ArticleMalaria journal2026
Cross-border molecular epidemiology of Plasmodium falciparum drug susceptibility: insights from the Uganda-Democratic Republic of the Congo border.
Article in Malaria journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Genomic profiling of drug resistance markers in Plasmodium falciparum samples from the Democratic Republic of the Congo (2017) and Tanzania (2020-2021).The Journal of antimicrobial chemotherapy · 2026Article
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Abstract
backgroundCross-border parasite movement drives resistance emergence in endemic regions. In Uganda, Plasmodium falciparum with artemisinin partial resistance emerged early and spread rapidly, making it a focal point for surveillance. In northeastern Democratic Republic of Congo (DRC), a key trade corridor bordering Uganda, we investigated molecular markers of artemisinin partial resistance and resistance to partner drugs used in artemisinin-based combination therapies (ACTs). Monitoring these resistance markers in DRC is essential for guiding regional containment efforts.
methodsFrom May to June 2023, we conducted active and passive malaria case detection in 20 villages and a central hospital, respectively. Molecular analyses included copy number variation (CNV) in pfmdr1 and pfpm2/3, and genotyping of pfkelch13, pfmdr1, and pfcrt. For pfmdr1 CNV determination, we adopted a quantitative real-time PCR threshold of 1.4, recently proposed for parasite populations with frequent multiclonal infections. Whole-genome sequencing (WGS) was performed on hospital-derived samples to assess parasite relatedness and trace resistance spread.
resultsAmong the 536 individuals sampled from the villages, 49.8% tested positive for P. falciparum by PCR. The pfmdr1 N86 allele was fixed, and 50.3% of samples carried the NFD haplotype (amino acid positions 86, 184, and 1246), a marker associated with reduced lumefantrine susceptibility in Africa. Pfmdr1 CNV was detected in 4.4% of samples using the conventional threshold (≥ 1.5), increasing to 11.7% with the 1.4 threshold. Pfpm2/3 CNVs, which may influence piperaquine susceptibility, were identified in 7.0% of samples. The validated pfkelch13 mutations A675V and C469Y, associated with artemisinin partial resistance, were detected in 4.3% and 1.3% of village samples, respectively. Principal component analysis of WGS data showed that DRC parasites carrying A675V or C469Y clustered closely with Ugandan strains, supporting cross-border spread of resistant parasites between DRC and Uganda.
conclusionOur findings identified the presence of molecular markers associated with artemisinin partial resistance and reduced susceptibility to lumefantrine in northeastern DRC, along with evidence of cross-border parasite migration from Uganda. Given opposing selection pressures of lumefantrine and amodiaquine on pfmdr1 and pfcrt, alternative ACTs such as artesunate-amodiaquine may merit further evaluation. To sustain ACT efficacy, integrated genomic surveillance, clinical monitoring, and coordinated regional policy responses are essential.
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