Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study

Aung Pyae Phyo, Standwell Nkhoma, Kasia Stepniewska, Elizabeth A. Ashley, Shalini Nair, Rose McGready, Carit Ler Moo, Salma Al-Saai, Arjen M. Dondorp, Khin Maung Lwin, Pratap Singhasivanon, Nicholas P J Day, Nicholas J. White, Tim J C Anderson, François Nosten

Research output: Contribution to journalArticle

561 Citations (Scopus)

Abstract

Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international eff ort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≤4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5-2·7) in 2001, to 3·7 h (3·6-3·8) in 2010, compared with a mean of 5·5 h (5·2-5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≤6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identifi ed, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand-Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2-6 years.

Original languageEnglish (US)
Pages (from-to)1960-1966
Number of pages7
JournalThe Lancet
Volume379
Issue number9830
DOIs
StatePublished - May 2012
Externally publishedYes

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Thailand
Malaria
Longitudinal Studies
Parasites
Cambodia
Myanmar
Falciparum Malaria
Plasmodium falciparum
Infection
artemisinine
Single Nucleotide Polymorphism
Half-Life
Erythrocytes
Genotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Phyo, A. P., Nkhoma, S., Stepniewska, K., Ashley, E. A., Nair, S., McGready, R., ... Nosten, F. (2012). Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study. The Lancet, 379(9830), 1960-1966. https://doi.org/10.1016/S0140-6736(12)60484-X

Emergence of artemisinin-resistant malaria on the western border of Thailand : A longitudinal study. / Phyo, Aung Pyae; Nkhoma, Standwell; Stepniewska, Kasia; Ashley, Elizabeth A.; Nair, Shalini; McGready, Rose; Moo, Carit Ler; Al-Saai, Salma; Dondorp, Arjen M.; Lwin, Khin Maung; Singhasivanon, Pratap; Day, Nicholas P J; White, Nicholas J.; Anderson, Tim J C; Nosten, François.

In: The Lancet, Vol. 379, No. 9830, 05.2012, p. 1960-1966.

Research output: Contribution to journalArticle

Phyo, AP, Nkhoma, S, Stepniewska, K, Ashley, EA, Nair, S, McGready, R, Moo, CL, Al-Saai, S, Dondorp, AM, Lwin, KM, Singhasivanon, P, Day, NPJ, White, NJ, Anderson, TJC & Nosten, F 2012, 'Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study', The Lancet, vol. 379, no. 9830, pp. 1960-1966. https://doi.org/10.1016/S0140-6736(12)60484-X
Phyo AP, Nkhoma S, Stepniewska K, Ashley EA, Nair S, McGready R et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study. The Lancet. 2012 May;379(9830):1960-1966. https://doi.org/10.1016/S0140-6736(12)60484-X
Phyo, Aung Pyae ; Nkhoma, Standwell ; Stepniewska, Kasia ; Ashley, Elizabeth A. ; Nair, Shalini ; McGready, Rose ; Moo, Carit Ler ; Al-Saai, Salma ; Dondorp, Arjen M. ; Lwin, Khin Maung ; Singhasivanon, Pratap ; Day, Nicholas P J ; White, Nicholas J. ; Anderson, Tim J C ; Nosten, François. / Emergence of artemisinin-resistant malaria on the western border of Thailand : A longitudinal study. In: The Lancet. 2012 ; Vol. 379, No. 9830. pp. 1960-1966.
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abstract = "Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international eff ort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≤4{\%} infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95{\%} CI 2·5-2·7) in 2001, to 3·7 h (3·6-3·8) in 2010, compared with a mean of 5·5 h (5·2-5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≤6·2 h) increased from 0·6{\%} in 2001, to 20{\%} in 2010, compared with 42{\%} in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identifi ed, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30{\%} between 2001 and 2004, to 66{\%} between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand-Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2-6 years.",
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AU - Phyo, Aung Pyae

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AU - Ashley, Elizabeth A.

AU - Nair, Shalini

AU - McGready, Rose

AU - Moo, Carit Ler

AU - Al-Saai, Salma

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AU - Lwin, Khin Maung

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N2 - Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international eff ort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma) border. Methods In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≤4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms. Findings 3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5-2·7) in 2001, to 3·7 h (3·6-3·8) in 2010, compared with a mean of 5·5 h (5·2-5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≤6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identifi ed, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010. Interpretation Genetically determined artemisinin resistance in P falciparum emerged along the Thailand-Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2-6 years.

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