RISK FACTORS AND EFFECTS OF ANTIMALARIAL DRUGS ON PLASMODIUM FALCIPARUM GAMETOCYTAEMIA IN NIGERIAN CHILDREN

Abstract

Gametocytes are the sexual forms of Plasmodium species that are essential for the transmission of malaria. However, there is little information on the factors that influence their generation or carriage, a measure of transmission potential of Plasmodium falciparum in Nigeria children. The objectives of the studies were to determine; the risk factors for gametocyte carriage and effects of seasons on carriage in children with acute falciparum malaria, and the effects of selected antimalarial drugs on gametocyte carriage, intensities of carriage, morphological stages and sex ratio changes (GSR). Overall, 2,317 symptomatic children (M, F- 1024, 1293), aged 0.5-14 years, with microscopically-confirmed P.falciparum malaria treated with standard doses of the antimalaria drugs (Chloroquine (CQ), pyrimethamine-sulfadoxine (PS) , trimethoprim-sulfamethoxazole (TS), Chloroquine plus Chlorpheniramine (CQCP), pyrimethamine-sulfadoxine plus probenecid (PSP) and amodiaquine (AQ) plus pyrimethamine-sulfadoxine AQPS were studied. Before, during and following therapy, densities of asexual parasites and of the morphologically distinct development stages of gametocytes were quantified in blood over 14-18 days using standard methods. Temporal changes in density ratio of Perpheral Young Gametocytes (PYG), Peripheral Mature Gametocyte (PMG) was used as an index of continuing gametocyte generation after treatment. GSR, defined as the proportion gametocytes that were morpholigically males, was determined by high performance liquid chromatography. Responses of infections to therapy were classified as sensitive or resistant. Data were analysed using student t-test, analysis of variance, chi-square, Kaplan Meier survival test and Multiple logistic regression models. Gametocyte carriage in the recruited patients was 15% at enrollment. Four factors were found to be independent risk factors for gametocyte carriage at presentation male gender (adjusted odd ratio, AOR =0.55, 95% Confidence Interval, CI=0.36-0.83, P=0.005), absence of fever (AOR=1.61, 95% CI=1.05-2.5, P=0.03), duration of illness >3d (AOR=1.57, 95% CI= 1.0-2.4, P=0.047), and asexual parasitaemia <5000/uL (AOR=0.04, 95%, CI=0.02-0.07, P<0.05). However, 15.6% of all the children developed patent gametocytaemia following treatment. Except for male gender in the low transmission season, the identified risk factors for gametocyte carriage were little affected by season. A total of 220 children failed to respond to antimalaria drug treatment. Children with CQ -resistant infections (37.1%), and those treated with PS irrespective of outcome, were significantly at risk of gametocyte carriage compared with other antiimalarials. CQCP-resistant infection and treatment with PS signignificantly increased PYG-PMG ratio (P<0.05). In contrast, AQPS significantly increased the ratio. PSP and TS, like PS, alone, enhanced gametocyte carriage and increased GSR. Antimalaria drugs modulate gametocyte generation particulary when resistance hads developed and may potentially facilitate disease transmission. Presence of peripheral young gametocytes (PYG) was an index of resistance to CQCP but not to PS or AQPS. PS may ehance influx of young gametocyte into circulation.