Intestinal microsporidiosis in HIV-positive patients with chronic unexplained diarrhea in Rio de Janeiro, Brazil: diagnosis, clinical presentation and follow-up

Brasil, Patrícia; Sodré, Fernando C.; Cuzzi-Maya, Tullia; Gutierrez, Maria Clara G.F.S.; Mattos, Haroldo; Moura, Hércules

doi:10.1590/S0036-46651996000200003

Abstracts

After the diagnosis of two cases of microsporidial intestinal infection in 1992, in Rio de Janeiro, we have started looking for this parasite in HIV-infected patients with chronic unexplained diarrhea. We have studied 13 patients from Hospital Evandro Chagas, IOC-FIOCRUZ. Fecal specimens from these patients were examined for the presence of Cryptosporidia and Microsporidia, in addition to routine examination. Spores of Microsporidia were found in the stools of 6 (46.1%) of the 13 patients studied, with 2 histological jejunal confirmations. The Microsporidia-infected patients presented chronic diarrhea with about 6 loose to watery bowel movements a day. Five infected patients were treated with Metronidazole (1.5 g/day). They initially showed a good clinical response, but they never stopped eliminating spores. After about the 4th week of therapy, their diarrhea returned. Two patients utilized Albendazole (400 mg/day-4 weeks) with a similar initial improvement and recurrence of the diarrhea. Intestinal Microsporidiosis seems to be a marker of advanced stages of AIDS, since 5 of our 6 infected patients were dead after a 6 month period of follow-up. The present study indicates that intestinal microsporidiosis may be a burgeoning problem in HIV-infected patients with chronic diarrhea in Brazil, which deserves further investigation.

Microsporidia; Diarrhea; Albendazole therapy; Intestinal infection

Após o diagnóstico, em 1992, de 2 pacientes eliminando esporos de microsporídeos, o presente estudo foi realizado com o objetivo de determinar a ocorrência destes organismos em pacientes HIV-positivos com diarréia crônica sem etiologia definida. O grupo estudado era constituído de 13 pacientes acompanhados no Hospital Evandro Chagas, IOC, FIOCRUZ. Amostras fecais de cada paciente foram examinadas pelos métodos de rotina, além de colorações especiais para a pesquisa de Cryptosporidium e de microsporídeos. Esporos de microsporídeos foram observados nas fezes de 6 (46,1%) dos 13 pacientes. Em 2 a confirmação foi feita por biópsia de jejuno, pela observação de formas evolutivas intracelulares do parasito. Os pacientes infectados por microsporídeos apresentaram diarréia crônica com uma média de 6 evacuações diárias, fezes amolecidas ou aquosas, sem leucócitos ou hemácias. Outros sinais e sintomas incluíram dor abdominal difusa, náuseas, vômitos, anorexia e caquexia. Em 5 dos pacientes positivos o tratamento com Metronidazol (1,5 g/dia) foi iniciado. Todos apresentaram melhora das manifestações clínicas, inclusive com ganho ponderal. Entretanto, todos continuaram eliminando esporos de microsporídeos e houve recorrência da diarréia a partir da 4ª semana de tratamento com Metronidazol. Em 2 dos pacientes foi utilizado Albendazol (400 mg/dia / 4 semanas), com aparente melhora clínica. A microsporidiose intestinal parece ser doença terminal, pois dos 6 pacientes positivos estudados, apenas 1 continuava vivo após 6 meses de observação. Os dados obtidos sugerem que estas infecções são importantes entre os pacientes com AIDS também no Brasil, de forma semelhante ao que ocorre em outras partes do mundo.

