Swiss Tropical Institute, Department of Medical Parasitology and Infection Biology, and Department of Public Health and Epidemiology, Socinstrasse 57, PO Box, CH-4002 Basel, Switzerland.
Malar J. 2010 Jan 7;9:8. doi: 10.1186/1475-2875-9-8.
Molecular 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.
Between 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.
PCR-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.
The 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.
寄生虫耐药性的分子监测已成为制定合理抗疟药物政策的重要辅助手段。社区调查提供了寄生虫群体的代表性样本，并且可以比从临床病例中积累样本更快地进行，但尚不清楚临床病例中的遗传耐药性标记的频率是否与总体人群中的频率不同，或者此类社区调查是否可以很好地预测治疗失败率。
在 2003 年至 2005 年期间，在巴布亚新几内亚的三个地点测定了阿莫地喹或氯喹加磺胺多辛-乙胺嘧啶的体内药物疗效。通过使用基于 DNA 微阵列的方法，同时在各自卫生机构的集水区中收集的 639 个社区样本中评估了寄生虫耐药性的基因药物（即 33 个疟原虫 falciparum crt、mdr1、dhfr、dhps 和 ATPase6 的单核苷酸多态性）。确定了突变等位基因和单倍型的频率，并研究了它们与每年每个地点的治疗失败率的关系。
PCR 校正的体内治疗失败率在 12%至 28%之间，因地点和年份而异，具有不同的纵向趋势。在社区样本中，pfcrt 和 pfmdr1 的突变频率很高，并且随着时间的推移没有明显变化。pfdhfr 的突变等位基因频率适中，pfdhps 的突变等位基因频率较低。在 pfATPase6 中未检测到突变。站点之间的变异远大于时间，站点内的等位基因和单倍型频率变异。这种变异与治疗失败率相关性不大。同一地点的临床和社区样本中的等位基因和单倍型频率非常相似。
寄生虫遗传学与体内治疗失败率之间的关系并不简单。抗疟药物的遗传抗性标记的频率在社区和临床样本中似乎非常相似，但不能用于准确预测临床结果。因此，基于分子数据的指标必须谨慎考虑，并在当地背景下进行解释，特别是要考虑到先前的药物使用情况和预先存在的免疫水平。对社区样本进行分子药物耐药性标志物检测是一种辅助工具，有助于为最佳治疗方案和适当的潜在替代方案做出决策。
