Vol. 19 No. 2, June 2004
Tanzania Medical Journal
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SERO – PREVALENCE OF HEPATITIS B SURFACE ANTIGEN AMONG INDIVIDUALS WITH HIV – RELATED
CUTANEOUS DISORDERS AT A TERTIARY REFERRAL DERMATOLOGY CLINIC IN DAR ES SALAAM.
YM Mgonda
Summary
Background: HIV and hepatitis B virus (HBV) infections are common
in sub Saharan Africa. HIV/AIDS is associated with a wide variety of
cutaneous disorders which herald the onset of severe
immunosuppression. In sub Saharan Africa, HBV is transmitted
mainly horizontally through skin contact. Few studies if any have
determined the prevalence of HBV infection among HIV sero-positive
individuals with HIV – related cutaneous disorders.
Objective: To determine the sero – prevalence of hepatitis B surface
antigen among HIV – seropositive individuals with HIV- related
cutaneous disorders.
Setting: Tertiary referral Dermatology clinic, Muhimbili National
Hospital, Dar es Salaam.
Design and methods: Hospital based controlled study whereby
consecutive patients with HIV – related cutaneous disorders were
enrolled. After filling in a questionnaire and undergoing dermatological
examination blood was drawn for HBsAg and HIV antibody screening.
Adult and secondary school student blood donors were used as
controls.
Results: 384 patients with HIV-related skin lesions were enrolled into
the study. 354 (92%) were HIV sero positive while 30 (8%) were seronegative. The majority, 204/354 (58%) had PPE alone or co existing
with other cutaneous lesions. Thirty of the 354 (8%) HIV - positive
patients were co infected with hepatitis B virus. Of the adult voluntary
blood donors, 28/333 (8%) were HIV sero positive, 32/333 (10%) were
HBsAg positive while 4/333 (1.2%) had HIV and HBV co infection. For
student blood donors, 2/120 (2%) were HIV positive while 10/120 (8%)
were HBsAg positive and none of them had HIV and HBV co infection.
The sero prevalence of HBsAg did not differ significantly between
patients with HIV – related skin disorders, adult and secondary school
student blood donors (p= 0.64)
Conclusion: Although the prevalence of HBsAg among HIV positive
individuals with HIV related cutaneous disorders was apparently
similar to that of adult and student blood donors, the HBV and HIV co
infection rate of 8% among individuals with HIV related cutaneous
disorders may pose a significant challenge in terms of the implicated
liver - related mortality and rational choice of anti- retroviral drugs
especially in this era of HAART.
Key words: HBsAg, HIV, HIV – related skin diseases.
Introduction
Hepatitis B virus (HBV) infection is endemic
throughout sub Saharan Africa where it is associated with
significant morbidity and mortality.(1) On average, 10 - 11%
of the general population has chronic HBV infection
(HBsAg carriers).(2) Horizontal transmission by skin contact
is the most important transmission route in sub Saharan
Africa.(3) The prevalence of HIV infection is highest in the
same areas where hepatitis B virus infection is very
common.(4) HIV and HBV are transmitted by similar
mechanisms but differ in their infectivity and the
predominance of the modes of transmission. HBV, whose
transmission in sub Saharan Africa is mostly horizontal, is
about 100 times more infective than HIV which on the
Correspondence to: Mgonda YM, Box 65001, Muhimbili University College of Health
Sciences
Department of Internal Medicine
contrary, is mainly transmitted heterosexually.(3) Studies
have shown that the onset of some of the HIV – related skin
diseases predicts the occurrence of an advanced stage of
immunosuppression with an increased risk of acquiring
opportunistic infections.(5) Hepatitis B virus is a welldocumented opportunistic pathogen among HIV infected
individuals. The presence of HIV – related skin lesions, may
make horizontal transmission of HBV more likely. (3)
Furthermore, HIV disease causes multidimensional
immunosuppression, which could compromise one’s ability
to recover spontaneously from an acute HBV infection thus
leading to a chronic disease.(6)
The prevalence of HBV infection among individuals
with HIV related cutaneous disorders is largely unknown,
particularly in sub Saharan Africa although the prevalence of
both infections in the general population is alarmingly high.
The effect of HIV infection on those infected with HBV is
not clearly understood. Some studies suggest that the
progression of liver disease is diminished, which might be
expected since the pathogenesis of hepatitis B is
immunologically mediated and the immunity is
compromised in the presence of HIV infection. (7) However,
other studies suggest that the progression of liver destruction
is increased leading to early chronic active hepatitis, liver
cirrhosis and finally hepatocellular carcinoma the
mechanism of which is not very clear.(6, 12) The effect of HIV
infection on the natural course of hepatitis B could also be
modified by the highly active antiretroviral therapy
(HAART).(7) The HAART associated liver toxicity and
immune restoration could both accelerate liver damage
leading to increased of early liver related death. (7)
There is therefore a need to determine the disease
burden of HBV co infection among different categories of
HIV positive individuals, like those with HIV- related
cutaneous lesions many of which are potentially ulcerative
and markers of severe immunosuppression. This knowledge
would challenge clinicians to take appropriate preventive
and therapeutic interventions including rational choice of
anti retro viral drugs. It was on this background that this
study was conducted with the main objective of determining
the prevalence of HBV co infection among HIV –
seropositive individuals with HIV- related cutaneous
disorders.
