NCT07527182

Artemisinin Partial Resistance in Ethiopian Plasmodium Falciparum: A Multisite Clinical, Molecular and In Vitro Study

Confirmation of Artemisinin Partial Resistance in Plasmodium Falciparum Using WHO Criteria: A Multisite Clinical, Molecular and Phenotypic Study Across Five Sentinel Sites in Ethiopia, 2024-2025

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 277 (actual)
• Sponsor: Didier Menard · Academic / Other
• Sex: All
• Age: 6 Months
• Healthy volunteers: Not accepted

Summary

Artemisinin-based combination therapies (ACTs) are the main treatment for falciparum malaria in Africa. Artemisinin partial resistance (ART-R), characterized by delayed parasite clearance after treatment, has been confirmed in four sub-Saharan African countries. In Ethiopia, molecular surveys have detected the Pfkelch13 R622I mutation associated with ART-R at multiple sites, but no study has yet combined clinical, molecular, and in vitro evidence to confirm ART-R per WHO criteria. This multisite study conducted across five sentinel sites in Ethiopia (2024-2025) assessed day-3 parasite positivity after artemether-lumefantrine treatment, Pfkelch13 genotyping, and ring-stage survival assay on culture-adapted field isolates, to determine whether ART-R is confirmed in Ethiopian Plasmodium falciparum populations.

Detailed description

This study integrated three WHO-required lines of evidence to confirm artemisinin partial resistance (ART-R) in Ethiopia: (1) clinical evidence through day-3 parasite positivity assessment after artemether-lumefantrine treatment in therapeutic efficacy studies; (2) molecular evidence through Pfkelch13 propeller domain genotyping; and (3) phenotypic in vitro evidence through ring-stage survival assay (RSA0-3h) on culture-adapted field isolates. Five sentinel sites were selected across malaria-endemic regions of Ethiopia. Blood samples were collected at enrollment (day 0) and day 3. Isolates were cryopreserved and shipped to France (Strasbourg) for RSA.

Conditions

• Malaria (Plasmodium Falciparum)
• Drug Resistance
• Artemisinin-resistant
• Ethiopia

Interventions

Type	Name	Description
DRUG	Artemether-Lumefantrine Tab 20-120mg	Artemether-lumefantrine (Coartem) administered orally twice daily for 3 days at weight-based dosing per Ethiopian national malaria treatment guidelines.

Timeline

• Start date: 2024-05-01
• Primary completion: 2025-10-30
• Completion: 2026-04-07
• First posted: 2026-04-14
• Last updated: 2026-04-14

Locations

5 sites across 1 country: Ethiopia