Affiliation:
1. Niger Medical and Health Research Center
2. Abdou Moumouni School of Health Sciences, Niger University
3. National Malaria Control Program
4. U.S. President’s Malaria Initiative, USAID
5. U.S. President’s Malaria Initiative Impact Malaria Project
Abstract
Abstract
Background
Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapies (ACTs) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program (NMCP) in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya in Niger.
Methods
A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1,000-200,000 asexual parasites/µL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfK13 propeller, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance.
Results
A total of 225 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4–101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1–101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance.
Conclusion
The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 propeller mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations.
Trial registration:
NCT05070520, October 7, 2021
Publisher
Research Square Platform LLC
Reference31 articles.
1. MPH-NMCP. Plan stratégique de lutte contre le paludisme au Niger 2017–2021. 2016.
2. A refined estimate of the malaria burden in Niger;Doudou MH;Malar J,2012
3. WHO. Traitement du paludisme [Internet]. [cited 2022 Oct 31]. Available from: https://www.who.int/fr/teams/global-malaria-programme/case-management/treatment.
4. MSP_PNLP. Manuel de prise en charge du paludisme au Niger. 2020.
5. Artemisinin-Resistant Plasmodium falciparum Malaria;Fairhurst RM;Microbiol Spectr,2016