Parasitological Society of Southern Africa

Although eliminating the pathogenic asexual stages of Plasmodium falciparum is pivotal for the successful treatment of individual symptomatic patients, at a population level reducing the carriage of viable gametocytes is crucial for limiting the transmission of malaria parasites. Gametocytes are the non-pathogenic sexual stages of the P. falciparum parasite responsible for transmission of the infection from the human (or other vertebrate) host to the mosquito vector. The probability of a mosquito being infected depends on the duration and density of viable infectious gametocyte carriage in the human host, although immune responses also influence transmission. For P. falciparum there is a clear, albeit variable, relationship between gametocyte density and transmissibility. Antimalarial drug resistance spreads because of the increased transmission potential of resistant infections. The association between gametocyte prevalence and density (and thus predicted infectivity) with 1) pre-treatment asexual parasite density, 2) dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutation frequency, 3) clinical and parasitological response to treatment, and 4) artemisinin-based combination therapy was studied in South Africa and Mozambique. Increased gametocyte carriage was the earliest indicator of increasing sulfadoxine-pyrimethamine resistance, preceding a significant increase in asexual parasites or treatment failure rates. Relatively higher gametocyte carriage in the primary infection, as well as in the recrudescent infection, fuels the spread of the sulfadoxinepyrimethamine resistant genotype. Artemisinin-based combination therapy was associated with highly significant reductions in gametocyte carriage. The implications of these findings on malaria transmission and the spread of antimalarial resistance will be presented.