An outbreak of artemisinin resistant falciparum malaria in Eastern Thailand

Abstract

Artemisinin resistant falciparum malaria is an increasing problem in Southeast Asia, but has not been associated with increased transmission of the disease, yet. During a recent outbreak in 2014 in Ubon Ratchatani, Eastern Thailand, parasites from 101 patients with falciparum malaria were genotyped for antimalarial drug resistance markers. Mutations in the Kelch13 marker for artemisinin resistance were present in 93% of samples, mainly C580Y from 2 major clusters as identified by microsatellite typing. Resistance markers for antifolates and chloroquine were also highly prevalent. Most strains (91%) carried single copy number PfMDR1, suggesting sustained sensitivity to mefloquine, the partner drug in the local first-line artemisinin combination therapy (ACT). The high prevalence of artemisinin resistance in this recent malaria outbreak suggests but does not prove a causative role in increased transmission. Careful monitoring of ACT efficacy and additional genetic epidemiological studies are warranted to guide the public health response to the outbreak.

Figure 1

(a) Pie charts representing proportions of mutations or gene-amplification in five resistance genes (Pfkelch, pfcrt, pfdhfr, pfdhps and pfmdr1) observed in P. falciparum isolates from Ubon Ratchathani. A total of 101 samples were genotyped, but full genotyping of all resistance markers was not accomplished in all samples (see denominators shown next to pie charts) The map was created using Adobe^® Photoshop^® CS6 version 13.1.2 × 64 software (Copyright© 1990–2012 Adobe Systems Incorporated). (b) Bar chart representing the patterns observed in the five antimalarial drug resistance genes assessed in this study.

Figure 2. Dendrogram showing inter-strain relatedness of P. falciparum strains carrying the C580Y Pfkelch mutation obtained from patients with a first presentation of uncomplicated falciparum malaria in Buntharik district hospital in Ubon Ratchatani province in eastern Thailand.

Complete microsatellite typing was successful in 57/65 (88%) of parasite strains with the C580Y mutation. Microsatellite types were compared to 20 typed strains from Guinea. Cluster analysis was based on typing of 9 microsatellites using genetic similarity indexes obtained by unweighted pair group method arithmetic averages (UPGMA). The analysis revealed 2 separate clusters within the Ubon Ratchathani isolates.