NCT06347471

The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy

The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy: a Longitudinal Study

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Infectious Diseases Research Collaboration, Uganda · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

Summary

A prospective study will be carried out in an area where parasites with reduced sensitivity to malaria drugs (artemisinins) have recently emerged. The study will recruit participants from patients who attend the clinic with uncomplicated malaria and asymptomatically infected individuals. Participants are treated with conventional artemisinin-combination therapies (ACT) as part of standard clinical care. From this population, we will select P. falciparum gametocyte carriers. Before, during and after ACT treatment, the transmission potential of artemisinin resistant and wild type infections will be assessed by microscopy, molecular methods, parasite culture and mosquito feeding assays. Parasite clearance will be determined in the first days (d0-3) after treatment. The study population will consist of passively recruited patients with uncomplicated P. falciparum malaria and asymptomatically infected individuals who are microscopy positive for gametocytes. Participants will be treated with conventional therapies for uncomplicated malaria without randomization: artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA-PPQ). All doses are supervised. Parasite clearance is assessed ex vivo by ring-stage survival assays and by daily slides during the first days of treatment. Gametocyte carriage and gametocyte commitment/production will be determined for resistant and wild type infections before, during and after treatment. In addition, venous blood will be collected at three timepoints to assess transmission to mosquitoes before (d0), during (d2) and after treatment (d7). The total duration of participation will be 7 days, the primary endpoint will be the reduction in mosquito infection rates at d2 (artemether-lumefantrine) or d7 (dihydroartemisinin-piperaquine) compared to pre-treatment.

Conditions

• Falciparum; Malaria

Interventions

Type	Name	Description
DRUG	Artemether-lumefantrine	Participants in the Artemether-Lumefantrine arm will be treated with standard doses of AL (Coartem, Novartis). Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered per manufacturer guidelines. All doses will be given under direct supervision with fatty food.
DRUG	Dihydroartemisinin-Piperaquine	Participants in the DHA-PPQ arm will be treated with standard doses of DHA-PPQ. Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine tablets (Eurartesim, Sigma Tau or Duocotecxin, Beijing Holley-Cotect Pharmaceutical Co) will be administered per manufacturer guidelines. All doses will be given under direct supervision on an empty stomach, as per manufacturer instructions.

Timeline

• Start date: 2024-05-28
• Primary completion: 2025-12-01
• Completion: 2026-04-01
• First posted: 2024-04-04
• Last updated: 2025-03-10

Locations

2 sites across 1 country: Uganda