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
Highlights
The majority of anti-malarial drug treatments target the asexual blood stages of Plasmodium falciparum that are responsible for clinical disease and death
Adequate clinical and parasitological response (ACPR) on day 42 after treatment was observed in 71.7% (38/53) of the children treated with SP+AS and in 67.9% (36/53) of those treated with SP+AS+PQ (x2 = 1.70; p = 0.64)(table 2)
This study shows that a single dose of primaquine (PQ) is of significant additive value in clearing gametocytes in an area of high malaria endemicity in Tanzania
Summary
The majority of anti-malarial drug treatments target the asexual blood stages of Plasmodium falciparum that are responsible for clinical disease and death. ACT efficiently reduces microscopic levels of gametocytes [4,5,6,7], submicroscopic gametocytes (detected by molecular analysis) may persist after treatment and allow post-treatment malaria transmission [4]. In combination with sulphadoxine-pyrimethamine (SP) and AS, PQ was found to be safe and highly efficacious in clearing asexual parasites and P. falciparum gametocytes detected by microscopy [12]. P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. PQ 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.
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