Summary
A medRxiv preprint analysing 16 Ugandan districts from 2017 to 2022 found that higher prevalence of Kelch13 artemisinin-resistance markers was associated with higher confirmed malaria incidence. The observational analysis also found associations with partner-drug resistance markers, climate and malaria-control coverage.
A medRxiv preprint analysing malaria data from 16 Ugandan districts between 2017 and 2022 reports that districts with a higher prevalence of Plasmodium falciparum Kelch13 mutations associated with partial artemisinin resistance also had higher confirmed malaria incidence. In a multivariable analysis, each 10-percentage-point increase in Kelch13 mutation prevalence was associated with a 13.1% higher incidence rate (adjusted incidence rate ratio 1.131; 95% confidence interval 1.090 to 1.174).
The study combined molecular resistance data with monthly malaria incidence, climate, malaria-control and other antimalarial-resistance data. Its results describe associations across districts over time; they do not by themselves show that resistance mutations caused the higher incidence. The preprint was posted on 20 October 2026 and has not yet undergone peer review.
Resistance markers and malaria incidence
Kelch13 mutations are genetic markers used to track partial resistance to artemisinin, a key component of malaria treatment. Partial resistance refers to reduced parasite susceptibility to the drug; it is distinct from establishing that a treatment has failed. The study reports that the combined prevalence of World Health Organization-validated and candidate Kelch13 mutations increased during the period examined.
The authors used negative binomial regression to assess monthly confirmed malaria incidence. They also found that each 10% increase in prevalence of the partner-drug resistance marker pfcrt K76T was associated with a 24% increase in malaria transmission, as reported in the preprint abstract. The two results point to a relationship between resistance-marker prevalence and malaria burden in this setting, while the analysis cannot determine the direction of that relationship. The authors note that it may be bidirectional.
Climate and control measures also mattered
The analysis placed resistance markers alongside other conditions associated with incidence. Insecticide-treated net distribution above 80%, indoor residual spraying coverage above 90%, and higher altitude were associated with lower incidence. Temperatures of 25 to 30°C, relative humidity of 60 to 80%, and higher precipitation were associated with higher incidence.
These findings underline why resistance surveillance is most informative when considered with local transmission conditions and malaria-control activity. The study’s results are specific to the 16 districts and the 2017–2022 period it analysed. Because this is an observational, district-level analysis, it identifies patterns rather than demonstrating that changing resistance-marker prevalence alone would change malaria incidence.