Preliminary data from a malaria genomic surveillance study in Zambia show that the pfKelch13 C580Y mutation — the genetic signature of artemisinin partial resistance first documented in Southeast Asia — has reached a prevalence of 79% in samples from Western Province, accompanied by a day-3 parasite positivity rate of 28% among treated patients, compared with 0% day-3 positivity and less than 1% mutation prevalence in Eastern Province, according to a preprint posted to bioRxiv.

This work is a preprint and has not undergone peer review.

The pfKelch13 C580Y mutation disrupts the ring-stage susceptibility of Plasmodium falciparum to artemisinins, slowing parasite clearance after treatment. It was first identified in the Greater Mekong Subregion, where it contributed to artemisinin-based combination therapy failures. Subsequent genomic surveillance detected C580Y in Rwanda in 2020 and Uganda in 2021; its appearance at 79% prevalence in a Zambian province — in the heart of sub-Saharan Africa’s high-transmission zone — represents a qualitatively new stage of the mutation’s westward spread.

Day-3 positivity — the persistence of detectable parasitaemia three days after initiating artemisinin therapy — is the clinical correlate of partial resistance. At 28%, the rate in Western Zambia approaches thresholds recorded in the Mekong during the period when resistance began driving clinical failures. The critical distinction between partial and full resistance is that current ACT partner drugs, including lumefantrine and amodiaquine, remain active against C580Y strains, and cure rates with complete ACT courses remain high. The margin for error narrows as artemisinin clearance slows.

Zambia uses artemether-lumefantrine as its first-line ACT. A 79% mutation prevalence in a high-transmission province would, if confirmed, constitute a Category I resistance situation under WHO definitions — the threshold at which treatment policy review is triggered. The authors state that findings have been submitted to the WHO Global Malaria Programme’s Malaria Threat Registry. Independent replication is required.