Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

Meira, Domingos Alves; Pereira, Paulo Camara Marques; Marcondes-Machado, Jussara; Mendes, Rinaido Poncio; Barraviera, Benedito; Pirola, José Antonio G.; Guimarães, Maria Regina Cotrim; Curi, Paulo Roberto; Rodrigues, Renato Pedro

doi:10.1590/S0037-86821988000300005

Abstracts

A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7th, 24th, 21st, 28th and 35th day both clinically and parasitologically (blood test). Eighty three (40.1%) had moderate or severe malaria, and 97 (46.8%) had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%), two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.

treatment; Plasmodium falciparum; Clindamycin

De 1981 a 1984, 207 doentes com malária, causada pelo Plasmodium falciparum, foram tratados com 5 esquemas de clindamicina: A - 89 doente tratados com 20 mg/kg/dia, pelas vias endovenosa e oral, ou intramuscular e oral, em duas aplicações diárias, durante 5 a 7 dias; B - 40 doentes tratados com 20 mg/kg/dia, por via oral, em duas tomadas diárias, durante 5 a 7 dias; C - 27 doentes tratados com 20 mg/kg/dia, por via oral ou endovenosa, em duas tomadas diárias, durante 3 dias; D - 16 doentes tratados com 20 a 40 mg/kg/dia, por vias oral, e/ou, endovenosa, em uma única dose diária, durante 5 a 7 dias; E - 35 doentes tratados com 5 mg/kg/dia, por via oral, em duas doses diárias, durante 5 dias. Os doentes foram examinados, diariamente, durante o tratamento e reexaminados no 7.°, 14.°, 28.° e 35.° dias, tanto pelo exame clínico, quanto pelo parasitológico de sangue. Oitenta e três (40,1%) tinham malária moderada ou grave e 97 (46,8%) tinham apresentado resistência à cloroquina, ou à associação sulfadoxina e pirimetamina. Os resultados mostraram que a proporção de curados foi superior a 95% nos doentes tratados pelos esquemas A e B. Os efeitos colaterais observados foram ocasionais e de pequena intensidade. Houve três casos de óbito (1,4%), dois dos quais atendidos desde o inicio com quadro muito grave. A clindamicina: portanto, mostrou ser muito útil no tratamento de doentes com malária causada pelo Plasmodium falciparum, recomenda-se o esquema A para os casos moderados e o B para os benignos.

Tratamento da malária; Plasmodium falciparum; Clindamicina

ARTICLES

Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

Domingos Alves Meira^I; Paulo Camara Marques Pereira^I; Jussara Marcondes-Machado^I; Rinaido Poncio Mendes^I; Benedito Barraviera^I; José Antonio G. Pirola^I; Maria Regina Cotrim Guimarães^I; Paulo Roberto Curi^II; Renato Pedro Rodrigues^I

^IDepartamento de Moléstias Infecciosas e Parasitárias, Dermatologia e Radiologia, Faculdade de Medicina, Campus de Botucatu - UNESP

^IIDepartamento de Cirurgia, Faculdade de Medicina, Campus de Botucatu - UNESP

^{Adress to correspondence} Adress to correspondence: Domingos Alves Meira Departamento de Moléstias Infecciosas e Parasitárias Dermatologia e Radiologia Faculdade de Medicina de Botucatu - UNESP Caixa Postal 522 18610 Botucatu - São Paulo - Brasil.

ABSTRACT

A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7^th, 24^th, 21^st, 28^th and 35^th day both clinically and parasitologically (blood test). Eighty three (40.1%) had moderate or severe malaria, and 97 (46.8%) had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%), two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.

Keywords: treatment. Plasmodium falciparum. Clindamycin.

