The roles of the pfcrt 76T and pfmdr1 86Y mutations, immunity and the initial level of parasitaemia, in predicting the outcome of chloroquine treatment in two areas with different transmission intensities
The roles of the pfcrt 76T and pfmdr1 86Y mutations, immunity and the initial level of parasitaemia, in predicting the outcome of chloroquine treatment in two areas with different transmission intensities
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DOI：
10.1179/136485905x46441
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发表时间：
2005-07-01
影响因子：
--
通讯作者：
Bygbjerg, IC
中科院分区：
文献类型：
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作者：
Khalil, IF;Alifrangis, M;Bygbjerg, IC
恶性疟原虫对氯喹的抗性可能是由pfcrt和pfmdr 1基因的点突变介导的。本研究的目的是调查，在接受CQ治疗的患者中，宿主因素（如免疫力和寄生虫血症的初始水平）与清除携带关键氯喹耐药（CQR）突变pfcrt 76 T和pfmdr 1 86 Y的恶性疟原虫寄生虫的能力之间的关联。在来自坦桑尼亚西北部基巴赫的51名幼儿（年龄< 5岁）和来自苏丹东部Darawish的44名患者（年龄3-57岁）中进行了相同的CQ疗效试验。在这两个地区，所有CQ治疗失败的患者在治疗前都感染了76 T和86 Y等位基因。虽然这两个等位基因的存在与苏丹的治疗失败显著相关（P=0.001），但在坦桑尼亚的相应关联未达到统计学显著性（P=0.1）。在来自Darawish的39名患者和来自基巴赫的44名患者中，分别有12名和19名患者成功清除了寄生虫血症。清除CQR寄生虫的能力与寄生虫血症的初始水平（坦桑尼亚P值为0.05，苏丹P值为0.01）和年龄（流行地区保护性免疫的最佳替代指标）显著相关（坦桑尼亚P值为0.02，苏丹P值为0.001）。这些结果证实了先前的观察结果，即76 T和86 Y等位基因在CQR的机制中发挥作用，尽管其他因素，如治疗时的寄生虫血症水平和年龄也很重要。76 T和86 Y等位基因在非免疫个体和低传播地区仍可作为CQR的预测标记。
The resistance of Plasmodium falciparum to chloroquine (CQ) is probably mediated by point mutations in two genes: pfcrt and pfmdr1. The aim of the present study was to investigate, in patients treated with CQ, the association between host factors, such as immunity and initial level of parasitaemia, and the ability to clear P. falciparum parasites carrying the key chloroquine-resistance (CQR) mutations, pfcrt 76T and pfmdr1 86Y. Identical CQ-efficacy trials were performed in 51 young children (aged < 5 years) from Kibaha, in north-western Tanzania, and 44 patients (aged 3-57 years) from Darawish, in eastern Sudan. In both areas, all the CQ-treatment failures had infections with the 76T and 86Y alleles before treatment. Although the presence of these two alleles was significantly associated with treatment failure in Sudan (P=0.001), the corresponding association in Tanzania did not reach statistical significance (P=0.1). Of the 39 patients from Darawish and 44 from Kibaha who harboured parasites with the CQR mutations, 12 and 19, respectively, managed to clear their parasitaemias. The ability to clear CQR parasites was significantly associated with the initial level of parasitaemia (with P-values of 0.05 in Tanzania and 0.01 in Sudan) and with age - the best surrogate for protective immunity in endemic areas (with P-values of 0.02 in Tanzania and 0.001 in Sudan). These results confirm previous observations that indicated that the 76T and 86Y alleles play a role in the mechanism of CQR, although other factors, such as level of parasitaemia when treated and age, are also important. The 76T and 86Y alleles could still be used as predictive markers for CQR, in non-immune individuals and low-transmission areas.