed by
moderate depression (30.8%), normal to mild depression (19.2%) and severe depression (11.5%).
Table 3.
Severity of symptoms of depression in respondents with major depressive
disorder (n=26)
Depression (PHQ-9)
Frequency
Percentage
5
8
10
3
19.2%
30.8%
38.5%
11.5%
Normal to mild
Moderate
Moderately severe
severe
Table 4.
Quality of life mean rank scores (EORTC QLQ-C30) between depressed and nondepressed hematological cancer patients (n=105)
Non-depressed
Mean rank
Depressed
Mean Rank
z
p-value
58.68
57.36
56.82
60.82
56.76
59.01
48.03
48.04
52.37
50.51
48.09
49.49
50.07
50.03
46.98
35.73
39.75
41.40
29.25
41.58
34.75
68.10
68.08
54.90
60.58
67.9
63.65
61.09
62.04
71.29
-3.378
-2.568
-2.319
-4.607
-2.261
-3.585
-2.94
-3.142
-0.379
-1.725
-3.133
-2.146
-1.816
-2.118
-3.669
**0.001
**0.005
*0.010
***0.000
*0.012
***0.000
**0.002
**0.001
0.353
*0.043
**0.001
*0.016
*0.035
*0.017
***0.000
Global health status/QoL
Physical functioning
Role functioning
Emotional functioning
Cognitive functioning
Social functioning
Fatigue
Nausea and vomiting
Pain
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
*p<0.05; **p<0.01; ***p<0.001.
Table 4 shows the comparison of depressed and non-depressed hematological cancer patients with their quality
of life mean rank scores. The quality of life domains include functioning domains such as physical, role, emotional,
cognitive and social domains. Symptom domains include fatigue, (nausea and vomiting), pain, a global health status
domain and six single-item domains such as dyspnea, insomnia, appetite loss, constipation, diarrhea and financial
71
difficulties. A Mann-Whitney U-test, one tailed test was performed to examine the level of significance at p<0.05,
and the result showed that the depressed hematological cancer patients had significantly reduced physical (p=0.005),
role (p=0.01), emotional (p<0.001), cognitive (p=0.012) and social functioning (p<0.001) compared to non-depressed
patients. The depressed hematological cancer patients also had significantly more symptoms of fatigue (p=0.002),
nausea and vomiting (p=0.001), dyspnea (p=0.043), Insomnia (p=0.001), appetite loss (p=0.016), constipation
(p=0.035), diarrhea (p=0.017) and financial difficulties (p<0.001). They also had significantly poor global health
statuses (p=0.001).
Additionally, this study found a slightly higher prevalence of MDD in male compared to female respondents
at 53.8% and 46.2% respectively. Among the depressed respondents, there was a higher preponderance of Malays
(53.8%), followed by Indians (23.1%), Chinese (19.2%), other ethnic groups (3.8%). There was a high proportion
of depressed respondents who were married (69.2%), achieved an educational level of MCE or less (65.4%), were
working (42.3%), had a household income of RM 1000 or less (60.0%) or had children (61.5%). However, no significant
difference was found between depressed hematological cancer patients and gender, time since diagnosis, ethnicity,
religion, marital status, children status, highest level of formal education, highest certificate obtained, occupational
status, working sector or monthly income.
DISCUSSION
This report provides information about the prevalence of MDD among hematological cancer patients in a Malaysian
tertiary referral centre for hematological cancer. The present study showed that the prevalence of MDD among
Malaysian hospitalized hematological cancer patients was 24.8%. The prevalence found in this study was comparable
with a study among cancer patients in hospital wards by Bukberg et al., which found that the overall prevalence of
MDD was 24.0%[17] and severity of MDD was 24.0%.[18] Of 24.8% respondents with MDD, more than one-tenth
(11.5%) had severe MDD. However, the comparison of severity of depression among cancer patients is difficult
because different studies use different severity scales.
Four main causes for depression among cancer patients were identified based on various studies. First, sociodemographic factors such as age[4], gender[2, 19] and education level[19] play an important role in depression. Clinical
factors such as type of cancer[19] and its treatment,[19-22] severity of cancer, [21, 23] stage[22]and duration of illness[2] were
also found to be related to depression. The third most important factors are psychosocial factors like physical,[4-5, 24]
role,[4, 24] emotional,[5, 24] cognitive,[5, 22, 24] social functioning,[5, 22, 24] global quality of life[5] and coping styles.[19, 25-26]
Finally, clinical symptoms such as fatigue,[4, 23] pain,[4, 23] dyspnea,[4, 23] insomnia,[4, 23] appetite loss[4] and constipation[4]
also contributed to the development of depression in cancer patients. If a psychiatric disorder is left untreated it will
cause shorter survival rates[1, 5] suicidality,[27] poor quality of life[20, 22-23, 28] and increased lengths of stay in hospitals.[3]
In this study, there was a preponderance of male respondents with MDD (53.8%) compared to female respondents.
This finding mirrors results from a previous study by Pandey et al. who found that male cancer patients were more
depressed compared to female cancer patients.[29] However, our finding was in contrast with other studies, which
found that women scored higher in depression and anxiety measures compared to men.[2, 19] The respondents of this
study represent all three predominant ethnicities of the Malaysian population, and the proportion of each ethnicity
was consistent with reported proportions in the national cancer registry in 2006.[7] Among the various ethnic groups in
Malaysia, the prevalence of MDD was alarmingly high in the Malays (53.8%), followed by the Indians (23.1%), the
Chinese (19.2%), and other ethnic groups (3.8%).
We also found that most of the depressed patients were married (69.2%) and had an education level of MCE or
less (65.4%). The higher rates of MDD in the married respondents were in contrast with the study by Staci et al., who
found that the married patients were less depressed compared to the unmarried group.[30] The prevalence of MDD in
respondents with low educational attainment was expected and similar to that in another study that found less educated
patients were more depressed compared to others.[30] There was a high preponderance of respondents who were
unemployed (42.3%) and had a household income less than or equal to RM 1000 (60.0%) who were diagnosed with
MDD. This is consistent with a study that found that higher distress cancer patients were coming from lower income
group.[31] Patients with children were found to be more depressed in the present study. However the comparison with
other studies is difficult because limited research has intensively investigated this factor.
However, MDD diagnosis did not yield any significant difference with these certain clinical and socio-demographic
factors. Similarly, other studies among the cancer patients also found there is no significant correlation between
depression and socio-demographic profiles.[32] The reason for non-significant result might be due to inconsistent or
unequal number of patients by their gender, time since diagnosis, ethnicity, religion, marital status, highest level of
formal education, highest certificate obtained, occupational status, working sector and monthly income.
Analysis also showed that compared to non-depressed hematological cancer patients, the depressed hematological
cancer patients had significantly reduced physical, role, emotional, cognitive and social functioning. They also had
significantly more symptoms of fatigue, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea
72
and financial difficulties. The poor quality of life associated with depressed hematological cancer patients in this study
is consistent with the findings of the previous study. Pamuk et al. found that depression among hematological cancer
patients had a negative effect on the global quality of life and level of functioning. Quality of life was negatively
correlated with the physical, role, emotional, cognitive, social functioning and global quality of life scores.[5]
The possible explanation for this finding could be due to side effects of the treatments received by the respondents.
In a study among hematological cancer patients regarding quality of life, it was found that patients who were under
active treatment had reduced physical functioning, poor appetite and fatigue compared to patients in non-active
treatment.[4] On the other hand, it is also known that the worsening of quality of life of hematological cancer patients
before and after treatment in the context of their physical status, energy level and systemic symptomatology was
associated with fluctuations in depression level. Thus, a marked increase of depression level also contributes to poor
physical health status after intensive treatment.[2]
The significance of the study is to show that hematological cancer is a life threatening illness that is not only
causes significant psychological disturbances, including MDD, but also has impact on quality of life. Thus, awareness,
early recognition and appropriate interventions of MDD, both pharmacological and psychosocial, in an oncology
setting should become part of a holistic approach in the management of cancer patients. Thus oncologists, primary
care practitioners, and mental health professionals should be informed about the psychological consequences of a
hematological cancer diagnosis, and further steps must be implemented to minimize the undiagnosed MDD that is left
untreated among the patients.
From the treatment perspective, intervention should be started as soon as a diagnosis is revealed to the patient
because the psychological distress after receiving the diagnosis is prolonged for at least a few months and does not
decrease overtime in a clinical setting. The psychiatrist or mental health professionals should carry out an individualbased support program with psychotherapy and pharmacotherapy as efficient strategies to overcome patients’
psychological problems.[33] Early detection of emotional problems of hospitalized hematological cancer patients might
enhance quality of life, prevent patients’ difficulties in treatment and reduce the patients’ sufferings.[2]
LIMITATIONS
We should note some of the limitations of this study. First, investigating depression and quality of life specifically
among hematological cancer patients is a very challenging task because of the participants’ difficulties in responding
actively during the interview due to physical weakness and the severe nature of their illness. Thus, the results of the
present study should be interpreted with caution. The response of the participants may be influenced by the physical
and emotional state at the time of the interview. Furthermore, some part of this research used self-rated questionnaires
that were answered by the respondents themselves or were read to them to clarify their responses. The truthfulness of
the information given depended on the integrity of the respondents themselves and on the patients’ memory.
CONCLUSION
The present study found that the prevalence of MDD among the hematological cancer patients in the Malaysian
tertiary referral center hospital is 24.8%. Those who were depressed had reduced quality of life, especially in physical,
role, emotional, cognitive and social domains and had significantly more symptoms of fatigue, nausea and vomiting,
dyspnea, insomnia, appetite loss, constipation and diarrhea in addition to financial difficulties and poor global health
status.
ACKNOWLEDGEMENT
The authors would like to thank University Putra Malaysia (UPM) for the financial support under the Research
University Grant Scheme (RUGS) (Project No.: 04-03-08-0458RU [91463]), National Science Fellowship Scheme by
Ministry of Science Technology and Innovation, the director of Ampang Hospital, Consultant Hematologist: Dr. Ong
Tee Chuan and Dr. Chang Kian Meng, the staff of the hematological units as well as the patients who participated in
the study.
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The Beck Anxiety Inventory for Malays (BAI-Malay): A Preliminary Study on
Psychometric Properties
M Firdaus* & Z Nor Sheereen
Department of Psychiatry, Faculty of Medicine & Health Sciences
Universiti Putra Malaysia, 43400 Serdang , Selangor, Malaysia
ABSTRACT
Introduction: The purpose of the present study was to investigate exploratory factor analysis of the
Beck Anxiety Inventory (BAI) and reports its reliability and validity in Malaysia. Method: One thousand
and ninety participants from four different samples (namely students, general population, medical and
psychiatric patients) completed the Malay version of Beck Anxiety Inventory, as well as additional
questionnaires such as Fear Questionnaire, Anxiety Sensitivity Index, Depression Anxiety Stress Scale,
and Catastrophic Cognition Questionnaire. Results: Exploratory factor analysis revealed a three factor
solution and accounted for 48.01% of the total variance. The three-factor structure appeared to be;
subjective anxiety, autonomic, and neurophysiology. The Cronbach alpha coefficients (α) ranged from
0.66 to 0.89 with satisfactory overall alpha value (.91). Evidence was also found acceptable concurrent
validity of the BAI-Malay (range between r=.22 to r=.67). Conclusion: This study shows that the BAIMalay is a reliable and valid instrument to measure symptoms of anxiety in the Malay population
and can be used in research and clinical service in Malaysia. However, replication of study by using
confirmatory factor analysis and application of the instrument among anxiety patients worth of further
investigation.
Keywords:
Beck anxiety inventory, Malay, reliability, validity, Malaysia
INTRODUCTION
The Beck Anxiety Inventory (BAI) is commonly used to measure the level of anxiety[1] in adolescents and adults[2].
The BAI was originally developed to differentiate the behavioural, emotional and physiological symptoms between
individuals with anxiety and depression[3] and to assess response to treatment of groups patients with anxiety disorders
by clinicians and researchers to determine the cognitive and somatic aspects of the symptoms of anxiety [4-8].
A large number of studies in the West have shown interest in the psychometric characteristics of the BAI with
various populations, specifically clinical and non-clinical population [9]. The psychometric properties including factor
structure, reliability and validity of the BAI have been examined and researchers have found various finding for the
scale. This may be due to the type of sample of the study as well as the analysis conducted by the researcher [10]. Beck
et al., Hewit and Norton and Steer et al. found two factor structure of the BAI [1, 4, 11] while others[1, 7-8, 12-13] found that
the BAI contained four and even six factors [7].
Beck et al. conducted the first principal component analysis revealing two factors which were somatic and
subjective anxiety and panic [4]. The somatic factor contained 12 physical symptoms such as numbness and difficulty
in breathing, while the subjective anxiety and panic factor included nine psychological symptoms including nervous,
terrified and unable to relax. However, some item loadings were found to be rather low.
Beck and Steer performed another study using an exploratory factor analysis of the BAI in a sample of 393 outpatient
adults [14]. They reported that the BAI comprised of four factor structures which were termed neurophysiological,
subjective, autonomic, and panic symptoms of anxiety. These factors contributed to approximately 59% of the total
variance. These same factors were also studied by Steer et al. in a sample of 470 individuals with different psychological
disorders [15] and were found to produce similar results. Indigestion and heart pounding were the only items with a
loading below 0.45.
Borden, Peterson and Jackson also conducted a study to validate the factor structure of the BAI with a sample
of 293 undergraduates [16]. Their analyses indicated that five factors emerged from the principal component analysis
namely subjective fear (8 items), somatic nervousness (5 items), neurophysiological (5 items), muscular/motoric,
and respiration (3 items). However, Borden et al. reported that some items loaded on more than one factor and they
determined 26 items for the five factors BAI. However, they did not report the internal consistency estimates for the
BAI.
76
Various studies have found that the BAI has satisfactory reliability and validity in diversity of sample (e.g psychiatric
patient, adolescents with mental disorder, general population, university students) [17]. Osman et al. reported that the
total BAI score was found to have high internal consistency (α=.92) and one-week test-retest reliability (rn=.75) in a
sample of 83 adult psychiatric outpatients [12]. Their finding was further supported by the study done by Magán, Sanz,
García-vera [17] who reported a reliability of alpha coefficient of .93 [17]. Their results were also replicated findings from
previous studies[18-20].
Additionally, Osman et al. found that the BAI had support for convergent validity based on the correlation value
with other self-report measures of anxiety [12]. Steer and Wilson et al. found that BAI total scores have moderate to high
convergent validities (rs>0.50) with other self-report and clinical rating scales of anxiety and moderate discriminant
validities (rs<0.65) with respect to instruments measuring other types of psychopathology in both psychiatric and
nonpsychiatric populations [10, 21].
Although the efficacy of the BAI’s general utility in clinical and non-clinical population is well established, very
little is known about its use in Malaysian sample. After extensive review of important bibliography database up to
January 2010, we have not found any study that specifically analyses the psychometric properties of the BAI-Malay
translation. Therefore, it is the aim of this study to conduct an exploratory factor analysis to determine the factor
structure, reliability and validity of the BAI among Malay population.
Participants
Student sample. The subjects in this study were 315 undergraduate students from various faculties of two universities
(medicine, dentistry, allied health sciences, and human sciences). Subjects participated voluntarily in this study to
partially satisfy a research requirement of their course. All of the data for this study were collected through group
administrators. Each subject was provided with a self-administered battery of questionnaires, with an explanation and
accompanying directions for their use.
General community sample. Members of the general public participated in this study by completing questionnaires
that had been randomly distributed in public places (shopping complexes, community complexes etc) by research
assistants, and returning them in envelopes supplied.
Medical patients sample. The Malay medical patients recruited in this study were from primary care clinics, an obesity
clinic, Ear, Nose and Throat (ENT) clinics, and primary care clinics. The medical patients participated in this study by
completing questionnaires that had been distributed by research assistants, and returning them in envelopes supplied.
Patients with depression.
depression Malay patients with depression were invited via mail, phone or through referral from
psychiatrists who had been informed of the study. A letter of invitation and information regarding the study was
provided and those participants who were willing to participate presented at the psychiatric clinic for the intake
procedure assessment. Early diagnosis on depression was determined by psychiatrists using a structured clinical
interview from the Diagnosis and Statistical Manual of Mental Disorder- Fourth Edition (DSM-IV) to ascertain
participants’ eligibility.
Subjects’ data in all categories was discarded from the study if they were current drug or alcohol abusers, had a
history of organically based cognitive dysfunction, demonstrated reading difficulties, were not fluent in Malay, or
were non-Malays.
Measures
Demographic data sheet. Participants filled-up a demographic data sheet that consist of information on their personal
background including age, gender and level of education.
Beck Anxiety Inventory. The BAI-Malay is a translated version of the original BAI[13]with 21 items that provide lists
symptoms of anxiety. Participants respond to questions in relation to how much each symptom has bothered them
over the past week, with higher scores indicating more severe anxiety symptoms. The symptoms rated on a four-point
scale, ranging from “not at all” (0) to severely (3). The instrument has excellent internal consistency (α=.92) and high
test-retest reliability (r=.75) [13] in previous study.
Fear Questionnaire. Subjects responded to the 15-items Fear Questionnaire (FQ)[22] and their scores ranged from 0 to
120, yielding a “Total Phobia” score. The 15 items measure agoraphobia, blood injury, and social phobia. The scale
ranges from 0 (would avoid it) to 8 (always avoid it) on situations that create uneasy feelings to the subjects such as
eating with other people, hospital, walking alone and so forth.
