Abstract

BackgroundArtemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear.MethodsIn annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up. Patients received the national recommended first-line treatment dihydroartemisinin-piperaquine for three days.ResultsOver the 5 years the proportion of patients with detectable parasitaemia on day 3 rose steadily from 38 to 57% (P < 0.001). In Binh Phuoc province, the parasite clearance half-life increased from 3.75 h in 2011 to 6.60 h in 2015 (P < 0.001), while treatment failures rose from 0% in 2012 and 2013, to 7% in 2014 and 26% in 2015 (P < 0.001). Recrudescence was associated with in vitro evidence of artemisinin and piperaquine resistance. In the treatment failures cases of 2015, all 14 parasite isolates carried the C580Y Pfkelch 13 gene, marker of artemisinin resistance and 93% (13/14) of them carried exoE415G mutations, markers of piperaquine resistance.ConclusionsIn the south of Vietnam recent emergence of piperaquine resistant P. falciparum strains has accelerated the reduced response to artemisinin and has led to treatment failure rates of up to 26% to dihydroartemisinin-piperaquine, Vietnam’s current first-line ACT. Alternative treatments are urgently needed.

Highlights

  • Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts

  • Study sites The study was conducted from August 2011 to December 2015 in (i) the Bu Gia Map and Dak O communes located in the Bu Gia Map district, Binh Phuoc province, 130 km northeast of Ho Chi Minh City and 100 km west of the Cambodian border (In 1989, Binh Phuoc was the first province in Vietnam to use artemisinin monotherapy); (ii) the IaTo commune, Ia Grai district, and the Krong Pa Medical Center, both are in Gia Lai province in the southern highlands; (iii) the Phuoc Thang commune, Bac Ai district, Ninh Thuan province in central Vietnam (2013–present) (Fig. 1)

  • The proportion of patients with a microscopy detected parasitaemia on day 3 (D3) post-DP treatment was highest in the Binh Phuoc site and increased progressively with time: 38, 41, 54, and 57% in 2012, 2013, 2014, and 2015, respectively (P < 0.001) (Fig. 3)

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Summary

Introduction

Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. Over the past 30 years there have been substantial reductions in malaria mortality and morbidity across the Greater Mekong sub-region. This has been driven largely by increased deployment of artemisinin-based. Neighbouring countries have set malaria elimination targets for the near future. These laudable objectives are threatened by the emergence and spread of artemisinin resistant Plasmodium falciparum. This study reports on the results of sequential studies conducted in the southern provinces Binh Phuoc, Ninh Thuan, and Gia Lai of Vietnam

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