Mem Inst Oswaldo Cruz, Rio de Janeiro, 93 (Suppl.I) October 1998
Prognosis of Schistosomiasis Mansoni Patients Infected with Hepatitis B Virus
Departamento de Medicina Preventiva , Serviço de Doenças Infecciosas e Parasitárias, Hospital Universitário Clementino Fraga Filho
*Departamento de Patologia, Serviço de Anatomia Patológica, Universidade Federal do Rio de Janeiro, Av. Brigadeiro Trompowsky s/nu00ba, 21941-590 Rio de Janeiro, RJ, Brasil
A clinical study on the evolution of patients with schistosomiasis mansoni has been conducted since 1983 at the outpatient clinic of the Infectious and Parasitic Disease Service in the Clementino Fraga Filho University Hospital in Rio de Janeiro, Brazil, comparing prevalence of positive tests for HBsAg, anti-HBsAg, and anti-HBc among patients infected withu00a0Schistosoma mansoniu00a0coming from various regions of Brazil and with different clinical forms of the disease. A non-significant predominance of HBsAg, anti-HBsAg, and anti-HBc was detected among patients with the hepatosplenic form of schistosomiasis, who presented a more severe clinical evolution with a higher frequency of hematemesis and/or melena, in addition to the development of macronodular cirrhosis and a worse prognosis as compared to patients with the toxemic form, schistosomiasis-infection and the hepatointestinal form.
Schistosomiasis mansoni and hepatitis B are endemic in various regions of Brazil and have posed a persistent challenge to the public health system due to the difficulty in their control. Prevalence of schistosomiasis is some 10% of the total Brazilian population and has tended to remain high, due to erratic human migratory patterns, leading to the appearance of foci in previously unaffected areas (Neiva 1947). As for prevalence of hepatitis B, Wakimoto (1997) quotes data from the Brazilian Ministry of Health pointing to high rates in the western Amazon Region (states of Acre, Amazônia, Rondônia, and Roraima) as well as areas in the State of Espírito Santo, intermediate rates in the eastern Amazon (Amapá, Pará, and Tocantins), middle west (Goiás, Mato Grosso do Sul, and Federal District), and northeast, and low rates in the south and southeast.
The combination of schistosomiasis mansoni and hepatitis B has been reported by Andrade (1965), Prince (1970), Lyra et al. (1976), Bassily et al. (1979, 1983), among other authors. Gayoto (1984) performed a serological survey on the prevalence of HBsAg in different geographical areas and detected positive rates ranging from 0.3 to 0.5%. However, Kamel et al. (1994) found no epidemiological association between the two infections when they studied 1,850 inhabitants of northern Egypt. Chieffi (1992) referred to both the interaction between the two infections and the risk of occurring a clinical evolution different from that expected, resulting from two main factors, i.e., persistent viremia and aggravated hepatopathy. According to Andrade and Andrade (1984), in individuals with asymptomatic Schistosoma mansoniinfection, hepatic lesions are limited to the portal system. Coutinho (1979) emphasized the possibility of an aggravated course of infection in the hepatosplenic forms of the disease. Such forms attain prevalence rates of up to 10% in some areas of Brazil (Coutinho & Domingues 1988). Lyra et al. (1976) in Brazil and Bassily et al. (1979) in Egypt emphasized the high frequency of markers for hepatitis B infection in patients hospitalized with the uncontrolled hepatosplenic form. However, Pereira et al. (1994) suggested that in order to avoid bias, patient samples with severe chronic hepatic lesions not be included in studies.
Since the above was a controversial, medically relevant theme, the current study was planned with the objective of assessing blood markers for the hepatitis B virus in outpatients infected with S. mansoni, with different clinical forms of the disease and coming from various endemic areas of Brazil, in addition to assessing the prognosis for coinfected patients.
PATIENTS AND METHODS
The study included 398 outpatients, as well as 50 other patients in the control group, all treated at the Infectious and Parasitic Disease Service, Clementino Fraga Filho University Hospital, School of Medicine, Universidade Federal do Rio de Janeiro. Etiologic diagnosis of S. mansoniwas based on up to six parasitological stool tests using the Kato method (1960), as modified by Katz et al. (1972) and/or rectal biopsy. Clinical classification was that proposed by Pessoa and Barros (1953), as modified by Barbosa (1966).
Sera from all patients were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBsAg), and antibody to hepatitis B core antigen (anti-HBc), using enzyme-linked immunoassay (ELISA). Patient clinical data were identified beginning in 1983, emphasizing specific prior treatment for schistosomiasis mansoni (both parenteral and enteral), reports of previous surgery, blood transfusions, complaints of nausea, vomiting, abdominal pain, hematemesis and/or melena, bloody stools, choluria, acholia, jaundice, telangiectasis, palmar erythema, hepato- and/or splenomegaly, hypersplenism, ascites, edema, and signs and symptoms of somatic and/or sexual underdevelopment. Tests included aminotransferase, bilirubin, complete blood cell count, total protein, and protein electrophoresis. Statistical analysis of the data used the Fisher's exact test, considering a p value of 0.05 as significative.
