The Gametocytocidal Efficacy of Different Single Doses of Primaquine with Dihydroartemisinin-piperaquine in Asymptomatic Parasite Carriers in The Gambia: A Randomized Controlled Trial

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2016 Nov 10

PMID 27825738

Citations 21

Authors

Joseph Okebe

Teun Bousema

Muna Affara

Gian Luca Di Tanna

Edgard Dabira

Abdoulaye Gaye

Frank Sanya-Isijola

Henry Badji

Simon Correa

Davis Nwakanma

Jean-Pierre Van Geertruyden

Chris Drakeley

Umberto DAlessandro

Affiliations

Soon will be listed here.

Abstract

Background: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown.

Methods: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0.20mg/kg, 0.40mg/kg, or 0.75mg/kg on Plasmodium falciparum gametocytaemia, infectiousness to mosquitoes and hemoglobin change in asymptomatic, malaria-infected, glucose-6-phosphate dehydrogenase (G6PD) normal individuals. Randomization was done using a computer-generated sequence of uneven block sizes with codes concealed in sequentially numbered opaque envelopes. The primary endpoint was the prevalence of P. falciparum gametocytemia at day 7 of follow-up determined by quantitative nucleic acid sequence based assay and analysis was by intention to treat. The trial has been concluded (registration number: NCT01838902; https://clinicaltrials.gov/ct2/show/NCT01838902).

Results: A total of 694 asymptomatic, malaria-infected individuals were enrolled. Gametocyte prevalence at day 7 was 37.0% (54/146; 95% CI 29.2-45.4), 19.0% (27/142; 95% CI 12.9-26.4), 17.2% (25/145; 95% CI 11.0-23.5) and 10.6% (15/141; 95% CI 6.1-16.9) in the DHAP alone, 0.20mg/kg, 0.40mg/kg, and 0.75mg/kg PQ arms, respectively. The main adverse events reported include headache (130/471, 27.6%), cough (73/471, 15.5%), history of fever (61/471, 13.0%) and abdominal pain (57/471, 12.1%). There were five serious adverse events however, none was related to the interventions.

Interpretation: A single course of PQ significantly reduces gametocyte carriage in malaria-infected asymptomatic, G6PD-normal individuals without increasing the risk of clinical anemia. The limited number of successful mosquito infections suggests that post-treatment transmission potential in this asymptomatic population is low.

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