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

Abstract

SummaryBackgroundArtemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort 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.MethodsIn 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.Findings3202 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 identified, 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.InterpretationGenetically 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.FundingThe Wellcome Trust and National Institutes of Health.

Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

“…Although high-grade resistance has not yet been seen in southeast Asia, the artemisinin-resistant phenotype (delayed parasite clearance and treatment failure after several weeks) has been confirmed in several locations. 21,22 In the past, high-grade parasite resistance has often been used interchangeably for both the parasite phenotype, as characterised in vitro by its confirmed ability to survive a threshold concentration of the drug in standard conditions of continuous culture, and in reference to therapeutic failure after the administration of a standard dose of a drug. Therapeutic failure is used in the WHO standard in-vivo test protocol.…”

“…68 Tolerance, and now resistance, has been confirmed for the artemisinin class of drugs in southeast Asia. 21,22 WHO recommends that 10% of patients remaining parasite-positive after 3 days should serve as a definition for suspected resistance. 25 A review 69 of parasite-clearance data (from more than 18 000 clinical trial patients), mostly from southeast Asia, suggests that the expected frequency of parasite positivity at 72 h after treatment with a 3 day artemisinin-based combination therapy regimen in patients with initial parasitaemia between 10 000 and 100 000 per μL of blood is less than 3%.…”

“…[21][22][23] A consensus has not been reached about whether artemisinin resistance should be declared a public health emergency of international concern, in accordance with the revised international health regulations. 24 The reasons advanced by those against such a declaration are largely political and economic rather than technical.…”

Étude de la résistance dePlasmodium falciparumaux antipaludiques au sein du réseau international des Instituts Pasteur (RIIP-Palu)

“…Les dérivés des artémisinines ont une place à part dans l'arsenal thérapeutique, car ils sont les seuls à agir sur toutes les formes de développement du parasite et ont une action remarquablement rapide. Malheureusement, ces médicaments sont maintenant menacés par l'apparition de parasites présentant une sensibilité diminuée aux artémisinines en Asie du Sud-Est [9][10][11][12]. Pour faire face à cette menace, un plan a été élaboré par l'OMS début 2011 [34] qui vise à endiguer et à prévenir la dissémination des souches résistantes aux artémisinines.…”

“…Ces combinaisons sont maintenant recommandées dans la plupart des pays d'endémie, mais leur accès est encore loin d'être général. Aujourd'hui, une des préoccupations majeures est que l'on assiste en Asie du Sud-Est aux premiers signes d'émergence de parasites résistants aux dérivés des artémisinines [9][10][11][12]. Aucune solution thérapeutique de remplacement n'est actuellement disponible.…”