Schistosoma mansoni: protective immunity in mice cured by chemotherapy at the chronic phase of the disease

Bezerra, Fernando Schemelzer de Moraes; Coelho, Paulo Marcos Zech; Tavares, Carlos Alberto Pereira

doi:10.1590/S0036-46651993000400006

Abstracts

Aiming at demonstrating a decrease of acquired immunity after chemotherapeutic cure, a group of mice was infected with 25 Schistosoma mansoni cercariae (LE strain). A part of these animals was treated with 400 mg/kg oxamniquine, at 120 days after infection. Challenge infections were carried out at 45, 90 and 170-day-intervals after treatment (185, 210 and 290 days after primoinfection, respectively). Recovery of worms at 20 days after reinfections showed that a residual immunity remains up to 90 days after treatment, and disappears at 170 days after cure. Using the ELISA method, it was possible to detect a decrease of antibody levels (total IgG) in the treated group, when antigens from different evolutive stages of S. mansoni were used. The epidemiological implications of the present results, and the possible mechanisms involved in the decrease of acquired immunity after treatment are discussed.

Schistosoma mansoni; Chemotherapy; Residual immunity; Concomitant immunity

Para evidenciar a queda da imunidade adquirida após cura quimioterápica, um lote de camundongos foi infectado com ±25 cercárías de S. mansoni (cepa LE). Parte destes animais foi tratada aos 120 dias com 400 mg/kg de oxamniquina. Foram feitos desafios em intervalos de 45, 90 e 170 dias após o tratamento (185, 210 e 290 dias após a primoinfecção, respectivamente). A recuperação aos 20 dias após as infecções desafio, dos vermes das reinfecções mostrou que a imunidade residual persiste até os 90 dias após o tratamento e desaparece aos 170 dias após a cura. Com o soro dos camundongos, através do método de ELISA, evidenciou-se uma queda nos níveis de anticorpos (IgG total) no grupo tratado em relação a vários antígenos de estágios evolutivos do S. mansoni. As implicações epidemiológicas dos presentes resultados e os possíveis mecanismos envolvidos na queda da imunidade adquirida após tratamento são discutidos.

ORIGINAL ARTICLES

Schistosoma mansoni: protective immunity in mice cured by chemotherapy at the chronic phase of the disease

Schistosoma mansoni: imunidade protetora em camundongos curados por quimioterapia na fase crônica da doença

Fernando Schemelzer de Moraes Bezerra^I; Paulo Marcos Zech Coelho^II; Carlos Alberto Pereira Tavares^III

^IDepartamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal do Ceará. Fortaleza, CE, Brasil

^IIDepartamento de Parasitologia do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

^IIIDepartamento de Bioquímica-Imunologia, do Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

^{Address for correspondence} Address for correspondence: Prof. Paulo Marcos Z. Coelho Deptº Parasitologia, ICB/UFMG Caixa Postal 2486 30.161-970 Belo Horizonte, MG, Brasil

SUMMARY

Aiming at demonstrating a decrease of acquired immunity after chemotherapeutic cure, a group of mice was infected with 25 Schistosoma mansoni cercariae (LE strain). A part of these animals was treated with 400 mg/kg oxamniquine, at 120 days after infection. Challenge infections were carried out at 45, 90 and 170-day-intervals after treatment (185, 210 and 290 days after primoinfection, respectively). Recovery of worms at 20 days after reinfections showed that a residual immunity remains up to 90 days after treatment, and disappears at 170 days after cure.

Using the ELISA method, it was possible to detect a decrease of antibody levels (total IgG) in the treated group, when antigens from different evolutive stages of S. mansoni were used.

The epidemiological implications of the present results, and the possible mechanisms involved in the decrease of acquired immunity after treatment are discussed.

Key words: Schistosoma mansoni; Chemotherapy, Residual immunity; Concomitant immunity.

