Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker

Abstract

SummaryBackgroundEmergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.MethodsWe did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.FindingsOverall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.InterpretationArtemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.FundingWellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.

In vitro inhibition of Plasmodium falciparum early and late stage gametocyte viability by extracts from eight traditionally used South African plant species

“…While the benefits of adopting these measures have been evident (Bhatt et al, 2015), unfortunately so too has been the emergence of insecticide resistant mosquitoes (Benelli, 2015;Dai et al, 2015;Edi et al, 2012;Ranson et al, 2011) and drug resistant strains of Plasmodium falciparum parasites Dondorp et al, 2009;Tun et al, 2015). There is thus a dire need to advance the efficacy of these approaches with novel interventions, drugs and insecticides in the fight against this disease.…”

K13 Kelch Propeller Domain and mdr1 Sequence Polymorphism in Field Isolates From Northeast Region, India

“…Different crosssectional studies have described the scenario of prevailing and predominating K13 mutations in SEA, particularly, C580Y has reached fixation at the Myanmar-Thailand border and M476I prevailing in eastern border of Myanmar. 8,14,19,22,24,46,47 In this study, neither C580Y nor M476I allele has been recorded in circulating isolates within this region. Moreover, evidence of F446I mutation in recent study indicates that it has either emerged in this region or spread from near most foci.…”

“…16 Also, F446I mutation has been considered as the most prevalent in China-Myanmar border than other mutations. 24 Recently, G533A novel mutation has been reported in P. falciparum isolates of Northeast region, India along with other non-synonymous S549Y,…”

Artemisinin resistance, some facts and opinions

“…More recently, a mutation on the K13-Propeller locus has been observed to be associated to DPC in Cambodia [9]; subsequently, additional mutations on the same gene have been observed in other regions in South Asia [10][11][12][13][14][15][16]. This promising marker is currently used in association with DPC to identify ART resistance but both still require a substantial clinical validation.…”