Jose Tavares-NetoI; Aluízio PrataII; Raymundo ParanáI; Vanderléia Bárbaro ValenteIII; Ludmila VitvitskiIV; José Fernando C. FigueiredoIII
IFaculty of Medicine of Bahia, Federal University of Bahia, Salvador, BA IITriângulo Mineiro Medical Faculty, Uberaba, MG IIIRibeirão Preto Blood Center, SP. Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP IVINSERM Unité 271, Lyon, France
ABSTRACT
The association of hepatitis C virus infection and the hepatosplenic form of schistosomiasis mansoni has been claimed to result in the concomitant evolution of the two pathologies, with a poor prognosis due to aggravated liver disease. Recently, however, some authors have begun to reject the hypothesis of a higher susceptibility of hepatosplenic schistosomal patients to HCV. The aim of the present transverse study carried out between July and August 1990 was to determine the possible association between SM and HCV markers in residents of Catolândia, Bahia State. Anti-HCV markers were assayed by ELISA-II and RIBA-II in serum samples obtained from 1,228 residents (85.8%). The anti-HCV antibody (ELISA-II) was positive in six (0.5%) individuals, eight (0.6%) cases were inconclusive and 1,214 (98.9%) were negative. However, only in one ELISA-positive serum sample (0.08%) were antibodies confirmed by RIBA-II, while two other samples assayed by RIBA-II were indeterminate. These three patients presented the hepatointestinal form of SM during the follow-up period (1976 to 1996). In conclusion, no association was observed between HCV and SM in the endemic area studied, especially among patients with the hepatosplenic form of the disease.
Key-words: Schistosomiasis mansoni. Hepatitis C. Schistosoma mansoni. Brazil.
RESUMO
Alguns autores passaram a rejeitar a hipótese da maior susceptibilidade dos equistossomóticos com a forma clínica hepatosplênica ao vírus da hepatite C, justificando que a associação foi descrita em pacientes hospitalizados ou acompanhados em serviços de saúde e, conseqüentemente, mais expostos à transmissão destes vírus, durante os procedimentos diagnóstico e/ou terapêuticos. Desse modo, o objetivo foi verificar se há ocorrência de associação da esquistossomose mansônica e marcador do VHC em moradores de Catolândia (Bahia, Brasil). Neste estudo transversal, os anticorpos anti-VHC foram pesquisados (ELISA-II) em 1.228 (85,8%) moradores, com os seguintes resultados: Seis (0,5%) soropositivos, oito (0,6%) inconclusivos e 1.214 (98,9%) soronegativos. Todavia, somente em um soro ELISA-positivo (0,08%) os anticorpos foram confirmados pelo RIBA-II e dois outros (ELISA-II positivos) apresentaram RIBA-II indeterminado esses três casos, durante período de seguimento (1976 1996), sempre tiveram a forma hepatointestinal da esquistossomose mansônica. Em conclusão a hipótese de associação entre a esquistossomose mansônica e o VHC nesta área endêmica foi rejeitada, especialmente entre os portadores da esquistossomose mansônica com a forma clínica hepatosplênica.
Palavras-chaves: Esquistossomose mansônica. Hepatite C. Schistosoma mansoni. Brasil.
Several lines of evidence have favored an association between hepatitis B virus (HBV) infection and the hepatosplenic form of schistosomiasis mansoni (SM)26. More recently, however, this association has been revised6 24 29, with the conclusion that it is due to a greater exposure to HBV rather than to a higher susceptibility of individuals with SM to hepatotropic viruses, i.e., HBV and hepatitis C virus (HCV).
Despite phylogenetic differences between HBV and HCV, their mechanisms of transmission show some similarities11. Thus, one might speculate that HCV infection is associated with SM, especially among patients with the severe hepatosplenic form of the disease.
Before the HCV era, some patients with hepatosplenic schistosomiasis and a histopathology compatible with chronic viral hepatitis did not present HBV markers in serum or hepatic tissue16 17. Similar findings have been reported in Brazil by Andrade et al3 4.
After characterization of HCV by Choo et al7 and the consequent possibility of detecting HCV markers in serum, Lins16 showed that the frequency of individuals with anti-HCV antibodies does not differ between patients with the hepatointestinal form of SM and those with the hepatosplenic form.
Other authors1 2 5 8 10 12 13 14 15 31 have provided evidence suggesting that the presence of anti-HCV antibodies is associated with schistosomiasis, but contradictory data exist. However, it should be noted that these authors used different serologic methods. In addition, these studies were conducted on patients recruited from referral centers and not from rural Brazilian communities where Schistosoma mansoni is endemic.
Based on the clinical and immunological peculiarities of SM and hepatitis C in Brazil, the aim of the present study was to determine the possible association between the two diseases in an area endemic for SM.