PARASITOLOGY

Intestinal microsporidiosis in HIV-positive patients with chronic unexplained diarrhea in Rio de Janeiro, Brazil: diagnosis, clinical presentation and follow-up

Microsporidiose intestinal em pacientes HIV-positivos com diarréia crônica no Rio de Janeiro, Brasil: diagnóstico, clínica e acompanhamento

Patrícia Brasil^I; Fernando C. Sodré^I,II; Tullia Cuzzi-Maya^I; Maria Clara G.F.S. Gutierrez^I; Haroldo Mattos^II; Hércules Moura^I,II

^ILaboratórios de Parasitologia e de Patologia, Hospital Evandro Chagas, Instituto Oswaldo Cruz (IOC), FIOCRUZ

^IIDisciplina de Parasitologia e Laboratório de Informática Médica, Departamento de Patologia e Laboratórios, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ) Rio de Janeiro, RJ, Brazil

^{Correspondence to} Correspondence to: Dr. Hércules Moura Universidade do Estado do Rio de Janeiro (UERJ), FCM - Disc. Parasitologia Av. 28 de Setembro, 87 - Fundos/5º andar, Vila Isabel 20551-001 Rio de Janeiro, RJ, Brasil E-mail: hercules@vmesa.uerj.br

SUMMARY

After the diagnosis of two cases of microsporidial intestinal infection in 1992, in Rio de Janeiro, we have started looking for this parasite in HIV-infected patients with chronic unexplained diarrhea. We have studied 13 patients from Hospital Evandro Chagas, IOC-FIOCRUZ. Fecal specimens from these patients were examined for the presence of Cryptosporidia and Microsporidia, in addition to routine examination.

Spores of Microsporidia were found in the stools of 6 (46.1%) of the 13 patients studied, with 2 histological jejunal confirmations. The Microsporidia-infected patients presented chronic diarrhea with about 6 loose to watery bowel movements a day.

Five infected patients were treated with Metronidazole (1.5 g/day). They initially showed a good clinical response, but they never stopped eliminating spores. After about the 4^th week of therapy, their diarrhea returned. Two patients utilized Albendazole (400 mg/day-4 weeks) with a similar initial improvement and recurrence of the diarrhea.

Intestinal Microsporidiosis seems to be a marker of advanced stages of AIDS, since 5 of our 6 infected patients were dead after a 6 month period of follow-up. The present study indicates that intestinal microsporidiosis may be a burgeoning problem in HIV-infected patients with chronic diarrhea in Brazil, which deserves further investigation.

Keywords: Microsporidia, AIDS; Diarrhea; Albendazole therapy; Intestinal infection.

RESUMO

Após o diagnóstico, em 1992, de 2 pacientes eliminando esporos de microsporídeos, o presente estudo foi realizado com o objetivo de determinar a ocorrência destes organismos em pacientes HIV-positivos com diarréia crônica sem etiologia definida. O grupo estudado era constituído de 13 pacientes acompanhados no Hospital Evandro Chagas, IOC, FIOCRUZ. Amostras fecais de cada paciente foram examinadas pelos métodos de rotina, além de colorações especiais para a pesquisa de Cryptosporidium e de microsporídeos.

Esporos de microsporídeos foram observados nas fezes de 6 (46,1%) dos 13 pacientes. Em 2 a confirmação foi feita por biópsia de jejuno, pela observação de formas evolutivas intracelulares do parasito. Os pacientes infectados por microsporídeos apresentaram diarréia crônica com uma média de 6 evacuações diárias, fezes amolecidas ou aquosas, sem leucócitos ou hemácias. Outros sinais e sintomas incluíram dor abdominal difusa, náuseas, vômitos, anorexia e caquexia.

Em 5 dos pacientes positivos o tratamento com Metronidazol (1,5 g/dia) foi iniciado. Todos apresentaram melhora das manifestações clínicas, inclusive com ganho ponderal. Entretanto, todos continuaram eliminando esporos de microsporídeos e houve recorrência da diarréia a partir da 4ª semana de tratamento com Metronidazol. Em 2 dos pacientes foi utilizado Albendazol (400 mg/dia / 4 semanas), com aparente melhora clínica.

