Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia
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Lim, Pharath, et al. Pfmdr1 Copy Number and Arteminisin Derivatives Combination Therapy Failure In Falciparum Malaria In Cambodia. BioMed Central Ltd, 2009. https://doi.org/10.17615/1b6r-y543APA
Lim, P., Alker, A., Khim, N., Shah, N., Incardona, S., Doung, S., Yi, P., Bouth, D., Bouchier, C., Puijalon, O., Meshnick, S., Wongsrichanalai, C., Fandeur, T., Le Bras, J., Ringwald, P., & Ariey, F. (2009). Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia. BioMed Central Ltd. https://doi.org/10.17615/1b6r-y543Chicago
Lim, Pharath, Alisa P Alker, Nimol Khim, Naman K Shah, Sandra Incardona, Socheat Doung, Poravuth Yi et al. 2009. Pfmdr1 Copy Number and Arteminisin Derivatives Combination Therapy Failure In Falciparum Malaria In Cambodia. BioMed Central Ltd. https://doi.org/10.17615/1b6r-y543- Creator
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Lim, Pharath
- Other Affiliation: Institut Pasteur in Cambodia, 5 Monivong Boulevard, P.O Box 983, Phnom Penh, Cambodia
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Alker, Alisa P
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Khim, Nimol
- Other Affiliation: Institut Pasteur in Cambodia, 5 Monivong Boulevard, P.O Box 983, Phnom Penh, Cambodia
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Shah, Naman K
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Incardona, Sandra
- Other Affiliation: Institut Pasteur in Cambodia, 5 Monivong Boulevard, P.O Box 983, Phnom Penh, Cambodia
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Doung, Socheat
- Other Affiliation: National Center for Parasitology, Entomology and Malaria Control (CNM), Phnom Penh, Cambodia
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Yi, Poravuth
- Other Affiliation: National Center for Parasitology, Entomology and Malaria Control (CNM), Phnom Penh, Cambodia
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Bouth, Denis
- Other Affiliation: World Health Organization, Phnom Penh, Cambodia
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Bouchier, Christiane
- Other Affiliation: Pasteur Genopole Ile de France, Institut Pasteur, France
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Puijalon, Odile
- Other Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, France
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Meshnick, Steven R.
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Wongsrichanalai, Chansuda
- Other Affiliation: Independent Scholar, 130 Sub Street, Bangkok 10500, Thailand
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Fandeur, Thierry
- Other Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, France
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Le Bras, Jacques
- Other Affiliation: Faculté des sciences pharmaceutiques et biologiques, EA209 Université Paris Descartes, France
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Ringwald, Pascal
- Other Affiliation: Global Malaria Department, World Health Organization, Headquarters, Geneva, Switzerland
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Ariey, Frédéric
- Other Affiliation: Institut Pasteur in Cambodia, 5 Monivong Boulevard, P.O Box 983, Phnom Penh, Cambodia
- Abstract
- Abstract Background The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Methods Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group) in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group) in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. Results The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p < 0.001). This was not observed in the patients treated with AL (n = 96, p = 0.364). The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR) = 7.80 [95%CI: 2.09–29.10], N = 115), p = 0.002) but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24–4.44], N = 109, p = 0.969). Conclusion This study shows that pfmdr1 copy number is a molecular marker of AM treatment failure in falciparum malaria on the Thai-Cambodian border. However, while it is associated with increased IC50 for lumefantrine, pfmdr1 copy number is not associated with AL treatment failure in the area, suggesting involvement of other molecular mechanisms in AL treatment failures in Cambodia.
- Date of publication
- January 12, 2009
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Pharath Lim et al.; licensee BioMed Central Ltd.
- License
- Journal title
- Malaria Journal
- Journal volume
- 8
- Journal issue
- 1
- Page start
- 11
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1475-2875
- Bibliographic citation
- Malaria Journal. 2009 Jan 12;8(1):11
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- August 23, 2012
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