RESUMO

De 1981 a 1984, 207 doentes com malária, causada pelo Plasmodium falciparum, foram tratados com 5 esquemas de clindamicina: A - 89 doente tratados com 20 mg/kg/dia, pelas vias endovenosa e oral, ou intramuscular e oral, em duas aplicações diárias, durante 5 a 7 dias; B - 40 doentes tratados com 20 mg/kg/dia, por via oral, em duas tomadas diárias, durante 5 a 7 dias; C - 27 doentes tratados com 20 mg/kg/dia, por via oral ou endovenosa, em duas tomadas diárias, durante 3 dias; D - 16 doentes tratados com 20 a 40 mg/kg/dia, por vias oral, e/ou, endovenosa, em uma única dose diária, durante 5 a 7 dias; E - 35 doentes tratados com 5 mg/kg/dia, por via oral, em duas doses diárias, durante 5 dias. Os doentes foram examinados, diariamente, durante o tratamento e reexaminados no 7.°, 14.°, 28.° e 35.° dias, tanto pelo exame clínico, quanto pelo parasitológico de sangue. Oitenta e três (40,1%) tinham malária moderada ou grave e 97 (46,8%) tinham apresentado resistência à cloroquina, ou à associação sulfadoxina e pirimetamina. Os resultados mostraram que a proporção de curados foi superior a 95% nos doentes tratados pelos esquemas A e B. Os efeitos colaterais observados foram ocasionais e de pequena intensidade. Houve três casos de óbito (1,4%), dois dos quais atendidos desde o inicio com quadro muito grave. A clindamicina: portanto, mostrou ser muito útil no tratamento de doentes com malária causada pelo Plasmodium falciparum, recomenda-se o esquema A para os casos moderados e o B para os benignos.

Palavras-chave: Tratamento da malária. Plasmodium falciparum. Clindamicina.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Recebido para publicação em 14/12/87.

Department of Medicine, Federal University of Bahia Medical School, Salvador BA Brazil.

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Brazil (Grant n° 407670/85CL).