Materials and methods
The study was conducted at the tertiary referral
dermatology unit of Muhimbili National Hospital in Dar es
Salaam, between June 2002 and July 2003. During this
period, consecutive patients with HIV - related cutaneous
disorders were recruited into the study after obtaining their
fully informed verbal consent. Each patient underwent a full
physical and dermatological examination. Diagnoses of HIV
related - skin diseases were made clinically in most cases
Vol. 19 No. 2, June 2004
Tanzania Medical Journal
except for doubtful dermatoses as well as cases of cutaneous
Kaposi’s sarcoma where skin biopsies were performed for
histological confirmation. A structured questionnaire was
used for data recording.
After a pre – test counseling, whole blood for HIV and
HBsAg screening was collected in empty sterile vacutainer
tubes from which plasma was separated. A qualitative
immunoassay for the detection of antibodies to HIV 1&2
was done using Determine TM kit (Abbot Japan Co Ltd.
Minato – Ku Tokyo, Japan). Screening for HBsAg was
performed with Virotect – HBsAg kit (Omega diagnostics
Ltd, Omega House, Scotland, UK). Post – test counseling
was offered to all subjects.
Samples of blood from all adult and student voluntary
blood donors who came to the hospital over a randomly
selected period of three months within the study period were
anonymously collected and screened for HIV and HBV
using the same techniques as for the study subjects. These
were used as controls.
Data were entered into a computer and validated to
ensure that all entries were accurate. Analysis was done
using Epi info version 6 software and p – value was
considered to be significant if it was less than 0.05.
Results
A total of 384 patients with skin disorders suggestive of
HIV infection were enrolled into the study. Of these, 354
(92%) tested HIV sero positive while 30 (8%) were sero
negative. Out of 354 - sero positive individuals, 171(48%)
were males while183 (52%) females. The age (table 1)
ranged from 2 to 57 years with a mean of 35 years. The 25th
and 75th centiles were 30 and 42 years of age respectively.
Overall, the age group that was mostly affected was 31 – 40
years (43%) followed by 41 – 50 (22%) and 21 – 30 years
(17%).
Table 1: Age and sex distribution of patients with HIV
related skin disorders (n=354)
Age
0 - 10
11 – 20
21 – 30
31 – 40
41 – 50
51 – 60+
Total
Male (%)
12 (3)
12 (3)
18 (5)
63 (18)
54 (15)
12 (3)
171 (48)
Sex
Female (%)
3 (1)
12 (3)
42(12)
87 (25)
24 (7)
15 (4)
183 (52)
Total (%)
15 (4)
24 (7)
60 (17)
150 (43)
78 (22)
27 (7)
54 3 (100)
Table 2 shows the different HIV – related skin diseases
among the 354 HIV – positive patients. The majority,
204/354 (58%) had PPE either alone or co existing with
other cutaneous lesions. PPE presented alone in 168 (47%)
patients. Cutaneous epidemic Kaposi’s sarcoma (CEKS) was
seen in 60/354 (17%) of whom, 48 (80%) had this lesion
alone. All patients with CEKS alone or in combination with
other skin diseases were HIV sero - positive. Psoriasis alone
or in combination with seborrhoeic eczema (sebo –
2
psoriasis) was seen in 36/354 (10%). Herpes zoster with or
without other skin conditions was seen in 27 (8%) patients.
Eighteen patients (5%) had genital herpes simplex in
addition to other cutaneous lesions. The other skin
conditions encountered with numbers in brackets included;
superficial mycosis including onychomycosis (18), plane
warts (12), molluscum contagiosum (9), genital warts (9)
and lichen planus subtropicus (3).
Table 2: HIV related skin disorders among HIV positive
patients (n=354)
Skin disorder
PPE alone
PPE +other cutaneous disorders
Cutaneous KS (with or without other skin diseases)
Psoriasis + seborrhoeic eczema
Herpes zoster
Genital herpes simplex
Superficial mycosis (+onychomycosis)
Plane warts
Genital warts
Molluscum contagiosum
Lichen planus subtropicus
No. (%)
168 (47.5)
36 (10)
60 (17)
36 (10)
27 (8)
18 (5)
18 (5)
12 (3)
9 (2.5)
9 (2.5)
3 (1)
Thirty of the 354 (8%) HIV - positive patients were co
infected with hepatitis B virus. Of these only three subjects
(10%) had received blood transfusion in the past. Twentyfour HBV positive individuals (80%) were males while 6
(20%) were females. The age among the HIV and HBV co
infected patients ranged from 11 to 50 years. None of the 30
HIV – negative individuals had HBV infection.
There were 333 adult voluntary and 120 secondary
school student voluntary blood donors respectively who
were included in the study as controls. Of the adult voluntary
blood donors, 28/333 (8%) were HIV sero positive, 32/333
(10%) were HBsAg sero positive while 4/333 (1.2%) had
HIV and HBV co infection. For the student blood donors,
2/120 (2%) were HIV positive, 10/120 (8%) were HBsAg
sero positive while none had HBV and HIV co infection.
