Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children.
BACKGROUND
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.


METHODS
350 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.


RESULTS
91% 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.


CONCLUSIONS
Addition 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.
Sowunmi
Akintunde
A
Department of Pharmacology & Therapeutics, Institute for Medical Research and Training, University College Hospital, Ibadan, Nigeria. akinsowunmi@hotmail.com
Nkogho
Oluchi O
OO
Okuboyejo
Titilope M
TM
Gbotosho
Grace O
GO
Happi
Christian T
CT
Adewoye
Elsie O
EO
D000293:Adolescent; D000818:Animals; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001769:Blood / Q000469:parasitology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000302:isolation & purification*; D011446:Prospective Studies
D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine