Schistosoma mansoni: evaluation of the activity of oxamniquine on schistosomules, at 24 hours after infection

Coelho, Paulo Marcos Zech; Mello, Rômulo Teixeira de; Gerken, Silvia Elizabeth

doi:10.1590/S0036-46651993000600013

Abstracts

Mice transcutaneously infected with about 400 cercariae were submitted to treatment with oxamniquine (400 mg/kg), 24 hours after infection. The recovery of schistosomules, at 4, 24, 48 and 72 hours and 35 days after treatment, showed the activity of the drug on the parasites, thus practically preventing their migration from the skin to the lungs. Worm recovery performed in the lungs (96 hours after treatment) showed recovery means of 0.6 worms/mouse in the treated group and 53.8 in the control group (untreated). The perfusion of the portal system carried out at 35 days after treatment clearly showed the elimination of all the parasites in the treated group, whereas a recovery mean of 144.7 worms/mouse was detected in the control group (untreated). These findings confirm the efficacy of oxamniquine at the skin phase of infection, and also show similarity with the immunization method that uses irradiated cercariae. The practical application of these findings in the medical clinic is discussed too

Schistosoma mansoni; Oxamniquine; Schistosomules; Migration; Chemotherapeutic treatment

Camundongos infectados transcutaneamente com cerca de 400 cercárias foram submetidos a tratamento com oxamniquina (400 mg/kg), 24 horas após a infecção. A recuperação dos esquistossômulos a nível da pele mostrou a atividade da droga nos parasitos e impediu praticamente sua migração para os pulmões. A recuperação a nível pulmonar (96 horas após tratamento) mostrou uma média de 0,6 vermes por camundongo no grupo tratado e 53,8 no grupo controle, não tratado. A perfusão do sistema porta, realizada aos 35 dias após infecção, mostrou claramente a eliminação de todos os parasitos no grupo tratado, enquanto foi recuperada uma média de 144,7 vermes no grupo controle, não tratado. Estes achados vem comprovar a eficácia da oxamniquina na fase cutânea da infecção e mostra analogia com o sistema de imunização que usa cercárias irradiadas. Também se discute a aplicação destes resultados na clínica

THERAPEUTIC TRIAL

Schistosoma mansoni: evaluation of the activity of oxamniquine on schistosomules, at 24 hours after infection

Schistosoma mansoni: avaliação da atividade da oxamniquina (Mansil*) em esquistossômulos com 24 horas após infecção

Paulo Marcos Zech Coelho^I; Rômulo Teixeira de Mello^II; Silvia Elizabeth Gerken^I

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

^IIDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia da Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil

^{Address for correspondence} Address for correspondence: Prof. P.M.Z. Coelho Departamento de Parasitologia, ICB/UFMG Caixa Postal 2486. 30161-970 Belo Horizonte, MG, Brazil

SUMMARY

Mice transcutaneously infected with about 400 cercariae were submitted to treatment with oxamniquine (400 mg/kg), 24 hours after infection. The recovery of schistosomules, at 4, 24, 48 and 72 hours and 35 days after treatment, showed the activity of the drug on the parasites, thus practically preventing their migration from the skin to the lungs. Worm recovery performed in the lungs (96 hours after treatment) showed recovery means of 0.6 worms/mouse in the treated group and 53.8 in the control group (untreated). The perfusion of the portal system carried out at 35 days after treatment clearly showed the elimination of all the parasites in the treated group, whereas a recovery mean of 144.7 worms/mouse was detected in the control group (untreated).

These findings confirm the efficacy of oxamniquine at the skin phase of infection, and also show similarity with the immunization method that uses irradiated cercariae. The practical application of these findings in the medical clinic is discussed too.

Keywords:Schistosoma mansoni; Oxamniquine; Schistosomules; Migration; Chemotherapeutic treatment.

RESUMO

Camundongos infectados transcutaneamente com cerca de 400 cercárias foram submetidos a tratamento com oxamniquina (400 mg/kg), 24 horas após a infecção. A recuperação dos esquistossômulos a nível da pele mostrou a atividade da droga nos parasitos e impediu praticamente sua migração para os pulmões. A recuperação a nível pulmonar (96 horas após tratamento) mostrou uma média de 0,6 vermes por camundongo no grupo tratado e 53,8 no grupo controle, não tratado. A perfusão do sistema porta, realizada aos 35 dias após infecção, mostrou claramente a eliminação de todos os parasitos no grupo tratado, enquanto foi recuperada uma média de 144,7 vermes no grupo controle, não tratado.

