de Almeida Afonso, Arez Ana Paula, Cravo Pedro Vl, do Rosário Virgílio E
Universidade Nacional de Timor Leste, Avenida Cidade de Lisboa, Díli, Timor Leste.
Malar J. 2009 Apr 9;8:59. doi: 10.1186/1475-2875-8-59.
In response to chloroquine (CQ) resistance, the policy for the first-line treatment of uncomplicated malaria in the Democratic Republic of East Timor (DRET) was changed in early 2000. The combination of sulphadoxine-pyrimethamine (SP) was then introduced for the treatment of uncomplicated falciparum malaria.
Blood samples were collected in two different periods (2003-2004 and 2004-2005) from individuals attending hospitals or clinics in six districts of the DRET and checked for Plasmodium falciparum infection. 112 PCR-positive samples were inspected for genetic polymorphisms in the pfcrt, pfmdr1, pfdhfr and pfdhps genes. Different alleles were interrogated for potential associations that could be indicative of non-random linkage.
Overall prevalence of mutations associated with resistance to CQ and SP was extremely high. The mutant form of Pfcrt (76T) was found to be fixed even after five years of alleged CQ removal. There was a significant increase in the prevalence of the pfdhps 437G mutation (X2 = 31.1; p = 0.001) from the first to second survey periods. A non-random association was observed between pfdhfr51/pfdhps437 (p = 0.001) and pfdhfr 59/pfdhps 437 (p = 0.013) alleles.
Persistence of CQ-resistant mutants even after supposed drug withdrawal suggests one or all of the following: local P. falciparum may still be inadvertently exposed to the drug, that mutant parasites are being "imported" into the country, and/or reduced genetic diversity and low parasite transmission help maintain mutant haplotypes. The association between pfdhfr51/pfdhps437 and pfdhfr 59/pfdhps 437 alleles indicates that these are undergoing concomitant positive selection in the DRET.
为应对氯喹（CQ）耐药性问题，东帝汶民主共和国（DRET）于2000年初改变了非复杂性疟疾一线治疗政策。随后引入了磺胺多辛-乙胺嘧啶（SP）联合用药方案来治疗非复杂性恶性疟。
在两个不同时期（2003 - 2004年和2004 - 2005年）从DRET六个地区的医院或诊所就诊的个体中采集血样，检查是否感染恶性疟原虫。对112份PCR阳性样本检测pfcrt、pfmdr1、pfdhfr和pfdhps基因的遗传多态性。对不同等位基因进行分析，以寻找可能表明非随机连锁的潜在关联。
与CQ和SP耐药相关的突变总体流行率极高。即使在据称停用CQ五年后，仍发现Pfcrt的突变形式（76T）固定存在。从第一次调查期到第二次调查期，pfdhps 437G突变的流行率显著增加（X2 = 31.1；p = 0.001）。观察到pfdhfr51/pfdhps437（p = 0.001）和pfdhfr 59/pfdhps 437（p = 0.013）等位基因之间存在非随机关联。
即使在假定停药后，CQ耐药突变体仍持续存在，这表明以下一种或全部情况：当地恶性疟原虫可能仍在无意中接触该药物，突变寄生虫正被“输入”该国，和/或遗传多样性降低以及寄生虫传播率低有助于维持突变单倍型。pfdhfr51/pfdhps437和pfdhfr 59/pfdhps 437等位基因之间的关联表明，这些等位基因在DRET正在经历伴随的正选择。
