A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon
A thirteen-year analysis of Plasmodium falciparum populations reveals high conservation of the mutant pfcrt haplotype despite the withdrawal of chloroquine from national treatment guidelines in Gabon
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DOI：
10.1186/1475-2875-10-304
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发表时间：
2011-10-17
期刊：
影响因子：
3
通讯作者：
Kremsner, Peter G.
中科院分区：
文献类型：
--
作者：
Frank, Matthias;Lehners, Nicola;Kremsner, Peter G.
背景：马拉维、基尼亚和坦桑尼亚将氯喹从国民治疗指南中删除后，氯喹耐药性(CR)下降。在2003年加蓬国民治疗指南从氯喹(CQ)改为青蒿琥酯加阿莫地喹(AQ)前后，检测了携带突变pfcrt等位基因的氯喹抗性(CQR)及其相关染色体单倍型的患病率。方法：采用聚合酶链式反应片段限制性内切酶消化和直接测序的方法，对2005-07年间144株分离株进行野生型pfcrt等位基因的检测。对1995/96(43株)、2002(47株)和2005-07(55株)共145个分离株进行单倍型分析。结果：突变的pfcrt等位基因频率从1995/96和2002年的100%下降到2005-07年的97%。单倍型分析表明，1995/96年79%的分离株在pfcrt基因座周围39kb的染色体片段中携带相同的微卫星等位基因。在2002年和2005-07年，这种单倍型的患病率分别为62%和58%。Pfcrt单倍型分析显示，所有野生型等位基因均为CVMNK。结论：CQ退出国家治疗指南4年后，突变型pfcrt等位基因的患病率仍保持在97%。这些数据表明，青蒿琥酯和AQ的结合可能导致即使在停止使用CQ后仍继续选择突变的pfcrt单倍型。
Background: Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania. In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003.Methods: The prevalence of the wild type pfcrt allele was assessed in 144 isolates from the years 2005 - 07 by PCR fragment restriction digest and direct sequencing. For haplotype analysis of the chromosomal regions flanking the pfcrt locus, microsatellite analysis was done on a total of 145 isolates obtained in 1995/96 (43 isolates), 2002 (47 isolates) and 2005 - 07 (55 isolates).Results: The prevalence of the mutant pfcrt allele decreased from 100% in the years 1995/96 and 2002 to 97% in 2005 - 07. Haplotype analysis showed that in 1995/96 79% of the isolates carried the same microsatellite alleles in a chromosomal fragment spanning 39 kb surrounding the pfcrt locus. In 2002 and 2005 - 07 the prevalence of this haplotype was 62% and 58%, respectively. Pfcrt haplotype analysis showed that all wild type alleles were CVMNK.Conclusion: Four years after the withdrawal of CQ from national treatment guidelines the prevalence of the mutant pfcrt allele remains at 97%. The data suggest that the combination of artesunate plus AQ may result in continued selection for the mutant pfcrt haplotype even after discontinuance of CQ usage.