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

NCT07527182 | Completed

• 1 other identifier: ETH-ARTR-2024
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

Artemisinin partial resistance; Plasmodium falciparum; Pfkelch13; Ring-stage survival assay; Day-3 positivity; Ethiopia; Artemether-lumefantrine; Antimalarial drug resistance

Outcome Measures

Primary Outcomes (1)

• Day-3 Parasite Positivity Rate

  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.

  Day 3 (72 hours after treatment initiation)

Secondary Outcomes (2)

• Prevalence of Pfkelch13 R622I Mutation

  Day 0 (enrollment)

• Ring-Stage Survival Rate

  Assessed on culture-adapted isolates collected at Day 0

Study Arms (1)

Artemether-Lumefantrine

EXPERIMENTAL

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.

Drug: Artemether-Lumefantrine Tab 20-120mg

Interventions

Artemether-Lumefantrine Tab 20-120mg DRUG

Artemether-lumefantrine (Coartem) administered orally twice daily for 3 days at weight-based dosing per Ethiopian national malaria treatment guidelines.

Also known as: Coartem

Artemether-Lumefantrine

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Didier Menard: lead

Study Sites (5)

Mehoni Health Center

Mersa, Tigray, Ethiopia

Location

Bako Health Center

Bako, Ethiopia

Location

Workamba Health Center

Kechemo, Ethiopia

Location

Metahara Health Center

Metehara, Ethiopia

Location

Rama Health Center

Rama, Ethiopia

Location

Related Publications (4)

• Uwimana A, Legrand E, Stokes BH, Ndikumana JM, Warsame M, Umulisa N, Ngamije D, Munyaneza T, Mazarati JB, Munguti K, Campagne P, Criscuolo A, Ariey F, Murindahabi M, Ringwald P, Fidock DA, Mbituyumuremyi A, Menard D. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020 Oct;26(10):1602-1608. doi: 10.1038/s41591-020-1005-2. Epub 2020 Aug 3.

  PMID: 32747827 RESULT

• Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana SI, Yamauchi M, Opio W, Emoto S, Anywar DA, Kimura E, Palacpac NMQ, Odongo-Aginya EI, Ogwang M, Horii T, Mita T. Evidence of Artemisinin-Resistant Malaria in Africa. N Engl J Med. 2021 Sep 23;385(13):1163-1171. doi: 10.1056/NEJMoa2101746.

  PMID: 34551228 RESULT

• Mihreteab S, Platon L, Berhane A, Stokes BH, Warsame M, Campagne P, Criscuolo A, Ma L, Petiot N, Doderer-Lang C, Legrand E, Ward KE, Zehaie Kassahun A, Ringwald P, Fidock DA, Menard D. Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea. N Engl J Med. 2023 Sep 28;389(13):1191-1202. doi: 10.1056/NEJMoa2210956.

  PMID: 37754284 RESULT

• Fola AA, Feleke SM, Mohammed H, Brhane BG, Hennelly CM, Assefa A, Crudal RM, Reichert E, Juliano JJ, Cunningham J, Mamo H, Solomon H, Tasew G, Petros B, Parr JB, Bailey JA. Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia. Nat Microbiol. 2023 Oct;8(10):1911-1919. doi: 10.1038/s41564-023-01461-4. Epub 2023 Aug 28.

  PMID: 37640962 RESULT

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Didier Menard, Professor

  University Hospital, Strasbourg, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Single-arm therapeutic efficacy study. All enrolled patients with uncomplicated Plasmodium falciparum malaria received artemether-lumefantrine (AL) per Ethiopian national treatment guidelines. Clinical, molecular, and in vitro outcomes were assessed to determine whether artemisinin partial resistance meets WHO confirmation criteria.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start: May 1, 2024
• Primary Completion: October 30, 2025
• Study Completion: April 7, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 6 months after publication
• Access Criteria: Researchers who provide a methodologically sound proposal. Requests should be directed to the corresponding author. Data will be shared after signing a data access agreement.

Locations

ET (5)