77
Depression Anxiety Stress Scale-21. The Malay version of the Depression, Anxiety, Stress Scale-21 (DASS21)[23]
was based on the first instance on the original (English) version of the instrument. The English DASS21 is a 21-item
instrument measuring current (“over the past week”) symptoms of depression, anxiety, and stress. Each of the three
scales contains seven items. Subjects were asked to use a 4-point combined severity/frequency scale to rate the extent
to which they have experienced each item over the past week. The scale ranges from 0 (did not apply to me at all) to 3
(applied to me very much, or most of the time). Scores for Depression, Anxiety, and Stress are calculated by summing
the scores for the relevant items and multiplying by two. Musa [23] reported good reliability and validity of DASS-21
to be used in Malaysian context.
Anxiety Sensitivity Index. The Anxiety Sensitivity Index (ASI)[24]scale was developed to measure anxiety sensitivity,
which was believed to be related to the development of anxiety disorders. The scale was shown to have sound
psychometric properties for two samples of college students. The test-retest reliability coefficient was .75, and the
alpha coefficient was .84 for the present sample. In addition, the criterion validity of the index was demonstrated by
its ability to discriminate between patients with agoraphobia and other anxiety disorders as well as between anxietydisorder patients and college students.
Catastrophic Cognition Questionnaire. The original 50-item Catastrophic Cognition Questionnaire (CCQ)[25] was
developed by Khawaja and Oei[25]. Later a modified, shorter, 21-item version of the scale was developed by the same
authors[26]. This short form could be used to measure catastrophic cognitions in panic disorder patients and nonclinical
populations. The scale was found to be internally consistent (ranging from .83 to .91), with a good test-retest reliability
(r=.63) and concurrent validity. For the present sample, the alpha coefficient was moderately high (r=.86).
Procedure
The Malay version of all instruments was translated using back-translating procedures by four psychologists with at
least a Master’s level of study and bilingual expertise. A professional language interpreter was recruited to proofread
the translated questionnaires to ensure their overall suitability and to resolve issues of word ambiguity after translation.
The back-translated versions were similar to the original versions and to each other. Minor differences in colloquial
expressions in both languages were reconciled.
Signed informed consent was obtained from all participants in the study before they undertook the assessment.
Ethical approval was sought from the Medical Research Ethics Committee of the Ministry of Health of Malaysia and
all the hospitals and institutions that participated in this study.
Statistical analyses
Statistical Program Social Sciences (SPSS version 14.0; SPSS, Chicago, IL) was used to analyse data in this study.
A number of statistical procedures were used such as descriptive statistics for data screening. In addition, Cronbach’s
alpha coefficients (α) were computed to evaluate the reliability of the questionnaire, and correlations were calculated
to examine the concurrent validity of the BAI, using the total sample. Factor analysis was also used to determine factor
structure of the BAI. Prior to conducting the primary analysis, the data were examined for accuracy, missing values,
outliers and multivariate assumptions. Details of the assumption testing of the data are presented in our previous
study[27].
RESULTS
A total of 1090 participants were recruited for this study. The sample consisted of 315 students (28.9%), 495 members
of the general community (45.4%), 167 patients from a primary care unit (15.3%), and 113 patients diagnosed with
depression from a psychiatric clinic (10.4%); Majority of participants were female (75.2%), and the participant’s ages
ranged from 18 to 63 years, with a mean of 26 years. The educational backgrounds of the participants included high
school certificate (47.6%), diploma/certificate level (17.1%) and university degree (32.5%); 1% of the total number of
participants had only completed primary school and 1.8% did not specify their level of education.
Exploratory Factor Analysis
The present study investigated the factorial validity of the BAI. The 21 items of the BAI were submitted to a principal
axis factoring with oblique rotations as suggested by Tabachnick and Fidell’s[28]. A significant number of correlations
with value greater than 0.33 were found indicative of favourability of the data set. Furthermore, the values of the
Kaiser-Meyer-Olkin (0.95) and Bartlett’s Test of Sphericity ((p< .001) suggested the suitability of the data for factor
analysis. The number of factors to retain was conducted based on several criteria which were; 1) minimum eigenvalues
of 1, 2) minimum factor loadings of 0.40, 3) minimal factorial complexity (multiple loading), and 4) meaningful
78
interpretation of factors.
Analysis yielded three factor structure of the BAI. Table 1 presents the item descriptions, factor loadings and
communality estimates. The three factors accounted for 48.01% of the variance. Factor 1 which labelled as subjective
anxiety accounted for 36.32% of the variance, factor 2 accounted for 6.59% of variance was labelled as autonomic and
factor 3, which we labelled neurophysiology accounted for 5.10% of the variance.
Table1.
Item
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Eigenvalues
Total % of
variance
Cronbach α
Rotated Component matrix of Exploratory Factor Analysis for the BAIMalay
Title
Numbness
Hot
Legs
Relax
Fear
Dizzy
Racing
Unsteady
Terrified
Nervous
Chocking
Trembling
Shaky
Control
Breathing
Dying
Scared
Indigestion
Faint
Flushed
Sweat
Factor 1 Factor 2 Factor 3 Communalities
.69
.74
.52
.54
.67
.52
.69
.67
.72
.69
.66
.42
.69
.55
.65
.49
.65
.48
36.32
.71
.53
.54
6.59
5.10
48.01
23.97
13.40
10.64
0.91
0.89
.75
.66
.56
.59
.42
.36
.51
.48
.52
.49
.62
.56
.48
.41
.56
.46
.49
.31
.53
.44
.51
.38
.43
Reliability and Validity of the BAI-Malay
Internal consistency
The reliability of the BAI was calculated by using the Chronbach’s alpha. Result showed in Table 1 that the BAI
had an overall good alpha value of 0.91, specifically the reliability for Factor 1(subjective anxiety) was .89, Factor
2 (autonomic) was .75 and Factor 3 (neurophysiology) was .66. This indicates that the 21-items BAI is a reliable
instrument.
Concurrent Validity
The three concurrent factors of the BAI were measured using the Pearson correlation coefficient. Descriptions of the
scales and their intercorrelations are presented in Table 2.
Existence of the concurrent validity was shown by a significantly positive relationship between the BAI-Malay
79
total scores with the FQ (r=.32), CCQ (r=.23), DASS (r=.68) and ASI (r=.56). Furthermore, the results also revealed
that Factor 1 (subjective anxiety) had a significant relationship with FQ (r=.33), CCQ (r=.22), DASS-21 (r=.67) and
ASI (r=.52). Factor 2 (autonomic) also showed significant relationship with the other four measures (FQ; r=.23, CCQ;
r=.16, DASS; r=.53, ASI; r=.48). Additionally, the third factor (neurophysiology) was also found to have significant
relationship with FQ (r=.24), CCQ (r=.20), DASS (r=.49) and ASI (r=.45). Due to large sample size, this indicates
that the total scores of BAI-Malay shown acceptable concurrent validity.
Table 2.
Intercorrelations for BAI-Malay scores and FQ,
CCQ, DASS, ASI
Variables
Total BAI-Malay
Factor 1
Factor 2
Factor 3
FQ
CCQ
DASS
ASI
.32**
.33**
.23**
.24**
.23**
.22**
.16**
.20**
.68**
.67**
.53**
.49**
.56**
.52**
.48**
.45**
**p< .01 level
DISCUSSION
In general, the findings of the present study provide support for three factor structure of the BAI-Malay. The exploratory
factor analysis (EFA) result revealed three correlated factors, one reflecting subjective anxiety, autonomic and the
other is neurophysiology. The results did not support in most studies among Western population such as, two factor
structures (somatic, subjective anxiety/panic) such in Beck and Hewit & Norton studies [4, 11], four factors (Subjective,
neurophsyicological, panic, and autonomic) in Steer, Beck and Steer, and Osman et al. studies [1, 4, 8, 15], and 5 factors
in Borden, Peterson and Jackson study[16].
One explanation on the discrepancy could be due to homogeneity (either just clinical or non-clinical samples) of
the population in their studies. Meanwhile in the present study, four different samples inclusive of student, general
population, medical and psychiatric patients were used which resulted in significant results. However, three items in
subjective anxiety factor in our study are specifically consistent with Beck’s study which consist of inability to relax,
terrified and nervous. Although items fear and dying do not belong to subjective anxiety in the Beck’s study, it was
reported consistent in one study among Norwegian [18]. Three items in autonomic factor in this study were also found
consistent in Osman et al. studies which consist of items chocking, trembling and difficulty breathing. Meanwhile, to
support item loadings in third factor, neurophysiological were again reported consistently in Osman et al. study which
include numbness, feelings hot, and wobbliness leg [8, 12]. There is a slight lower percentage of total variance (48%) in
this study compared to Beck’s study (59%), but the result did not restrict the robustness of the overall findings.