A microsporidiose intestinal parece ser doença terminal, pois dos 6 pacientes positivos estudados, apenas 1 continuava vivo após 6 meses de observação. Os dados obtidos sugerem que estas infecções são importantes entre os pacientes com AIDS também no Brasil, de forma semelhante ao que ocorre em outras partes do mundo.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

ACKNOWLEDGMENTS

To Dr. G. S. VIVESVARA, BDB, NCID, Centers for Disease Control, Atlanta, GA, for valuable suggestions and the gift of the anti-Septata rabbit serum.

This work was financially supported by CNPq (Proj.Integr.#520437/93-94) and PAPES FIOCRUZ (#135)

Recebido para publicação em 01/02/1996

Aceito para publicação em 04/03/1996

This paper was presented in part (abstract) at the International Workshop "Microsporidiosis and Cryptosporidiosis in Immunodeficient Patients", September 28 - October 1, 1993, Ceske Budejovice, Czech Republic.

1. BARTLETT, J.; BELITOS, P. & SEARS, C. - AIDS enteropathy. Clin. infect. Dis., 15: 726-735, 1992.
2. BRYAN, R.T. - Microsporidiosis as an AIDS-related opportunistic infection. Clin. infect. Dis., 21 (suppl.1): S62-S65, 1995.
3. BRYAN, R.T.; CALI, A.; OWEN, R.L. & SPENCER, H.C. - Microsporidia: opportunistic pathogens in patients with AIDS, In: SUN, T, ed. Progress in clinical Parasitology. Philadelphia, Field and Wood, 1991. p. 1-26.
4. CALI, A.; KOTLER, D.P. & ORENSTEIN, J.M. - Septata intestinalis N.G., N.Sp., an intestinal microsporidian associated with chronic diarrhea and dissemination in AIDS patients. J. Euk. Microbiol., 40: 101-112, 1993.
5. CANNING, E. & HOLLISTER, W.S. - Enterocytozoon bieneusi (Microspora): prevalence and pathogenicity in AIDS patients. Trans. roy. Soc. trop. Med. Hyg 84: 181-186, 1990.
6. CANNING, E. & HOLLISTER, W.S. - Microsporidia of mammals - widespread pathogens or opportunistic curiosities? Paratit. today, 3: 262-273, 1987.
7. CENTERS FOR DISEASE CONTROL - Revision of the case definition of acquired immunodeficiency syndrome for national reporting - United States. MMWR, 34: 373-375, 1985.
8. DESPORTES, I.; LE CHARPENTIER, Y.; GALIAN, A. et al. - Occurrence of a New Microsporidan: Enterocytozoon bieneusi n.g., n. sp., in the enterocytes of human patient with AIDS. J. Protozool.,32: 250-254, 1985.
9. EEFTINCK SCHATTENKERK, J.K.M.; VAN GOOL, T. & VAN KETEL, R.J. - Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals. Lancet, 337: 895-898, 1991.
10. GREENSON, J.K.; BELITSOS, P.C.; YARDLEY, J.H. et al.. - AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea. Ann. intern. Med., 114: 366-372, 1991.
11. HARTSKEERL, R.A.; VAN GOOL, T.; SCHUITEMA, A.R.J. et al. - Genetic and immunological characterization of the microsporidian Septata intestinalis Cali, Kotler and Orenstein, 1993: reclassification to Encephalitozoon intestinalis. J. Parasit., 110: 277-285, 1995.
12. HIRSCHFELD, M.P.M.; CURY, A.E.; MOURA, H. et al. - Identificaçăo de Microsporidia em 5 pacientes com AIDS no município de Săo Paulo. In: CONGRESSO BRASILEIRO DE PARASITOLOGIA, 13, Rio de Janeiro. 1993. Resumos p. 95.
13. JANOFF, E.N. & SMITH, P.D. - Perspectives on gastrointestinal infections in Aids. Gastroent. Clin. N. Amer., 17: 451-463, 1988.
