Polymorphisms in PFCRT, PFMDR1, DHFR genes and in vitro responses to antimalarials in Plasmodium falciparum isolates from Bangui, Central African Republic
Polymorphisms in PFCRT, PFMDR1, DHFR genes and in vitro responses to antimalarials in Plasmodium falciparum isolates from Bangui, Central African Republic
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DOI：
10.4269/ajtmh.2006.75.381
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Talarmin, Antoine
中科院分区：
文献类型：
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作者：
Menard, Didier;Yapou, Ferdinand;Talarmin, Antoine
抗药性可能是大多数疟疾控制项目面临的最大挑战。鉴于用于其他疟疾控制措施的资源有限，合理用药至关重要。寄生虫抗性的分子标记，如pfcrt，pfutdr-1和dhfr，有可能以综合的方式使用，为决策者提供及时有用的信息。因此，我们评估了这些基因的多态性恶性疟原虫和他们的关联在体外抗疟药物耐药性的135个寄生虫样本收集在班吉在2004年。对于dhfr基因，我们发现dhfr基因型和乙胺嘧啶的化疗敏感性之间有很强的关联。对于pfcrt基因，我们发现具有突变型等位基因的单倍型导致氯喹、单去乙基阿莫地喹和奎宁的IC 50值发生显著变化。我们没有发现pfmdr 1基因的相关性。这些发现表明，定期监测和筛选抗叶酸剂和氯喹的耐药标志物可以作为体内试验的辅助手段。
Drug resistance is probably the greatest challenge to most malaria-control programs. Given the limited resources for other malarial-control measures, rational drug used is crucial. Molecular markers for parasite resistance such as pfcrt, pfutdr-1, and dhfr have the potential to be used in an integrated fashion to provide timely information that is useful to policy makers. Therefore, we evaluated polymorphisms in these genes from Plasmodium falciparum and their association with in vitro antimalarial drug resistance to 135 parasites samples collected in Bangui in 2004. For the dhfr gene, we found a strong association between the dhfr genotype and chemosensitivity to pyrimethamine. For the pfcrt gene, we found that haplotypes with mutant-type alleles led to significant changes in the IC50 values for chloroquine, monodesethylamodiaquine, and quinine. We found no correlations for the pfmdr1 gene. These findings suggest that a regular monitoring and screening for resistance markers for antifolates and for chloroquine could act as an adjunct to in vivo trials.