Further finding in this study is the internal consistency (i.e reliability) that estimates of the BAI were satisfactory
for most sub-scales (.66 to .89) but, considered good (.91) in total scores. Results revealed good internal consistent
were consistently in agreement with other previous study both in Western [29] or non-Western [12] researches. This
means that the BAI in Malay version is reliable to be used in future research in Malaysia.
In addition to establishing the factorial validity of the BAI-Malay, correlation scores examined between the BAI
and other measures of anxiety showed significant relationships. Consistent with previous investigation, the BAI
total and correlate significantly with all related anxiety measures [12]. Specifically, the BAI-Malay showed highly
significant relationship to DASS and ASI. This means that, the specific state symptoms of anxiety that measure in BAI
is considered sensitive to symptoms of stress and anxiety assessed in DASS and ASI. Meanwhile, the lower significant
relationship shown between BAI and VVQ, could best be explained by the background of the participants who are
mostly in healthy range population. The psychiatric patients who undertook this study were mostly suffering from
depression rather than anxiety diagnosis. Future research can further confirm and validate to see the sensitivity level of
the BAI and CCQ among patients with anxiety disorders. Moreover, the FQ also showed low significant relationship
to FQ which was in similar explanation with CCQ. This is because the measurement is specific on certain phobia such
as social phobia, blood injury and agoraphobia which are not common among healthy populations but patients with
anxiety disorders. This finding was also consistent in which the relationship between BAI and FQ is low as in a study
where most of the participants are not having anxiety disorders such as in one study among Norwegian population
[18]
.
This study has specific problems that limit the generalizibility of the findings. Our sample consists primarily of
80
Malay population. Besides that, other measures used for correlation have yet to be validated in the Malay sample.
Despite these limitations, the present study is the first to extend investigation of the factorial validity of the BAI beyond
the primary factors. In addition, our data argue strongly for the BAI used as an assessment of state anxiety. In general,
the results support the use of BAI-Malay in both research and clinical work among Malay population in Malaysia.
This is one of the first studies to validate the BAI-Malay for use within a large and culturally different population
and in which three subscales were subjected to factor analysis. This study provides clear evidence that the BAIMalay is sufficiently reliable and a valid measure of state anxiety symptoms. In conclusion, despite the limitation, the
findings show that the BDI-Malay has sound psychometric properties and is a reliable instrument for measuring levels
of depression among Malays in Malaysia. Therefore, it can be used with confidence in the future.
ACKNOWLEDGEMENT
We wish to extend our warmest gratitude to all participants in this study for their perseverance and determination
throughout the completion of this project.
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Kumar G, Steer R, Beck A. Factor structure of the Bek Anxiety Inventory with adolescent psychiatric impatients.
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Osman A, Kopper B, Barrios F, Osman J, Wade T. The Beck Anxiety Inventory: Reexamination of factor structure
and psychometric properties. Journal of Clinical Psychology 1997; 53: 7-14.
[9]
Steer RA. Amount of General Factor Saturation in the Beck Anxiety Inventory Responses of Outpatients with
Anxiety Disorders Journal of Psychopathology and Behavioral Assessment. 2009; 31(2): 112-8.
[10] Steer R, Beck A. The Beck Anxiety. Zalaquett CP, Wood RJ, editors. Lanham, MD: Scarecrow; 1997.
[11] Hewitt P, Norton G. The Beck Aniety Inventory: A psychometric analysis. Psychological Assessment 1993: 40812.
[12] Osman A, Hoffman J, Barrios F, Kopper B, Breitenstein J, Hahn S. Factor structure, reliability, and validity of the
Beck Anxiety Inventory in adolescent psychiatric inpatients. Journal of Clinical Psychology 2002; 58: 443-56.
[13] Beck AT, Steer RA. Manual for the Beck Anxiety Inventory. San Antonio, TX: Psychological Corporation
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[14] Beck AT, Steer RA. Relationship between the Beck Anxiety Inventory and the Hamilton Anxiety Rating Scale
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[15] Steer RA, Rissmiller DJ, Ranieri WF, Beck AT. Structure of the computer-assisted Beck Anxiety Inventory with
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properties. Journal of Psychopathology and Behavioral Assessment. 1991; 13: 345-57.
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(BAI) in general population. The Spanish Journal of Psychology. 2008; 11(2): 626-40.
[18] Nordhagen T. Beck Anxiety Inventory: Translation and validation of a Norwegian version. Bergen, Norway:
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[19] Yim JY, Mahalingam R. Culture, masculinity, and psychological well-being in Punjab, India. Sex Roles. 2006;
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[20] Jylhä P, Isometsä E. Temperament, character and symptoms of anxiety and depression in the general population.
Eur Psychiatry. 2006; 21: 389-95.
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[24] ReissS, Peterson RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety freuqnecy and the prediction of
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Educational and Psychological Measurement. 2005; 65(5): 742-56.
Physical Activity and Sedentary Behaviour among Adolescents in Petaling District,
Selangor, Malaysia
1
CC Kee*, 1K H Lim, 1MG Sumarni, 2MN Ismail, 2BK Poh & 1NM Amal
1
Epidemiology and Biostatistics Unit,
Institute for Medical Reseach, 50588 Kuala Lumpur.
2
Department of Nutrition & Dietetics, Faculty of Allied Health Sciences,
National University of Malaysia, 50588 Kuala Lumpur.
ABSTRACT
Physical inactivity is strongly associated with obesity and an increased risk of cardiovascular disease in
children and adolescents. A cross-sectional study using multistage random sampling was conducted to
determine associations between demographic characteristics, sedentary behaviours and physical activity
among adolescents. Data were collected from 785 (414 males and 371 females) Form four students
attending 15 schools in Petaling District, Selangor using an adapted self-administered questionnaire.
Results showed that more females (50.1%) were physically inactive compared to males (39.6%) (Adjusted
odds ratio (OR): 1.55, 95% confidence interval (CI): 1.12-2.15). Physically inactive adolescents were
less likely to participate in intramural/house league sports (OR: 1.71, 95% CI: 1.19-2.44), school team
sports (OR: 1.45, 95% CI: 1.03-2.04) and individual physical activities outside school (OR: 1.53, 95%
CI: 1.11-2.12) compared to their physically active counterparts. Physically inactive adolescents were
also less engaged in sedentary activities, such as television watching (OR: 0.69, 95% CI: 0.50-0.94),
playing computer/video game (OR: 0.44, 95% CI: 0.28-0.72), talking on the telephone/mobile phone
text messaging (OR: 0.47, 95% CI: 0.32-0.69) and reading (OR:0.45, 95% CI: 0.24-0.86) compared
to those who were physically active. In this study, physical activity coexists with sedentary behaviour
in adolescents. Sedentary activities may not necessarily displace physical activity among youth. In
addition, these data suggest that promoting organised sports in school and outside the school among
youths may be a potential strategy for increasing physical activity in this population.
Keywords:
Physical activity, sedentary behaviour, adolescent
INTRODUCTION
Physical activity is important for the normal growth, maintenance of physical fitness and psychosocial well being of
children and adolescents.[1] Physical inactivity is strongly associated with cardiovascular disease risk factors (high
blood pressure, hypercholesterolemia, high triglyceride and high percentage body fat mass) and an increased risk of
obesity in children and adolescents.[2, 3, 4] Therefore, identifying the factors related to physical activity in this population
is crucial to address the increasing prevalence of obesity and is of particular concern in children and adolescents.[5]
In European and North American countries, the prevalence of physical activity (at least 60 minutes per day of
moderate to vigorous physical activity for the past 7 days) ranged between 16-26% among children and adolescents
(11-15 year olds). [6] Reported prevalences of physical activities in Asian countries range from 2.8% in the Philippines
to 30.2% in India.[7] Figures on physical activity among children and adolescents in Malaysia are scarce. One study in
Kuantan, Pahang which used the Physical Activity Questionnaire for Older Children to classify adolescents’ physical
activity levels based on mean scores, reported 35% of adolescents engaged in low physical activity, 61.5% moderate
physical activity and only 3.0% high physical activity levels.[8]
Adolescents spend most of their leisure time watching television compared to other sedentary activities.[9]
Therefore, television viewing is the most commonly used marker of sedentary activity.[6, 10] The American Academy of
Paediatrics[11] has recommended that children and adolescents spend no more than 2 hours per day watching television.
However, the jury is still out on the usage of television viewing as a marker of sedentary activity for various reasons.
For one, the amount of television watched per person has not changed for 40 years.[12] Furthermore, reports on the
association between television watching and physical inactivity among children and adolescents have been mixed.
