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.

K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016

“…One particularly interesting feature was the increase in the predominance of the Cys580Tyr mutation at all sites, a pattern similar to that observed in neighboring Cambodia (8), Laos (15), and Thailand (16). One key question is whether K13 mutant parasites—and Cys580Tyr mutants in particular—were imported from other countries in the region or whether they emerged independently in Vietnam as a result of local drug pressure.…”

Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia

“…The neighbouring countries such as Thailand, Myanmar and Cambodia have actively reported the prevalence of C580Y which was the marker for slow-clearing P . falciparum in malaria patients treated with artemisinin and ACT [19, 20, 22]. Although the delayed parasite clearance after treatment with ACT has not yet been reported in Malaysia, characterizing the diversity of this gene is important to assess the potential for ACT drug resistance and to provide a baseline for future surveillance.…”

Artemisinin-Resistant Plasmodium falciparum Malaria

“…While some of these mutations have already been associated with slow parasite clearance in patients at other sites, most have not and require validation. Currently, C580Y predominates along the Cambodia-Thailand (29, 41-44, 54) and Thailand-Myanmar borders (29, 41, 47), and F446I predominates along the China-Myanmar and the Myanmar-India borders (26, 47, 49, 50). It is not known how C580Y has essentially approached fixation in Western Cambodia given that it confers lower % survival in the RSA 0-3h than R539T and I543T (29-31).…”

“…Several recent findings have supported this recommendation. For example, increases in DHA-piperaquine failures have been accompanied by contemporaneous reductions in mefloquine IC 50 values and in the prevalence of multiple copies of pfmdr1 – a genetic marker of mefloquine resistance (84) – in the parasite population (44, 54, 79, 85). Moreover, following DHA-piperaquine treatment, recrudescent parasites had lower mefloquine IC 50 values than their non-recrudescent counterparts, and none carried the multicopy pfmdr1 genotype (28).…”