1. Alecrim MG, Dourado H, Alecrim W, Albuquerque BC, Wanssa E, Wanssa MC Tratamento damalaria (P. falciparum) com clindamicina. Revista do Instituto de Medicina Tropical de São Paulo 23: 86-91, 1981.
2. Alecrim MGC, Alecrim WD, Albuquerque BC de, Dourado HV, Wanssa MC. Resistência "in vivo" do Plasmodium falciparum à associação sulfametoxazol mais trimetoprin na Amazônia Brasileira. Revista do Instituto de Medicina Tropical de São Paulo 24: (Supl. 6): 48-51, 1982.
3. Alecrim WD, Albuquerque BC, Alecrim MGC, Dourado H. Tratamento da malária (P. falciparum) com clindamicina. II - Esquema posológico em cinco dias. Revista do Instituto de Medicina Tropical de São Paulo 24 (Supl. 6): 40-43, 1982.
4. Alecrim WD, Dourado H, Alecrim M das G, Passos LF, Wanssa E, Albuquerque B. Resistência "in vivo" do Plasmodium falciparum à associação sulfadoxina mais pirimetamina, a nível de R III, no Amazonas, Brasil. Re vista do Instituto de Medicina Tropical de São Paulo 24(Supl. 6): 52-53, 1982.
5. Almeida Neto JC, Oliveira GSC, Sampaio JAA. Resistência do P. falciparum à associação sulfamídicos na região Centro-Oeste do Brasil. Dados referentes ao estudo de 104 pacientes. Revista de Patologia Tropical de Goiás 3: 385-393. 1972.
6. Boriello SP. Clostridium difficile and gut disease. In: CS Goode (ed) Microbes and Infectious of the gut. Scientific Publications. Date Late 327-346, 1983.
7. Cabrera BD, Rivera DG, Lara NT. Study on clindamycin in the treatment of falciparum malaria. Re vista do Institute de Medicina Tropical de São Paulo 24: (Supl. 6j: 62-69, 1982.
8. Clyde DF, Gilmar RH, Mc Carthy VC. Antimalarial effects of clindamycin in man. American Journal of Tropical Medicine and Hygiene 24: 369-370, 1975.
9. DeHaan RM, Metzler CM, Schellenberg D, Vandenbosh WD. Pharmacockinetic studies of clindamycin phosphate. Journal of Clinical Pharmacology 13:190- 209, 1973.
10. Dourado H. Terapêutica da malária com minociclina. Revista Brasileira de Clínica e Terapêutica 2: 10-12, 1973.
11. Fleiss JL. Statistical methods for rates and proportions. John Wiley & Sons, New York, 1973.
12. Geary TG, Divo AA, Jensen JB. An in vitro assay system for the identification of potential antimalarial drugs. Journal of Parasitology 69: 577-5S3, 1983.
13. Geary TG, Jensen JB. Effects of antibiotics on Plasmodium falciparum in vitro. American Journal of Tropical Medicine and Hygiene 32:221-225, 1983.
14. Hollander M, Wolfe DA. Nonparametric Statistical Methods. John Wiley & Sons, New York, 1973.
15. IES - Informações Epidemiológicas SUCAM. Casos notificados de malária por área de erradicação a longo e curto prazo e por unidade. N? 26, dezembro, 1984.
16. Lewis C. Antiplasmodial activity of halogenated lincomycin analogues in Plasmodium falciparum infected mice. In: Antimicrobial Agents and Chemotherapy, p. 537-542, 1967.
17. Lewis C. Antiplasmodial activity of 7-halogenated lincomycins. The Journal of Parasitology 54:169-170, 1968.
18. Meira DA, Curi PR, Barraviera B. Malaria in Humaita county, Amazonas State, Brazil. XXIX - Some comparative epidemiologic aspects in 1976,1979 and 1983. In: Proceedings of IV Japan-Brazil Symposium on Science and Technology São Paulo 2: 136-143, 1984.
19. Meira DA, Curi PR, Marcondes J, Matsuoka ES, Favrin MA, El - Khoury AB, Motta NGS. Malaria at Humaita County, Amazonas State, Brazil. XVII - Immune response in patients with Plasmodium falciparum according to gametocytes. Re vista do Instituto de Medicina Tropical de São Paulo 27:229-237,1985.
20. Meira DA, Marcondes J, Barraviera B, Pereira PCM, Rui P, Cury PR. Malaria at Humaita County, Amazonas State, Brazil. XVI - Gametocytes and lymphocytes studied in patients with Plasmodium falciparum Re vista do Instituto de Medicina Tropical de São Paulo 24:(Supl. 6): 32-39, 1982.
21. Meira DA, Pellegrino Júnior J, Marcondes Machado J, Tsuji K, Matsuoka ES, Haida E, El Khoury AB. Frequency of human leukocyte antigen (HLA) in patients with malaria and in the general population of Humaita county, Amazonas State, Brasil, Revista da Sociedade Brasileira de Medicina Tropical 20: 153-158, 1987.
22. Miller LH, Glew RH, Wyler DJ, Howard WA, Collins WE, Contacos PG, Neva FA. Evaluation of clindamycin in combination with quinine against multi drug- resistant strains of Plasmodium falciparum American Journal of Tropical Medicine and Hygiene 23: 565-569, 1974.
23. OPAS - Manual de Diagnóstico Microscópico da Malaria. Publicação Científica nP 276, p. 109, 1975.
24. Pereira PCM, Marcondes J, Barraviera B, Meira DA, Mendes RP, Vadileti C, Sogayar R, Rui P. Malária no município de Humaitá, Estado do Amazonas. XIII - Uso da clindamicina no tratamento de doentes com infecção causada pelo Plasmodium falciparum Revista do Instituto de Medicina Tropical de São Paulo 24: (Supl. 6): 16-23, 1982.
25. Peters W. Chemotherapy of malaria. In: Julius P. Kreier, (ed) Malaria. Vol. 1, Academic Press, p. 145- 283, 1980.
26. Powers KG, Jacob RL. Activity of two chlorinated lincomycin analogues against chloroquine resistent falciparum malaria in owl monkeys. In: Antimicrobial Agents and Chemotherapy 49-53, 1972.
27. Rieckmann KH, Powell RD, McNamara JV, Willerson Jr D, Kass L, Frischer H, Carson PE. Effects of tetracycline against chloroquine-resistant and chloroquine sensitive Plasmodium falciparum American J oumal of T ropical Medicine and Hygiene 20:811-815, 1971.
28. Rivera DG, Cabrera, BD, Lara NT. Treatment of falciparum malaria with clindamycin. Revista do Instituto de Medicina Tropical de São Paulo 24 (Supl. 6): 70-75, 1982.
29. Schimidt LH, Harrison J, Ellison R, Worcester P. The activities of chlorinated lincomycin derivatives against infections with Plasmodium cynomolgi in Macaca mullatta American journal of Tropical Medicine and Hygiene 19: 1-11, 1970.
30. Seaberg LS, Parquette AR, Gluzman IY, Phillips-Jr. GW, Brodasky TF, Krogstad DJ. Clindamycin activity against chloroquine resistant Plasmodium falciparum Journal of Infections Diseases 150: 904-911, 1984.
31. Silva JR, Lopes PF A, F erreira LF, Morteo R, N aveira JB. Resistência do P. falciparum à ação da cloroquina. Nota prévia. O Hospital 60:581-594, 1961.