The sero prevalence of HBsAg infection did not differ
significantly among patients with HIV – related skin
diseases, adult and student voluntary blood donors (p= 0.64).
Discussion
Certain skin diseases predict fairly accurately the
presence of HIV infection even before testing and more
importantly, they correlate well with the severity of the
underlying immunosuppression.(5, 8) Studies have shown for
example, that the presence of PPE in an individual is
associated with 99% chances of being HIV – 1 positive and
70% chances of having CD 4+ T – lymphocyte count of
200cells/ml or less, i.e. having AIDS by CDC criteria . In
this study, 92% of all individuals who presented with skin
lesions suggestive of HIV infection turned out to be HIV
positive and the majority (58%) had PPE.
HIV and HBV co infection has been shown by many
studies to be common due to shared modes of transmission 7.
Chloe et al found that among 326 HBsAg positive men
having sex with men, 213 (65%) were co infected with HIV
Vol. 19 No. 2, June 2004
– 1.(7) This study has determined the sero prevalence of
HBsAg among individuals with HIV related skin diseases
and compared it with that in adult and student blood donors
as controls. The prevalence of HBsAg did not differ
significantly between the three groups which were 8%, 10%
and 8% respectively for HIV infected individuals with
cutaneous manifestations, adult blood donors and student
blood donors.
The HBsAg sero prevalence of 8% among the HIV
positive patients with HIV – related cutaneous disorders, is
almost the same as what has been observed in the general
population. This may have several explanations. Firstly, the
level of HBsAg in the general population could have
stabilized during the ‘teenager’ period when the majority of
HBV infections in sub Saharan Africa occur, and that HIV
infection occurs much later during youth hood and
adulthood when individuals have already acquired HBV
infection. Secondly, the low prevalence of HBsAg positive
may be due to HBsAg false negative results among HIV
infected individuals with compromised immunity. Studies
have shown that false negative HBsAg is possible among
immunocompromised patients.(9) In order to detect all true
HBsAg positives, other sero markers like serum HBV DNA
and HBeAg should have been performed but this was not
logistically feasible in this study.
The HIV and HBV co infection rate of 8% in
individuals with HIV related skin diseases in this study,
although seemingly low, (possibly also due to presence of
HBsAg false negatives) has significant repercussions.
Studies have shown an increased risk of death from liver
disease in persons infected with either HIV – 1 or HBV, but
the risk is highest in individuals who are co infected with
both viruses.(7) Furthermore, rates of liver – related deaths
are higher in individuals with the lowest CD4+ T - cell
nadir.(7) It has already been established that the majority of
HIV positive patients with some HIV – related skin
disorders like PPE have very low CD4+ T – cell counts(8,10)
who could therefore be at a higher risk of liver related death
if they happen to be co infected with HBV. The increased
risk of liver – related mortality among HBsAg positive
individuals co infected with HIV – 1 although notable has
got no clear explanation. HIV – 1 may destroy CD 4+
lymphocytes which are normally activated to combat HBV
infection and stop disease initiation and progression.
However, it is not clear how depletion of CD 4+ T –
lymphocytes would directly enhance liver damage, which
has been linked with a more vigorous cytotoxic T – cell
response.(7) The increased risk of liver – related deaths
among individuals co infected with HIV and HBV has also
been noted since the introduction of HAART in 1996. (11, 12)
This has been attributed to several factors including direct
hepatotoxicity from individual drugs, as well as the immune
restoration induced by HAART which might reactivate HBV
infection leading to disease progression as has been noted
with other infections like tuberculosis and cytomegalovirus
infection.(6, 7)
This study therefore, implicitly emphasizes the
importance of considering comprehensive measures to
accurately define the HBV disease burden among
Tanzania Medical Journal
3
individuals infected with HIV – 1 who present with
cutaneous lesions that may increase the risk of HBV
infection leading to early liver – related death particularly in
this era of HAART. More logistically sound studies need to
be conducted which will have to include detection of all
markers of HBV infection such as HBeAg and HBV DNA in
order to offset the problem of HBsAg false negativity in
HIV infected immunocompromised individuals. The liver
injury in co infected individuals should also be
comprehensively ascertained using both indirect measures
like serum liver enzymes and directly by liver biopsy and
histology.
Conclusion
Although the prevalence of HBsAg among HIV sero
positive individuals with HIV related cutaneous disorders in
this study was apparently the same as that of adult and
student blood donors who were used as controls, the HBV
and HIV co infection rate of 8% among individuals with
HIV related cutaneous disorders may pose significant
challenges in terms of the implicated liver - related mortality
and the rational choice of anti- retroviral drugs especially in
this era of HAART.
Acknowledgement
The author would like to thank Sister Mary Nkaina for smoothly organizing
the clinic at the time of this study. She also helped with collection of all
blood samples for screening. Mrs. Mlalasi of the clinical research laboratory
performed all the HIV and HBsAg screening tests and is being highly
acknowledged. The other costs including stationeries and the purchase of
reagents were met by the author.
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