Some found a positive relationship [13], while others reported a weak and negative relationship.[12]
The “displacement hypothesis” proposes that sedentary behaviour is a competitor to physical activity. Increased time
spent in sedentary activities such as television viewing may displace time allocated for physical activity in children and
adolescents.[14] But, the relationship between sedentary behaviours and physical activity is rather complex and requires
84
further investigation. Many studies have shown that increased sedentary behaviours such as television viewing, playing
video/computer game and surfing the internet are associated with less physical activity[15, 16, 17], while, other studies
failed to establish a relationship between sedentary behaviour and physical activity.[18, 12, 10] In addition, physical activity
may be differentially associated with different types of sedentary pursuit. [19, 20] Hence, the main objective of our study
is to evaluate the relationship between the amount of time spent on sedentary activities and physical activity. We have
included other sedentary activities, i.e. video/computer games playing, surfing internet, chatting on the telephone and
other productive sedentary activities (reading or doing homework) which are common among adolescents.
Study design
A cross sectional study was carried out between June and December, 2008 in secondary schools in Petaling District,
Selangor. Formal permission to conduct this study was obtained from the Ministry of Education of Malaysia. Ethical
approval was obtained from the Universiti Kebangsaan Malaysia Research Ethics Committee. Participation was
voluntary and written consent was obtained from students and their parents prior to the study. Non return of parental
consent forms were considered as giving consent to participate in the study.
Sampling method
A list of 66 secondary schools in Petaling District (i.e., areas of Subang, Petaling, Damansara, Puchong/Seri Kembangan
and Shah Alam), Selangor was obtained from the Selangor State Education Department. Fifteen secondary schools
were chosen randomly consisting of 3 schools from each subdistrict i.e Subang, Petaling and Damansara. Four schools
were selected from Puchong/Seri Kembangan and another two from Shah Alam, all added up to a total of 15 schools.
A list of all Form 4 students from the selected schools were obtained from the school authorities and students were
selected by simple random sampling. Epinfo version 6 was used to calculate the sample size based on estimated 7% of
overweight. [21] The estimated form four students population was 16,327. The sample size calculated was 904 students
based on 2.0% desired precision with design effect of 1.5 and confidence interval of 95%. An additional 10% was
added to the figure to compensate for non-response. The final sample size was 994 students.
Selection criteria
The inclusion criteria were healthy Form four students in selected schools. Students with mental or physical disability
and those with recent physical injury or using walking aid devices were excluded from the study.
Data collection
The level of physical activity and sedentary behaviours were assessed with an adapted adolescent physical activity recall
questionnaire that has been validated and found to have moderate reliability and validity in Canadian adolescents. [22]
This questionnaire was translated into the Malay language and translated back into English by a language expert. The
final Malay version questionnaire was evaluated by a small group of experts to check for appropriateness, relevance
and comprehension. Socio-demographic characteristics including age, gender, ethnicity and parental education level
were also recorded.
All members of the research team (research officer, staff nurses, research assistants) were given proper training
pertaining to the study questionnaire. A detailed explanation was given to the students on each question in the
questionnaire prior to administration at each data collection session. While students were answering the questionnaire,
the research team stood by and provided assistance to those who had difficulty understanding the questions.
Physical activity
The participating students were asked to report on the frequency and duration (in hours or minutes) of moderate to
vigorous physical activity they had performed in the past 7 days. These included school-related activities such as
physical education. Vigorous physical activity is defined as physical activities that cause sweating, heavy breathing
and increased heart rate. Meanwhile moderate physical activity is defined as physical activities of lower intensity that
do not cause adolescents to sweat or breathe heavily. [6, 25, 29] Physical activity level was dichotomised into physically
active and physically inactive, using the following criteria: physically active if performed at least 60 minutes or more
of moderate to vigorous physical activity everyday for the past 7 days; physically inactive if less than 60 minutes daily
of moderate to vigorous physical activity on all 7 days during the past 7 days. [23]
Sedentary behaviours assessment
Activities such as television watching, playing video/computer games and internet surfing, also called screen time
activities, are commonly used measurements of sedentary behaviour. [24] Adolescents spend most of their leisure time
85
watching television compared to any other activity. [9] Our questionnaire captured data on frequency and duration
(hours) engaged in sedentary activities in the past 7 days. Sedentary activities included watching TV/movies, playing
video/computer game, surfing the internet, talking/text messaging on the phone, reading for leisure (magazines, story
books, newspaper) and doing homework (written school assignments). In addition, students were asked to report
on how they commuted to school whether actively (walking or cycling), passively (taking a bus, car, motorcycle
or other motorised transports) or a mix of both (actively and passively). Lastly, the students were asked about their
participation in intramural/house league sport, sport team (football, volleyball, basketball) or other physical activities
in school (gymnastic, yoga) and individual physical activities (jogging, swimming, cycling,) after school.
Time duration variables from hours and minutes were converted into minutes only before being analysed. Cases with
missing, illogical or outlying values were removed from the analysis. Cases where the total amount of time for both
sedentary and moderate to vigorous physical activity exceeded 960 minutes (16 hours), were also excluded from the
analysis, based on the assumption that on average a person sleeps 8 hours a day. This procedure of data cleaning has
been widely accepted for assessing time spent for physical activity (http://www.ipaq.ki.se/scoring.pdf). After excluding
cases with missing or extreme values (n=154) and absent students (n=55), the total number of respondents remaining
in the final data set was 785.
All statistical analyses were done using SPSS 11.5. Descriptive statistics were used to describe socio-demographic
characteristics, physical activity and sedentary behaviour of the students. The Chi-square test for independence was
conducted to determine the association between socio-demographic variables and physical activity; participation in
sports and sedentary behaviour; and, physical activity and sedentary behaviour. Multivariate logistic regression was
performed to identify the interrelation of socio-demographic factor, physical activity and sedentary behaviour.
RESULTS
A total of 785 form four students, comprising of 414 males (52.7%) and 371 females (47.3%) were assessed. A large
majority of the students were Malays (62.7%), followed by Chinese (26.2%) and Indians (11.1%). Analysis of parental
education level showed that 42.5% of the students’ fathers had tertiary education, while almost half of the students’
mothers had secondary or lower education (Table 1). Mean amount of time spent on physical activity and sedentary
activities by gender are shown in Table 2. Females engaged in more moderate physical activity compared to males,
while males perform more vigorous physical activity. Females spent more time watching television, talking on the
phone, reading and doing homework, while males spend more time playing computer/video games and surfing the
internet (Table 2).
Table 1.
Sociodemographic characteristic of students (n = 785)
Variable
n
%
Gender
Male
Female
414
371
52.7
47.3
Age
14
15
16
17
3
18
748
16
4
2.3
95.3
2
Ethnicity
Malay
Chinese
Indian
492
206
87
62.7
26.2
11.1
Father’s education level
None
Primary
Secondary
Tertiary
Others
9
99
317
334
26
1.1
12.6
40.4
42.5
3.3
Mother’s education level
None
Primary
Secondary
Tertiary
Others
20
82
383
281
19
2.5
10.4
48.8
35.8
2.4
86
Table 2.
Time spent on physical activity and sedentary activities by gender
Male (n=414)
mean
±SD
Female (n=371)
Mean
±SD
Physical activity (Total)
Moderate (hour/day)
Vigorous (hour/day)
1.37
1.27
1.46
1.15
1.43
1.23
1.23
1.42
1.03
1.19
1.74
1.08
Sedentary activities
Television watching (hour/day)
Playing computer or video game (hour/day)
Internet surfing (hour/day)
Talking on phone or text messaging (hour/day)
Reading for leisure (hour/week)
Homework (hour/week)
2.53
1.25
0.94
1.2
6.41
4.85
1.78
1.35
1.16
1.86
9.27
5.83
2.8
0.46
0.77
1.68
7.49
7.88
1.91
0.83
1.11
2.18
9.64
7.88
About 50.1% of female and 39.6% male students did not meet the recommendation of at least 60 minutes/day of
moderate to vigorous physical activity. Male students were significantly more active compared to female students (p=
0.003). There was a significant association between ethnic group and physical activity (p=0.031). Students of Chinese
descent were found to be less physically active compared to Malay and Indian students. There was no association
between parental education level and physical activity level.
Table 3.
