- Design
- Cross-sectional molecular surveys plus clinical day-3 follow-up
- Population
- Malaria isolates from all 10 Zambian provinces (n=1,949) and patients in Kaoma district
- Primary outcome
- Pfkelch13 A724E prevalence; day-3 parasite positivity after ACT
- Effect
- Day-3 positive 28% (mutant) vs 0% (wild type); Kaoma prevalence 0% (2018) to 79% (2026)
A molecular and clinical study in The Lancet Infectious Diseases (7 October) genotyped Plasmodium falciparum across all ten provinces of Zambia in 2024. A previously undescribed kelch13 mutation, A724E, was found in about 52% of isolates from Western Province, 51% from North-Western Province and 12% nationally.
In Kaoma district, 28% of patients carrying the mutant parasites were still positive on day 3 after artemisinin combination therapy (ACT), against none of 23 with wild-type parasites. Its local prevalence climbed from 0% of isolates in 2018 to 79% in 2026. Laboratory susceptibility testing did not show reduced killing by dihydroartemisinin, so the mechanism is not yet clear.
Artemisinin partial resistance slows clearance and puts more pressure on the partner drug; if that fails too, ACTs fail. For clinicians outside Africa, the immediate point is travel: a patient returning from southern or eastern Africa whose parasitaemia does not clear as expected needs follow-up smears and early specialist advice.
- Ask about travel to southern and eastern Africa in every patient with falciparum malaria
- Repeat the smear on day 3 in returning travellers treated with an ACT
- Report persistent day-3 parasitaemia to public health and seek specialist advice
- Treatment remains ACT-based; this finding does not change first-line choices yet
Why it matters
A new route to artemisinin resistance has emerged independently in Africa, where most malaria deaths occur.
Don't overread it
Laboratory susceptibility was not reduced, and the clinical comparison rests on 98 patients in one district.
The statistics, in plain English
The 28% day-3 positivity (95% CI 18% to 40%) against 0% (0% to 15%) is a clear difference, but the wild-type group was only 23 people. The rising prevalence over eight years is the more worrying signal, because it suggests the mutation gives parasites an advantage.
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