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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Tran Tinh Hien, Nguyen Thanh Thuy-Nhien, Nguyen Hoan Phu, Maciej F Boni, Ngo Viet Thanh, Nguyen Thuy Nha-Ca, Le Hong Thai, Cao Quang Thai, Pham Van Toi, Phung Duc Thuan, Le Thanh Long, Le Thanh Dong, Laura Merson, Christiane Dolecek, Kasia Stepniewska, Pascal Ringwald, Nicholas J White, Jeremy Farrar, Marcel Wolbers
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-355) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests. PR is a staff member of the World Health Organization. The author alone is responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization.

Authors’ contribution

TTH, PR, NJW, MW, KS and JF contributed to the design of the study. TTH, NTTN, NHP, NVT, NTNC, LHT, CQT, PVT, PDT, CD, LTL, LTD and LM participated in recruitment of participants and data collection. MW and MFB performed the statistical analysis. TTH drafted the first version and all authors reviewed and approved for submission. All authors read and approved the final manuscript.

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
Zusatzmaterial
Additional file 1: Table S1. Summary of primary and secondary endpoints by treatment group (per protocol population). (DOCX 21 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Literatur
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