RESUMO

Para evidenciar a queda da imunidade adquirida após cura quimioterápica, um lote de camundongos foi infectado com ±25 cercárías de S. mansoni (cepa LE). Parte destes animais foi tratada aos 120 dias com 400 mg/kg de oxamniquina. Foram feitos desafios em intervalos de 45, 90 e 170 dias após o tratamento (185, 210 e 290 dias após a primoinfecção, respectivamente). A recuperação aos 20 dias após as infecções desafio, dos vermes das reinfecções mostrou que a imunidade residual persiste até os 90 dias após o tratamento e desaparece aos 170 dias após a cura.

Com o soro dos camundongos, através do método de ELISA, evidenciou-se uma queda nos níveis de anticorpos (IgG total) no grupo tratado em relação a vários antígenos de estágios evolutivos do S. mansoni. As implicações epidemiológicas dos presentes resultados e os possíveis mecanismos envolvidos na queda da imunidade adquirida após tratamento são discutidos.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGMENT

Thanks are due to Mrs. Vera de Paula Ribeiro for translating the manuscript; Mr. Alberto G. dos Santos, Mrs. Alice Neni F. Balzuweit, Miss Zenir de Sousa, Mr. Adelino Ferreira and Mrs. Kátia Moraes Costa for excellent technical assistance.

Recebido para publicação em 25/09/1992

Aceito para publicação em 13/05/1993

This work was supported by CAPES, CNPq, FINEP.