14. KATZ, N.; CHABES, A. & PELLEGRINO, J. - A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev. Inst. Med. trop. S. Paulo, 14: 397-400, 1972.
15. KOTLER, D.P; FRANCISCO, A.F.; CLAYTON, F. et al. - Small intestinal injury and parasitic diseases in AIDS. Ann. intern.Med., 113: 444-449, 1990.
16. KOTLER, D.P.; GAETZ, H.P; LANGE, M. et al. - Enteropathy associated with the acquired immunodeficiency syndrome. Ann. intern. Med., 101: 421-427, 1984.
17. MOLINA, J.M.; SARFATI, C.; BEAUVAIS, S. et al. - Intestinal microsporidiosis in human immunodeficiency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biologic features. J. infect. Dis., 167: 217-221, 1993.
18. MORAES, R.G. - Contribuiçăo para o estudo do Strongyloides stercoralis e da estrongiloidíase no Brasil. Rev. Serv. esp. Saúde públ., 1: 507-624, 1948.
19. MOURA, H.; FERNANDES, O.; VIOLA, J. P. et al. - Enteric parasites and HIV infection: occurrence in AIDS patients in Rio de Janeiro, Brazil. Mem. Inst. Oswaldo Cruz, 84: 527-533, 1989.
20. MOURA, H.; CARDOSO, R.R.; VELOSO, C.G.; CAVALCANTE, S.C. & VISVESVARA, G.S. - Microsporidia e diarréia crônica em AIDS: identificaçăo de Enterocytozoon em 2 pacientes no Rio de Janeiro. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 29, Fortaleza, 1993. Resumos p. 180.
21. ORENSTEIN, J.; CHIANG, J.; STEINBERG, W. et al. - Intestinal microsporidiosis as a cause of diarrhea in human immunodeficiency virus-infected patients: a report of 20 cases. Hum. Path., 21: 475-481, 1990.
22. ORENSTEIN, J.M.; DIETERICH, D.T. & KOTLER, D.P. - Systemic dissemination by a newly recognized intestinal microsporidia species in AIDS. AIDS, 6: 1143-1150, 1992.
23. RITCHIE, L.S. - Sedimentation technique for routine stool examinations. Bull. U.S. Army med. Dep., 8: 326, 1948.
24. SMITH, P.D. & MAI, V.E.H. - Immunopathophysiology of gastrointestinal disease in HIV infection. Gastroent. Clin. N. Amer., 21: 331-345, 1992.
25. SMITH, P.D.; QUINN, T.C. & STROBER, W. - Gastrointestinal infections in Aids. Ann. intern. Med., 116: 63-77, 1992.
26. VISVESVARA, G.S.; DA SILVA, A.J.; CROPO, G.P. et al. - In vitro culture and serologic and molecular identification of Septata intestinalis isolated from urine of a patient with AIDS. J. clin. Microbiol., 33: 930-936, 1995.
27. WANKE, C.A. - Case records of the Massachusetts General Hospital. New Engl. J. Med., 329: 1946-1954, 1993.
28. WEBER, R.; BRYAN, R.T.; OWEN, R.L. et al. - Improved light-microscopical detection of microsporidia spores in stool and duodenal aspirates. New Engl. J. Med., 326: 161-166, 1992.
29. WEBER, R.; BRYAN, R.T.; SCHWARTZ, D.A. et al. - Human microsporidial infections. Clin. Microbiol. Rev., 7:426-461, 1994.
30. WEBER, R.; MULLER, A.; SPYCHER, M.A. et al. - Intestinal Enterocytozoon bieneusi microsporidiosis in an HIV-infected patient: diagnosis by ileo-colonoscopic biopsies and long-term follow up. Clin. Invest., 70: 1019-1023, 1992.
31. WUHIB, T; SILVA, T.M.J. & NEWMAN, R.D. - Cryptospotidial and microsporidial infections in human immunodeficiency virus-infected patients in Northeastern Brazil. J. infect. Dis., 170: 494-497, 1994.

