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In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam

Tran Tinh Hien16*, Nguyen Thanh Thuy-Nhien1, Nguyen Hoan Phu2, Maciej F Boni16, Ngo Viet Thanh1, Nguyen Thuy Nha-Ca1, Le Hong Thai1, Cao Quang Thai1, Pham Van Toi1, Phung Duc Thuan3, Le Thanh Long4, Le Thanh Dong3, Laura Merson16, Christiane Dolecek16, Kasia Stepniewska68, Pascal Ringwald7, Nicholas J White56, Jeremy Farrar16 and Marcel Wolbers16

Author Affiliations

1 Wellcome Trust Major Overseas Programme (MOP), Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam

2 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

3 Institute of Malariology, Parasitology, and Entomology (IMPE), Ho Chi Minh City, Vietnam

4 Phuoc Long Hospital, Binh Phuoc Province, Vietnam

5 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

6 Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK

7 Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland

8 World Wide Anti-malarial Resistance Network (WWARN), Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, Oxford, UK

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Malaria Journal 2012, 11:355  doi:10.1186/1475-2875-11-355

Published: 26 October 2012

Abstract

Background

By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam.

Methods

From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time.

Results

166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04).

Conclusions

This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam. Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed. Currently, the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam.

Trial registration

NTC01165372

Keywords:
Plasmodium falciparum; Artesunate; Parasite clearance half-life; Parasite reduction ratio; Parasite clearance of >72 hours