1. ANDRADE, Z.A. & BRITO, P.A. - Curative chemotherapy and resistance to reinfection in murine schistosomiasis. Amer. J. trop. Med. Hyg., 31: 116-121, 1982.
2. ANDRADE, Z. & BINA, J.C. - The changing pattern of pathology due to S. mansoni infection. Mem. Inst. Oswaldo Cruz, 80: 363-366, 1985.
3. ANDRADE, Z. - Esquistosomose mansoni. Patologia da forma hepato-esplęnica. In: CASTRO, P.L.; CUNHA, A.S. & ROCHA, P.R.S. - Tópicos em Gastroenterologia-2. Rio de Janeiro, Ed. Médica e Científica, 1991. cap. 2, p. 23-26.
4. ASKENASE, P.W. - Immune inflammatory response to parasite: the role of basophils, mast cells and vasoactive ammines. Amer. J. trop. Med. Hyg., 26: 96-103, 1977.
5. BARBOSA, M.A.; PELLEGRINO, J. & COELHO, P.M.Z. - Quantitative aspects of the asynchronism in the development of S. mansoni in mice. Rev. Inst. Med. trop. S. Paulo., 20: 121-132, 1978.
6. BINA, J.C. & PRATA, A.R. - A regressăo da hepatoesplenomegalia pelo tratamento específico da esquistossomose. Rev. Soc. bras. Med. trop., 16: 213-218, 1983.
7. CAPRON, M.A.; CAPRON, A.; TORPIER, G.; BAZIN, H.; BOUT, D. & JOSEPH, M. Eosinophil-dependent cytotoxity in rat schistosomiasis. Involvement of IgG2a antibody and role of mast cells. Europ. J. Immunol., 8: 127-133, 1978.
8. CAPRON, A.; DESSAINT, J.P.; CAPRON, M.; JOSEH, M. & PESTEL, J. - Role of anaphylatic antibodies in immunity to schistosomiasis. Amer. J. trop. Med. Hyg., 29: 849-857, 1980.
9. COELHO, P.M.Z. & TAVARES, C.A.P. - ELISA detection of specific circulating antibodies against S. mansoni in mice after treatment with oxamniquine. Braz. J. med. biol. Res., 24: 485-493, 1991.
10. COUTINHO, A. - A new dynamic approach to the diagnosis of Symmers fibrosis in schistosomiasis by ultrasound. Rev. Inst. Med. trop. S. Paulo, 32: 73-77, 1990.
11. COUTINHO, A. & DOMINGUES. A.L.C. - Specific treatment of advanced schistosomiasis liver disease in man: favorable results. Mem. Inst. Oswaldo Cruz, 82: 335-340, 1987.
12. DEAN, D.A. - A review of Schistosoma and related genera: acquired resistance in mice. Exp. Parasit., 55: 1-104, 1983.
13. DEAN, D.A.; BUKOWSHI, M.A. & CHEEVER, A.W. - Relationship between acquired resistance portal hypertension and lung granulomas in ten strains of mice infected with Schistosoma mansoni. Amer. J. trop. Med. Hyg., 30: 806-814, 1981.
14. DIETZE, R. & PRATA, A.R. - Rate of reversion of hepatosplenic schistosomiasis after specific therapy. Rev. Soc. bras. Med. trop., 19: 69-73, 1988.
15. DOENHOFF, M.; BICKLE, Q.; BAIN, J.; WEBBE, G.; & NELSON, G. - Factors affecting the acquisiton of resistance against Schistosoma mansoni in the mouse. V. reduction in the degree of resistance to reinfection after chemotherapeutic elimination of recently patent primary infections. J. Helminth., 54: 7-16, 1980.
16. DOENHOFF, M.J.; DUNNE, D.W. & LILLYTWHITE, J.E. - Serology of Schistosoma mansoni infections after chemotherapy. Trans. roy. Soc. trop. Med. Hyg., 83: 237-238, 1989.
17. FAIRLEY, N.H.; MACKIE, F.P. & JASUDASAN, F. - Studies on Schistosoma spindale Part IV. Further observations on spontaneous cure in Macacus sinicus. Indian med. Res. Mem., 17: 53-59, 1930.
18. FUJINAMI, A. - Kann die erworbene Immunität bei makroparasitärer Erkrankung vorkommen? Kyoto Igaku Zasshi, 13: 176-185, 1916.
19. FUJINAMI, A. & SUEYASU, Y. - Ueber die Hautinvasion des Schistosomum japonicum und Beitrag zur Kenntnis der Naturlichen Immunität der Schistosomatium-Krankheit. Kyoto Igaku Zasshi, 14: 126-141, 1917.
20. GERKEN, S.E. - Schistosoma mansoni: resistęncia cutânea de camundongos normais e portadores de infecçăo primária. Belo Horizonte, 1986. (Tese de Doutoramento - Instituto de Cięncias Biológicas da Universidade Federal de Minas Gerais).
21. GERKEN, S.E.; MOTA-SANTOS, T.A.; VAZ, N.M.; CORREA-OLIVEIRA, R.; DIAS DA SILVA, W. & GAZZINELLI, G. - Recovery of schistosomula of Schistosoma mansoni from mouse skin: involvement of mast cells and vasoactive amines. Braz. J. med. biol. Res., 17: 301-307, 1984.
22. GRZYCH, J.M.; CAPRON, M.; BAZIN, A. & CAPRON, A. - "In vitro" and "in vivo" effector function of rat IgG2a monoclonal anti-Schistosoma mansoni monoclonal antibodies. J. Immunol., 129: 2739, 1982.
23. HOMEIDA, M.A.; AHMED, S.; DEFALLA, A.A.; SULLIMAN, S.; ELTON, J.; NASH, T. & BENNETT, J.L. - Morbity associated with Schistosoma mansoni infection as determined by ultrasound: a study in Gezira, Sudan. Amer. J. trop. Med. Hyg., 39: 196-201, 1988a.