Correspondence to:

Dr. Hércules Moura

Universidade do Estado do Rio de Janeiro (UERJ), FCM - Disc. Parasitologia

Av. 28 de Setembro, 87 - Fundos/5º andar, Vila Isabel

20551-001 Rio de Janeiro, RJ, Brasil

E-mail:

hercules@vmesa.uerj.br

Publication Dates

Publication in this collection
22 Sept 2006
Date of issue
Apr 1996

History

Accepted
04 Mar 1996
Received
01 Feb 1996

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

[1] 1. BARTLETT, J.; BELITOS, P. & SEARS, C. - AIDS enteropathy. Clin. infect. Dis., 15: 726-735, 1992.

[2] 2. BRYAN, R.T. - Microsporidiosis as an AIDS-related opportunistic infection. Clin. infect. Dis., 21 (suppl.1): S62-S65, 1995.

[3] 3. BRYAN, R.T.; CALI, A.; OWEN, R.L. & SPENCER, H.C. - Microsporidia: opportunistic pathogens in patients with AIDS, In: SUN, T, ed. Progress in clinical Parasitology. Philadelphia, Field and Wood, 1991. p. 1-26.

[4] 4. CALI, A.; KOTLER, D.P. & ORENSTEIN, J.M. - Septata intestinalis N.G., N.Sp., an intestinal microsporidian associated with chronic diarrhea and dissemination in AIDS patients. J. Euk. Microbiol., 40: 101-112, 1993.

[5] 5. CANNING, E. & HOLLISTER, W.S. - Enterocytozoon bieneusi (Microspora): prevalence and pathogenicity in AIDS patients. Trans. roy. Soc. trop. Med. Hyg 84: 181-186, 1990.

[6] 6. CANNING, E. & HOLLISTER, W.S. - Microsporidia of mammals - widespread pathogens or opportunistic curiosities? Paratit. today, 3: 262-273, 1987.

[7] 7. CENTERS FOR DISEASE CONTROL - Revision of the case definition of acquired immunodeficiency syndrome for national reporting - United States. MMWR, 34: 373-375, 1985.

[8] 8. DESPORTES, I.; LE CHARPENTIER, Y.; GALIAN, A. et al. - Occurrence of a New Microsporidan: Enterocytozoon bieneusi n.g., n. sp., in the enterocytes of human patient with AIDS. J. Protozool.,32: 250-254, 1985.

[9] 9. EEFTINCK SCHATTENKERK, J.K.M.; VAN GOOL, T. & VAN KETEL, R.J. - Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals. Lancet, 337: 895-898, 1991.

[10] 10. GREENSON, J.K.; BELITSOS, P.C.; YARDLEY, J.H. et al.. - AIDS enteropathy: occult enteric infections and duodenal mucosal alterations in chronic diarrhea. Ann. intern. Med., 114: 366-372, 1991.

[11] 11. HARTSKEERL, R.A.; VAN GOOL, T.; SCHUITEMA, A.R.J. et al. - Genetic and immunological characterization of the microsporidian Septata intestinalis Cali, Kotler and Orenstein, 1993: reclassification to Encephalitozoon intestinalis. J. Parasit., 110: 277-285, 1995.

[12] 12. HIRSCHFELD, M.P.M.; CURY, A.E.; MOURA, H. et al. - Identificaçăo de Microsporidia em 5 pacientes com AIDS no município de Săo Paulo. In: CONGRESSO BRASILEIRO DE PARASITOLOGIA, 13, Rio de Janeiro. 1993. Resumos p. 95.

[13] 13. JANOFF, E.N. & SMITH, P.D. - Perspectives on gastrointestinal infections in Aids. Gastroent. Clin. N. Amer., 17: 451-463, 1988.

[14] 14. KATZ, N.; CHABES, A. & PELLEGRINO, J. - A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev. Inst. Med. trop. S. Paulo, 14: 397-400, 1972.

