Plasmodium falciparum resistance to anti-malarial drugs in Papua New Guinea: evaluation of a community-based approach for the molecular monitoring of resistance

Malaria Journal

Research

Blaise Genton¹  Hans-Peter Beck¹  Jutta Marfurt¹  Thomas A Smith¹  Ian M Hastings²  Ivo Müller³  Moses Baisor³  Albert Sie³  Olive Oa³  John C Reeder³ 

[1] Department of Medical Parasitology and Infection Biology, and Department of Public Health and Epidemiology, Swiss Tropical Institute, PO Box, CH-4002, Socinstrasse 57, Basel, Switzerland;Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK;Papua New Guinea Institute of Medical Research, PO Box 60, EHP 441, Goroka, Papua New Guinea;

关键词: Haplotype Frequency;    Parasite Population;    North Coast;    Treatment Failure Rate;    Mutant Allele Frequency;   

DOI  :  10.1186/1475-2875-9-8

 received in 2009-09-06, accepted in 2010-01-07,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMolecular monitoring of parasite resistance has become an important complementary tool in establishing rational anti-malarial drug policies. Community surveys provide a representative sample of the parasite population and can be carried out more rapidly than accrual of samples from clinical cases, but it is not known whether the frequencies of genetic resistance markers in clinical cases differ from those in the overall population, or whether such community surveys can provide good predictions of treatment failure rates.MethodsBetween 2003 and 2005, in vivo drug efficacy of amodiaquine or chloroquine plus sulphadoxine-pyrimethamine was determined at three sites in Papua New Guinea. The genetic drug resistance profile (i.e., 33 single nucleotide polymorphisms in Plasmodium falciparum crt, mdr1, dhfr, dhps, and ATPase6) was concurrently assessed in 639 community samples collected in the catchment areas of the respective health facilities by using a DNA microarray-based method. Mutant allele and haplotype frequencies were determined and their relationship with treatment failure rates at each site in each year was investigated.ResultsPCR-corrected in vivo treatment failure rates were between 12% and 28% and varied by site and year with variable longitudinal trends. In the community samples, the frequencies of mutations in pfcrt and pfmdr1 were high and did not show significant changes over time. Mutant allele frequencies in pfdhfr were moderate and those in pfdhps were low. No mutations were detected in pfATPase6. There was much more variation between sites than temporal, within-site, variation in allele and haplotype frequencies. This variation did not correlate well with treatment failure rates. Allele and haplotype frequencies were very similar in clinical and community samples from the same site.ConclusionsThe relationship between parasite genetics and in vivo treatment failure rate is not straightforward. The frequencies of genetic anti-malarial resistance markers appear to be very similar in community and clinical samples, but cannot be used to make precise predictions of clinical outcome. Thus, indicators based on molecular data have to be considered with caution and interpreted in the local context, especially with regard to prior drug usage and level of pre-existing immunity. Testing community samples for molecular drug resistance markers is a complementary tool that should help decision-making for the best treatment options and appropriate potential alternatives.

【 授权许可】

Unknown   
© Marfurt et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.