Association between selected sociodemographic characteristics, sedentary activities and sport
participation with physical activity (n=785)
Physical activity
Active †
Inactive††
n
%
n
%
Variable
df
χ2*
p-value
Gender
Male
Female
250
185
60.4
49.9
164
186
39.6
50.1
1
8.766
0.003
Ethnicity
Malay
Chinese
Indian
286
98
51
58.1
47.6
58.6
206
108
36
41.9
52.4
41.4
2
6.958
0.031
Father’s education level
≤Secondary
> Secondary
Others
240
179
16
56.5
53.6
61.5
185
155
10
43.5
46.4
38.5
2
1.035
0.596
Mother’s education level
≤Secondary
> Secondary
Others
271
152
12
55.9
54.1
63.2
214
129
7
44.1
45.9
36.8
2
0.702
0.704
< 2 hours
≥ 2 hours
145
290
49.0
59.3
151
199
51.0
40.7
1
7.946
0.005
Television watching /day
Physical activity
Active †
Inactive††
n
%
n
%
Variable
87
df
χ2*
p-value
Playing computer or video
game /day
< 2 hours
≥ 2 hours
341
94
51.9
73.4
316
34
48.1
26.6
1
20.108
<0.001
Internet surfing /day
< 1 hour
≥ 1 hour
265
170
52.0
61.8
245
105
48.0
38.2
1
7.027
0.008
Talking on phone or text
messaging
< 2 hours
≥ 2 hours
312
123
51.3
69.5
296
54
48.7
30.5
1
18.33
<0.001
Reading for leisure/ week
< 1 hour
1-6 hours
≥ 6 hours
37
241
157
40.7
57.4
57.3
54
179
117
59.3
42.6
42.7
2
9.07
0.011
Homework/ week
< 1 hour
1-6 hours
≥ 6 hours
30
260
145
42.3
60.0
51.6
41
173
136
57.7
40.0
48.4
2
10.391
0.006
Intramural/house league
sports
Yes
No
194
241
66.4
48.9
98
252
33.6
51.1
1
22.871
<0.001
School team
Yes
No
258
177
63.2
46.9
150
200
36.8
53.1
1
21.034
<0.001
Other physical activities in
school
Yes
No
258
177
59.3
50.6
177
173
40.7
49.4
1
5.995
0.014
Individual physical
activities outside of school
Yes
No
216
219
63.0
49.5
127
223
37.0
50.5
1
14.091
<0.001
Actively
Inactively
Mixed
156
196
83
60.5
55.1
48.5
102
160
88
39.5
44.9
51.5
2
5.955
0.051
Sports participation
Commuting to school
* Chi-square test for independence; † Physically active is defined as ≥ 60 minutes/day of moderate to vigorous physical
activity; †† Physically inactive is defined as < 60 minutes/day of moderate to vigorous physical activity (U.S Department
of Health and Human Services Department 2008)
Increased sedentary activities were positively associated with physical activity level (Table 3). Students who spent
more than two hours daily on television viewing, playing video/computer game, internet surfing and talking on the
phone or mobile phone text messaging were more physically active compared to their counterparts who spent less than
two hours daily for the same activities. Those who spent more than one hour per week reading for leisure and doing
homework were also more active than those who spent less than one hour per week.
Sixty percent of the students were actively commuting to school compared to 55.1% passive commuters and 48.5%
mixed (active and passive) commuting (Table 3). However, no association was found between commuting to school
and physical activity.
88
Multiple logistic regression tests were used to identify the factors related to physical activity. All variables with p
value less than 0.25 in univariate analysis were included in the model (Table 3). After adjusting for all other variables,
females were found 1.6 times more likely to be physically inactive compared to male students. Physically active
adolescents were more likely to engage in sedentary activities, such as television watching, playing computer/video
game, talking on the telephone/mobile phone text messaging and reading compared to their physically inactive
counterparts (Table 4). In addition, participation in intramural/house league sports, school team sports and individual
physical activities outside school were significantly associated with physical activity (p<0.05) (Table 4). No interaction
was observed among the variables.
Table 4.
Factors related to physical inactivity# (n=785)
Variable
n
Crude OR
95% CI
Adjusted OR†
95% CI
Male
Female
414
371
1
1.53**
(1.16, 2.03)
1.55*
(1.12, 2.15)
Malay
Chinese
Indian
492
206
87
1
1.53*
0.98
(1.10, 2.12)
(0.62, 1.56)
1.32
1.00
(0.92, 1.89)
(0.60, 1.67)
< 2 hours
≥ 2 hours
296
489
1
0.66**
(0.49, 0.88)
0.69*
(0.50, 0.94)
Playing computer or video game
/day
< 2 hours
≥ 2 hours
657
128
1
0.39**
(0.26, 0.60)
0.44*
(0.28, 0.72)
Internet surfing /day
< 1 hour
≥ 1 hour
510
275
1
0.67**
(0.50, 0.90)
0.98
(0.69, 1.38)
Talking on phone or short message < 2 hours
sending
≥ 2 hours
608
177
1
0.46**
(0.32, 0.66)
0.47**
(0.32, 0.69)
Reading for leisure/ week
< 1 hour
1-6 hours
≥ 6 hours
91
420
274
1
0.51**
0.51**
(0.32, 0.81)
(0.32, 0.83)
0.53*
0.45*
(0.30, 0.95)
(0.24, 0.86)
< 1 hour
1-6 hours
≥ 6 hours
71
433
281
1
0.49**
0.69
(0.29, 0.81)
(0.41, 1.16)
0.63
0.85
(0.33, 1.18)
(0.42, 1.70)
Yes
No
292
493
1
2.07**
(1.53, 2.80)
1.71*
(1.19, 2.44)
Yes
No
408
377
1
1.94**
(1.46, 2.59)
1.45*
(1.03, 2.04)
Yes
No
435
350
1
1.43*
(1.07, 1.89)
0.95
(0.68, 1.33)
Sociodemography characteristics
Gender
Ethnicity
Television watching /day
Homework/ week
Participation in sports
Intramural/house league sports
School team
Other physical activities in school
Variable
89
n
Crude OR
95% CI
Adjusted OR†
95% CI
1.53*
(1.11, 2.12)
Individual physical activities
outside of school
Yes
No
343
442
1
1.73**
(1.30, 2.31)
Commuting to school
Inactively
Actively
Mixed
196
156
83
1
0.80
1.30
(0.58, 1.11)
(0.90, 1.87)
Hosmer and Lemeshow test - χ2 = 7.342, p= 0.500,# Physically inactive is defined as <60 minutes/day of moderate to vigorous
physical activity (U.S Department of Health and Human Services 2008).† Adjusted for all the other variables; *p<0.05;
**p<0.001.
Logistic regression equation: Z (physical activity) = 0.203 + 0.439 (male) + 0.000 (Indian) + 0.533 (Intramural/house league
sports) + 0.374 (school team) – 0.050 ( Other physical activities in school) + 0.426 ( Individual physical activities outside of
school) – 0.467 (homework 1-6 hours/week) – 0.166 (homework ≥ 6 hours/week) -0.629 (reading for leisure 1- 6 hours/week)
– 0.795 (reading for leisure ≥ 6 hours/week) ¬– 0.373 (watching TV ≥ 2 hours/week) – 0.023 ( Internet surfing ≥ 1 hour/day)
– 0.809 ( Playing computer or video game ≥ 2 hours /day) – 0.759 ( Talking on phone or short message sending ≥ 2 hours/day)
DISCUSSION
Numerous studies estimating the prevalence of physical activity have been done among children and adolescents
around the world.[6, 25] However, to compare physical activity prevalences across different countries pose a difficulty
due to differences in methodology, scales, analysis and reporting as well as proposed physical activity criteria. [26, 24]
Differences in proposed physical activity may cause prevalence estimates to differ dramatically.
The present study found that the prevalence of adolescents who met the 60 minutes moderate and vigorous
physical activity (MVPA) was 60.4% among males and 49.9% among females. This is similar to the rates reported in
Kuantan, Pahang (77.9% among males and 54.9% among female adolescents in the moderate/high physical activity
level category).[8] Studies in Xi’an, China and Singapore also reported similar rates (63% among males and 47%
among females in Xi’an [27] and in Singapore (73% overall). [28]
But, the prevalence of physical activity (perform 60 minutes MVPA) reported in this study is higher compared to
East Asian countries, European and North American countries.[6, 25, 29] The prevalences in East Asian countries (India,
China, Sri Lanka, Philippines, Thailand, Myanmar and Indonesia) reported from the Global School-based Student
Health Survey (GSHS) from 2003 to 2008 ranged from 3.7 to 31% for males and 2.1 to 29.1% for females.[25, 29] While,
the Health Behaviour in School-aged Children (HBSC) study, WHO 2005/2006 reported 20% male and 12% female
adolescents (15 year olds) perform 60 minutes MVPA in Europe and North America.[6] The prevalence found in our
study is far higher than the GSHS and the HBSC, which may be because of the substantial difference in sample size.
Therefore, a larger scale and more representative study is needed to provide a better estimate of the prevalence of
physical activity among adolescents in this country.
