Population structure of Plasmodium falciparum gametocyte sex ratios in malarious children in an endemic area

The gametocyte sex ratio (proportion of gametocytes that are male) of Plasmodium falciparum may influence transmission. The distribution of P. falciparum sex ratios, the extent of inbreeding, the relationship between clone multiplicity and sex ratio, and the pre- and post-treatment factors influencing a sex ratio of 0.5 were determined in 1609 children, with acute malaria. Gametocytes were sexed by morphological appearance and asexual clone multiplicity was determined by polymerase chain reaction (PCR) using polymorphic loci of merozoite surface proteins-1 and -2 (MSP-1, MSP-2) and glutamine-rich protein (GLURP). The weighted mean population sex ratio on presentation in 162 gametocyte carriers was 0.22, that is, 3.5 female to 1 male (95% CI 0.15-0.28), with an estimated inbreeding rate (f) (the proportion of a mother's daughters that is fertilized by her sons) of 0.56 (95% CI 0.44-0.70). Sex ratio was significantly higher when clone multiplicity was >1 infecting clone than when it was 1 (P = 0.02). The frequency of a pre-treatment sex ratio of 0.5 was low (3%), and was significantly increased by non-artemisinin but not by artemisinin - mono or combination - drugs by day 7 after therapy commenced (P = 0.03 and P = 0.44, respectively). No factor was associated with a pre-treatment sex ratio of 0.5 but two factors were independent predictors of a sex ratio of 0.5 by day 7 after therapy commenced: an age ≥5 years and anaemia. These population data provide some empirical support for the predictions of local mate competition (LMC) theory and, in conjunction with effects of antimalarials on a sex ratio of 0.5, may have implications for malaria control efforts in endemic settings.