Adress to correspondence:

Domingos Alves Meira

Departamento de Moléstias Infecciosas e Parasitárias

Dermatologia e Radiologia

Faculdade de Medicina de Botucatu - UNESP

Caixa Postal 522

18610

Botucatu - São Paulo - Brasil.

Publication Dates

Publication in this collection
28 May 2013
Date of issue
Sept 1988

History

Received
14 Dec 1987
Accepted
14 Dec 1987

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

[1] 1. Alecrim MG, Dourado H, Alecrim W, Albuquerque BC, Wanssa E, Wanssa MC Tratamento damalaria (P. falciparum) com clindamicina. Revista do Instituto de Medicina Tropical de São Paulo 23: 86-91, 1981.

[2] 2. Alecrim MGC, Alecrim WD, Albuquerque BC de, Dourado HV, Wanssa MC. Resistência "in vivo" do Plasmodium falciparum à associação sulfametoxazol mais trimetoprin na Amazônia Brasileira. Revista do Instituto de Medicina Tropical de São Paulo 24: (Supl. 6): 48-51, 1982.

[3] 3. Alecrim WD, Albuquerque BC, Alecrim MGC, Dourado H. Tratamento da malária (P. falciparum) com clindamicina. II - Esquema posológico em cinco dias. Revista do Instituto de Medicina Tropical de São Paulo 24 (Supl. 6): 40-43, 1982.

[4] 4. Alecrim WD, Dourado H, Alecrim M das G, Passos LF, Wanssa E, Albuquerque B. Resistência "in vivo" do Plasmodium falciparum à associação sulfadoxina mais pirimetamina, a nível de R III, no Amazonas, Brasil. Re vista do Instituto de Medicina Tropical de São Paulo 24(Supl. 6): 52-53, 1982.

[5] 5. Almeida Neto JC, Oliveira GSC, Sampaio JAA. Resistência do P. falciparum à associação sulfamídicos na região Centro-Oeste do Brasil. Dados referentes ao estudo de 104 pacientes. Revista de Patologia Tropical de Goiás 3: 385-393. 1972.

[6] 6. Boriello SP. Clostridium difficile and gut disease. In: CS Goode (ed) Microbes and Infectious of the gut. Scientific Publications. Date Late 327-346, 1983.

[7] 7. Cabrera BD, Rivera DG, Lara NT. Study on clindamycin in the treatment of falciparum malaria. Re vista do Institute de Medicina Tropical de São Paulo 24: (Supl. 6j: 62-69, 1982.

[8] 8. Clyde DF, Gilmar RH, Mc Carthy VC. Antimalarial effects of clindamycin in man. American Journal of Tropical Medicine and Hygiene 24: 369-370, 1975.

[9] 9. DeHaan RM, Metzler CM, Schellenberg D, Vandenbosh WD. Pharmacockinetic studies of clindamycin phosphate. Journal of Clinical Pharmacology 13:190- 209, 1973.

[10] 10. Dourado H. Terapêutica da malária com minociclina. Revista Brasileira de Clínica e Terapêutica 2: 10-12, 1973.

[11] 11. Fleiss JL. Statistical methods for rates and proportions. John Wiley & Sons, New York, 1973.

[12] 12. Geary TG, Divo AA, Jensen JB. An in vitro assay system for the identification of potential antimalarial drugs. Journal of Parasitology 69: 577-5S3, 1983.

[13] 13. Geary TG, Jensen JB. Effects of antibiotics on Plasmodium falciparum in vitro. American Journal of Tropical Medicine and Hygiene 32:221-225, 1983.

[14] 14. Hollander M, Wolfe DA. Nonparametric Statistical Methods. John Wiley & Sons, New York, 1973.

[15] 15. IES - Informações Epidemiológicas SUCAM. Casos notificados de malária por área de erradicação a longo e curto prazo e por unidade. N? 26, dezembro, 1984.

