Respuesta terapéutica de Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia / Therapeutic response of Plasmodium vivax to chloroquine in Bolivia

Introducción. La determinación de la eficacia de la cloroquina contra Plasmodium vivax permite mejorar la capacidad de vigilancia de la resistencia a los antipalúdicos. Objetivo. Evaluar la eficacia terapéutica de la cloroquina como tratamiento de malaria no complicadapor P. vivax en Riberalta, Guayaramerín y Yacuiba, Bolivia. Materiales y métodos. Se llevó a cabo un estudio de la eficacia in vivo en pacientes mayores de cinco años; se suministró cloroquina (25 mg/kg en tres días) y se hizo seguimiento por 28 días, midiendo los niveles de cloroquina en sangre y desetilcloroquina, el día dos y el día de registro de reaparición de parasitemia. Para la evaluación de la incidencia acumulada de falla del tratamiento, se usó el análisis de supervivencia de Kaplan-Meier. Resultados. Se estudiaron 223 pacientes (Riberalta, 84; Guayaramerín, 80; Yacuiba, 59). Las medias de densidad parasitaria (formas asexuadas) del día 0 en Riberalta fueron de 6.147, en Guayaramerín, 4.251, y en Yacuiba, 5.214 parásitos/μl de sangre. En el mismo orden, los promedios de concentraciones sanguíneas de cloroquina-desetilcloroquina del día 2 fueron de 783, 817 y 815 ng/ml. Mientras en Yacuiba no se presentaron fracasos terapéuticos, en Riberalta ocurrieron con frecuencia de 6,2 % y en Guayaramerín de 10 %. Los valores de cloroquina y desetilcloroquina en sangre de pacientes con fracaso terapéutico fueron menores de 70 ng/ml en el día de reaparición de parasitemia. Conclusión. No se evidenció resistencia de P. vivax a la cloroquina en las tres regiones de evaluación en Bolivia. Se requieren mayores estudios de la concentración de la cloroquina en sangre.

Introduction. Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. Objective. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. Materials and methods. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. Results. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Conclusion. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

Resurgence of malaria in Mumbai--is escalating chloroquine resistance a cause?

OBJECTIVES: Given the steep increase in the incidence of malaria in the city of Mumbai in the nineties, we decided to study the causes for the same as well as analyse the resistance pattern of P. falciparum in the city. METHODS: Smear positive cases of acute uncomplicated P. falciparum malaria who presented to us in 1994, 1995 and 1996 were analysed for their response to full dose chloroquine (25 mg/kg over 3 days). Samples of those patients who satisfied criteria for in vitro resistance testing to chloroquine and other antimalarials, were also studied. Chloroquine level in all patients was studied on Day 3 by HPLC. In vivo response to chloroquine was studied in 30, 71 and 78 patients while in vitro response was studied in 17, 35 and 30 patients respectively in the above years. RESULTS: We found in vivo chloroquine resistance figures of 36.78%, 45% and 53.8% in the years '94, '95 and '96 and the in vitro resistance figures of 41.17%, 54.28% and 66.6% in the same years. CONCLUSIONS: Our previous studies documenting 15% chloroquine resistance in 1993 and the increasing incidence in subsequent years suggests resistance to chloroquine as one of the causes of resurgence and maintenance of malaria in the city. If patients of uncomplicated P. falciparum malaria are to be treated with chloroquine, rigorous monitoring for nonresponse and timely rescue medication is necessary. Alternative antimalarial drugs such as mefloquine, artemisinin derivatives and sulfadoxine-pyrimethamine should be used in patients where this is not possible.

Experimental analysis of gossypol and chloroquine interaction in serum and in liver of rat.

Interactive effects of gossypol and chloroquine as determined by activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and liver lactate dehydrogenase (LDH), alkaline phosphatase (ALK-pase), glucose-6-phosphatase (G-6-pase) and cholesterol level were investigated in rats. Administration of gossypol for eight weeks, at a concentration of 20 mg per kg body wt. per day with or without chloroquine had no effect on the serum enzymes and glucose-6-phosphatase activities. When chloroquine at a concentration of 5 mg per kg body wt. thrice a week was administered alone, there was a marked decrease in total protein content and ALK-pose activities, while a significant increase in LDH activity was observed. Administration of either gossypol or chloroquine decreased the level of cholesterol. A greater decrease was recorded when both were given together. It is suggested that gossypol can be employed as a male contraceptive among malaria-infected populations.

Eficácia de quatro esquemas terapêuticos para malaria vivax em crianças / Clinical efficacy of four schemes for vivax malaria treatment in children

Objetivo: A cura da malaria vivax permanece dificultada por um fator determinante de recaídas: a duraçäo do tratamento. Em Belém, a observaçäo de que um grande número de pacientes com malária vivax curava-se, a despeito do abandono do tratamento, levou à concretizaçäo deste estudo objetivando avaliar a eficácia de esquemas mais operacionais para malária em crianças. Métodos: Foi realizado ensaio clínico prospectivo e randomizado, em 200 crianças com malária vivax, atendidas ambulatorialmente. Variáveis observadas: velocidade de negativaçäo da parasitemia e respostas a quatro esquemas: a) cloroquina 10mg/kg - dose única (cloroquina DU) + primaquina 0,50/kg/dia por 7 dias; b) cloroquina DU + primaquina 0,25/kg/dia por 7 dias; c) cloroquina DU + primaquina 0,50/kg/dia por 5 dias; e d) cloroquina DU + primaquina 0,25/kg/dia por 5 dias. Para comparaçäo das resposwtas obtidas foi utilizado o teste exato de Fisher. Resultados: Todas as 144 crianças que completaram o estudo apresentaram negativaçäo da parasitemia até o quarto dia de tratamento. A comparaçäo das respostas aos esquemas, mostrou resultados significativos entre os esquemas A e D (p=0,022), e entre os esquemas C e D (p=0,005). Quanto à dose diária e ao tempo de duraçäo, a comparaçäo mostrou resultados significativos nos esquemas de doses duplicadas em relaçäo aos de dose padräo(p=0,0042)...

The effect of aspirin, paracetamol and analgin on pharmacokinetics of chloroquine.

The effect of Aspirin, paracetamol and analgin on the kinetic profile of a single oral dose of chloroquine was studied in 8 healthy subjects. Aspirin did not alter the kinetic parameters of chloroquine whereas paracetamol and analgin significantly enhanced the Cmax and AUC0-alpha of chloroquine (P < 0.01, < 0.05 respectively).