Estes achados vem comprovar a eficácia da oxamniquina na fase cutânea da infecção e mostra analogia com o sistema de imunização que usa cercárias irradiadas. Também se discute a aplicação destes resultados na clínica.

Full text available only in PDF format.

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ACKNOWLEDGEMENTS

This work was supported by FAPEMIG, CNPq and FINEP, Brazil, and by WHO, Switzerland.

The authors are indebted to Mrs. Vera de Paula Ribeiro for translating the manuscript.

They also wish to thank Mr. Alberto G. dos Santos, Miss Zenir de Souza and Mrs. Alice Neni F. Balzuweit for technical assistance.

Recebido para publicação em 26/04/1993

Aceito para publicação em 26/07/1993.

1. BARBOSA, M.A.; PELLEGRINO, J.; COELHO, P.M.Z. & SAMPAIO, I.B.M. - Quantitative aspects of the migration and evolutive asynchronism of Schistosoma mansoni in mice. Rev. Inst. Med. trop. S. Paulo, 20: 121-132, 1978.
2. BICKLE, Q.D. & ANDREWS, B.J. - Resistance following drug attenuation (RO-113128 or oxamniquine) of early Schistosoma mansoni in mice. Parasitology, 90: 677-678, 1985.
3. BICKLE, Q.D.; DOBINSON, T. & JAMES, E.R. - The effects of gamma irradiation on migration and survival of Schistosoma mansoni schistosomula in mice. Parasitology, 79: 223-230, 1979.
4. CARDOSO, G.S. & COELHO, P.M.Z. - Schistosoma mansoni: evoluçăo de vermes oriundos de cercárias irradiadas a nivel de sistema porta, no camundongo. Rev. Soc. bras. Med. trop., 22: 199-210, 1989.
5. CARDOSO, G.S. & COELHO, P.M.Z. - Schistosoma mansoni: aspectos quantitativos de evoluçăo de cercárias irradiadas a nivel da pele, pulmőes e sistema porta, em camundongos. Rev. Inst. Med. trop. S. Paulo, 31: 313-321, 1989.
6. COELHO, P.M.Z.; MELLO, R.T. & GERKEN, S.E. - Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive and pulmonary phases. Rev. Inst. Med. trop. S. Paulo, 33: 28-31, 1991.
7. DEAN, D.A. - A review. Schistosoma mansoni and related genera: acquired resistance in mice. Exp. Parasit., 55: 1-104, 1983.
8. FOSTER, R. - The preclinical development of oxamniquine. Rev. Inst. Med. trop. S. Paulo, 15: 1-9, 1973.
9. FOSTER, R. & CHEETHAM, B.L. - Studies with the schistosomicide oxamniquine (UK-4271). I - Activity in rodents and in vitro. Trans. roy. Soc. trop. Med. Hyg., 67: 674-684, 1973.
10. FOSTER, R.; CHEETHAM, B.L. & KING, D.F. - Studies with the schistosomicide oxamniquine (UK-4271). II - Activity in primates. Trans. roy. Soc. trop. Med. Hyg., 67: 685-693, 1973.
11. GERKEN, S.E.; CORREA-OLIVEIRA, R. & MOTA-SANTOS, T.A. - Local de morte do Schistosoma mansoni no camundongo. Cięnc. e Cult., 32: 617, 1980.
12. GERKEN, S.E.; MOTA-SANTOS, T.A.; VAZ, N.M.; CORREA-OLIVEIRA, R.; DIAS DA SILVA, W.J. & 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.
13. KATZ, N. - Experięncias com quimioterapia em grande escala no controle da esquistossomose no Brasil. Rev. Inst. Med. trop. S. Paulo, 22: 40-51, 1980.
14. KATZ, N.; PELLEGRINO, J.; GRINBAUM, E.; CHAVES, A. & ZICKER, F. - Preliminary clinical trials with oxamniquine, a new antischistosomal agent. Rev. Inst. Med. trop. S. Paulo, 15: 25-29, 1973.
15. MANGOLD, B.L. & DEAN, D.A. - The migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host parasite contact in relation to induction of resistance in mice. Parasitology, 88: 249-266, 1984.
16. MASTIN, A.J.; WILSON, R.A. & BICKLE, Q.D. - Induction of resistance in mice by chemotherapy: migration of schistosomula in primary and challenge infection. Parasitology, 90: 519-528,1985.
17. ORGANIZACIÓN MUNDIAL DE LA SALUD - Esquistosomiasis y lucha. Informe de un comité de expertos de la OMS. Org. mund. Salud Ser. Inf. técn., (643), 1980.
18. PELLEGRINO, J.; PEREIRA, L.H. & MELLO, R.T. - Chemoprophylactic activity of known antischistosomicidal agents. Rev. Inst. Med. trop. S. Paulo, 19: 43-46, 1977.
19. PELLEGRINO, J. & SIQUEIRA, A.F. - Técnica de perfusăo para colheita de Schistosoma mansoni em cobaias experimentalmente infectadas. Rev. bras. Malar., 8: 589-597, 1956.
20. PERLOWAGORA-SZUMLEWICZ, A. & OLIVIER, L. - Schistosoma mansoni: development of challenge infections in mice exposed to irradiated cercariae. Science, 140: 411-412, 1963.
21. PEREIRA, L.H.; PELLEGRINO, J. & MELLO, R.T. - Activity of known antischistosomal agents on early developing forms of Schistosoma mansoni. J. Parasit., 61: 249-252, 1975.
22. RADKE, M.G. & SADUN, E.H. - Resistance produced in mice by exposure to irradiated Schistosoma mansoni cercariae. Exp. Parasit., 13: 134-142, 1963.
23. SMITHERS, S.R. & GAMMAGE, R. - Recovery of Schistosoma mansoni from the skin, lungs and hepatic portal system of naive mice and mice previously exposed to S. mansoni: evidence of two phases of parasite attriction in immune mice. Parasitology, 80: 289-300,1980.
24. SNEDECOR, G.W. & COCHRAN, W.G. - Two-way classification. In: SNEDECOR, G.W. & COCHRAN, W.G., ed. Statistical methods. Iowa, The Iowa State University Press, 1971. v. 2, p. 327-329.
25. VILLELLA, J.B.; GOMBERG, H.G. & GOULD, S.E. - Immunization to Schistosoma mansoni in mice inoculated with radiated cercariae. Science, 134: 1073-1075, 1961.
26. WARREN, K.S. - The immunopathogenesis of schistosomiasis. A multidisciplinary approach. Trans. roy. Soc. trop. Med. Hyg., 6: 417-434, 1972.

