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Research · 02 of 06

Artemisinin resistance markers are spreading while partner-drug resistance recedes

Artemisinin partial-resistance markers have reached 10-25% in parts of east Africa, so slow clearance in a patient infected there deserves parasitological follow-up rather than an assumption of poor adherence.

Design
systematic review and meta-analysis with generalised linear mixed models, PROSPERO-registered, studies published 2010-2024
Population
172-196 studies per marker of Plasmodium falciparum molecular resistance markers across sub-Saharan Africa
Primary outcome
pooled prevalence of PfKelch13, Pfcrt, Pfmdr1 and Pfdhfr/Pfdhps mutations by region and period
Effect
validated PfKelch13 mutations 10-25% in Rwanda, Uganda and Tanzania; Pfcrt K76T 76% (49-91) in 2010 to 9% (8.7-9.5) in 2023; Pfmdr1 N86Y 34% to zero (0-11)

Molecular surveillance is how antimalarial resistance is tracked between clinical failures. This meta-analysis pooled prevalence data for mutations in PfKelch13, Pfcrt, Pfmdr1 and Pfdhfr/Pfdhps from studies published between 2010 and 2024 across sub-Saharan Africa — 172 to 196 studies per marker.

The picture is not uniform. Validated PfKelch13 mutations associated with artemisinin partial resistance — R622I, R561H, A675V — expanded primarily in east Africa between 2014 and 2023, reaching 10-25% prevalence in Rwanda, Uganda and Tanzania; central Africa saw emergence from 2021 at under 5%, and west Africa only sporadic detections under 1%. Meanwhile resistance markers to older partner drugs fell sharply: Pfcrt K76T from 76% in 2010 to 9% in 2023, and Pfmdr1 N86Y from 34% to effectively zero. Sulfadoxine-pyrimethamine markers behaved differently again, with Pfdhfr N51I, C59R, S108N and Pfdhps A437G near fixation and the more severe mutations clustering in east and central Africa.

None of this is Indian data, and Indian resistance patterns are surveilled separately. Its relevance here is to the traveller and the returning migrant, and to the general principle that a treatment failure has a geography. For a patient with falciparum malaria acquired in east Africa, artemisinin partial resistance is now a plausible contributor to slow clearance rather than an exotic possibility, and the response is parasitological follow-up rather than an assumption of non-adherence.

  • Take a precise travel history: resistance geography now differs sharply within Africa
  • Slow parasite clearance in falciparum acquired in east Africa warrants day 3 and day 7 films, not just reassurance
  • Chloroquine and amodiaquine resistance markers have fallen, but this does not license their clinical use
  • Sulfadoxine-pyrimethamine markers remain near fixation, which matters for intermittent preventive therapy in pregnancy
  • Report suspected treatment failure to the national programme; surveillance depends on it

The statistics, in plain English

Heterogeneity is extreme throughout — I-squared above 96% for the Pfcrt and Pfmdr1 estimates — which is expected when pooling prevalence across countries and years, and means the pooled figures are summaries of a moving, geographically split picture rather than estimates of a single quantity. The Pfmdr1 N86Y estimate of zero with an interval up to 11% illustrates the point: 'zero' here means no mutations in the sampled isolates, not absence from the population. Prevalence data depend entirely on where sampling happened, and sampling follows research funding rather than disease burden.

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