preprint · medRxiv
This research conducted molecular surveillance in Tanzania's Kagera region from 2021 to 2023 to track artemisinin partial resistance (ART-R) and other antimalarial drug mutations in Plasmodium falciparum. The study found that the WHO-validated K13 mutation R561H, associated with ART-R, persisted in border districts and spread eastward into new areas, with its regional average prevalence increasing from 2021 to 2022 before stabilising in 2023. Other artemisinin resistance mutations were also detected at low frequencies. While some partner-drug resistance markers showed minimal change, antifolate resistance was entrenched and exhibited significant spatial variation. These findings highlight the micro-geographic heterogeneity and ongoing spread of drug resistance.
Monitoring the spread of antimalarial drug resistance is vital to ensure that current treatments remain effective against malaria. Understanding where and how resistance mutations emerge and spread allows public health organisations to adapt treatment policies, preserve the efficacy of essential drugs, and prevent widespread treatment failures, particularly in East Africa.
The abstract indicates a need for improved surveillance tools and strategies to detect emerging drug resistance hotspots. This research could inform the development of advanced molecular diagnostic kits or services for real-time, district-level monitoring of antimalarial resistance markers. Such tools would be valuable for public health organisations, research institutions, and potentially pharmaceutical companies involved in drug development or resistance tracking, supporting evidence-based treatment policy decisions. This is early-stage research informing surveillance needs.
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ABSTRACT Artemisinin-based combination therapies (ACTs) remain the cornerstone of malaria treatment, yet the emergence of artemisinin partial resistance (ART-R) in Africa threatens their efficacy. ART-R is primarily associated with mutations in the Plasmodium falciparum kelch13 (K13) gene, notably R561 H , which has been linked to delayed parasite clearance in East Africa. We conducted longitudinal molecular surveillance in Tanzania’s Kagera region from 2021 to 2023 to characterize temporal and spatial trends in ART-R and other antimalarial resistance markers. Using molecular inversion probes targeting key antimalarial resistance genes, we genotyped 2,826 isolates from seven districts. The WHO-validated K13 mutation R561 H persisted in border districts of Karagwe and Kyerwa, with prevalence ranging from 14-26%, and appeared for the first time in Muleba (5.0%) and Bukoba rural district (0.7%) in 2023, indicating eastward spread toward Lake Victoria. Regional average prevalence of R561 H rose from 5.5% in 2021 to 11.3% in 2022, then stabilized at 6.9% in 2023. Additional validated (A675 V ) and candidate (V568 G , P441 L ) mutations were detected at low frequencies, suggesting ongoing diversification of the parasite population under local selection pressures. Partner-drug resistance markers showed minimal change: MDR1 N 86Y remained near fixation, while CRT K76 T declined from 5.9% (2021) to 2.4% (2023). Antifolate resistance was entrenched, with early DHFR and DHPS mutations near fixation and high-level resistance markers (DHFR I164 L and DHPS A581 G ) exhibiting marked spatial heterogeneity, peaking at 38.1% and 48.1%, respectively, in eastern districts. These findings reveal micro-geographic heterogeneity in resistance and ongoing spread, emphasizing the need for district-level surveillance to detect emerging hotspots and guide interventions. Sustained molecular monitoring is critical to inform treatment policy, preserve ACT efficacy, and mitigate the risk of widespread resistance in East Africa. Artemisinin-based combination therapies (ACTs) remain the cornerstone of malaria treatment, yet the emergence of artemisinin partial resistance (ART-R) in Africa threatens their efficacy. ART-R is primarily associated with mutations in the Plasmodium falciparum kelch13 (K13) gene, notably R561 H , which has been linked to delayed parasite clearance in East Africa. We conducted longitudinal molecular surveillance in Tanzania’s Kagera region from 2021 to 2023 to characterize temporal and spatial trends in ART-R and other antimalarial resistance markers. Using molecular inversion probes targeting key antimalarial resistance genes, we genotyped 2,826 isolates from seven districts. The WHO-validated K13 mutation R561 H persisted in border districts of Karagwe and Kyerwa, with prevalence ranging from 14-26%, and appeared for the first time in Muleba (5.0%) and Bukoba rural district (0.7%) in 2023, indicating eastward spread toward Lake Victoria. Regional average prevalence of R561 H rose from 5.5% in 2021 to 11.3% in 2022, then stabilized at 6.9% in 2023. Additional validated (A675 V ) and candidate (V568 G , P441 L ) mutations were detected at low frequencies, suggesting ongoing diversification of the parasite population under local selection pressures. Partner-drug resistance markers showed minimal change: MDR1 N 86Y remained near fixation, while CRT K76 T declined from 5.9% (2021) to 2.4% (2023). Antifolate resistance was entrenched, with early DHFR and DHPS mutations near fixation and high-level resistance markers (DHFR I164 L and DHPS A581 G ) exhibiting marked spatial heterogeneity, peaking at 38.1% and 48.1%, respectively, in eastern districts. These findings reveal micro-geographic heterogeneity in resistance and ongoing spread, emphasizing the need for district-level surveillance to detect emerging hotspots and guide interventions. Sustained molecular monitoring is critical to inform treatment policy, preserve ACT efficacy, and mitigate the risk of widespread resistance in East Africa.
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DOI: 10.1101/2025.11.26.25341086
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