Effects of chloroquine and sulfadoxine/pyrimethamine on gametocytes in patients with uncomplicated Plasmodium falciparum malaria in Colombia

Abstract

The effect of antimalarials on gametocytes can influence transmission and the spread of drug resistance. In order to further understand this relationship, we determined the proportion of gametocyte carriers over time post-treatment in patients with uncomplicated Plasmodium falciparum malaria who were treated with either chloroquine (CQ) or sulfadoxine/pyrimethamine (SP) In spite of several in vivo and in vitro studies (Hogh et al. 1998, Buckling et al. 1999, Robert et al. 2000, the effect of chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) on gametocytes in patients with Plasmodium falciparum malaria remains unclear. If after treatment a considerable proportion of patients carry gametocytes this would increase transmission. Likewise, if resistant parasites are more likely to develop gametocytes after treatment, the spread of drug resistance would be favoured. The present study examines the effect of these two antimalarials on gametocytaemia and explores the influence of treatment failure on gametocyte carriage. MATERIALS AND METHODSIn 1998, a 14-day in vivo randomized trial of the efficacy of CQ and SP to treat uncomplicated P. falciparum malaria in Quibdó, Colombia was conducted (Osorio et al. 1999). Thick blood film slides from 98 out of 141 patients who had participated in this study were examined for the presence and density of asexual and sexual parasites. Asexual parasitaemia was measured by dividing the number of asexual parasites found in 300 leukocytes by 300 and multiplying by 8,000 (the estimated number of leukocytes per microliter of blood). The presence of gametocytes was evaluated in 1,000 leukocytes (approximately 200 fields), and gametocyte density was estimated by counting the number of sexual forms in 1,000 leukocytes and multiplying by 8. Two laboratory technicians with expertise in malaria microscopy read all slides blinded. Discordant results were evaluated by a qualified third reader, who did not know the results of the previous readers. EPINFO 6.04b (CDC 1997) was used for data analysis. Data was compared using 2 x 2 tables. Continous variables were compared by Kruskal-Wallis test, and categorical data by Chi-squared or Fisher's exact test when required. RESULTSForty-two patients received CQ and 56 SP. As in the original study, in this subset CQ-and SP-treated groups were similar in demographic and malaria characteristics at enrollment but differed in the presence of CQ in urine and treatment failure (Table). The overall proportion of patients with gametocytes at enrollment was 25.5% (25/98). Most patients in the study developed gametocytes over 14 days of follow up, and the proportion of patients carrying gametocytes in blood peaked on day 7 (85.7% in CQtreated and 86% in SP-treated patients) (Figure). Factors such as age, parasite density at enrollment, duration of symptoms (fever) and presence of CQ in urine were not associated with gametocyte carriage at enrollment, nor at follow up.The geometric mean gametocyte density was comparable between groups at enrollment (61 gametocytes/µ...

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

“…En los pacientes de Quibdó (Chocó) con paludismo por P. falciparum se encontró una proporción de portadores de gametocitos antes del tratamiento de 25% y 5,9 días como promedio de evolución de la enfermedad; la duración de la enfermedad antes del tratamiento no se asoció con el estado de portador pretratamiento; la mayoría de los pacientes desarrollaron gametocitos durante los 14 días del seguimiento y la máxima proporción de portadores se alcanzó el día 7, con 85,7% en el grupo tratado con cloroquina y 86% en el grupo con sulfadoxina-pirimetamina; el riesgo de tener las células el día 14 fue mayor entre quienes presentaron falla del tratamiento que entre quienes respondieron adecuadamente (63).…”

Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia.

“…El efecto de la CQ y la SP sobre la gametocitemia no está bien establecido. Los estudios realizados al respecto muestran resultados diferentes y, por tanto, cualquier conclusión debe hacerse con cautela (7,(13)(14)(15)(16)(17)19,20). En nuestro estudio encontramos que los pacientes que fueron tratados con SP presentaron gametocitemia durante todo el seguimiento (en especial entre los días 3 y 14) más altas que los pacientes tratados con SP+CQ, pero las diferencias no fueron estadísticamente significativas; esto concuerda con lo encontrado en algunos estudios (15,17).…”

“…Diversos estudios han informado que el número de gametocitos circulantes en P. falciparum está influenciado tanto por aspectos del hospedero (la respuesta inmune), del parásito (la cantidad de parásitos asexuales y su capacidad para diferenciarse a gametocitos), como por aspectos externos (el tipo de medicamento suministrado en el control de los estadios asexuales) (1,3,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Además, algunos estudios muestran que los pacientes con falla al tratamiento antimalárico o aquéllos que requieren más tiempo para eliminar los parásitos asexuales, presentan mayor número de gametocitos circulantes que los pacientes que responden adecuadamente al tratamiento o cuya parasitemia asexual desaparece más rápidamente con el tratamiento suministrado (11,17,18).…”

“…Además, algunos estudios muestran que los pacientes con falla al tratamiento antimalárico o aquéllos que requieren más tiempo para eliminar los parásitos asexuales, presentan mayor número de gametocitos circulantes que los pacientes que responden adecuadamente al tratamiento o cuya parasitemia asexual desaparece más rápidamente con el tratamiento suministrado (11,17,18). Sin embargo, hay datos contradictorios acerca de la influencia que tienen los esquizonticidas sanguíneos sobre la gametocitemia de pacientes con malaria por P. falciparum (7,(12)(13)(14)(15)17,19).…”

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“…Inadequate treatment of drug resistant parasites with chloroquine can enhance gametocyte production and hence transmission [18,19]. The spread of drug resistant P. falciparum would cancel out the effect of the case detection system on transmission, effectively leading to a substantial increase in vectorial capacity and hence, potentially, a major epidemic.…”