A molecular assay to quantify male and female plasmodium falciparum gametocytes: Results from 2 randomized controlled trials using primaquine for gametocyte clearance

Will Stone, Patrick Sawa, Kjerstin Lanke, Sanna Rijpma, Robin Oriango, Maureen Nyaurah, Paul Osodo, Victor Osoti, Almahamoudou Mahamar, Halimatou Diawara, Rob Woestenenk, Wouter Graumans, Marga Van De Vegte-Bolmer, John Bradley, Ingrid Chen, Joelle Brown, Giulia Siciliano, Pietro Alano, Roly Gosling, Alassane DickoChris Drakeley, Teun Bousema

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalJournal of Infectious Diseases
Volume216
Issue number4
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • Artemisinin
  • Dihydroartemisinin
  • Piperaquine
  • Primaquine
  • Sex ratio

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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