Kinetics of Plasmodium falciparum Gametocyte Sex Ratios: Application to the Evaluation of the Potential of Antimalarial Drugs to Influence Malaria Transmission

ABSTRACT

A non-compartment pharmacokinetic model was used to evaluate the potential of antimalarial drugs to influence malaria transmission using the ratio of sex specific gametocyte half-lives male:female- the gametocyte maleness index (GMI), and the ratio of the sex specific area inscribed by the plot of gametocyte sex density versus time curves AUCmg:AUCfg- the gametocyte maleness load index (GMLI). Data on gametocyte sexes collected in children with symptomatic Plasmodium falciparum malaria who were treated with various antimalarial drugs in an endemic area were examined using the two indices. Both GMI and GMLI were positively correlated (r = 0.71, P < 0.0001) and with 95% limits of agreement of -9.7 to 13.8 using Altman-Bland plot. Based on the assumption that, a male-biased sex ratio, if gametocytaemia is low, may increase mosquito infectivity, both GMI and GMLI, consistently gave index ratios > 1 for 4- aminoquinolines and antifolates suggesting potential for increasing the chance of mosquito infectivity. By contrast, artesunate and artemisinin-based combination therapies (ACTs), artemether-lumefantrine, and artesunate-amodiaquine, and a non-ACT, amodiaquine plus sulfalene-pyrimethamine, had ratios < 1 suggesting potential for reducing the chance of mosquito infectivity. The advantages and drawbacks of using these indices as tools in assessing the influence of antimalarials on transmission potentials in endemic areas of malaria are discussed.