Drug susceptibility of Plasmodium falciparum in the western Amazon region, state of Acre, Brazil

Neifer, S.; Kremsner, P.G.

doi:10.1590/S0036-46651991000300007

Abstracts

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recomended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

Plasmodium falciparum; Drug resistance; Acre

Estudos de campo na Amazonia ocidental (Estado do Acre, Brasil) indicam que as 4-aminoquinolinas, assim como a sua combinação com sulfadoxina-pirimetamina não podem mais ser recomendadas para o tratamento e profilaxia das infecções pelo P. falciparum nesta região. A quinina permanece como droga efetiva quando usada corretamente. Entretanto, problemas podem surgir devido aos efeitos colaterais durante sua aplicação por período de 10 dias. Possibilidades de ultrapassar estes problemas combinando curto espaço de administração da quinina com outras drogas estão no momento limitadas devido à falta de um composto associado adequado. Por esta razão, a combinação quinina/clindamicina parece ser a terapêutica mais adequada para a malária pelo P. falciparum. Nossos estudos in vitro sugerem que a mefloquina é outra alternativa efetiva para o tratamento da malária falciparum nesta região da Amazônia.

THERAPEUTIC ASSAYS

Drug susceptibility of Plasmodium falciparum in the western Amazon region, state of Acre, Brazil

Susceptibilidade a droga, do Plasmodium falciparum, na Amazônia Ocidental, Estado do Acre, Brasil

S. Neifer^I; P.G. Kremsner^II,III

^ILandesinstitut für Tropenmedizin Berlin

^IIInstitut für Spezifische Prophylaxe und Tropenmedizin, University of Vienna, Austria

^IIIP.G. Kremsner was on research fellowship at "Superintendência de Campanhas de Saúde Pública". Acre, Brazil in 1987 (FWF Austria, grant P6233M)

^{Address for correspondence} Address for correspondence: Dr. P.G. Kremsner Landesinstitut für Tropenmedizin Berlin Königin Elisabeth Straße 32 D-1000 Berlin 19

SUMMARY

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recomended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

Key words: Plasmodium falciparum; Drug resistance; Acre

RESUMO

Estudos de campo na Amazonia ocidental (Estado do Acre, Brasil) indicam que as 4-aminoquinolinas, assim como a sua combinação com sulfadoxina-pirimetamina não podem mais ser recomendadas para o tratamento e profilaxia das infecções pelo P. falciparum nesta região. A quinina permanece como droga efetiva quando usada corretamente. Entretanto, problemas podem surgir devido aos efeitos colaterais durante sua aplicação por período de 10 dias. Possibilidades de ultrapassar estes problemas combinando curto espaço de administração da quinina com outras drogas estão no momento limitadas devido à falta de um composto associado adequado. Por esta razão, a combinação quinina/clindamicina parece ser a terapêutica mais adequada para a malária pelo P. falciparum. Nossos estudos in vitro sugerem que a mefloquina é outra alternativa efetiva para o tratamento da malária falciparum nesta região da Amazônia.

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Recebido para publicação em 11/9/1990

