A new kelch13 mutation linked to slow artemisinin clearance is spreading in Zambia

Design

Two national cross-sectional surveys plus a district clinical and molecular study

Population

Isolates from 1,949 people nationally; 98 treated patients in Kaoma

Primary outcome

Pfkelch13 A724E prevalence and day-3 parasite positivity

Effect

Day-3 positivity 28% (21 of 75) mutant vs 0% (0 of 23) wild type, p=0.0026

Two nationwide cross-sectional surveys in Zambia in 2024 genotyped the Pfkelch13 gene, the main marker of artemisinin partial resistance. A mutation not previously described, A724E, was found in 52% of isolates from Western Province, 51% from North-Western Province and 11.7% nationally.

In Kaoma district, 28% of patients whose parasites carried A724E were still parasite-positive on day 3 after artemisinin-based combination therapy (21 of 75), against none of 23 with the wild-type gene. The mutant share rose among those slow clearers after treatment. Its prevalence in Kaoma climbed from 0% in 2018 to 79% in 2026. Laboratory exposure to dihydroartemisinin did not show reduced susceptibility, so the clinical signal is the main evidence.

Partial resistance slows clearance rather than causing outright treatment failure; the partner drug in the combination still has to clear the remainder. The concern is that loss of the artemisinin component puts pressure on partner drugs, as happened in South-East Asia. For clinicians elsewhere, including India, the immediate relevance is travellers from the region and the reminder that day-3 parasitaemia is the warning sign worth recording.

• In falciparum malaria acquired in western Zambia, expect slower parasite clearance after artemisinin-based therapy.
• Ask about travel to Zambia and neighbouring countries in patients with falciparum malaria.
• Record a day-3 smear and report persistent parasitaemia to the surveillance programme.
• Partial resistance is not treatment failure; follow up to day 28 where possible to detect true failure.

Why it matters

Artemisinin partial resistance, first contained to South-East Asia and then east Africa, now appears to be spreading in southern Africa.

Don't overread it

Day-3 positivity is partial resistance; the study did not show that combination therapy is failing to cure.

The statistics, in plain English

The day-3 comparison rests on 98 patients and only 23 with the wild-type gene, so the 0% figure has a confidence interval up to 15%. The trend over time is drawn from different surveys, which adds uncertainty, but a rise from 0% to 79% is too large to be sampling noise.

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