[16] 16. Lewis C. Antiplasmodial activity of halogenated lincomycin analogues in Plasmodium falciparum infected mice. In: Antimicrobial Agents and Chemotherapy, p. 537-542, 1967.

[17] 17. Lewis C. Antiplasmodial activity of 7-halogenated lincomycins. The Journal of Parasitology 54:169-170, 1968.

[18] 18. Meira DA, Curi PR, Barraviera B. Malaria in Humaita county, Amazonas State, Brazil. XXIX - Some comparative epidemiologic aspects in 1976,1979 and 1983. In: Proceedings of IV Japan-Brazil Symposium on Science and Technology São Paulo 2: 136-143, 1984.

[19] 19. Meira DA, Curi PR, Marcondes J, Matsuoka ES, Favrin MA, El - Khoury AB, Motta NGS. Malaria at Humaita County, Amazonas State, Brazil. XVII - Immune response in patients with Plasmodium falciparum according to gametocytes. Re vista do Instituto de Medicina Tropical de São Paulo 27:229-237,1985.

[20] 20. Meira DA, Marcondes J, Barraviera B, Pereira PCM, Rui P, Cury PR. Malaria at Humaita County, Amazonas State, Brazil. XVI - Gametocytes and lymphocytes studied in patients with Plasmodium falciparum Re vista do Instituto de Medicina Tropical de São Paulo 24:(Supl. 6): 32-39, 1982.

[21] 21. Meira DA, Pellegrino Júnior J, Marcondes Machado J, Tsuji K, Matsuoka ES, Haida E, El Khoury AB. Frequency of human leukocyte antigen (HLA) in patients with malaria and in the general population of Humaita county, Amazonas State, Brasil, Revista da Sociedade Brasileira de Medicina Tropical 20: 153-158, 1987.

[22] 22. Miller LH, Glew RH, Wyler DJ, Howard WA, Collins WE, Contacos PG, Neva FA. Evaluation of clindamycin in combination with quinine against multi drug- resistant strains of Plasmodium falciparum American Journal of Tropical Medicine and Hygiene 23: 565-569, 1974.

[23] 23. OPAS - Manual de Diagnóstico Microscópico da Malaria. Publicação Científica nP 276, p. 109, 1975.

[24] 24. Pereira PCM, Marcondes J, Barraviera B, Meira DA, Mendes RP, Vadileti C, Sogayar R, Rui P. Malária no município de Humaitá, Estado do Amazonas. XIII - Uso da clindamicina no tratamento de doentes com infecção causada pelo Plasmodium falciparum Revista do Instituto de Medicina Tropical de São Paulo 24: (Supl. 6): 16-23, 1982.

[25] 25. Peters W. Chemotherapy of malaria. In: Julius P. Kreier, (ed) Malaria. Vol. 1, Academic Press, p. 145- 283, 1980.

[26] 26. Powers KG, Jacob RL. Activity of two chlorinated lincomycin analogues against chloroquine resistent falciparum malaria in owl monkeys. In: Antimicrobial Agents and Chemotherapy 49-53, 1972.

[27] 27. Rieckmann KH, Powell RD, McNamara JV, Willerson Jr D, Kass L, Frischer H, Carson PE. Effects of tetracycline against chloroquine-resistant and chloroquine sensitive Plasmodium falciparum American J oumal of T ropical Medicine and Hygiene 20:811-815, 1971.

[28] 28. Rivera DG, Cabrera, BD, Lara NT. Treatment of falciparum malaria with clindamycin. Revista do Instituto de Medicina Tropical de São Paulo 24 (Supl. 6): 70-75, 1982.

[29] 29. Schimidt LH, Harrison J, Ellison R, Worcester P. The activities of chlorinated lincomycin derivatives against infections with Plasmodium cynomolgi in Macaca mullatta American journal of Tropical Medicine and Hygiene 19: 1-11, 1970.

[30] 30. Seaberg LS, Parquette AR, Gluzman IY, Phillips-Jr. GW, Brodasky TF, Krogstad DJ. Clindamycin activity against chloroquine resistant Plasmodium falciparum Journal of Infections Diseases 150: 904-911, 1984.

[31] 31. Silva JR, Lopes PF A, F erreira LF, Morteo R, N aveira JB. Resistência do P. falciparum à ação da cloroquina. Nota prévia. O Hospital 60:581-594, 1961.