Plasmodium falciparum gametocyte sex ratios in symptomatic children treated with antimalarial drugs

The sex ratios of Plasmodium falciparum gametocytes, defined as the proportion of gametocytes in peripheral blood that were male, were evaluated in 1609 children with acute, symptomatic, uncomplicated malaria, pre- and post-treatment with various antimalarial drugs, over an 8-year period (1999–2006) in an endemic area of southwest Nigeria. Gametocyte carriage on presentation was 10% (162 children). In 162 children in whom 5797 gametocytes were sexed on presentation, the weighted mean sex ratio was 0.18 (95% confidence interval 0.13–0.25). Following therapy, in 446 children in whom 38,519 gametocytes were sexed, the weighted mean sex ratio was 0.38 (95% CI 0.33–0.43) on day 3 and 0.70 (95% CI 0.63–0.75) (P < 0.000001) by day 7 after therapy commenced. Non-artemisinin monotherapy significantly increased sex ratio producing a male-biased ratio, but artemisinin combination therapy significantly reduced the sex ratio producing a female biased ratio. Pre-treatment sex ratio correlated negatively with haematocrit (r = −0.229, P = 0.003) or gametocytaemia (r = −0.435, P < 0.0001) but not with other clinical or parasitological parameters. The ratio of the sex-specific half lives male:female, the ‘gametocyte maleness index’ (GMI), was >1 with non-artemisinin monotherapy but <1 with artesunate and artemisinin-based combinations. In a multiple regression model, anaemia, low gametocytaemia, and enrolment before 2004 were independent predictors of a male-biased sex ratio pre-treatment. A pre-treatment haematocrit <25%, enrolment before 2004 and treatment with non-artemisinin monotherapy were independent predictors of a male-biased sex ratio 7 days postinitiation of therapy. These findings may have implications for malaria management efforts in sub-Saharan Africa.