Gametocytaemia after drug treatment of asymptomatic Plasmodium falciparum

Abstract

Objectives: Treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) is followed by a sharp rise in the prevalence and density of gametocytes. We did a randomized trial to determine the effect of treatment of asymptomatic infections with SP or SP plus one dose of artesunate (SP+AS) on gametocyte carriage.

Design: The study was a three-arm open-label randomized trial. We randomized asymptomatic carriers of P. falciparum to receive antimalarial treatment or placebo, and recorded the prevalence and density of gametocytes over the next 2 mo.

Setting: The trial was conducted during the dry (low malaria transmission) season in four rural villages in Gambia.

Participants: Participants were adults and children aged over 6 mo with asexual P. falciparum infection and confirmed free of clinical symptoms of malaria over a 2-d screening period.

Interventions: Participants were randomized to receive a single dose of SP or SP+AS or placebo.

Outcome measures: The outcome measures were the presence of gametocytes 7 and 56 d after treatment, and the duration and density of gametocytaemia over 2 mo.

Results: In total, 372 asymptomatic carriers were randomized. Gametocyte prevalence on day 7 was 10.5% in the placebo group, 11.2% in the SP group (risk difference to placebo 0.7%, 95% confidence interval -7.4% to 8.7%, p = 0.87), and 7.1% in the SP+AS group (risk difference to placebo 4.1%, 95% confidence interval -3.3% to 12%, p = 0.28). By day 56, gametocyte prevalence was 13% in the placebo group and 2% in both drug-treated groups. Gametocyte carriage (the area under the curve of gametocyte density versus time), was reduced by 71% in the SP group, and by 74% in the SP+AS group, compared to placebo. Gametocyte carriage varied with age and was greater among children under 15 than among adults.

Conclusions: Treatment of asymptomatic carriers of P. falciparum with SP does not increase gametocyte carriage or density. Effective treatment of asexual parasitaemia in the dry season reduces gametocyte carriage to very low levels after 4 wk.

Figure 1. Smoothed Estimate of Gametocyte Prevalence in Relation to Age (in Years) among 1,048 Children and Adults Who Were Screened

Dashed lines indicate 95% CIs.

Figure 2. Trial Profile

Figure 3. Prevalence of Asexual Parasitaemia and Gametocytes after Treatment

(A) Prevalence of asexual parasitaemia over the 2 mo following treatment. The profile for the 39 clinical cases, who were treated with SP+AS, is also shown. (B) Prevalence of gametocytes. (C) Prevalence of gametocytes in the subset of participants who were gametocyte negative on D0.