The American Academy of Paediatrics[11] in 2001 recommended that children and adolescents should not spend
more than two hours watching television per day. In our study, 62.5% of the respondents (59.9% males and 65%
females) spent two or more hours per day watching television. This prevalence is higher than the rates reported for
adolescents in China and in Vietnam which were 24% [27] and 29.7% [30], respectively. However, the prevalence is
similar to that reported from the HBSC (Health Behaviour in School-aged Children) among 15- year olds in developing
countries in Europe and North America which was 68% overall.[6]
Univariate analysis and multivariate analysis showed that female adolescents were significantly less physically
active compared to boys. Our finding is consistent with findings from previous studies in other countries.[7, 13, 20, 31] This
may be explained by the fact that male adolescents’ prefer more vigorous activities and team sports.[32, 33] In addition,
female adolescents’ perceived barriers of physical activity were consistently higher compared to males. Among the
main barriers to physical activity reported by female adolescents were time allocated for schoolwork, family activities
and not being in the mood for physical activity [34], prefer to watch television and play electronic games to physical
activities, and having no one to be physically active with.[35]
Ethnicity was not associated with level of physical activity. While in Western countries, differences in physical
activity levels between ethnic groups have been shown. McMurray et al.[37] in 2000 found that African Americans
adolescents perform physical activities of varying intensity more frequently compared to whites adolescents. In
contrast, Eisenmann et al.[36] in 2002 reported that more white adolescents performed moderate and vigorous compared
to Hispanic and African-American teens. Prior to that, a review by Sallis et al.[13] in 2000 had concluded that there was
consistent evidence that Non-Hispanic Whites are more physically active compared to other ethnic groups. But, the
90
review was limited to studies from Europe and North America and did not include Asian countries.
There was no association between parental education level and adolescent physical activity in this study. This
finding is consistent with a report by Chen et al. in 2007. [38] Shi et al.[39] in 2006 reported that children of high
socioeconomic status were found to spend more time reading, doing schoolwork and less time on outdoors because
of stricter parental monitoring.[39] But, other studies have shown that adolescents with highly educated parents were
more physically active (spent more time for extra-curricular activity and sports club) compared to those whose parents
were less educated.[40, 41]
This study showed that adolescents who are active in team sports and house league sports and individual physical
activity outside school were more physically active compared to those who did not participate in sports activities.
Similarly, Santos [33] found that physically active adolescents engaged in more organised sports (with guidance of
a coach) and team sports compared to less active adolescents. Participation in organised sports[42], extracurricular
exercises (team or individual), number of events organised annually and number of physical education sessions per
week in school[43] was found to increase adolescent physical activity.
The relationship between level of physical activity and sedentary behaviour is complex. In this study, students
who were physically active were also engaged in sedentary activities. Other studies reported a positive relationship
or no relationhip between sedentary behaviour and child or adolescent physical activity level. Sedentary behaviour
does not necessarily oppose physical activity, but on the contrary, may coexist with it. An adolescent may perform
physical activity for more than 60 minutes a day, and also engage in sedentary activities.[44] A longitudinal study
in 2007 by Taveras et al. [10] found that the variation in time spent watching TV was not associated with leisure
physical activity. In the same year, Chen et al. [38] reported that highly physically active youths spent more time
on sedentary activities (sitting) compared to those who were less active physically, and explained that this may be
because Taiwanese adolescents spend more time studying especially during public and university entrance exam years,
therefore, adolescents may be trying to balance long study hours with sports or exercise. The review by Sallis et al.
[13]
suggested that there is no association between time watching television and physical activity level. Another recent
systematic review suggested that there was no firm evidence showing sedentary behaviour (playing video games and
using the computer) reduces physical activity among children and adolescents.[45]
This contradicts the ‘Displacement Hypothesis’ that an increase in a certain type of activity will displace other types
of activities[14], which has been observed in previous studies. Increase in screen time (watching television and playing
video or computer games) were associated with decreased physical activity.[16, 17, 20] A recent meta analysis found a
weak and negative relationship between watching television and computer/video gaming with physical activity.[15]
Eventhough to date, there is lack of conclusive proof that sedentary behaviour displaces physical activity in
adolescents, sedentary behaviour should still be limited as it contributes to reduced energy consumption and encourages
positive energy balance.[44] Furthermore, some studies have shown that sedentary behaviour is linked to consumption
of snacks and high energy foods among children and adolescents. [46, 47]
Self-reported physical activity using validated self-administered questionnaires is necessary in epidemiological
studies and surveys where objective measurement is not practicable. Among the advantages of this method are; its
convenience and does not cause discomfort besides the ability to record physical activity history and low cost. [48]
However, other studies have shown that objective measurements such as accelerometry are more accurate and suitable
for use in large-scale studies involving children and adolescents.[49] The questionnaire used in this study was developed
for Canadian adolescents, but comprehensibility and relevancy of the questionnaire were assessed and adjusted to
suit the local context. While frequency, duration and intensity of physical activity were assessed using the self-report
questionnaire, information on the types of physical activity frequently performed by adolescents such as type of
games and individual or team sports were not. Future studies need to evaluate the types of physical activities preferred
by adolescents so that more effective programs may be implemented such as providing access to the facilities and
equipments for adolescents to play sports. Assessing physical activity in children and adolescents using questionnaires
may result in overestimated or underestimated physical activity levels.[49, 50] Comparisons of physical activity prevalence
with previous studies are limited as the other studies used different self-administered questionnaires designed for
different purposes resulting in a wide variation in questionnaire validity.[51] As the design of the present study was
cross-sectional it is not possible to infer causal relationships. Longitudinal studies are required in order to further
explore and confirm these findings and better understand the predictors of physical activity and sedentary behaviour
among Malaysian adolescents.
In conclusion, our findings show that more females are physically inactive compared to males. Physically inactive
adolescents are less likely to participate in intramural/house league sports, school team sports and individual physical
activities outside school compared to their physically active counterparts. Therefore, promoting organised sports
in school and outside the school among youths may be a potential strategy for increasing physical activity in this
population. Physically inactive adolescents are also less engaged in sedentary activities, such as television watching,
playing computer/video game, talking on the telephone/mobile phone text messaging and reading compared to those
91
who are physically active. In this study, physical activity coexists with sedentary behaviour in adolescents. Sedentary
activities do not necessarily displace physical activity among youth.
ACKNOWLEDGEMENTS
We would like to thank the Director-General of Health Malaysia for his permission to publish this paper. We would
also like to thank the Ministry of Education, the schools, students, involved in the study and all those who assisted in
data collection and management for their support and cooperation.
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[47] Giammattei J, Blix G, Marshak HH, Wollitzer AO, Pettitt DJ. Television watching and soft drink consumption.
Arch Pediatr Adolesc Med 2003; 157: 882-886.
[48] Trost SG. State of the art reviews: Measurement of physical activity in children and adolescents. Am J Lifestyle
Medicine 2007; 1: 299-313.
[49] Riddoch CJ, Bo Andersen L, Wedderkopp N et al. Physical activity levels and patter.ns of 9- and 15-yr-old
European children. Med Sc Sports Exerc 2004; 36: 86-92.
[50] Adamo KB, Prince SA, Tricco AC, Connor-Gorber S, Tremblay M. A comparison of indirect versus direct
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[51] Sallis JF, Saelens BE. Assessment of physical activity by self-report: Status, limitations and future directions.
Res Q Exerc Sport 2000; 7(Suppl 2): S1-S4.
Malaysian Journal of Medicine and Health Sciences Vol. 7 (1) January 2011: 95
LETTER TO EDITOR
School Bag Weight
Viroj Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok Thailand 10160
Editor, I read the recent publication on school bag weight with a great interest [1]. Nor Azlin et al.
concluded that “Students from all the three mediums primary schools, in particular Chinese medium
school carry school bag heavier than that generally recommended, with unnecessary materials weigh up
to 2kg [1].” I agree that this is an important problem and it is wise to suggest to the parents to help take
care of their children’s school bad weight and for the school to provide school lockers. However, an
important concern might be the things within the students school bag. It is interesting to know what is
exactly in the school bag. It cannot be presumptively assigned as only learning materials. There might
be other unnecessary things such as cartoon books, games, deserts, etc. For sure, these things might be
bought and collected into the school bag on the way to school that cannot be controlled by the parents.
The study on this topic is useful to assess the actual behavior of school student on carrying things to
schools. Last, it should also be mentioned that not only weight but also other factors including duration
of carriage, and method of transport to school can result in the pain of school children [2].
REFERENCES
[1]
Nor Azlin MN, 1Asfarina Z, Chee WL. Schoolbag Weight, its Content, and Incidence of Back Pain in Different
Medium Primary Schools in Kuala Lumpur. Malaysian J Med Health Sci. 2010 Jun; 6(2): 59-64.
[2]
Haselgrove C, Straker L, Smith A, O’Sullivan P, Perry M, Sloan N. Perceived school bag load, duration of
carriage, and method of transport to school are associated with spinal pain in adolescents: An observational
study. Aust J Physiother. 2008; 54(3): 193-200.
