Evaluation of Plasmodium Falciparum Gametocyte Carriage after Artemether-Lumefantrine or Dihydroartemisinin /Piperaquine Treatment in Children from Busia County, Kenya

Abstract

Malaria remains the most significant public health problem in sub-Saharan Africa, affecting 200 million people annually resulting in half a million deaths annually. The prevailing theory is that, malaria eradication is not likely to be attained without understanding the transmission dynamics using sensitive tools that target Plasmodium falciparum gametocytes and emphasis has been placed on developing transmission blocking interventions or gametocytocidal drugs. Artemether-lumefantrine(AL) and Dihydroartemisinin-piperaquine (DP) continue to have excellent activity against asexual parasite stages. However, is still less clear whether these antimalarial drugs have pontential for gametocytes (sexual stages) clearance. Gametocyte carriage reduction after treatment has been associated with significant drops in transmission intensity and malaria cases therefore, the study sought to determine gametocyte clearance trends after treatment with either AL or DP. A total of 334 children (age, 6 months to 12 years) with uncomplicated P. falciparum malaria were randomly allocated to AL (n =166) or DP (n =168) treatment. Filter blood spot samples were collected on days 0, 1,2,3,7, 14, 21, 28, and 42 following treatment during the peak transmission season and preserved. Gametocyte density and duration of gametocyte carriage was determined by qRT-PCR and compared between the two treatment arms. At enrollment, all the 334 children were positive for asexual parasite by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) patients had gametocytes by RT-qPCR. Gametocytes prevalence by RT-qPCR declined from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4 % (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The estimated mean duration of gametocyte carriage by qRT-PCR was shorter in the AL group (4.5 days) than in the DP group (5.1 days) but this difference was not significant (p=0.301). Submicroscopic gametocytes persisted in some patients up to day 42 despite all paticipants being microscopy negative for malaria parasite by day 7. Multiple logistic regression model identified four independent risk factors at enrollment for persistence or development of gametocytes during follow-up; gametocyte on admission (adjusted odd ratio, [AOR]=6.7, 95% CI=3.314.2, p<0.001), recrudescent infections (AOR=4.1, 95% CI=2.67.1, p<0.001), anemia on admission (Hb <10g/dl) (AOR=3.6, 95% CI=1.110.1, p=0.02) and age below 5 years (AOR =2.3, 95% CI=0.775.2, p<0.001). The study detected no significant difference in gametocyte clearance rate between AL and DP. Persistence of P. falciparum gametocytes after treatment was observed in minority of individuals up to 6 weeks in both treatment arms. An addition of gametocytocidal drug to ACT regimens, will be effective in reducing malaria transmission more efficiently.