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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 277
- Locations
- 5
- Primary Endpoint
- Day-3 Parasite Positivity Rate
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 6 Months to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 6 months
- •Microscopically confirmed uncomplicated Plasmodium falciparum monoinfection
- •Axillary temperature ≥ 37.5°C or history of fever in the past 24 hours
- •Ability to take oral medication
- •Written informed consent from patient or parent/guardian
- •Residence in the study area with intention to remain during follow-up
Exclusion Criteria
- •Severe or complicated malaria (WHO criteria)
- •Mixed Plasmodium infection
- •Pregnancy or breastfeeding
- •Known hypersensitivity to artemether-lumefantrine
- •Antimalarial treatment in the 4 weeks prior to enrollment
- •Severe malnutrition
- •Concomitant febrile illness other than malaria requiring systemic treatment
Arms & Interventions
Artemether-Lumefantrine
Patients with uncomplicated Plasmodium falciparum malaria received artemether-lumefantrine (AL) twice daily for 3 days per Ethiopian national treatment guidelines, with clinical follow-up on days 0 and 3.
Intervention: Artemether-Lumefantrine Tab 20-120mg (Drug)
Outcomes
Primary Outcomes
Day-3 Parasite Positivity Rate
Time Frame: Day 3 (72 hours after treatment initiation)
Proportion of patients with microscopically detectable Plasmodium falciparum parasitaemia on day 3 (72 ± 2 hours) after initiation of artemether-lumefantrine treatment, assessed by Giemsa-stained thick blood smear examination.
Secondary Outcomes
- Prevalence of Pfkelch13 R622I Mutation(Day 0 (enrollment))
- Ring-Stage Survival Rate(Assessed on culture-adapted isolates collected at Day 0)
Investigators
Didier Menard
Professor
Louis Pasteur University, Strasbourg