[15] 15. KOTLER, D.P; FRANCISCO, A.F.; CLAYTON, F. et al. - Small intestinal injury and parasitic diseases in AIDS. Ann. intern.Med., 113: 444-449, 1990.

[16] 16. KOTLER, D.P.; GAETZ, H.P; LANGE, M. et al. - Enteropathy associated with the acquired immunodeficiency syndrome. Ann. intern. Med., 101: 421-427, 1984.

[17] 17. MOLINA, J.M.; SARFATI, C.; BEAUVAIS, S. et al. - Intestinal microsporidiosis in human immunodeficiency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biologic features. J. infect. Dis., 167: 217-221, 1993.

[18] 18. MORAES, R.G. - Contribuiçăo para o estudo do Strongyloides stercoralis e da estrongiloidíase no Brasil. Rev. Serv. esp. Saúde públ., 1: 507-624, 1948.

[19] 19. MOURA, H.; FERNANDES, O.; VIOLA, J. P. et al. - Enteric parasites and HIV infection: occurrence in AIDS patients in Rio de Janeiro, Brazil. Mem. Inst. Oswaldo Cruz, 84: 527-533, 1989.

[20] 20. MOURA, H.; CARDOSO, R.R.; VELOSO, C.G.; CAVALCANTE, S.C. & VISVESVARA, G.S. - Microsporidia e diarréia crônica em AIDS: identificaçăo de Enterocytozoon em 2 pacientes no Rio de Janeiro. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 29, Fortaleza, 1993. Resumos p. 180.

[21] 21. ORENSTEIN, J.; CHIANG, J.; STEINBERG, W. et al. - Intestinal microsporidiosis as a cause of diarrhea in human immunodeficiency virus-infected patients: a report of 20 cases. Hum. Path., 21: 475-481, 1990.

[22] 22. ORENSTEIN, J.M.; DIETERICH, D.T. & KOTLER, D.P. - Systemic dissemination by a newly recognized intestinal microsporidia species in AIDS. AIDS, 6: 1143-1150, 1992.

[23] 23. RITCHIE, L.S. - Sedimentation technique for routine stool examinations. Bull. U.S. Army med. Dep., 8: 326, 1948.

[24] 24. SMITH, P.D. & MAI, V.E.H. - Immunopathophysiology of gastrointestinal disease in HIV infection. Gastroent. Clin. N. Amer., 21: 331-345, 1992.

[25] 25. SMITH, P.D.; QUINN, T.C. & STROBER, W. - Gastrointestinal infections in Aids. Ann. intern. Med., 116: 63-77, 1992.

[26] 26. VISVESVARA, G.S.; DA SILVA, A.J.; CROPO, G.P. et al. - In vitro culture and serologic and molecular identification of Septata intestinalis isolated from urine of a patient with AIDS. J. clin. Microbiol., 33: 930-936, 1995.

[27] 27. WANKE, C.A. - Case records of the Massachusetts General Hospital. New Engl. J. Med., 329: 1946-1954, 1993.

[28] 28. WEBER, R.; BRYAN, R.T.; OWEN, R.L. et al. - Improved light-microscopical detection of microsporidia spores in stool and duodenal aspirates. New Engl. J. Med., 326: 161-166, 1992.

[29] 29. WEBER, R.; BRYAN, R.T.; SCHWARTZ, D.A. et al. - Human microsporidial infections. Clin. Microbiol. Rev., 7:426-461, 1994.

[30] 30. WEBER, R.; MULLER, A.; SPYCHER, M.A. et al. - Intestinal Enterocytozoon bieneusi microsporidiosis in an HIV-infected patient: diagnosis by ileo-colonoscopic biopsies and long-term follow up. Clin. Invest., 70: 1019-1023, 1992.

[31] 31. WUHIB, T; SILVA, T.M.J. & NEWMAN, R.D. - Cryptospotidial and microsporidial infections in human immunodeficiency virus-infected patients in Northeastern Brazil. J. infect. Dis., 170: 494-497, 1994.