Hepatic biopsies were obtained from patients with the hepatosplenic form during therapeutic ablation of spleen, and processed for routine diagnosis.
Of the 398 patients infected with S. mansoni, 52.5% were females and 47.5% males. Age varied from 10 to 62 years (Table I). This same age bracket included 50 patients from the control group who were negative for S. mansoni infection and had normal aminotransferase levels. As for clinical forms in the 398 patients, 5.5% had the toxemic form, 56.8% schistosomiasis-infection, 24.6% hepatointestinal form, and 12.3% hepatosplenic form (Table II). Positive rates for HBsAg were 3.8% for the toxemic form, 7% for schistosomiasis-infection, 9.2% for the hepatointestinal form, and 12.2% for the hepatosplenic form (Table III). There was no statistical difference (p = 0.54) between clinical forms.
Positive rates for anti-HBsAg and/or anti-HBc were nil in individuals with the toxemic form, 5.3% in schistosomiasis-infection, 6.1% in the hepato-intestinal form, and 10.2% in the hepatosplenic form (p.0.05) (Table IV). Of the 50 members of the control group, one was positive for HBsAg, while 6% (3/50) tested positive for anti-HBsAg and/or anti- Hbc, data significative when compared with infected patients disregarding clinical forms.
In this study, positive rates for HBV markers in patients infected with S. mansoni showed no significant differences between the toxemic, schistosomiasis-infection, hepatointestinal, and hepatosplenic forms. However, this difference did exist in relation to the control (non-infected) group, in which there was one positive case (HBsAg). Studies by Lyra et al. (1976), Bassily et al. (1979), and Madwar et al. (1989) emphasized the prevalence of HBV markers in the hepatosplenic form as compared to non-infected individuals. Larouze et al. (1987) found no association between S. mansoni and hepatitis B virus infection in patients from Egypt. Hyams et al. (1987) concluded that there was no correlation between S. mansoni infection, with or without hepatosplenomegaly and HBsAg positivity. The study of Serufo et al. (1997) in endemic area from Minas Gerais also did not show association between schistosomiasis and HBV. In Brazil, Guimarães (1975) recorded 4.4% of patients infected with hepatitis B virus among patients with hepatosplenic schistosomiasis (as compared to 1.5% in the hepatointestinal form and 0.6% in controls); Lyra (1976) found 7.8% of HBV markers in the hepatosplenic form of schistosomiasis (as compared to 1.5% in the hepatointestinal form and 1.3% in controls). Silva (1979) found 22.5% of patients with HBV markers in the hepatosplenic form (as compared to 0.9% in the hepatointestinal form and 0% in controls). Hammad et al. (1995) found positive HBsAg in 58% of children with schistosomiasis hepatic fibrosis and 2% in controls. Chieffi (1992) emphasized the relevance of coinfection and the risk of aggravating hepatic lesions during the course of schistosomiasis. According to Strauss and Lacet (1986), the risk increases as the infection becomes chronic.
In the current study, due to the low rate of HBV markers in the control group, it was not possible to determine whether the markers remained for a longer period in patients with the hepatosplenic form. However, this correlation has been described by Lyra et al. (1976) and Ghaffar et al. (1991). There is no clear definition for either the causes of HBV infection or its persistence in patients with the hepatosplenic form (Pereira et al. 1994). Ellner et al. (1980) cite T-cell dysfunction as a probable factor in these patients. Madwar et al. (1983) suggested that the principal cause is the absence of HBsAg clearance in hepatosplenic patients.
The current study found no association between positive HBsAg status and prior history of parenteral treatment for schistosomiasis. Bassily et al. (1983) also failed to find such a correlation. However, Madwar et al. (1989) observed a marker rate twice as high in individuals who had received such treatment. Hyams et al. (1987) studied 1,234 Egyptians and concluded that parenteral therapy for schistosomiasis can be a risk factor for hepatitis B virus antigenemia. Despite the lack of a significant difference in HBV markers in patients with the hepatosplenic form of schistosomiasis, the group displayed more nausea, vomiting, abdominal pain, hematemesis and/or melena (in six patients), worse evolution of bilirubin and aminotransferase, and hypersplenism. Hepatic biopsy in this group showed macronodular cirrhosis, making the prognosis more somber as compared to patients with the toxemic, schistosomiasis-infection, and hepatointestinal forms. Follow-up has been maintained on the progression of these patients in an attempt to shed light on interrelations between the two infections.
Andrade Z 1965. Hepatic schistosomiasis: morphological aspects, p. 228-242. In H Popper, F Schaffner (eds), Progress in Liver Diseases, Grune & Stratton, New York.
Andrade Z, Andrade SG 1984. Patologia da esquistossomose hepatoesplênica, p. 103-131. In Centro de Estudos de Doenças Regionais. Aspectos peculiares da infecção por Schistosoma mansoni, Universidade Federal da Bahia, Salvador.
Barbosa FAS 1966. Morbidade da esquistossomose. Rev Bras Malariol D Trop 8: 353-357.
