Phase 2 Efficacy Study of Primaquine and Methylene Blue

Efficacy, Safety, and Pharmacokinetics of Sulphadoxine-pyrimethamine-amodiaquine (SP-AQ), SP-AQ Plus Primaquine, Dihydroartemisinin-piperaquine (DP), DP Plus Methylene Blue for Preventing Transmission of P. Falciparum Gametocytes in Mali

The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.

Protocol will be shared on request.

Inclusion Criteria:

• Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test
• Absence of symptomatic falciparum malaria, defined by fever upon enrollment
• Presence of P. falciparum gametocytes on thick blood film at a density >30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells)
• No allergies to study drugs
• No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant)
• Hemoglobin ≥ 10 g/dL
• Individuals weighing <80 kg
• No evidence of severe or chronic disease
• Written, informed consent

Exclusion Criteria:

• Age < 5 years or > 50 years
• Female gender
• Blood thick film negative for sexual stages of malaria
• Previous reaction to study drugs/known allergy to study drugs
• Signs of severe malaria, including hyperparasitemia, defined as asexual parasitemia > 100,000 parasites / µL)
• Signs of acute or chronic illness, including hepatitis
• Use of other medications (with the exception of paracetamol and/or aspirin)
• Consent not given