Aceito para publicação em 29/11/1990

1. ALECRIM, W.D.; ALBUQUERQUE, B.C.; ALECRIM, M.G.C. & DOURADO, H. - Tratamento da malária (P. falciparum) com clindamicina. I. Esquema posológico em cinco dias. Rev. Inst. Med. trop. S. Paulo, 24: 40-43, 1982.
2. ALMEIDA-NETTO, J.C.; OLIVEIRA, G.S.C. & SAMPAIO, J.A.A. - Resistęncia do P. falciparum a associaçăo sulfamídicos-antfólicos na regiăo centro-oeste do Brasil. Dados referentes ao estudo de 104 casos. Rev. Pat. trop., 1: 385-393, 1972.
3. BJÖRKMAN, A. & PHILLIPS-HOWARD, P.A. - The epidemiology of drug resistant malaria. Trans. roy. Soc. trop. Med. Hyg., 84: 177-180, 1990.
4. BOULOS, M.; DI SANTI, S.M.; BARATA, L.C.B.; SEGURADO, A.A.C.; DUTRA, A.P. & CAMARGO NEVES, V.L.F. - Some aspects of treatment, prophylaxis and chemoresistance of Plasmodium falciparum malaria. Mem. Inst. Oswaldo Cruz, 81 (Suppl. 2): 255-257, 1986.
5. CABRERA, B.D.; RIVERA, D.G. & LARA, N.T. - Study on clindamycin in the treatment of falciparum malaria. Rev. Inst. Med. trop. S. Paulo, 24 (Supl. 6): 62-69, 1982.
6. COOK, G.C. - Prevention and treatment of malaria. Lancet, 1: 32-37, 1988.
7. CRUZ MARQUES, A. - Migrations and the dissemination of malaria in Brazil. Mem. Inst. Oswaldo Cruz, 81 (Suppl. 2): 17-30, 1986.
8. DI SANTI, S.M.; CAMARGO NEVES, V.J.F.; BOULOS, M.; DUTRA, A.P.; RAMOS, A.M.S.V.; SANTOS, M. & BARATA, L.C.B. - Avaliaçăo da resposta do P. falciparum a cloroquina, quinino e mefloquina. Rev. Inst. Med. trop. S. Paulo, 30: 147-152, 1988.
9. EL WAKEEL, S.; HOMEIDA, M.M.A.; ALI, H.M. GEARY, T.G. & JENSEN, J.B. - Clindamycin for the treatment of falciparum malaria in Sudan. Amer. J. trop Med. Hyg., 34: 1065-1068, 1985.
10. ESPINAL, C.A.; CORTES, G.T.; GUERRA, P. & ARIAS, A.E. - Sensitivity of Plasmodium falciparum to antimalarial drugs in Colombia. Amer. J. trop. Med. Hyg., 34: 675-680, 1985.
11. ESPINAL, C.; URIBE, L.M.; ESLAVA, A. & RODRIGUES, M.E. - Resistance of Plasmodium falciparum to the combination sufadoxine pyrimethamine. Description of 3 primary cases in Colombia. Biomedica, 1: 213-217, 1981.
12. GRAB, B. & WERNSDORFER, W.H. - Evaluation of ir vitro tests for drug sensitivity in Plasmodium falciparum: probit analysis of logdose response test from 3-8 point assay. WHO document MAP/87.2, 1983.
13. KREMSNER, P.G. - Clindamycin in malaria treatment. J. Antimicrob. Chemother., 25: 9-14, 1990.
14. KREMSNER, P.G.; FELDMEIER, H.; ROCHA, R.M. & GRANINGER, W. - Multiresistant malaria in Brazil cured with low dose clindamycin. Rev. Inst. Med. trop. S. Paulo, 30: 118-119, 1988.
15. KREMSNER, P.G. & WERNSDORFER, W.H. - Criteria for the in vitro response of Plasmodium falciparum to amodiaquine. J. Antimicrob. Chemother., 24: 268-269, 1989.
16. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.: BIENZLE, U.; JANSEN-ROSSECK, R.; GRANINGER W.; ROCHA, R.M. & WERNSDORFER, W.H. - Differences in drug response of Plasmodium falciparum within an area of the Amazon region. Trans. roy. Soc. trop. Med. Hyg., 83: 158-161, 1989.
17. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; KOLLARITSCH, H.; WIEDERMANN, G.; ROCHA, R.M. & WERNSDORFER, W.H. - In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil. Bull. Wld. Hlth. Org., 67: 289-293, 1989.
18. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; ROCHA, R.M. & WIEDERMANN, G.- A comparative trial of three regimens for treating uncomplicated falciparum malaria in Acre, Brazil. J. infect. Dis., 158: 1368-1371, 1988.
19. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; WESTERMAN, R.L. & ROCHA, R.M. - Cllindamycin treatment of falciparum malaria in Brazil. J. Antimicrob. Chemother., 23: 275-281, 1989.
20. KREMSNER, P.G.; ZOTTER, G.M.; GRANINGER, W. & FELDMEIER, H. - Amodiaquine-resistant malaria in Brazil. Lancet, 2: 684, 1987.
21. MOORE, D.V. & LANIER, S.R. - Observations on two Plasmodium infections with an abnormal response to chloroquine. Amer. J. trop. Med. Hyg., 10: 5-9, 1961.
22. PANISKO, D.M. & KEYSTONE, J.S. - Treatment of malaria. Drugs, 39: 160-189, 1990.
23. PEREIRA, P.C.M.; MARCONDES, J. BARRA VIERA, B.; MEIRA, D.A.; MENDES, R.P.; VADILETI, C.; SOGAYAR, R. & RUI, P. - Malária no município de Humaitá, estado do Amazonas. XIII-Uso da clindamicina no tratamento de doentes com infecçăo causada pelo Plasmodium falciparum. Rev. Inst. Med. trop. S. Paulo, 24: 16-23, 1982.
24. REYES, S. - Infecçőes maláricas por Plasmodium falciparum resistente ao tratamento com cloroquina. Situaçăo no Brasil (1960-1981). Rev. bras. Malar., 33: 109-130, 1981.
25. RIECKMANN, K.; SYX, L.; CAMPBELL, G.H. & MREMA, J.S. - Drug sensitivity to Plasmodium falciparum, an in vitro microtechnique. Lancet, 1: 22-23, 1978.
26. RIVERA, D.G.; CABRERA, B.D. & LARA, N.T. - Treatment of falciparum malaria with clindamycin. Rev. Inst. Med. trop. S. Paulo, 24: 70-75, 1982.
27. RODRIGUES, D.P. - Cases of Plasmodium falciparum malaria resistant to treatment with chloroquine. Arq. Hig. (S.Paulo), 26: 231-235, 1961.
28. SOUZA, J.M. DE; SHETH, U.K.; OLIVEIRA, R.M.G. de; GOMES, A.T. & CAVALCANTE, E.Q. - A phase I clinical trial of Fansimef (mefloquine plus sulfadoxine-pyrimethamine) in Brazilian male subjects. Bull. Wld. Hlth.Org., 63: 611-615, 1985.
29. VASCONCELOS, M.A. & ROSARIO, V.E. - Testes de sensibilidade in vitro de amostras de Plasmodium falciparum da bacia Amazônica (Brasil). Rev. bras. Malar., 35: 21-28, 1983.
30. WEIDEKAMM, E.; PLOZZA-NOTTEBROCK, H.; FROGO, I. & DUBACH, U.C. - Plasma concentrations of pyrimethamine and sulfadoxine and evaluation of pharma-cokinetic data by computerized curve fitting. Bull. Wld. Hlth. Org., 60: 115-122, 1982.

