Author(s):
|
Stone, W.J.; Sawa, P.;
Lanke, K.H.
;
Rijpma, S.R.
; Oriango, R.; Nyaurah, M.; Osodo, P.; Osoti, V.; Mahamar, A.; Diawara, H.; Woestenenk, R.;
Graumans, W.
;
Vegte-Bolmer, M. van de
; Bradley, J.; Chen, I.; Brown, J.; Siciliano, G.; Alano, P.; Gosling, R.; Dicko, A.; Drakeley, C.;
Bousema, T.
|
Subject:
|
Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences Tijdelijke code tbv inlezen publicaties Radboudumc - Alleen voor gebruik door Radboudumc |
Organization:
|
Medical Microbiology Laboratory Medicine Radboudumc Extern |
Journal title:
|
The Journal of Infectious Diseases
|
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.
|