24. HOMEIDA, M.A.; FENWICH, A.; DEFALLA, A.A.; SULLIMAN, S.; KARDAN, N.W.; ELTON, J.; NASH, T. & BENNETT, J.L. - Effect of anti-schistosomal chemotherapy on prevalence of Symmers periportal fibrosis in Sudanese Villages. Lancet, 2: 437-439, 1988b.
25. HOROWITZ, S.; SMOLARSHY, M. & ARNON, R. - Protection against Schistosoma mansoni achieved by immunization with sonicated parasite. Europ. J. Immunol., 12: 327-332, 1982.
26. KAGAN, I.G. & LEE, C.L. - Duration of acquired immunity of Schistosomatium douthitti infections in mice following treatment. J. infect. Dis., 92: 52-57, 1953.
27. KATZ, N.; ZICKER, F.; ROCHA, R.S. & OLIVEIRA, V.B. - Re-infection of patients in schistosomiasis mansoni endemic areas after specific treatment. Rev. Inst. Med. trop. S. Paulo, 20: 273-278, 1978.
28. KATZ, N. - Experięncias com quimioterapia em grande escala no controle da esquistosomose no Brasil. Rev. Inst. Med. trop. S. Paulo, 22: 40-51, 1980.
29. KAY, A.B. - The role of eosinophil. J. Allergy clin. Immunol., 64: 90-104, 1979.
30. KLOETZEL, H. - Selective chemotherapy for Schistosomiasis mansoni. Trans. roy. Soc. trop. Med. Hyg., 68: 344, 1974.
31. MOTT, K.E. & DIXON, H. - Collaborative stydy on antigens for immunodiagnosis of schistosomiasis. Bull. Wld. Hlth. Org., 60: 729-753, 1982.
32. MURREL, K.D.; DEAN, D. A. & STAFFORD, E.E. - Resistance to infection with Schistosoma mansoni after immunization with worm extract or live cercariae: role of cytotoxic antibody in mice and guinea pigs. Amer. J. trop. Med. Hyg., 24: 955-962, 1975.
33. OLIVER, L. & SCHNEIDERMANN, M. - Acquired resistance to Schistosoma mansoni infection in laboratory animals. Amer. J. trop. Med. Hyg., 2: 289-306, 1953.
34. OZAWA, M. - Experimental study on acquired immunity on schistosomiasis japonica. Jap. J. exp. Med., 8: 79-84, 1930.
35. PELLEGRINO, J. & SIQUEIRA, A.F. - Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Rev. bras. Malar., 8: 589-597, 1956.
36. PELLEGRINO, J. & MEMÓRIA, J.M.P. - A reaçăo intradérmica na esquistossomose mansoni. Rev. Inst. Med. trop. S. Paulo, 2: 335-340, 1960.
37. PRATA, A.R. - Esquistossomose mansoni. Fatores determinantes das formas anátomo-clínicas e evoluçăo da doença. In: CASTRO, P.L.; CUNHA, A.S. & ROCHA, P.R.S. - Tópicos em Gastroenterologia - 2. Rio de Janeiro, Ed. Médica e Científica, 1991. cap. 1, p. 3-12.
38. ROSSEAUX-PREVOST, R.R.; BAZIN, H. & CAPRON, A. - IgE in experimental schistosomiasis. I - Serum IgE levels after infection by Schistosoma mansoni in various strains of rats. Immunology, 33: 501-505, 1977.
39. SADUN, E.H. & GORE, R.W. - Schistosoma mansoni and Schistosoma haematobium: homocytotropic reagin-like antibodies in infection of man and experimental animals. Exp. Parasit., 28: 435-449, 1970.
40. SMITHERS, S.R. & TERRY, R.J. - Immunity in schistosomiasis. Ann. N. Y. Acad. Sci., 160: 826-840, 1969.
41. STIREWALT, M.A. - The influence of previous infection of mice with Schistosoma mansoni on a challenging infection with the homologous parasite. Amer. J. trop. Med. Hyg., 2: 867-882, 1953.
42. STURROCK, R.F.; BAIN, J.; WEBBE, G.; DOENHOFF, M.J. & STÖHLER, H. - Parasitological evaluation of curative and subcurative dose of 9 - acridanone-hydrazone drugs against adult Schistosoma mansoni in baboons and observations on changes in serum levels of anti-egg antibodies detected by ELISA. Trans. roy. Soc. trop. Med. Hyg., 81: 188-192, 1987.
43. TANAKA, S. - Über die Frage der erworbenen Immunitat bei der japanischen Schistosomum-Krankheit. Nippon Byori gakkai Kaishi, 16: 111-112, 1926.
44. TAVARES, C.A.P.; DE ROSSI, R.; PAYARES, G.; SIMPSON, A.J.G.; MCLAREN, D.J. & SMITHERS, S.R. - A monoclonal antibody raised against adult Schistosoma mansoni which recognizes a surface antigen on schistosomula. Parasit. Res., 70: 189-197, 1984.
45. WARREN, K.S.; PELLEY, R.P. & MAHMOUD, A.A.F. - Immunity and immunopathology following reinfection of mice cured of chronic schistosomiasis mansoni. Amer. J. trop. Med. Hyg., 26: 957-962, 1977.
46. WILSON, R.A.; COULSON, P.S. & MCHUG, S.M. - A significant part of the concomitant immunity of mice to Schistosoma mansoni is a consequence of a leaky hepatic portal system not immune killing. Paras. Immunol., 5: 595-601, 1983.

