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 journalArticle

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 Pf3D71469900 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, 0.432.9 of baseline; P 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 languageUndefined/Unknown
Pages (from-to)457-467
Number of pages11
JournalJournal of Infectious Diseases
Volume216
Issue number4
Publication statusPublished - Aug 15 2017

Cite this

A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance. / 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; Dicko, Alassane; Drakeley, Chris; Bousema, Teun.

In: Journal of Infectious Diseases, Vol. 216, No. 4, 15.08.2017, p. 457-467.

Research output: Contribution to journalArticle

Stone, W, Sawa, P, Lanke, K, Rijpma, S, Oriango, R, Nyaurah, M, Osodo, P, Osoti, V, Mahamar, A, Diawara, H, Woestenenk, R, Graumans, W, de Vegte-Bolmer, MV, Bradley, J, Chen, I, Brown, J, Siciliano, G, Alano, P, Gosling, R, Dicko, A, Drakeley, C & Bousema, T 2017, 'A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance', Journal of Infectious Diseases, vol. 216, no. 4, pp. 457-467.
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 ; Dicko, Alassane ; Drakeley, Chris ; Bousema, Teun. / A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance. In: Journal of Infectious Diseases. 2017 ; Vol. 216, No. 4. pp. 457-467.
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title = "A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance",
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 Pf3D71469900 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, 0.432.9 of baseline; P 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.",
author = "Will Stone and Patrick Sawa and Kjerstin Lanke and Sanna Rijpma and Robin Oriango and Maureen Nyaurah and Paul Osodo and Victor Osoti and Almahamoudou Mahamar and Halimatou Diawara and Rob Woestenenk and Wouter Graumans and {de Vegte-Bolmer}, {Marga van} and John Bradley and Ingrid Chen and Joelle Brown and Giulia Siciliano and Pietro Alano and Roly Gosling and Alassane Dicko and Chris Drakeley and Teun Bousema",
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TY - JOUR

T1 - A Molecular Assay to Quantify Male and Female Plasmodium falciparum Gametocytes: Results From 2 Randomized Controlled Trials Using Primaquine for Gametocyte Clearance

AU - Stone, Will

AU - Sawa, Patrick

AU - Lanke, Kjerstin

AU - Rijpma, Sanna

AU - Oriango, Robin

AU - Nyaurah, Maureen

AU - Osodo, Paul

AU - Osoti, Victor

AU - Mahamar, Almahamoudou

AU - Diawara, Halimatou

AU - Woestenenk, Rob

AU - Graumans, Wouter

AU - de Vegte-Bolmer, Marga van

AU - Bradley, John

AU - Chen, Ingrid

AU - Brown, Joelle

AU - Siciliano, Giulia

AU - Alano, Pietro

AU - Gosling, Roly

AU - Dicko, Alassane

AU - Drakeley, Chris

AU - Bousema, Teun

PY - 2017/8/15

Y1 - 2017/8/15

N2 - 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 Pf3D71469900 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, 0.432.9 of baseline; P 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.

AB - 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 Pf3D71469900 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, 0.432.9 of baseline; P 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.

M3 - Articolo

VL - 216

SP - 457

EP - 467

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 4

ER -