A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance.

Stone, WillORCID logo; Sawa, Patrick; Lanke, Kjerstin; Rijpma, Sanna; Oriango, Robin; Nyaurah, Maureen; Osodo, Paul; Osoti, Victor; Mahamar, Almahamoudou; Diawara, Halimatou; +12 more...Woestenenk, Rob; Graumans, Wouter; van de Vegte-Bolmer, Marga; Bradley, JohnORCID logo; Chen, Ingrid; Brown, Joelle; Siciliano, Giulia; Alano, Pietro; Gosling, RolyORCID logo; Dicko, Alassane; Drakeley, ChrisORCID logo; and Bousema, Teun (2017) A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance. The Journal of infectious diseases, 216 (4). pp. 457-467. ISSN 0022-1899 DOI: 10.1093/infdis/jix237
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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.


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