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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 97, Num. 2, 2002, pp. 197-198
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Mem Inst Oswaldo Cruz, Rio de
Janeiro, Vol. 97(2) 2002, pp.
197-198
SHORT COMMUNICATION
Relation between Hepatitis
B Carrier Status and Antibody against Synthetic Plasmodium falciparum
Erythrocyte Surface (pf155 - RESA) Antigen
Francisco José Dutra Souto/+,
Cor Jésus Fernandes Fontes, Ana Maria Coimbra Gaspar*
Núcleo de Estudos de Doenças
Infecciosas e Tropicais, Faculdade de Ciências Médicas, Universidade
Federal de Mato Grosso, Caixa Postal nº 3241, 78048-790 Cuiabá,
MT, Brasil *Departamento de Virologia, Instituto Oswaldo Cruz-Fiocruz, Rio de
Janeiro, RJ, Brasil
+Corresponding author. Fax: +55-65-6157302. E-mail: fsouto@nutecnet.com.br
Received 16 April 2001
Accepted 5 November 2001
Code Number: oc02036
A survey on Plasmodium infection
was carried out in gold mine camps located in the Brazilian Amazon. Antibody
against P. falciparum ring-infected erythrocyte surface antigen (RESA)
was quantified by an enzyme-immunoassay in order to assess P. falciparum
exposure. Hepatitis B, a common infection in this area, was also investigated
by serologic markers. Among 520 sampled subjects, 517 (99.4%) admitted previous
symptomatic malaria, 106 (20.4%) had positive thick smears for malaria, 82.9%
had HBV markers, and 7.1% were HBsAg positive. Anti-RESA titers was significantly
lower in HBV carriers than in people with resolved HBV infection suggesting
that the anti-RESA immune response could be supressed by HBV carrier status.
Moreover, immunedeficient responses to both infections may take place in some
subjects causing concomitant lower anti-RESA response and incapacity to clear
HBV.
Key words: malaria falciparum
- malaria antigen - hepatitis B virus - Brazilian Amazon
Falciparum malaria and hepatitis
B virus (HBV) infections are quite common in the Amazon Basin. Recent reports
have shown that this situation also prevails in the southernmost part of the
Brazilian Amazon, corresponding to the State of Mato Grosso (Andrade et al.
1995, Souto et al. 1998).
A cross-sectional survey of Plasmodium
infection was carried out in inhabitants of gold mine camps located in the county
of Apiacás, north of Mato Grosso, as reported elsewhere (Souto et al.
2001). Reactivity to antibody against P. falciparum ring-infected erythrocyte
surface antigen (RESA) was quantified by an enzyme-immunoassay (EIA) in order
to assess P. falciparum exposure. Gold miners generally have a high prevalence
of malaria and HBV infection and are considered to facilitate the spread of
both diseases throughout the region (Andrade et al. 1995, Souto et al. 1998).
To investigate any relation between malaria and HBV infection the participants
were tested for HBV markers as well. The ethical and methodological aspects
of this survey were approved by the Federal University of Mato Grosso Research
Ethical Committee. The objectives of the study were explained to all participants
and informed consent was obtained.
This study was performed between
March and June 1996. There were 16 gold mine camps in the county of Apiacás.
Five hundred and twenty out of 569 inhabitants of the camps were interviewed
and bled. Male subjects comprised 442 (85%) of the overall sample and their
age ranged from 3 to 66 years (mean = 32). Most of them (79.6%) were aged between
20 and 40 years.
Thick blood smears for identification
of Plasmodium were prepared. Aliquots of serum were sent to the Department
of Virology, Instituto Oswaldo Cruz, Rio de Janeiro, where they were analyzed
for HBV surface antigen and antibody (HBsAg and anti-HBs, respectively), and
total antibodies against HBV core antigen (anti-HBc), by an EIA from Organon
Teknika-Hepanostika, Boxtel, The Netherlands.
Antibodies against P. falciparum
were measured by an EIA using RESA produced by Bachem (California, USA), H6215,
Lot 119285. This test was standardised and performed at the Blood Bank of Universidade
Federal de Mato Grosso, Cuiabá, Brazil. A synthetic peptide {[(CTG-(EENV)4-OH)]2}
reproducing one of the repeats present in the RESA molecule was used in EIA.
