Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border

Ye, Run; Hu, Dong-wei; Zhang, Yilong; Huang, Yufu; Sun, Xin; Wang, Jian; Chen, Xuedi; Zhou, Hongning; Zhang, Dongmei; Mungthin, Mathirut; Pan, Weiqing

doi:10.1038/srep20100

Cited by 67 publications

(79 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The limited number of samples available from the 2014 TES study showed no evidence of K13 resistance alleles, including those samples with low parasite clearance rates. Although several mutations in K13 have been shown to be strongly associated with artemisinin resistance, some parasites with K13 wild-type alleles in Southeast Asia also exhibited a delayed parasite clearance phenotype (8,9). The lack of association between resistance phenotypes and K13 polymorphisms in some field isolates suggests that additional genes may be involved in the development of artemisinin resistance in P. falciparum.…”

Section: Figmentioning

confidence: 89%

Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

Chenet

Okoth

Kelley

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum. We genotyped the PfK13 propeller domain of P. falciparum in 40 samples as well as other mutations proposed to be associated with artemisininresistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia, but we found fixed resistance mutations for chloroquine (CQ) and sulfadoxine-pyrimethamine. Additionally, the PfCRT C350R mutation, associated with reversal of CQ resistance and piperaquine-selective pressure, was present in 62% of the samples. Our results from neutral microsatellite data also confirmed a high parasite gene flow in the Guiana Shield. Although recruiting participants for therapeutic efficacy studies is challenging in areas where malaria endemicity is very low due to the low number of malaria cases reported, conducting these studies along with molecular surveillance remains essential for the monitoring of artemisinin-resistant alleles and for the characterization of the population structure of P. falciparum in areas targeted for malaria elimination.

show abstract

Section: Figmentioning

confidence: 89%

Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

Chenet

Okoth

Kelley

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…2015b; Ye et al. 2016). Analysis of these isolates indicates that they lack certain elements of the genetic backbone found in much of the rest of Southeast Asia (Miotto et al.…”

Section: Determining the Extent Of Artemisinin Resistancementioning

confidence: 99%

The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread

Woodrow¹,

White²

2016

FEMS Microbiology Reviews

202

157

View full text Add to dashboard Cite

Artemisinins are the most rapidly acting of currently available antimalarial drugs. Artesunate has become the treatment of choice for severe malaria, and artemisinin-based combination therapies (ACTs) are the foundation of modern falciparum malaria treatment globally. Their safety and tolerability profile is excellent. Unfortunately, Plasmodium falciparum infections with mutations in the ‘K13’ gene, with reduced ring-stage susceptibility to artemisinins, and slow parasite clearance in patients treated with ACTs, are now widespread in Southeast Asia. We review clinical efficacy data from the region (2000–2015) that provides strong evidence that the loss of first-line ACTs in western Cambodia, first artesunate-mefloquine and then DHA-piperaquine, can be attributed primarily to K13 mutated parasites. The ring-stage activity of artemisinins is therefore critical for the sustained efficacy of ACTs; once it is lost, rapid selection of partner drug resistance and ACT failure are inevitable consequences. Consensus methods for monitoring artemisinin resistance are now available. Despite increased investment in regional control activities, ACTs are failing across an expanding area of the Greater Mekong subregion. Although multiple K13 mutations have arisen independently, successful multidrug-resistant parasite genotypes are taking over and threaten to spread to India and Africa. Stronger containment efforts and new approaches to sustaining long-term efficacy of antimalarial regimens are needed to prevent a global malaria emergency.

show abstract

“…Several molecular epidemiology studies, mostly in southeast Asia, 27,38,[41][42][43][44] China, [45][46][47][48] Indian subcontinent 49,50 and Africa, 27,51-58 investigated the frequency of K13 mutant alleles, their spatial distribution and, in some cases, their association with clinical artemisinin resistance (day 3 positivity rate or parasite clearance half-life). Only 13 independent K13 mutations of about 100 tested were found to be associated with clinical resistance, with evidence of the independent emergence of the same mutation in different areas.…”

Section: Resistance To Artemisinin Derivatives: Past and Present Resementioning

confidence: 99%

Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia

Duru

Witkowski

Ménard

2016

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years. BACKGROUND

show abstract

Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border

Cited by 67 publications

References 24 publications

Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread

Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia

Contact Info

Product

Resources

About