十年后的氯喹耐药状况:肯尼亚疟疾流行和流行地区敏感恶性疟原虫毒株再次出现

L. Wangai, S. Omar
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引用次数: 3

摘要

氯喹耐药性的发展和传播导致大多数疟疾流行国家停止使用氯喹。1998年在肯尼亚发生了这种情况,当时临床疗效下降到50%以下。在马拉维取消CQ的常规使用不到十年后,这种药物已经恢复了活性,并再次有效地用于一线治疗无并发症的疟疾。在肯尼亚,在没有复杂的恶性疟原虫疟疾治疗的10多年里,有可能出现类似的逆转活动。本研究的目的是通过考察疟疾高传播区、疟疾流行地区姆比塔和肯尼亚高地的一些疟疾流行地区,在撤出10年后确定该国对CQ的抗性状况。采用PCR-RFLP和dot blot方法,对2007年3 - 5月疫区采集的64份样本和同年4 - 7月疫区采集的38份样本进行了恶性疟原虫Pfcrt和Pfmdr1基因CQ耐药分子标记T76和Y86的流行情况调查。结果表明,67.3%的野外分离株Pfmdr1基因Y86突变,32.7%的野外分离株携带野生型N86等位基因,而2004年疫区Mwea的阳性率分别为94%和6% (χ 2 =10.08, P=0.00015, 95% CI=2.085 ~ 27.8)。1997年疫区Pfmdr1野生型N86等位基因的检出率分别为91.6%和8.4% (χ 2 =1.585, P=0.208, 95% CI=0.701 ~ 19.176),但在疫区现场分离株中仍有75%携带Y86突变,25%携带野生型N86等位基因。从该研究来看,在流行地区耐药基因型的比例发生了重大变化,而在流行地区,也有明显的变化,尽管不显著。因此,这表明该国正在缓慢但稳定地重新出现恶性疟原虫CQ敏感菌株。虽然不能保证将CQ重新引入疟疾治疗。
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Chloroquine resistance status a decade after: Re-emergence of sensitive Plasmodium falciparum strains in malaria endemic and epidemic areas in Kenya
Development and spread of chloroquine (CQ) resistance led to its withdrawal in most malaria endemic countries. In Kenya, this occurred in 1998 when clinical efficacy dropped below 50%. Less than a decade after CQ was removed from routine use in Malawi, the drug has reversed to activity and is again effective for first-line treatment of uncomplicated malaria. There is a probability of a similar reversed activity in Kenya for more 10 years of its absence in uncomplicated Plasmodium falciparum malaria treatment. The present study was aimed at establishing the CQ resistance status in the country, 10 years after its withdrawal, by looking at high malaria transmission zone, Mbita, a malaria endemic area and some malaria epidemic areas of the Kenyan highlands. The prevalence of T76 and Y86 P. falciparum molecular markers for CQ resistance in Pfcrt and Pfmdr1 genes were investigated by PCR-RFLP and dot blot analysis in 64 samples collected in March to May 2007 in the endemic area and 38 samples collected in April to July the same year in the epidemics. The study shows that 67.3% of field isolates from the endemic site still harbor Y86 mutation in Pfmdr1 while 32.7% have the wild type allele N86 compared to the 94% and 6 % prevalence observed in Mwea, an endemic area, in 2004 (χ 2 =10.08, P=0.00015, 95% CI=2.085-27.8). In the epidemics 75% of field isolates from the epidemic sites still harbor Y86 mutation in Pfmdr1 while 25% have the wild type allele N86 compared to the 91.6% and 8.4% prevalence observed in an epidemic area in 1997 (χ 2 =1.585, P=0.208, 95% CI=0.701-19.176). From the study there is a significant change in the proportions of the resistant genotypes in the endemic areas while in the epidemics, there was also a noticeable shift though not significant. This therefore indicates a slow but steady re-emergence of P. falciparum CQ sensitive strains in the country. Though does not warrant the reintroduction of CQ for malaria treatment.
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