Profiles of Kelch mutations in Plasmodium falciparum across South Asia and their implications for tracking drug resistance

Publication date: Available online 4 October 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Jyoti Chhibber-Goel, Amit SharmaAbstractArtemisinin-based combination therapy (ACT) offers highly successful treatment of malaria. Emergence and spread of Plasmodium falciparum (Pf) parasites with decreased susceptibility to ACT in South-East Asia has caused concern worldwide. The current accepted criteria to assess artemisinin (ART) resistance relies upon data on treatment failure, delayed parasite clearance at day 3 (DPC3), parasite clearance half-life (PCHL) and in-vitro/ex-vivo ring stage survival assays (RSAs). Interestingly, some studies suggest that DPC3 does not provide a distinct separation between ART sensitive/resistant strains, and RSA differences may also be inconclusive. More recently, recrudescence of ART treated Pf, independent of the presence of K13 mutation (C580Y), has been reported in the monkey malaria model suggesting that genes other than K13 like coronin, dhps, dhfr, crt, mdr1 and plasmepsin1 may contribute towards ACT failure. Here we have collated the distribution of K13 mutants from Pf strains in South Asia. A total of fifty Pf-K13 mutations have been studied for ART resistance in South Asia of which nine have been validated while eleven are potentials for ART resistance. The remaining thirty K13 mutations have been reported from various locations in South Asia but lack corroborative clinical data on ART resistance/ACT...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research