The gametocytocidal efficacy of primaquine in malaria asymptomatic carriers treated with dihydroartemisinin piperaquine in The Gambia (PRINOGAM): study protocol for a randomised controlled trial

Okebe, Joseph, Bousema, Teun, Affara, Muna, DiTanna, GianLuca, Eziefula, Alice C, Jawara, Musa, Nwakanma, Davis, Amambua-Ngwa, Alfred, Van geertruyden, Jean-Pierre, Drakeley, Chris and D’Alessandro, Umberto (2015) The gametocytocidal efficacy of primaquine in malaria asymptomatic carriers treated with dihydroartemisinin piperaquine in The Gambia (PRINOGAM): study protocol for a randomised controlled trial. Trials, 16 (70). pp. 1-7. ISSN 1745-6215

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Abstract

Background:
Finding efficacious tools to decrease and interrupt malaria transmission is essential to sustain the gains in malaria control and contain the emergence of artemisinin resistance. Primaquine is effective against Plasmodium falciparum gametocytes and recommended for treatment campaigns in (pre-)elimination settings. Safety concerns preclude its use in endemic African countries with variable proportions of glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The efficacy of the current recommended dose needs to be evaluated, particularly in individuals with an asymptomatic malaria infection.

Methods/design:
This is a four-arm, open label, randomized controlled trial that aims to determine and compare the effect of three different single doses of primaquine combined with dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, on gametocyte carriage in asymptomatic, malaria infected, G6PD-normal individuals. Approximately 1,200 participants are enrolled and followed for 42 days, with the primary endpoint being the prevalence of Plasmodium falciparum gametocyte carriage at day 7 of follow-up determined by quantitative nucleic acid sequence based amplification assay. Direct membrane feeding experiments to determine infectiousness to mosquitoes are conducted as a biological secondary endpoint.

Discussion:
Sub-Saharan Africa, with a relatively high but poorly characterized G6PD prevalence, could potentially benefit from the use of primaquine to further reduce or interrupt malaria transmission. However, G6PD screening may not be feasible given the cost and difficulties in interpreting test results in terms of risk of haemolysis. Because the haemolytic effect of primaquine is dose-dependent, determining the minimal gametocytocidal and transmission-blocking dose of primaquine is extremely important to help address public health concerns over its safety and validate the efficacy of lower than recommended dosages. By including infectiousness to mosquitoes, the trial provides complementary evidence for the potential of the drug to interrupt transmission to mosquitoes.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Subjects: R Medicine
Depositing User: Deborah Miller
Date Deposited: 28 Feb 2019 16:56
Last Modified: 01 Jul 2019 19:46
URI: http://sro.sussex.ac.uk/id/eprint/82268

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