Influence of Anemia on Plasmodium falciparum Gametocyte Sex Ratios in Acutely Symptomatic Children

Anemia is common in African children but little is known about how malarial anemia influences Plasmodium falciparum gametocyte sex ratios (PfGSR) and transmission in endemic areas in Africa. We investigated the changes in PfGSR in 1126 consecutive children with acute, symptomatic, uncomplicated falciparum malaria who did (n = 99) or did not (n = 1027) have anemia (defined as a hematocrit < 25%) and who were treated with various antimalarial drugs in an endemic area of southwest Nigeria. On presentation, anemic children were significantly younger and had a significantly higher PfGSR (0.28 + 0.07 (se) v 0.15 ± 0.02, P = 0.044). In anemic, but not in non-anemic children, a duration of illness > 3 d was associated with a male-biased sex ratio (defined as PfGSR ≥ 0.5) (P = 0.029). Hematocrit correlated negatively with PfGSR in non-anemic but not in anemic children (r = -0.219, P = 0.027 and r = -0.106, P = 0.697, respectively) suggesting that the critical hematocrit producing ‘all or none effect’ on PfGSR was a value below 25% in this cohort of children. Temporal changes showed that, in general, in anemic children, PfGSR was significantly higher at enrolment than in non-anemic children treated with chloroquine (CQ), amodiaquine (AQ) and amodiaquine-sulfalene-pyrimethamine (ASP) (P < 0.0007 in all cases), and remained significantly higher by day 7 or 14 in those treated with AQ and pyrimethaminesulfadoxine plus probenecid (PSP) (P < 0.007 in all cases). In children who received the same treatment, the ratio of the sex specific half-life male:female, the ‘gametocyte maleness index’, was one and a half to two folds higher in anemic than non-anemic children suggesting anemia prolongs the survival of microgametocytes and may encourage transmission. These findings have implications for malaria control efforts in endemic sub-Saharan countries where malarial anemia is common.