Address for correspondence:

Prof. Paulo Marcos Z. Coelho

Deptº Parasitologia, ICB/UFMG

Caixa Postal 2486

30.161-970 Belo Horizonte, MG, Brasil

Publication Dates

Publication in this collection
21 July 2006
Date of issue
Aug 1993

History

Accepted
13 May 1993
Received
25 Sept 1992

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ANDRADE, Z.A. & BRITO, P.A. - Curative chemotherapy and resistance to reinfection in murine schistosomiasis. Amer. J. trop. Med. Hyg., 31: 116-121, 1982.

[2] 2. ANDRADE, Z. & BINA, J.C. - The changing pattern of pathology due to S. mansoni infection. Mem. Inst. Oswaldo Cruz, 80: 363-366, 1985.

[3] 3. ANDRADE, Z. - Esquistosomose mansoni. Patologia da forma hepato-esplęnica. In: CASTRO, P.L.; CUNHA, A.S. & ROCHA, P.R.S. - Tópicos em Gastroenterologia-2. Rio de Janeiro, Ed. Médica e Científica, 1991. cap. 2, p. 23-26.

[4] 4. ASKENASE, P.W. - Immune inflammatory response to parasite: the role of basophils, mast cells and vasoactive ammines. Amer. J. trop. Med. Hyg., 26: 96-103, 1977.

[5] 5. BARBOSA, M.A.; PELLEGRINO, J. & COELHO, P.M.Z. - Quantitative aspects of the asynchronism in the development of S. mansoni in mice. Rev. Inst. Med. trop. S. Paulo., 20: 121-132, 1978.

[6] 6. BINA, J.C. & PRATA, A.R. - A regressăo da hepatoesplenomegalia pelo tratamento específico da esquistossomose. Rev. Soc. bras. Med. trop., 16: 213-218, 1983.

[7] 7. CAPRON, M.A.; CAPRON, A.; TORPIER, G.; BAZIN, H.; BOUT, D. & JOSEPH, M. Eosinophil-dependent cytotoxity in rat schistosomiasis. Involvement of IgG2a antibody and role of mast cells. Europ. J. Immunol., 8: 127-133, 1978.

[8] 8. CAPRON, A.; DESSAINT, J.P.; CAPRON, M.; JOSEH, M. & PESTEL, J. - Role of anaphylatic antibodies in immunity to schistosomiasis. Amer. J. trop. Med. Hyg., 29: 849-857, 1980.

[9] 9. COELHO, P.M.Z. & TAVARES, C.A.P. - ELISA detection of specific circulating antibodies against S. mansoni in mice after treatment with oxamniquine. Braz. J. med. biol. Res., 24: 485-493, 1991.

[10] 10. COUTINHO, A. - A new dynamic approach to the diagnosis of Symmers fibrosis in schistosomiasis by ultrasound. Rev. Inst. Med. trop. S. Paulo, 32: 73-77, 1990.

[11] 11. COUTINHO, A. & DOMINGUES. A.L.C. - Specific treatment of advanced schistosomiasis liver disease in man: favorable results. Mem. Inst. Oswaldo Cruz, 82: 335-340, 1987.

[12] 12. DEAN, D.A. - A review of Schistosoma and related genera: acquired resistance in mice. Exp. Parasit., 55: 1-104, 1983.

[13] 13. DEAN, D.A.; BUKOWSHI, M.A. & CHEEVER, A.W. - Relationship between acquired resistance portal hypertension and lung granulomas in ten strains of mice infected with Schistosoma mansoni. Amer. J. trop. Med. Hyg., 30: 806-814, 1981.

[14] 14. DIETZE, R. & PRATA, A.R. - Rate of reversion of hepatosplenic schistosomiasis after specific therapy. Rev. Soc. bras. Med. trop., 19: 69-73, 1988.

