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ABSTRACT: Background
Deployment of mefloquine-artesunate (MAS3) on the Thailand-Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of Plasmodium falciparum K13 mutations (a marker of artemisinin resistance) in reducing treatment efficacy remains controversial.Methods
Between 2003 and 2013, we studied the efficacy of MAS3 in 1005 patients with uncomplicated P. falciparum malaria in relation to molecular markers of resistance.Results
Polymerase chain reaction (PCR)-adjusted cure rates declined from 100% in 2003 to 81.1% in 2013 as the proportions of isolates with multiple Pfmdr1 copies doubled from 32.4% to 64.7% and those with K13 mutations increased from 6.7% to 83.4%. K13 mutations conferring moderate artemisinin resistance (notably E252Q) predominated initially but were later overtaken by propeller mutations associated with slower parasite clearance (notably C580Y). Those infected with both multiple Pfmdr1 copy number and a K13 propeller mutation were 14 times more likely to fail treatment. The PCR-adjusted cure rate was 57.8% (95% confidence interval [CI], 45.4, 68.3) compared with 97.8% (95% CI, 93.3, 99.3) in patients with K13 wild type and Pfmdr1 single copy. K13 propeller mutation alone was a strong risk factor for recrudescence (P = .009). The combined population attributable fraction of recrudescence associated with K13 mutation and Pfmdr1 amplification was 82%.Conclusions
The increasing prevalence of K13 mutations was the decisive factor for the recent and rapid decline in efficacy of artemisinin-based combination (MAS3) on the Thailand-Myanmar border.
SUBMITTER: Phyo AP
PROVIDER: S-EPMC4996140 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Phyo Aung Pyae AP Ashley Elizabeth A EA Anderson Tim J C TJC Bozdech Zbynek Z Carrara Verena I VI Sriprawat Kanlaya K Nair Shalini S White Marina McDew MM Dziekan Jerzy J Ling Clare C Proux Stephane S Konghahong Kamonchanok K Jeeyapant Atthanee A Woodrow Charles J CJ Imwong Mallika M McGready Rose R Lwin Khin Maung KM Day Nicholas P J NPJ White Nicholas J NJ Nosten Francois F
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20160616 6
<h4>Background</h4>Deployment of mefloquine-artesunate (MAS3) on the Thailand-Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of Plasmodium falciparum K13 mutations (a marker of artemisinin resistance) in reducing treatment efficacy remains controversial.<h4>Methods</h4>Between 2003 and 2013, we studied the efficacy of MAS3 in 1005 patients with uncomplicated P. falciparum malaria in relati ...[more]