Address for correspondence:

Prof. P.M.Z. Coelho

Departamento de Parasitologia, ICB/UFMG

Caixa Postal 2486. 30161-970 Belo Horizonte, MG, Brazil

Publication Dates

Publication in this collection
03 July 2006
Date of issue
Dec 1993

History

Received
26 Apr 1993
Accepted
26 July 1993

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

[1] 1. BARBOSA, M.A.; PELLEGRINO, J.; COELHO, P.M.Z. & SAMPAIO, I.B.M. - Quantitative aspects of the migration and evolutive asynchronism of Schistosoma mansoni in mice. Rev. Inst. Med. trop. S. Paulo, 20: 121-132, 1978.

[2] 2. BICKLE, Q.D. & ANDREWS, B.J. - Resistance following drug attenuation (RO-113128 or oxamniquine) of early Schistosoma mansoni in mice. Parasitology, 90: 677-678, 1985.

[3] 3. BICKLE, Q.D.; DOBINSON, T. & JAMES, E.R. - The effects of gamma irradiation on migration and survival of Schistosoma mansoni schistosomula in mice. Parasitology, 79: 223-230, 1979.

[4] 4. CARDOSO, G.S. & COELHO, P.M.Z. - Schistosoma mansoni: evoluçăo de vermes oriundos de cercárias irradiadas a nivel de sistema porta, no camundongo. Rev. Soc. bras. Med. trop., 22: 199-210, 1989.

[5] 5. CARDOSO, G.S. & COELHO, P.M.Z. - Schistosoma mansoni: aspectos quantitativos de evoluçăo de cercárias irradiadas a nivel da pele, pulmőes e sistema porta, em camundongos. Rev. Inst. Med. trop. S. Paulo, 31: 313-321, 1989.