[15] 15. DOENHOFF, M.; BICKLE, Q.; BAIN, J.; WEBBE, G.; & NELSON, G. - Factors affecting the acquisiton of resistance against Schistosoma mansoni in the mouse. V. reduction in the degree of resistance to reinfection after chemotherapeutic elimination of recently patent primary infections. J. Helminth., 54: 7-16, 1980.

[16] 16. DOENHOFF, M.J.; DUNNE, D.W. & LILLYTWHITE, J.E. - Serology of Schistosoma mansoni infections after chemotherapy. Trans. roy. Soc. trop. Med. Hyg., 83: 237-238, 1989.

[17] 17. FAIRLEY, N.H.; MACKIE, F.P. & JASUDASAN, F. - Studies on Schistosoma spindale Part IV. Further observations on spontaneous cure in Macacus sinicus. Indian med. Res. Mem., 17: 53-59, 1930.

[18] 18. FUJINAMI, A. - Kann die erworbene Immunität bei makroparasitärer Erkrankung vorkommen? Kyoto Igaku Zasshi, 13: 176-185, 1916.

[19] 19. FUJINAMI, A. & SUEYASU, Y. - Ueber die Hautinvasion des Schistosomum japonicum und Beitrag zur Kenntnis der Naturlichen Immunität der Schistosomatium-Krankheit. Kyoto Igaku Zasshi, 14: 126-141, 1917.

[20] 20. GERKEN, S.E. - Schistosoma mansoni: resistęncia cutânea de camundongos normais e portadores de infecçăo primária. Belo Horizonte, 1986. (Tese de Doutoramento - Instituto de Cięncias Biológicas da Universidade Federal de Minas Gerais).

[21] 21. GERKEN, S.E.; MOTA-SANTOS, T.A.; VAZ, N.M.; CORREA-OLIVEIRA, R.; DIAS DA SILVA, W. & GAZZINELLI, G. - Recovery of schistosomula of Schistosoma mansoni from mouse skin: involvement of mast cells and vasoactive amines. Braz. J. med. biol. Res., 17: 301-307, 1984.

[22] 22. GRZYCH, J.M.; CAPRON, M.; BAZIN, A. & CAPRON, A. - "In vitro" and "in vivo" effector function of rat IgG2a monoclonal anti-Schistosoma mansoni monoclonal antibodies. J. Immunol., 129: 2739, 1982.

[23] 23. HOMEIDA, M.A.; AHMED, S.; DEFALLA, A.A.; SULLIMAN, S.; ELTON, J.; NASH, T. & BENNETT, J.L. - Morbity associated with Schistosoma mansoni infection as determined by ultrasound: a study in Gezira, Sudan. Amer. J. trop. Med. Hyg., 39: 196-201, 1988a.

[24] 24. HOMEIDA, M.A.; FENWICH, A.; DEFALLA, A.A.; SULLIMAN, S.; KARDAN, N.W.; ELTON, J.; NASH, T. & BENNETT, J.L. - Effect of anti-schistosomal chemotherapy on prevalence of Symmers periportal fibrosis in Sudanese Villages. Lancet, 2: 437-439, 1988b.

[25] 25. HOROWITZ, S.; SMOLARSHY, M. & ARNON, R. - Protection against Schistosoma mansoni achieved by immunization with sonicated parasite. Europ. J. Immunol., 12: 327-332, 1982.

[26] 26. KAGAN, I.G. & LEE, C.L. - Duration of acquired immunity of Schistosomatium douthitti infections in mice following treatment. J. infect. Dis., 92: 52-57, 1953.

[27] 27. KATZ, N.; ZICKER, F.; ROCHA, R.S. & OLIVEIRA, V.B. - Re-infection of patients in schistosomiasis mansoni endemic areas after specific treatment. Rev. Inst. Med. trop. S. Paulo, 20: 273-278, 1978.

[28] 28. KATZ, N. - Experięncias com quimioterapia em grande escala no controle da esquistosomose no Brasil. Rev. Inst. Med. trop. S. Paulo, 22: 40-51, 1980.

