Primaquine Clears Submicroscopic Plasmodium falciparum Gametocytes that Persist after Treatment with Sulphadoxine-Pyrimethamine and Artesunate

Abstract

Background P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods.MethodologyThe study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3–15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500–100,000 parasites/µL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals.Results108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88–91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment.ConclusionsPQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.Trial RegistrationControlled-Trials.com ISRCTN61534963

Estudio piloto de la eficacia y de los efectos sobre los gametocitos del esquema artesunato-mefloquina-primaquina para la malaria por Plasmodium falciparum

“…Sin embargo, un estudio reciente, realizado en septiembre del 2006 en el este de Tanzania, demostró que al día 14 de seguimiento el 62,7% de los pacientes que recibieron el esquema de artesunato más sulfadoxina-pirimetamina permanecían con gametocitemias submicroscópicas detectadas mediante PCR. Dichas gametocitemias se eliminaron de forma eficiente con una dosis única de primaquina adicional al artesunato más sulfadoxina-pirimetamina; por lo tanto, se concluye que la primaquina es muy eficiente produciendo negatividad de las gametocitemias microscópicas y submicroscópicas que permanecen después del tratamiento con artesunato más sulfadoxina-pirimetamina y se demuestra el significativo valor aditivo de la primaquina en el esquema de primera línea para el tratamiento para P. falciparum en la reducción de la gametocitemia y de la transmisibilidad (49).…”

Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato

“…Está comprobada la capacidad de la primaquina para eliminar los gametocitos submiscroscópicos de P. falciparum dejados por los tratamientos con artesunato (artesunatosulfadoxina-pirimetamina), cuando la primaquina se aplica en la dosis usual de 0,75 mg/kg, lo cual es un importante paso para reducir la transmisión palúdica posterior al tratamiento (87).…”

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

“…By microscopy, gametocytes are invariably detected in fewer than 50% of clinical (25,55,147,279,412,455,532) and asymptomatic (52, 121, 337) P. falciparum infections. The question "why so few gametocytes?"…”

“…Gametocytes can be present in up to 40% of children upon presentation at a health center with symptomatic malaria, according to microscopy results (25,55,147,279,412,455,532). Gametocytes can also be found in asymptomatic individuals, although at a lower rate (52,121,337).…”