MATERIAL AND METHODS
A cross-sectional population-based study was conducted on residents from an SM endemic area in the county of Catolândia29, which is located in the western region of the State of Bahia, Brazil (12º8′ latitude South and 44º52′ longitude West of Greenwich).
A longitudinal study on the morbidity of SM was started in the study area in 1976, and since then the clinical forms of the disease were classified according to the criteria of Prata22 24. In addition, the clinical involution of the hepatosplenic forms of SM after antiparasitic treatment was observed along the study24 30.
Anti-HCV antibodies were screened using a second-generation enzyme immunoassay kit (ELISA-II, Abbott®, Chicago, IL, USA)31. Anti-HCV-positive sera, those providing doubtful results were tested by a second-generation recombinant immunoblot method (Ortho Diagnostic Systems Inc®, Emerville-CA, USA).
Clinical examination of the patients was carried out without knowledge of the anti-HCV result.
RESULTS
Of the 1,432 residents in the study region, 1,228 (88.9%) provided complete information and were tested for anti-HCV. Table 1 and Table 2 summarize the demographic characteristics (gender and age) and the frequency of different clinical forms of SM in this population.
With respect to the presence of anti-HCV antibodies, six (0.5%) patients were positive, eight (0.6%) were inconclusive, and 1,214 (98.9%) were negative.
In only one sample of 14 tested (6 positive, 8 inconclusive) by ELISA-II commercial Kits (Boehinger-Germany) anti-HCV was confirmed by the RIBA-II test (Chiron, Emerville, CA®). Two (0.2%) individuals presented results classified as indeterminate by RIBA-II (both showing antibodies against the recombinant protein c100-3).
All six residents presenting anti-HCV antibodies, as well as the eight individuals with inconclusive results, as determined by ELISA-II, had the hepatointestinal form of SM, with the age of these patients ranging from 5 to 66 years (18.9 ± 9.4).
DISCUSSION
Despite massive anti schistosomal treatment and improved sanitary conditions, the frequency of schistosomal infection continues to be high in this area. Progressively higher frequencies of individuals excreting S. mansoni eggs among those seeking the Catolândia public health service were observed during the period from 1993 (35.8%) to 1996 (65.4%)29. Thus, SM was the main cause of morbidity and mortality in Catolândia until the mid-eighties30. The hepatosplenic form was diagnosed in 187 (8.3%) registered residents (n=2,241) during the study period from 1976 to 1996.
Although the population of Catolândia shows a reasonable geographic and cultural isolation27 28, temporary residence and/or occupation in other states are frequent; for example, during the study period 273 (12.2%) of the 2,241 individuals registered migrated28.
In the early eighties, residents from Catolândia commonly underwent medical treatment in some nearby capitals. Thus, a temporary migratory flow might have facilitated the introduction or increased dissemination of HCV in the region, where the lack of health services represents another characteristic predisposing to the use of parenteral medication under inadequate conditions, a fact that could also have contributed to the dissemination of HCV in many regions of Brazil.
Based on the fact that this region is hyperendemic for SM, with patients developing upper gastrointestinal bleeding by rupture of the esophageal varices and receiving blood transfusions when treated at larger centers, the introduction and dissemination of HCV can be expected in this region.
The finding of the present study of only one individual with anti-HCV and without a history of travel to or residence in other towns supports the hypothesis that in this endemic SM area the risk of transmission of HCV was not increased. In addition, the seroprevalence of anti-HCV antibodies observed for residents from Catolândia was lower than the 1.7% prevalence estimated for blood donor candidates from the metropolitan region of Salvador, capital of the State of Bahia (Santana et al, unpublished data).
Silva et al25 observed a 1.2% prevalence of anti-HCV antibodies in individuals from the metropolitan region of Salvador, and a 0% prevalence of anti-HCV in a populational study carried out in the rural area of the State of Bahia, Northeast of Brazil. Other studies concerning the seroprevalence of HCV in the State of Bahia were carried out on populations at risk of acquiring HCV infection19 23, while there were no populational studies. However, the results reported by Silva et al indicate a very low prevalence of HCV among residents of rural communities also endemic for S. mansoni infection.
Based on these results we may also speculate that the S. mansoni occurring in the rural areas of the State of Bahia does not influence the transmission or dissemination of HCV. This finding contrasts with Egyptian studies that demonstrated high HCV prevalence in SM endemic areas probably due to parenteral treatment for schistosomiasis using non-disposal material32. In Brazil, non-disposal needles were used in the past but it seems that this practice was concentrated in larger urban centers20.
