Partial resistance to artemisinins in malarial parasites increasing in Uganda

1. In this surveillance study, the prevalence of markers of artemisinin resistance has increased to over 20% between 2016 and 2021 within 11 sampled districts in Uganda. 

2. The prevalence of 469V and 675V mutations has increased by approximately 54% in northern Uganda.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Malaria remains a significant public health challenge in certain global regions. The majority of global malaria cases and related deaths occur in Africa where control of malaria is primarily achieved through insecticides and artemisinin-based combination therapy. Although resistance to artemisinin-based therapies had previously mainly been reported in Southeast Asia, there has been growing concern that full or partial resistance has emerged and is spreading within Africa This study implemented a multi-site surveillance design across 16 sites in Uganda to characterize the degree of resistance through molecular analysis of mutations on the protein kelch 13. Results of the study found a growing prevalence of resistance markers to malaria across many regions of Uganda between 2016 to 2021, with 11 sites demonstrating a 20% prevalence of resistance markers. In certain areas, prevalence is estimated to be up to 54%, with the geographical spread of resistance mutations to surrounding regions in Uganda. A key limitation of the study is the relatively small sample sizes acquired at each site, which were between 50 to 100 samples, reducing the precision of calculations when estimating prevalence amongst the population. Overall, this study suggests that rates of treatment resistance are increasing in regions of Uganda.

Click to read the study in NEJM

In-Depth [surveillance study]: This was a multi-site surveillance study evaluating the spread and degree of resistance to artemisinin within the population in Uganda. The primary outcome of interest was the prevalence of markers of malaria resistance. This was measured using a proxy of mutations in the kelch protein K13 (PfK13) across various regions within Uganda temporally. Patients presenting symptomatically with uncomplicated malaria to designated sites between 2016 and 2022 were selected. Overall, 16 sites contributed to providing samples for further molecular analysis. The primary results of the study found that partial resistance to artemisinins is increasing, with many markers of partial resistance increasing their geographical spread across Uganda over time. Within northern Uganda, the prevalence of resistance markers within the PfK13 protein was measured to be up to 54%. Within southwestern Uganda, the prevalence of resistance markers was up to 40% regionally. The rising prevalence of resistance has been associated with discontinuing effective malaria control measures and unstable transmission. Key mutations of interest included the 469Y, 675V, 469F, 561H, and 441L. Although this study is limited by relatively small numbers of samples provided by each site for molecular typing, it provides evidence that resistance to artemisinin-based anti-malarial therapies may be increasing in Uganda.

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