The PfCRT (K76T) point mutation favours clone multiplicity and disease severity in Plasmodium falciparum infection

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Abstract
In Orissa, a malaria-hyperendemic area of India, we assessed the relationship between the PfCRT (K76T) point mutation of Plasmodium falciparum and the clinical severity of malaria. Forty uncomplicated and 36 severe malaria cases were selected, and parasite species, density and schizontaemia determined by examination of Giemsa-stained thick or thin blood films. The PfCRT point mutation was analysed by PCR–RFLP and genotypes of the parasite isolates investigated by nested PCR using the polymorphic region of the merozoite surface protein-2. We found that (i) the prevalence of the PfCRT point mutation was significantly higher (P < 0.01) in severe malaria cases and that (ii) heavy parasitaemia along with clone multiplicity was statistically more common (P < 0.01) in severe cases. These associations may be due to progression of uncomplicated to severe disease after chloroquine treatment failure and/or increased virulence of chloroquine-resistant parasites. The implications for antimalarial treatment policy are discussed.