Gametocytocidal and Transmission-blocking Efficacy of PQ in Combination With AL and TQ in Combination With SPAQ in Mali

London School of Hygiene and Tropical Medicine80 enrolled

Overview

The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artemether-lumefantrine (AL) with and without a single dose of 0.25mg/kg primaquine (PQ) and sulfadoxine-pyrimethamine with amodiaquine (SPAQ) with and without single dose of 1.66mg/kg tafenoquine (TQ). Outcome measures will include infectivity to mosquitoes at 2, 5 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.

Full protocol available on request.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Malaria,Falciparum

Interventions

Sulphadoxine-pyrimethamine with amodiaquineDRUG

Sulfadoxine/pyrimethamine tablets contain 500mg sulfadoxine and 25mg pyrimethamine. Amodiaquine tablets contain 150mg amodiaquine (as hydrochloride). Tablets will be administered according to weight as per manufacturer guidelines.

Eligibility

Sex: ALLMin age: 10 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 10 years and ≤ 50 years * G6PD-normal defined by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test * Absence of symptomatic falciparum malaria, defined by fever on enrolment * Presence of P. falciparum gametocytes on thick blood film at a density \>16 gametocytes/μL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells) * Absence of other non-P. falciparum species on blood film * Hemoglobin ≥ 10 g/dL * Individuals weighing \< = 80 kg * No evidence of acute severe or chronic disease * Written, informed consent Exclusion Criteria: * Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used. * Detection of a non-P. falciparum species by microscopy * 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 * The use of other medication (except for paracetamol and/or aspirin) * Use of antimalarial drugs over the past 7 days (as reported by the participant) * Clinically significant illness (intercurrent illness e.g., pneumonia, pre-existing condition e.g., renal disease, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhea or any signs of malnutrition as defined clinically) * Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child Pugh stage B or C) * Signs, symptoms or known renal impairment * Clinically significant abnormal laboratory values as determined by history, physical examination or routine blood chemistries and hematology values (laboratory guideline values for exclusion are hemoglobin \< 10 g/dL, platelets \< 50,000/μl, White Blood Cell count (WBC) \< 2000/μl, serum creatinine \>2.0mg/dL, or ALT or AST more than 3 times the upper limit of normal for age. * Blood transfusion in the last 90 days. * Consistent with the long half-life of tafenoquine, effective contraception should be continued for 5 half-lives (3 months) after the end of treatment. * History of psychiatric disorders

Outcomes

Primary Outcomes

Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7)

Within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and AL-PQ arms, and day 7 post-treatment in the SPAQ and SPAQ-TQ.

Time frame: 3 days (days 0, 2 and 7): 7 day span

Secondary Outcomes

Change in mosquito infection rate assessed through membrane feeding assays (all timepoints)

Within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points, with comparison within and between arms.