Evaluation of the effectiveness of artemether–lumefantrine and artesunate–pyronaridine each combined with single low-dose primaquine in adults with Plasmodium falciparum infection in Ethiopia: a phase 2/3, observer-masked, randomised, parallel-group trial
The Lancet Microbe·
- DOI
- 10.1016/j.lanmic.2025.101344
- PMID
- 42259352
- PMCID
- —
- OpenAlex
- W7163881583
- Study type
- Randomised controlled trial
- Publisher
- Elsevier BV
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The data substantiate the sustained implementation of artemether-lumefantrine paired with primaquine while positioning the alternative pyronaridine-artesunate regimen as a reliable secondary option for areas confronting evolving drug resistance and diagnostic reliability concerns.
Structured evidence summary
Research question
This investigation sought to determine the therapeutic efficacy and safety profile of two distinct artemisinin-based combination therapies supplemented with primaquine for managing uncomplicated Plasmodium falciparum infections in a region marked by prevalent artemisinin-resistance markers and rapid diagnostic test-interfering gene deletions.
Study design
The research employed a phase two-to-three, observer-masked, randomized, parallel-group clinical trial structure conducted across designated primary healthcare facilities in Ethiopia.
Population and setting
Enrollment focused on adult participants exhibiting fever and laboratory-confirmed uncomplicated Plasmodium falciparum disease, while systematically excluding individuals with severe anemia, underlying chronic illnesses, or current pregnancy and breastfeeding status.
Main findings
Both evaluated treatment protocols achieved robust PCR-corrected cure rates surpassing ninety-six percent by day twenty-eight, with the pyronaridine-artesunate formulation sustaining comparable efficacy through day forty-two. Early therapeutic failures were entirely absent, and recorded adverse reactions consisted primarily of transient mild symptoms such as headaches and fatigue, with zero severe events documented throughout the monitoring period.
Public-health relevance
The data substantiate the sustained implementation of artemether-lumefantrine paired with primaquine while positioning the alternative pyronaridine-artesunate regimen as a reliable secondary option for areas confronting evolving drug resistance and diagnostic reliability concerns.
Important limitations
Statistical power was allocated to evaluate each intervention individually rather than to generate direct comparative metrics between the two arms. Furthermore, strict exclusion criteria limited participation to non-pregnant adults without comorbidities, which may restrict the applicability of results to more diverse clinical demographics.
GIDS interpretation
This peer-reviewed article contributes structured clinical outcome data regarding antimalarial interventions within a defined geographic zone characterized by specific parasitic genetic markers. The record can be cataloged and retrieved alongside existing literature addressing regional malaria management strategies and pharmacological evaluation frameworks.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 12 auditable classifier relationships to diseases, places, topics, and study design.