Abstract
BackgroundThe gametocyte sex ratio of Plasmodium falciparum, defined as the proportion of gametocytes that are male, may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes.Methods350 children with uncomplicated P. falciparum malaria were enrolled in prospective treatment trial of mefloquine or artesunate-mefloquine between 2007 and 2008. Gametocytaemia was quantified, and gametocytes were sexed by morphological appearance, before and following treatment. The area under curve of gametocyte density versus time (AUCgm) was calculated by linear trapezoidal method.Results91% and 96% of all gametocytes appeared by day 7 and day 14, respectively following treatment. The overall rate of gametocytaemia with both treatments was 31%, and was significantly higher in mefloquine than in artesunate-mefloquine treated children if no gametocyte was present a day after treatment began (25.3% v 12.8%, P = 0.01). Gametocyte clearance was significantly faster with artesunate-mefloquine (1.8 ± 0.22 [sem] v 5.6 ± 0.95 d; P = 0.001). AUCgm was significantly lower in the artesunate mefloquine group (P = 0.008). The pre-treatment sex ratio was male-biased, but post-treatment sex ratio or the sex ratio of first appearing gametocytes, was significantly lower and female-biased two or three days after beginning of treatment in children given artesunate-mefloquine.ConclusionAddition of artesunate to mefloquine significantly modified the emergence, clearance, and densities of gametocytes and has short-lived, but significant, sex ratio modifying effects in children from this endemic area.
Highlights
The gametocyte sex ratio of Plasmodium falciparum, defined as the proportion of gametocytes that are male, may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes
The emergence and clearance gametocytes have been less frequently evaluated in therapeutic efficacy studies in general and have not been investigated in African children treated with mefloquine or atresunatemefloquine in particular
Anti-malarials may significantly influence the temporal changes in gametocyte sex ratio [10,11], the exact contribution of chemotherapy to these changes is difficult to quantify because many confounding variables such as gametocyte density, host anaemia, host cell preference and, kin discrimination in malaria parasites influence sex allocation strategies in the parasite [7,9,12,13]
Summary
The gametocyte sex ratio of Plasmodium falciparum, defined as the proportion of gametocytes that are male, may influence transmission but little is known of the effects of mefloquine or artesunate-mefloquine on gametocyte sex ratio and on the sex ratio of first appearing gametocytes. Gametocytes are crucial for malaria transmission from the human host to the mosquito vector. The exact mechanisms of gametocytogenesis are unclear and many individual mosquitoes that ingest gametocytes do not support their development to sporozoite stage [1], antimalarials, as well as other factors such as host genetic or immune status may significantly influence the process of gametocytogenesis and the development of gametocytes in individual mosquitoes [2,3]. The persistence, in peripheral blood, of Plasmodiun falciparum gametocytes has been estimated to vary from 3-21 days [4,5,6]. The Plasmodium spp gametocyte sex ratio is female biased, but this ratio can vary significantly during the course of individual infections [7,8,9]. Anti-malarials may significantly influence the temporal changes in gametocyte sex ratio [10,11], the exact contribution of chemotherapy to these changes is difficult to quantify because many confounding variables such as gametocyte density, host anaemia, host cell preference and, kin discrimination in malaria parasites influence sex allocation strategies in the parasite [7,9,12,13]
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