With respect to reviews6 26 proposing a possible association between the hepatosplenic form of SM and infection with hepatotropic viruses, notably HBV, one can also speculate that the same spurious association exists with HCV, i.e., the association reported between the hepatosplenic form and HBV26 and, more recently, between the hepatosplenic form and HCV1 2 5 8 10 14 13 15 21 32 , is more likely to be due to greater exposure to these viruses during diagnostic and/or therapeutic procedures at health services rather than to a higher susceptibility of hepatosplenic individuals to hepatotropic viruses.
Our results show that during the more than 20 years of the sentinel study in Catolândia co-infection with HCV was negligible in patients with SM29 30. In the only case with confirmed anti-HCV antibodies, hepatic biochemical tests, especially aminotransferases, were found to be normal. However, hepatic enzymes showed fluctuations in these individuals throughout the evaluation period, including periods of normality.
ACKNOWLEDGMENTS
We thank the technician Margarida Maria Passeri do Nascimento (FMRP, USP) for processing the serum samples.
REFERENCES
1. Abdel-Wahab MF, Zakaria S, Kamel M, Abdel-Khaliq MK, Mabrouk MA, Salama H, Esmat G, Thomas DL, Strickland GT. High seroprevalence of hepatitis C infection among risk groups in Egypt. The American Journal of Tropical Medicine and Hygiene 51: 563-567, 1994. [ Links ]
2. Al-Faleh FZ, Ramia S, Arif M, Ayoola EA, Al-Rashed RS, Al-Jeffry M, Hossain A, El-Hazmi M. Profile of hepatitis C virus and the possible modes of transmission of the virus in the Gizan area of Saudi Arabia: a community based study. Annals of Tropical Medicine and Parasitology 89: 431-437, 1995. [ Links ]
3. Andrade ZA, Lyra LG, Rebouças G. Esquistossomose hepática avançada e hepatite crônica viral. Revista da Associação Médica Brasileira 23:75-78, 1977. [ Links ]
4. Andrade ZA, Sadigursky M, Gomes LS. Hepatite crônica ativa e esquistossomose descompensada. Revista da Associação Médica Brasileira 24: 366-368, 1978. [ Links ]
5. Bassily S, Hyams KC, El-Marsry NA, Hassan NF, Watts DM. Hepatitis C virus infection and hepatosplenic schistosomiasis. Scandinavian Journal of Infectious Diseases 24: 687-688, 1992. [ Links ]
6. Chen M-G, Mott KE, Wang Q-H, Kane M. Hepatitis B and schistosomiasis: interaction or no interaction? Tropical Diseases Bulletin 90: R97-R115, 1993. [ Links ]
7. Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359-362, 1989. [ Links ]
8. Darwish MA, Raouf TA, Rushdy P, Constantine NT, Rao MR, Edelman R. Risk factors associated with a high seroprevalence of hepatitis C virus infection in Egyptian blood donors. The American Journal Of Tropical Medicine and Hygiene 49: 440-447, 1993. [ Links ]
9. El-Gohary A, Hassan A, Nooman Z, Lavanchy D, Mayerat C, El-Ayat A, Fawaz N, Gobran F, Ahmed M, Kawano F, Kiyokawa T, Yamaguchi AK. High prevalence of hepatitis C virus among urban and rural population groups in Egypt. Acta Tropica 59: 155-161, 1995. [ Links ]
10. El-Nanawy AA, El-Azzouni OF, Soliman AT, Amer AE, Demian RS, El-Sayed HM. Prevalence of hepatitis C antibody seropositivity in healthy Egyptian children and four high risk groups. Journal Tropical of Pediatrics 41: 341-343, 1995. [ Links ]
11. Esteban JI, Genesca J, Alter HJ, Hepatitis C: molecular biology, pathogenesis, epidemiology, clinical features, and prevention. In: Boyer JL, Ockner RK (eds) Progress in liver diseases. WB Saunders, Philadelphia, 10: 253-282, 1992. [ Links ]
12. Farghaly AG, Barakat RM. Prevalence, impact and risk factors of hepatitis C infection. Journal of the Egyptian Public Health Association 68: 63-79, 1993. [ Links ]
13. Kosby A, Al-Nakib B, Al-Mufti S, Madda JP, Hira PR. Anti-HCV-positive cirrhosis associated schistosomiasis. The American Journal of Gastroenterology 88: 1428-1431, 1993. [ Links ]
14. Lima RA. Marcadores sorológicos dos vírus B & C da hepatite em pacientes com esquistossomose mansoni. PhD thesis, Universidade Federal de Pernambuco, Recife, 1995. [ Links ]
