1. A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance.
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Stone, Will, Sawa, Patrick, Lanke, Kjerstin, Rijpma, Sanna, Oriango, Robin, Nyaurah, Maureen, Osodo, Paul, Osoti, Victor, Mahamar, Almahamoudou, Diawara, Halimatou, Woestenenk, Rob, Graumans, Wouter, de Vegte-Bolmer, Marga van, Bradley, John, Chen, Ingrid, Brown, Joelle, Siciliano, Giulia, Alano, Pietro, Gosling, Roly, and Dicko, Alassane
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PRIMAQUINE , *ARTEMISININ derivatives , *PLASMODIUM falciparum , *GERM cells , *SEX ratio , *PHYSIOLOGY , *PROTEIN metabolism , *QUINOLINE , *RNA metabolism , *ANTIMALARIALS , *COMPARATIVE studies , *DOSE-effect relationship in pharmacology , *RESEARCH methodology , *MEDICAL cooperation , *PROTEINS , *PROTOZOA , *RESEARCH , *RNA , *SAMPLE size (Statistics) , *EVALUATION research , *RANDOMIZED controlled trials , *THERAPEUTICS - Abstract
Background: Single low-dose primaquine (PQ) reduces Plasmodium falciparum infectivity before it impacts gametocyte density. Here, we examined the effect of PQ on gametocyte sex ratio as a possible explanation for this early sterilizing effect.Methods: Quantitative reverse-transcription polymerase chain reaction assays were developed to quantify female gametocytes (targeting Pfs25 messenger RNA [mRNA]) and male gametocytes (targeting Pf3D7_1469900 mRNA) in 2 randomized trials in Kenya and Mali, comparing dihydroartemisinin-piperaquine (DP) alone to DP with PQ. Gametocyte sex ratio was examined in relation to time since treatment and infectivity to mosquitoes.Results: In Kenya, the median proportion of male gametocytes was 0.33 at baseline. Seven days after treatment, gametocyte density was significantly reduced in the DP-PQ arm relative to the DP arm (females: 0.05% [interquartile range {IQR}, 0.0-0.7%] of baseline; males: 3.4% [IQR, 0.4%-32.9%] of baseline; P < .001). Twenty-four hours after treatment, gametocyte sex ratio became male-biased and was not significantly different between the DP and DP-PQ groups. In Mali, there was no significant difference in sex ratio between the DP and DP-PQ groups (>0.125 mg/kg) 48 hours after treatment, and gametocyte sex ratio was not associated with mosquito infection rates.Conclusions: The early sterilizing effects of PQ may not be explained by the preferential clearance of male gametocytes and may be due to an effect on gametocyte fitness. [ABSTRACT FROM AUTHOR]- Published
- 2017
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