[29] 29. KAY, A.B. - The role of eosinophil. J. Allergy clin. Immunol., 64: 90-104, 1979.

[30] 30. KLOETZEL, H. - Selective chemotherapy for Schistosomiasis mansoni. Trans. roy. Soc. trop. Med. Hyg., 68: 344, 1974.

[31] 31. MOTT, K.E. & DIXON, H. - Collaborative stydy on antigens for immunodiagnosis of schistosomiasis. Bull. Wld. Hlth. Org., 60: 729-753, 1982.

[32] 32. MURREL, K.D.; DEAN, D. A. & STAFFORD, E.E. - Resistance to infection with Schistosoma mansoni after immunization with worm extract or live cercariae: role of cytotoxic antibody in mice and guinea pigs. Amer. J. trop. Med. Hyg., 24: 955-962, 1975.

[33] 33. OLIVER, L. & SCHNEIDERMANN, M. - Acquired resistance to Schistosoma mansoni infection in laboratory animals. Amer. J. trop. Med. Hyg., 2: 289-306, 1953.

[34] 34. OZAWA, M. - Experimental study on acquired immunity on schistosomiasis japonica. Jap. J. exp. Med., 8: 79-84, 1930.

[35] 35. PELLEGRINO, J. & SIQUEIRA, A.F. - Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Rev. bras. Malar., 8: 589-597, 1956.

[36] 36. PELLEGRINO, J. & MEMÓRIA, J.M.P. - A reaçăo intradérmica na esquistossomose mansoni. Rev. Inst. Med. trop. S. Paulo, 2: 335-340, 1960.

[37] 37. PRATA, A.R. - Esquistossomose mansoni. Fatores determinantes das formas anátomo-clínicas e evoluçăo da doença. In: CASTRO, P.L.; CUNHA, A.S. & ROCHA, P.R.S. - Tópicos em Gastroenterologia - 2. Rio de Janeiro, Ed. Médica e Científica, 1991. cap. 1, p. 3-12.

[38] 38. ROSSEAUX-PREVOST, R.R.; BAZIN, H. & CAPRON, A. - IgE in experimental schistosomiasis. I - Serum IgE levels after infection by Schistosoma mansoni in various strains of rats. Immunology, 33: 501-505, 1977.

[39] 39. SADUN, E.H. & GORE, R.W. - Schistosoma mansoni and Schistosoma haematobium: homocytotropic reagin-like antibodies in infection of man and experimental animals. Exp. Parasit., 28: 435-449, 1970.

[40] 40. SMITHERS, S.R. & TERRY, R.J. - Immunity in schistosomiasis. Ann. N. Y. Acad. Sci., 160: 826-840, 1969.

[41] 41. STIREWALT, M.A. - The influence of previous infection of mice with Schistosoma mansoni on a challenging infection with the homologous parasite. Amer. J. trop. Med. Hyg., 2: 867-882, 1953.

[42] 42. STURROCK, R.F.; BAIN, J.; WEBBE, G.; DOENHOFF, M.J. & STÖHLER, H. - Parasitological evaluation of curative and subcurative dose of 9 - acridanone-hydrazone drugs against adult Schistosoma mansoni in baboons and observations on changes in serum levels of anti-egg antibodies detected by ELISA. Trans. roy. Soc. trop. Med. Hyg., 81: 188-192, 1987.

[43] 43. TANAKA, S. - Über die Frage der erworbenen Immunitat bei der japanischen Schistosomum-Krankheit. Nippon Byori gakkai Kaishi, 16: 111-112, 1926.

[44] 44. TAVARES, C.A.P.; DE ROSSI, R.; PAYARES, G.; SIMPSON, A.J.G.; MCLAREN, D.J. & SMITHERS, S.R. - A monoclonal antibody raised against adult Schistosoma mansoni which recognizes a surface antigen on schistosomula. Parasit. Res., 70: 189-197, 1984.

[45] 45. WARREN, K.S.; PELLEY, R.P. & MAHMOUD, A.A.F. - Immunity and immunopathology following reinfection of mice cured of chronic schistosomiasis mansoni. Amer. J. trop. Med. Hyg., 26: 957-962, 1977.

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