Address for correspondence:

Dr. P.G. Kremsner

Landesinstitut für Tropenmedizin Berlin

Königin Elisabeth Straße 32

D-1000 Berlin 19

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
June 1991

History

Accepted
29 Nov 1990
Received
11 Sept 1990

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

[1] 1. ALECRIM, W.D.; ALBUQUERQUE, B.C.; ALECRIM, M.G.C. & DOURADO, H. - Tratamento da malária (P. falciparum) com clindamicina. I. Esquema posológico em cinco dias. Rev. Inst. Med. trop. S. Paulo, 24: 40-43, 1982.

[2] 2. ALMEIDA-NETTO, J.C.; OLIVEIRA, G.S.C. & SAMPAIO, J.A.A. - Resistęncia do P. falciparum a associaçăo sulfamídicos-antfólicos na regiăo centro-oeste do Brasil. Dados referentes ao estudo de 104 casos. Rev. Pat. trop., 1: 385-393, 1972.

[3] 3. BJÖRKMAN, A. & PHILLIPS-HOWARD, P.A. - The epidemiology of drug resistant malaria. Trans. roy. Soc. trop. Med. Hyg., 84: 177-180, 1990.

[4] 4. BOULOS, M.; DI SANTI, S.M.; BARATA, L.C.B.; SEGURADO, A.A.C.; DUTRA, A.P. & CAMARGO NEVES, V.L.F. - Some aspects of treatment, prophylaxis and chemoresistance of Plasmodium falciparum malaria. Mem. Inst. Oswaldo Cruz, 81 (Suppl. 2): 255-257, 1986.

[5] 5. CABRERA, B.D.; RIVERA, D.G. & LARA, N.T. - Study on clindamycin in the treatment of falciparum malaria. Rev. Inst. Med. trop. S. Paulo, 24 (Supl. 6): 62-69, 1982.

[6] 6. COOK, G.C. - Prevention and treatment of malaria. Lancet, 1: 32-37, 1988.

[7] 7. CRUZ MARQUES, A. - Migrations and the dissemination of malaria in Brazil. Mem. Inst. Oswaldo Cruz, 81 (Suppl. 2): 17-30, 1986.

[8] 8. DI SANTI, S.M.; CAMARGO NEVES, V.J.F.; BOULOS, M.; DUTRA, A.P.; RAMOS, A.M.S.V.; SANTOS, M. & BARATA, L.C.B. - Avaliaçăo da resposta do P. falciparum a cloroquina, quinino e mefloquina. Rev. Inst. Med. trop. S. Paulo, 30: 147-152, 1988.

[9] 9. EL WAKEEL, S.; HOMEIDA, M.M.A.; ALI, H.M. GEARY, T.G. & JENSEN, J.B. - Clindamycin for the treatment of falciparum malaria in Sudan. Amer. J. trop Med. Hyg., 34: 1065-1068, 1985.

[10] 10. ESPINAL, C.A.; CORTES, G.T.; GUERRA, P. & ARIAS, A.E. - Sensitivity of Plasmodium falciparum to antimalarial drugs in Colombia. Amer. J. trop. Med. Hyg., 34: 675-680, 1985.

[11] 11. ESPINAL, C.; URIBE, L.M.; ESLAVA, A. & RODRIGUES, M.E. - Resistance of Plasmodium falciparum to the combination sufadoxine pyrimethamine. Description of 3 primary cases in Colombia. Biomedica, 1: 213-217, 1981.

[12] 12. GRAB, B. & WERNSDORFER, W.H. - Evaluation of ir vitro tests for drug sensitivity in Plasmodium falciparum: probit analysis of logdose response test from 3-8 point assay. WHO document MAP/87.2, 1983.