Bassily S, Dunn MA, Farid Z, Kilpatrick ME, El-Masry AG, Kamel IA, El-Alamy ME, Murphy BL 1983. Chronic hepatitis B in patients with schistosomiasis mansoni. J Trop Med Hyg 86: 67-71.
Bassily S, Farid Z, Highashi GL, Kamel IA, EL-Masry AG, Watten RH 1979. Chronic hepatitis B antigenemia in patients with hepatosplenic schistosomiasis. J Trop Med Hyg 82: 248-251.
Chieffi PP 1992. Interrelationship between schistosomiasis and concomitant diseases. Mem Inst Oswaldo Cruz 87: 291-296.
Coutinho A 1979. Fatores relacionados com o desenvolvimento das formas clínicas da esquistos-somose mansônica. Rev Assoc Med Bras 25: 185-188.
Coutinho A, Domingues ALC 1988. Esquistossomose mansoni, p. 1362-1386. In R Danni, LP Castro (eds), Gastroenterologia Clínica, 2nd ed., Ed. Guanabara Koogan, Rio de Janeiro.
Ellner JJ, Olds GR, Kamel R, Osman GS, Kholy AE, Mahmoud AAP 1980. Supression splenic T lymphocytes in human hepatosplenic schistosomiasis mansoni. J Immunol 125: 303-308.
Gayotto LCC 1987. Epidemiologia das hepatites. Moderna Hepatologia Especial 6: 9-15.
Ghaffar YA, Fattah SA, Kamel M, Badr RM, Mahomed FF, Strickland GT 1991. The impact of endemic schistosomiasis on acute viral hepatitis. Am J Trop Med Hyg 45: 743-750.
Hammad HA, El-Fattah MMZ, Morris M, Madiner EH, El-Abbasy AA, Soliman AMT 1990. Study on some hepatic functions and prevalence of hepatitis B surface antigenemia in Egyptian children with schistosomiasis hepatic fibrosis. J Trop Pediat 36: 126-130.
Hyams KC, El-Alamy ME, Pazzaglia G, El-Ghorab NM, Sidom O, Habib M, Dunn MA 1987. Risk of he patitis B infection among Egyptians with Schistosoma mansoni. Am J Trop Med Hyg 35: 1035-1039.
Kamel KC, El-Alamy ME, Miller FD, El-Masry AG, Zakaris S, Khattab M, Essmat G 1994. The epidemiology of Schistosoma mansoni, hepatitis B and hepatitis C infection in Egypt. Ann Trop Med Parasitol 88: 501-509.
Kato K 1960. A correct application of the thick-smear technique with cellophane paper cover. A pamphlet, p. 9. In Y Komyia & A Kobayashi (eds). Evaluation of Kato thick-smear technique with a cellophane cover for helminth eggs in Feces. Jap J Med Sci Biol 19: 58-64.
Katz N, Chaves A, Pellegrino J 1972.A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Rev Inst Med Trop São Paulo 14: 397-400.
Larouze B, Dazza MC, Gaudebout C Habib M, Elamy M, Cline B 1987. Absence of relationship between Schistosoma mansoni and hepatitis B virus infection in the Qalyub Governate - Egypt. Ann Trop Med Parasitol 81: 373-375.
Lyra LD, Rebouças G, Andrade Z 1976. Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis. Gastroenterology 71: 641-647.
Madwar MA, El-Tahawy M, Strickland GT 1989. The relationship between uncomplicated schistosomiasis and hepatitis B infection. Trans R Soc Trop Med Hyg 83: 233-236.
Neiva A 1947. Aspectos geográficos da imigração e colonização do Brasil. Rev Bras Geogr 9: 249- 270.
Pereira LMMB, Melo MCV, Lacerda C, Spinelli V, Domingues ALC, Massarolo P, Mies S, Saleh MG, Mcfarlane IG, William R 1994. Hepatitis B. virus infection in schistosomiasis mansoni. J Med Virol 42: 203-206.
Pessoa SB, Barros PS 1953. Notas sobre a epidemiologia da esquistossomose mansônica no Estado de Sergipe. Rev Med Cir São Paulo 13: 147-154.
Prince AM 1970. Prevalence of serum hepatitis related antigen (SH) in different geographic regions. Am J Trop Med Hyg 19: 872.
Serufo JC, Antunes CMF, Silva RAP, Lara RG, Drummond SC, Rayes A, Lambertucci JR 1997. Chronic carriers of HBsAg in an endemic area for schistosomiasis mansoni, p.173.Abstracts VI International Symposium on Schistosomiasis, Belo Horizonte, Minas Gerais.
Strauss E, Lacet CMC 1986. Hepatite e esquistossomose mansônica, p. 171-178. In LC Silva, Hepatites Agudas e Crônicas, Sarvier, São Paulo.
Wakimoto MD 1997. Avaliação de Qualidade do Sistema de Vigilância Epidemiológica no Município do Rio de Janeiro - 1994 a 1996, MSc Thesis, Escola Nacional de Saúde Pública, Rio de Janeiro, 185 pp.