15. Lima RA, Magalhães V, Moura I, Silva AE, Guimarães RX. Marcadores do vírus C da hepatite (HCV) em pacientes com esquistossomose mansoni. Revista da Sociedade Brasileira de Medicina Tropical 27 (supl I): 14, 1994. [ Links ]
16. Lins ALGP. Contribuição ao estudo dos marcadores sorológicos das hepatites B e C na esquistossomose mansônica. Master’s thesis, Universidade de São Paulo, São Paulo, 1993. [ Links ]
17. Lyra LGC. Esquistossomose e vírus B da hepatite. In: Azevêdo ES, Rebouças G, Rocha H, Lyra LGC, Teixeira RS, Andrade S, Andrade Z (eds) Aspectos peculiares da infecção por Schistosoma mansoni. Universidade Federal da Bahia, Centro de Estudos de Doenças Regionais, Centro Editorial e Didático da Universidade Federal da Bahia, Salvador, p. 75-102, 1984. [ Links ]
18. Paraná R. Estudo clínico sorológico da hepatite aguda não-A não-B em Salvador-Bahia. PhD thesis. Faculdade de Medicina da Universidade Federal da Bahia, Salvador 1997. [ Links ]
19. Parana R, Codes L, Andrade Z. Is splenectomy a cause of antiviral treatment failure in hepatitis C virus in splenectomized patients? Hepatology 33: 1340, 2001. [ Links ]
20. Paraná R, Lyra L, Trepo C. Intravenous vitamin complexes used in sporting activities and transmission of HCV in Brazil. American Journal of Gastroenterology 94: 857-858, 1999. [ Links ]
21. Pereira LM, Melo MC, Saleh MG, Massarolo P, Koskinas J, Domingues AL, Spinelli V, Mies S, Williams R, McFarlane IG. Hepatitis C virus infection in Schistosomiasis mansoni in Brazil. Journal of Medical Virology 45: 423-428, 1995. [ Links ]
22. Prata A. Como caracteriza a forma hepato-esplênica da esquistossomose? In: Prata A, Aboim E (eds) II Simpósio sôbre Esquistossomose. Diretoria de Saúde da Marinha/Universidade Federal da Bahia, Salvador, p. 179,1970. [ Links ]
23. Santana GO. Anti-HCV em pacientes sob programa de hemodiálise-Salvador-BA. Master’s thesis, Universidade Federal da Bahia, Salvador, 1995. [ Links ]
24. Serufo JR, Lambertucci JR. Esquistossomose e hepatites virais: uma revisão. Revista da Sociedade Brasileira de Medicina Tropical 30: 313-322, 1997. [ Links ]
25. Silva L, Paraná R, Cotrim H, Mota E, Boenec-Courtey ML, Trepo C, Lyra L. Prevalência do antiHCV na População Urbana e Rural do Nordeste – Brasil. Arquivos de Gastroenterologia 5: 3-6, 1999. [ Links ]
26. Strauss E. Hepatite e esquistossomose mansônica. In: Silva LC (ed) Hepatites agudas e crônicas. Sarvier, São Paulo, p. 253-258, 1995. [ Links ]
27. Tavares-Neto J. Recorrência familial e composição racial na esquistossomose mansônica. Master’s thesis, Universidade de Brasília, Brasília, 1987. [ Links ]
28. Tavares-Neto J. Estudo soro-epidemiológico do vesiculovírus Piry na população e entre os membros das famílias nucleares, em Catolândia Bahia. PhD thesis, Faculdade de Medicina de Ribeirão Preto/Universidade de São Paulo, 1992. [ Links ]
29. Tavares-Neto J. Marcadores sorológicos das hepatites B e C em residentes de área endêmica da esquistossomose mansônica. “Livre-Docência” thesis, Faculdade de Medicina da Universidade Federal da Bahia, 1997. [ Links ]
30. Tavares-Neto J, Prata A. Regressão da forma hepatosplênica da esquistossomose, após tratamento específico, associada à raça. Revista da Sociedade Brasileira de Medicina Tropical 21: 131-133, 1988. [ Links ]
31. Van der Poel CL, Cuypers HTM, Recsink HW, Weiner AJ, Quan S, Di Nello R, Van Boven JJP, Winkel I, Mulder-Folkerts D, Exel-Oehlers PJ, Schaasberg W, Leentvaar-Kuypers A, Polito A, Houghton M, Lelie PN. Confirmation of hepatitis C virus infection by a new four-antigen recombinant immunoblot assay. The Lancet 337: 317-319, 1991. [ Links ]
32. Waked IA, Saleh SM, Moustafa MS, Raouf AA, Thomas DL, Strickland GT. High prevalence of hepatitis C in Egyptian patients with chronic liver disease. GUT 37: 105-107, 1995. [ Links ]
Correspondence to
Prof. José Tavares-Neto
R. Marquês de Caravelas 262/101
40140-240 Salvador, BA, Brasil
Telefax: 55 71 3264-2443
E-mail: tavaneto@ufba.br
Recebido para publicação em 9/6/2003
Aceito em 8/4/2005
Research supported by PET-Medicina, CAPES / COFECUB and CNPq (process 52.0173/97-0)