[6] 6. COELHO, P.M.Z.; MELLO, R.T. & GERKEN, S.E. - Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive and pulmonary phases. Rev. Inst. Med. trop. S. Paulo, 33: 28-31, 1991.

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

[8] 8. FOSTER, R. - The preclinical development of oxamniquine. Rev. Inst. Med. trop. S. Paulo, 15: 1-9, 1973.

[9] 9. FOSTER, R. & CHEETHAM, B.L. - Studies with the schistosomicide oxamniquine (UK-4271). I - Activity in rodents and in vitro. Trans. roy. Soc. trop. Med. Hyg., 67: 674-684, 1973.

[10] 10. FOSTER, R.; CHEETHAM, B.L. & KING, D.F. - Studies with the schistosomicide oxamniquine (UK-4271). II - Activity in primates. Trans. roy. Soc. trop. Med. Hyg., 67: 685-693, 1973.

[11] 11. GERKEN, S.E.; CORREA-OLIVEIRA, R. & MOTA-SANTOS, T.A. - Local de morte do Schistosoma mansoni no camundongo. Cięnc. e Cult., 32: 617, 1980.

[12] 12. GERKEN, S.E.; MOTA-SANTOS, T.A.; VAZ, N.M.; CORREA-OLIVEIRA, R.; DIAS DA SILVA, W.J. & 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.

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

[14] 14. KATZ, N.; PELLEGRINO, J.; GRINBAUM, E.; CHAVES, A. & ZICKER, F. - Preliminary clinical trials with oxamniquine, a new antischistosomal agent. Rev. Inst. Med. trop. S. Paulo, 15: 25-29, 1973.

[15] 15. MANGOLD, B.L. & DEAN, D.A. - The migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host parasite contact in relation to induction of resistance in mice. Parasitology, 88: 249-266, 1984.

[16] 16. MASTIN, A.J.; WILSON, R.A. & BICKLE, Q.D. - Induction of resistance in mice by chemotherapy: migration of schistosomula in primary and challenge infection. Parasitology, 90: 519-528,1985.

[17] 17. ORGANIZACIÓN MUNDIAL DE LA SALUD - Esquistosomiasis y lucha. Informe de un comité de expertos de la OMS. Org. mund. Salud Ser. Inf. técn., (643), 1980.

[18] 18. PELLEGRINO, J.; PEREIRA, L.H. & MELLO, R.T. - Chemoprophylactic activity of known antischistosomicidal agents. Rev. Inst. Med. trop. S. Paulo, 19: 43-46, 1977.

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

[20] 20. PERLOWAGORA-SZUMLEWICZ, A. & OLIVIER, L. - Schistosoma mansoni: development of challenge infections in mice exposed to irradiated cercariae. Science, 140: 411-412, 1963.

[21] 21. PEREIRA, L.H.; PELLEGRINO, J. & MELLO, R.T. - Activity of known antischistosomal agents on early developing forms of Schistosoma mansoni. J. Parasit., 61: 249-252, 1975.

[22] 22. RADKE, M.G. & SADUN, E.H. - Resistance produced in mice by exposure to irradiated Schistosoma mansoni cercariae. Exp. Parasit., 13: 134-142, 1963.

[23] 23. SMITHERS, S.R. & GAMMAGE, R. - Recovery of Schistosoma mansoni from the skin, lungs and hepatic portal system of naive mice and mice previously exposed to S. mansoni: evidence of two phases of parasite attriction in immune mice. Parasitology, 80: 289-300,1980.

[24] 24. SNEDECOR, G.W. & COCHRAN, W.G. - Two-way classification. In: SNEDECOR, G.W. & COCHRAN, W.G., ed. Statistical methods. Iowa, The Iowa State University Press, 1971. v. 2, p. 327-329.

[25] 25. VILLELLA, J.B.; GOMBERG, H.G. & GOULD, S.E. - Immunization to Schistosoma mansoni in mice inoculated with radiated cercariae. Science, 134: 1073-1075, 1961.

[26] 26. WARREN, K.S. - The immunopathogenesis of schistosomiasis. A multidisciplinary approach. Trans. roy. Soc. trop. Med. Hyg., 6: 417-434, 1972.

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