Single Low Dose Tafenoquine to Reduce P. Falciparum Transmission in Mali (NECTAR2)

The purpose of this study is to assess the gametocytocidal and transmission reducing activity of dihydroartemisinin-piperaquine (DP) with and without various low doses of tafenoquine (TQ; 1.66mg/kg, 0.83mg/kg, or 0.415mg/kg). Outcome measures will include infectivity to mosquitoes at 2 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density.

Full protocol available on request.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 12 years and ≤ 50 years
* Glucose 6 phosphate dehydrogenase (G6PD) normal status defined by Carestart rapid diagnostic test or the G6PD qualitative test (OSMMR2000)
* 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
* No allergies to study drugs
* No 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 acute severe or chronic disease
* Written, informed consent

Exclusion Criteria:

* Age \< 12 years or \> 50 years
* Women who are pregnant or lactating
* Blood thick film negative for sexual stages of malaria
* 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 (with the exception of paracetamol and/or aspirin)
* Consent not given
* G6PD-deficiency by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
* Use of antimalarial drugs over the past 7 days (as reported by the participant)
* The use of other medication (with the exception of paracetamol and/or aspirin)
* 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.
* Family history of diseases leading to QT prolongation or recent treatment with drugs linked to QT prolongation
* 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