The gametocytocidal efficacy of different single doses of primaquine with dihydroartemisinin-piperaquine in asymptomatic parasite carriers in The Gambia: a randomized controlled trial

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 D'Alessandro

    Research output: Contribution to journalA1: Web of Science-article

    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 0.20 mg/kg, 0.40 mg/kg, or 0.75 mg/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, 0.20 mg/kg, 0.40 mg/kg, and 0.75 mg/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. (C) 2016 The Authors. Published by Elsevier B.V.

    Original languageEnglish
    JournalEBioMedicine
    Volume13
    Pages (from-to)348-355
    Number of pages8
    ISSN2352-3964
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Asymptomatic infection
    • Malaria
    • Primaquine
    • Plasmodium falciparum
    • Infectivity
    • Gametocyte carriage
    • Efficacy
    • Randomized trial
    • PLASMODIUM-FALCIPARUM GAMETOCYTES
    • INTERRUPT MALARIA TRANSMISSION
    • PLACEBO-CONTROLLED TRIAL
    • DOUBLE-BLIND
    • CARRIAGE
    • CHILDREN
    • DRUGS
    • RISK
    • INDIVIDUALS
    • ARTESUNATE

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