Micro-EIA plates were coated with 100 µl/well of the synthetic peptide
(2.5 mg/ml in phosphate-buffered saline - PBS) and incubated overnight at 4oC.
After spray-wash with PBS-Tween 20 (0.05% PBS-T), plates were blocked with 5%
non-fat powdered milk in PBS-T and incubated for 2 h at 37oC. After
washing plasma samples were added (100 µl/well) at a dilution of 1:50.
After 1 h incubation at 37oC plates were washed again and peroxidase-conjugated
goat anti-human IgG was used to detect bound antibodies. As the chromogenic
substrate we used 2,2'-azino-di-(3-etil-benztiazoline sulfonate). Optical densities
were read at 420 nm.
Thick blood smears were positive
in 106 (20.4%) out of the 520 subjects (P. falciparum, 56; P.
vivax, 47; and P. malarie 3); 517 (99.4%) admitted previous symptomatic
malarial episodes; 431 (82.9%) had been exposed to HBV: 37 (7.1%) were HBsAg
carriers and 394 had previous infection markers (anti-HBc plus anti-HBs, 297,
or anti-HBc as the sole marker, 97).
The mean anti-RESA titers of the
overall sample was 0.806, ranging from 0 to 3.256. The mean anti-RESA titers
of the HBsAg carriers (0.451) was significantly lower than the mean of the rest
of subjects (0.832) (P < 0.01) and this difference remained statistically
significant (P < 0.001) after multiple linear regression analysis (Stata
5.0, Stata Corporation, Texas, USA) adjusting for age and time living in the
study area. This last variable was also associated with the anti-RESA titers
but in a positive way (P < 0.05). There was no association between current
Plasmodium infection and HBV carrier status (8 out of 37, 21.6%, vs 98
out of 483, 20.3%).
Anti-RESA (pf155) is an antibody
that appears following intense and frequent exposure to P. falciparum.
Usually anti-RESA concentration is higher in older individuals and among those
living longer in malarial areas (Baird et al. 1991). High anti-RESA reactivity
may be associated with acquired protection against malaria (Migot et al. 1993,
Achidi et al. 1995, Al-Yaman et al. 1997), although some studies have shown
different findings (Deloron & Cot 1990, Astagneau et al. 1995).
Malaria and HBV infections are common
in vast tropical areas. Consequently, these infections overlap frequently. In
this study most of the surveyed people had already been infected by both. The
relation between these two infections has been investigated in some countries.
Thursz et al. (1995) showed an association between HBV carriage and more severe
malaria cases in Gambian children and suggested that reduced level of HLA antigen
expression on hepatocytes infected by HBV could impair clearance of liver stage
malaria parasites. In Thailand, Brown et al. (1992) verified that chronic asymptomatic
malaria falciparum may be accompanied by sustained periods of HBV reactivation.
In our study, HBsAg-positive subjects as well as HBsAg-negative ones had similar
number of malaria episodes (P = 0.8, data not shown), so that similar anti-RESA
reactivity would be expected. However, anti-RESA reactivity were significantly
lower in HBsAg carriers than in people with cleared HBV even after adjustment
for age and time living in the study area. This negative association could have
resulted from some other confounder. To investigate this hypothesis several
demographic, epidemiological and behavioral factors, such sharing needles, men
who have sex with men and previous sexual transmitted diseases were analyzed.
No other variable was inversely associated to anti-RESA response level. Human
immunodeficiency virus infection status of the sampled subjects was not assessed
since it was not the main objective of the study.
These findings suggest that the anti-RESA
immune response could be suppressed by HBV carrier status. However, immunedeficient
responses to both infections may take place in some subjects causing concomitant
lower anti-RESA concentration and incapacity to clear HBV. Further studies concerning
relation between P. falciparum and HBV infection are needed to assess
its potential influence in chronic hepatic disease in tropical areas.
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© 2002
Instituto Oswaldo Cruz - Fiocruz
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