The spread of a validated molecular marker of artemisinin partial resistancepfkelch13R622I and association withpfhrp2/3deletions in Eritrea

Abstract

Eritrea was the first African country to switch away from exclusive use of HRP2-based RDTs for the detection of P. falciparum due to high prevalence of pfhrp2/3-deleted P. falciparum parasites causing false-negative RDT results. While heavy reliance on malaria RDTs played a significant role in the rapid expansion of pfhrp2/3-deleted parasites in Eritrea, we hypothesize that the use of antimalarial (artesunate-amodiaquine) may have also contributed to their spread. We conducted a retrospective investigation of mutations in the propeller domain of the P. falciparum kelch13 gene in samples collected in 2016 (n=50) from the Northern Red Sea Zone before the RDT switch away from HRP2-RDTs and in samples collected in 2018-2020 (n=587) from the Gash Barka, Anseba and Debub Zones after the RDT switch. No mutations were identified in the 2016 samples. However, in 2018-2019 samples, we detected five different single non-synonymous mutations. The most prevalent mutation was pfk13 R622I, which was detected in samples collected from all health centres, with an overall prevalence of 11.9% (ranging from 5.9% to 28%). Parasites carrying the R622I mutation have diverse microsatellite marker haplotypes, indicating that they had evolved multiple times from different genetic backgrounds. The prevalence pfk13 R622I was significantly higher in single pfhrp3-deleted parasites (18.0%) compared to parasites without pfhrp2/3 deletions (6.2%) and dual pfhrp2/3-deleted parasites (9.0%), suggesting association between the pfk13 R622I mutation and the pfhrp2/3 deletions in Eritrea. Continuous monitoring the trends in pfhrp2/3 and pfk13 mutants is needed to inform effective malaria management strategies in Eritrea.

Temporal and spatial dynamics ofPlasmodium falciparumclonal lineages in Guyana

“…Delayed parasite clearance following ACT treatment was first observed in the Greater Mekong Subregion (GMS) of Southern Asia in early 2000s [15,16]. More recently, mutations associated with reduced susceptibility to artemisinin have also been detected in East Africa [17][18][19][20][21] and Papua New Guinea [22]. The most important artemisinin resistance mutation, a C to Y substitution at codon 580 (C580Y) in the propeller domain of a kelch-domain-containing protein on chromosome 13 (pfk13) was first observed in the Americas in samples collected in Guyana in 2010, where five out of 94 symptomatic cases were found to carry the pfk13 C580Y mutation [23].…”