97
Acknowledgement
The Editorial Board of the Medicine and Health Sciences gratefully acknowledge the following
individuals for reviewing the papers submitted for publication consideration:
Prof. Dr. Azhar Md. Zain
Prof. Dr. Elizabeth George
Prof. Dr. Lekhraj Rampal
Prof. Dr. Wan Omar Abdullah
Prof. Dr. Abdul Hamid Abdul Rashid
Prof. Dato’ Dr. Lye Munn Sann
Assoc. Prof. Dato’ Dr. Faisal Hj. Ibrahim
Assoc. Prof. Dr. Hairuszah Ithnin
Assoc. Prof. Dr. Brian Ho Kong Wai
Assoc. Prof. Dr. Hejar Abdul Rahman
Assoc. Prof. Dr. Lim Wai Kong
Assoc. Prof. Dr. Latiffah A. Latiff
Dr. Salmiah Md. Said
Dr. Maha Abdullah
Dr. Mohd. Nasir. Mohd. Taib
Prof. Dr. Wan Ariffin B. Abdullah
Prof. Dr. Nor Zuraida Binti Zainal
Dr. Hussain Imam Hj. Muhammad Ismail
Prof. Datin Dr. Ilina Ishak
Prof. Dato’ Dr. Khairul Anuar Abdullah
Dr. Lee Han Lim
Prof. Dr. Khor Geok Lin
Universiti Putra Malaysia
Universiti Malaya
Universiti Malaya
Hospital Kuala Lumpur
Hospital Universiti Kebangsaan Malaysia
MAHSA College
Institute of Medical Research (IMR)
International Medical University (IMU)
Malaysian Journal of Medicine and Health Sciences Vol. 6 (2) June 2010
Subscriptions
Malaysian Journal of Medicine and Health Sciences is published twice a year, in January and
June.
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MANUSCRIPT GUIDELINES
The Malaysian Journal of Medicine and Health Sciences invites submissions of articles of interest in English languange
on all aspects of medicine and health sciences in the form of original papers, short communications, case reports and
letters. All manuscripts must be accompanied by a covering letter signed by all contributing authors to the effect
that the article has not been submitted to, nor published previously elsewhere. Neither the Editorial Committee nor
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condition of publication that authors vest copyright in their articles, including abstracts, in the Faculty of Medicine
and Health Sciences, Universiti Putra Malaysia. The editor reserves the right to make editorial and literary corrections
including the style and if necessary shorten any material accepted for publication.
Manuscripts should be typed in 12 pt font on one side of A4 paper and double-spaced throughout with margins of at
least 2.5 cm. The manuscript should be written under separate headings in the following order – Abstract, Introduction,
Methods, Results, Discussion, Conclusion Acknowledgement, References, Tables, and Legends for Illustrations.
Each section should begin on a fresh page. The first page should state the title of the paper, initials and name(s) of
the author(s), degrees (limited to one degree or diploma) and address(es). The name and address of the author for
correspondence should be clearly indicated. Names of authors should be written in style of initials followed by the
surname or preferred name e.g., M Z Azhar for Azhar bin Md Zain, L Rampal for Lekhraj Rampal or T A Lim for Lim
Thiam Aun. Authors who have previously published should try as much as possible to keep the abbreviation of their
name consistent.
Abstract and Key Words: The second page should carry an abstract (of no more than 150 words for unstructured
abstract, 250 words for structured abstract). The abstract should state the purposes of the study or investigation, basic
procedures (selection of study subjects or experimental animals, observational and analytical methods), main findings
(give specific data and their statistical significance, if possible), and the principal conclusions. Emphasise new and
important aspects of the study or observations. Identity not more than five keywords that will assist in cross indexing
the article. These will be published with the abstract. Use terms from medical subject headings (MeSH). List of Index
Medicus; if suitable MeSH terms are not yet available for recently introduced terms, present terms may be used.
Scientific names, foreign words and Greek symbols should be clearly indicated and underlined.
Introduction: Clearly state the purpose of the article. Summarise the rationale for the study or observation. Give only
strictly pertinent references, and do not review the subject extensively.
Materials and Methods: Describe the selection of the observational or experimental subjects (patients or experimental
animals, including controls) clearly, identify the methods, apparatus (manufacturer’s name and address in parenthesis),
and procedures in sufficient detail to allow other workers to reproduce the results. Give references of established
methods, including statistical methods; provide references and brief descriptions of methods that have been published
but are not well-known; describe new or substantially modified methods, give reasons for using them and evaluate
their limitations. Identify precisely all drugs and chemicals used, including generic name(s), dosage(s) and route(s)
of administration. Do not use patients’ names, initials or hospital numbers. Include numbers of observation and the
statistical significance of the findings when appropriate. When appropriate, particularly in the case of clinical trials,
state clearly that the experimental design has received the approval of the relevant ethical committee(s).
Results: Present the results in a logical sequence in the text, tables, and illustrations. Do not repeat in the text all the
data in the tables or illustrations. Emphasise or summarise only important observations.
Discussion: Emphasise the new and important aspects of the study and conclusions that follow from them. Do not
repeat in detail data given in the Results section. Include in the Discussion the implications of the findings and their
limitations and relate the observations to other relevant studies.
Conclusion: Link the conclusions with the goals of the study but avoid unqualified statements and conclusions not
completely supported by your data. Recommendations, when appropriate, may be included.
Acknowledgements: Acknowledge grants awarded in aid of the study (state the number of the grant, name and
location of the institution or organisation), as well as persons who have contributed significantly to the study. Authors
are responsible for obtaining written permission from everyone acknowledged by name, as readers may infer their
endorsement of the data.
Tables: Type or print each Table double-spaced on a separate sheet. Do not submit table as photographs. Number
Tables consecutively in Arabic numerals (1, 2, etc) in the order of their first citation in the text. Provide a brief title at
the top of each table. Give each column a short or abbreviated heading. Place explanatory matter in the footnotes, not
in the heading. Explain in the footnotes all non-standard abbreviations that are used in each Table. Do not use internal
horizontal and vertical rules.
Illustrations and figures: Each illustration should be sent unmounted and have a label pasted on the back indicating
the title of the article, the figure number, the orientation and, for photomicrographs, the original magnification. The
authors are asked to provide two photocopies of each illustration, in addition to the original. A list of legends for each
figure must be supplied on a separate sheet of the manuscript. Unless specifically requested by the author, illustrations
will not be returned after publication. All illustration should be referred to in the text. Photographic illustrations
and radiographs should be submitted in the form of good quality prints (not
not X-ray negatives or slides). Illustrations
should be limited to those considered essential. Illustrations in colour are acceptable only if they illustrate important
points not demonstrable in black and white and if the author is willing to bear the additional cost. Line drawings
should be professionally drawn with lettering large enough to stand reduction. Figures: Figures should be numbered
consecutively in Arabic numerals (e.g. Fig. 1, 2) according to the order in which they have been first cited in the text.
Photographs of patients: Proof of permission and/ or consent from the patient must be submitted with the manuscript.
A statement on this must be included as a foot note to the relevant photograph.
Case Reports: Papers on case reports (one to five cases) must follow these rules: Maximum of 1,000 words; only one
table is allowed; maximum of two photographs; and up to five references only.
Letters: Questions or comments concerning published papers maybe sent to the Editor who will refer them to the
authors. Comments from readers and replies from authors may be subsequently published.
Review articles: Only invited reviews are accepted.
Communications: Short communications should not exceed 1,000 words and shall consist of an Abstract and the
Main Text. The number of figures and tables should be limited to three and the number of references to five.
References: Number references consecutively in the order of appearance in the text. Identify references in text, tables
and legends by Arabic numerals (in parenthesis). References cited only in the tables or legends to figures should be
numbered in accordance with a sequence established by the first identification in the text of the particular table or
illustration. “Personal communications” and “unpublished observation” may not be used as references. For accepted
manuscripts which are not yet published; designate the journal followed by “in press” (in parenthesis). The references
must be verified by the author(s) against the original documents. List all authors when six or less; when seven or more
list only three and add et al. Examples of reference styles are given below:
Journals
Standard Journal Article: Moss R, Munt B. Injection drug use and right sided endocarditis. Heart 2003; 89: 577581.
Corporate Author: Center for Disease Control and Prevention. Pertussis surveillance-United States. 1986-1988. Morb
Mort Wkly Rep 1990; 39: 57-66.
Books and Other Monographs
Personal Author(s): Hoftbrand AV, Pettit JE, Moss PAH. Essential Haematology (4th ed). Cambridge: Blackwell
Science, 1995.
Corporate Author: World Health Organization, International Agency for Research on Cancer. World Cancer Report.
Lyon: IARC Press, 2003.
Editor, Compiler, Chairman as Author: Gibney MJ, Margetts BM, Kearney JM et al. (eds). Public health nutrition.
Oxford: Blackwell Science, 2004.
Chapter in Book: White R. Stigmatization of mentally ill medical students – some strategies to tackle stigmatization
and discrimination. In: Crisp AH (eds). Every family in the land. Understanding prejudice and discrimination against
people with mental illness. London: Society of Medicine Press, 2003: Chap 9 part 2.

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