[13] 13. KREMSNER, P.G. - Clindamycin in malaria treatment. J. Antimicrob. Chemother., 25: 9-14, 1990.

[14] 14. KREMSNER, P.G.; FELDMEIER, H.; ROCHA, R.M. & GRANINGER, W. - Multiresistant malaria in Brazil cured with low dose clindamycin. Rev. Inst. Med. trop. S. Paulo, 30: 118-119, 1988.

[15] 15. KREMSNER, P.G. & WERNSDORFER, W.H. - Criteria for the in vitro response of Plasmodium falciparum to amodiaquine. J. Antimicrob. Chemother., 24: 268-269, 1989.

[16] 16. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.: BIENZLE, U.; JANSEN-ROSSECK, R.; GRANINGER W.; ROCHA, R.M. & WERNSDORFER, W.H. - Differences in drug response of Plasmodium falciparum within an area of the Amazon region. Trans. roy. Soc. trop. Med. Hyg., 83: 158-161, 1989.

[17] 17. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; KOLLARITSCH, H.; WIEDERMANN, G.; ROCHA, R.M. & WERNSDORFER, W.H. - In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil. Bull. Wld. Hlth. Org., 67: 289-293, 1989.

[18] 18. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; ROCHA, R.M. & WIEDERMANN, G.- A comparative trial of three regimens for treating uncomplicated falciparum malaria in Acre, Brazil. J. infect. Dis., 158: 1368-1371, 1988.

[19] 19. KREMSNER, P.G.; ZOTTER, G.M.; FELDMEIER, H.; GRANINGER, W.; WESTERMAN, R.L. & ROCHA, R.M. - Cllindamycin treatment of falciparum malaria in Brazil. J. Antimicrob. Chemother., 23: 275-281, 1989.

[20] 20. KREMSNER, P.G.; ZOTTER, G.M.; GRANINGER, W. & FELDMEIER, H. - Amodiaquine-resistant malaria in Brazil. Lancet, 2: 684, 1987.

[21] 21. MOORE, D.V. & LANIER, S.R. - Observations on two Plasmodium infections with an abnormal response to chloroquine. Amer. J. trop. Med. Hyg., 10: 5-9, 1961.

[22] 22. PANISKO, D.M. & KEYSTONE, J.S. - Treatment of malaria. Drugs, 39: 160-189, 1990.

[23] 23. PEREIRA, P.C.M.; MARCONDES, J. BARRA VIERA, B.; MEIRA, D.A.; MENDES, R.P.; VADILETI, C.; SOGAYAR, R. & RUI, P. - Malária no município de Humaitá, estado do Amazonas. XIII-Uso da clindamicina no tratamento de doentes com infecçăo causada pelo Plasmodium falciparum. Rev. Inst. Med. trop. S. Paulo, 24: 16-23, 1982.

[24] 24. REYES, S. - Infecçőes maláricas por Plasmodium falciparum resistente ao tratamento com cloroquina. Situaçăo no Brasil (1960-1981). Rev. bras. Malar., 33: 109-130, 1981.

[25] 25. RIECKMANN, K.; SYX, L.; CAMPBELL, G.H. & MREMA, J.S. - Drug sensitivity to Plasmodium falciparum, an in vitro microtechnique. Lancet, 1: 22-23, 1978.

[26] 26. RIVERA, D.G.; CABRERA, B.D. & LARA, N.T. - Treatment of falciparum malaria with clindamycin. Rev. Inst. Med. trop. S. Paulo, 24: 70-75, 1982.

[27] 27. RODRIGUES, D.P. - Cases of Plasmodium falciparum malaria resistant to treatment with chloroquine. Arq. Hig. (S.Paulo), 26: 231-235, 1961.

[28] 28. SOUZA, J.M. DE; SHETH, U.K.; OLIVEIRA, R.M.G. de; GOMES, A.T. & CAVALCANTE, E.Q. - A phase I clinical trial of Fansimef (mefloquine plus sulfadoxine-pyrimethamine) in Brazilian male subjects. Bull. Wld. Hlth.Org., 63: 611-615, 1985.

[29] 29. VASCONCELOS, M.A. & ROSARIO, V.E. - Testes de sensibilidade in vitro de amostras de Plasmodium falciparum da bacia Amazônica (Brasil). Rev. bras. Malar., 35: 21-28, 1983.

[30] 30. WEIDEKAMM, E.; PLOZZA-NOTTEBROCK, H.; FROGO, I. & DUBACH, U.C. - Plasma concentrations of pyrimethamine and sulfadoxine and evaluation of pharma-cokinetic data by computerized curve fitting. Bull. Wld. Hlth. Org., 60: 115-122, 1982.

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