The T76 mutation in the pfcrt gene of Plasmodium falciparum and clinical chloroquine resistance phenotypes in Papua, Indonesia
The T76 mutation in the pfcrt gene of Plasmodium falciparum and clinical chloroquine resistance phenotypes in Papua, Indonesia
复制标题
DOI：
10.1080/00034980120092516
复制
发表时间：
2001-09-01
影响因子：
--
通讯作者：
Baird, JK
中科院分区：
文献类型：
--
作者：
Maguire, JD;Susanti, AI;Baird, JK
pfcrt基因中的T76突变与恶性疟原虫的氯喹（CQ）抗性有关。pfcrt等位基因的基于PCR的分析是在来自107名患有恶性疟原虫感染并居住在印度尼西亚巴布亚的个体的治疗前样本上进行的。28天的体内试验结果显示，79份（74%）样品对CQ具有临床耐药性。pfcrt T76检测试剂盒检测CQ耐药感染的粗灵敏度为96%，粗特异性为52%。pfcrt基因型和体内表型之间的不一致性通过裂殖子表面蛋白-2的基因分型（以区分再感染和复发）或通过扩增恶性疟原虫特异性小亚基核糖体RNA（ssrRNA）基因，使用巢式PCR（以检测任何亚专利，但耐药寄生虫在感染误分类为敏感的体内测试）进行分析。当调整这些分析的结果时，pfcrt T76检测CQ耐药感染的灵敏度和特异性分别为93%和82%。总体而言，本结果表明，pfcrt T76测定可用于预测CQ耐药引起的治疗失败。验证需要探索的表型分类的基础上，在体内测试的结果，使用遗传分析，区分再感染复发和检测显微镜下亚专利寄生虫血症。
The T76 mutation in the pfcrt gene has been linked to chloroquine (CQ) resistance in Plasmodium falciparum. PCR-based analysis of pfcrt alleles was performed on pre-treatment samples from 107 individuals who had P. falciparum infections and lived in Papua, Indonesia. The results of a 28-day, in-vivo test revealed clinical resistance to CQ in 79 (74%) of the samples. The crude sensitivity of the pfcrt T76 assay for detecting the CQ-resistant infections in the samples was 96% and the crude specificity 52%. Discordance between pfcrt genotype and in-vivo phenotype was analysed either by genotyping of the merozoite surface protein-2 (to distinguish re-infection from recrudescence) or by amplification of the P. falciparum-specific small-subunit ribosomal RNA (ssrRNA) gene, using nested PCR (to detect any sub-patent but resistant parasites in infections misclassified as sensitive by the in-vivo test). When adjusting for the results of these analyses, the sensitivity and specificity of the pfcrt T76 assay for detecting the CQ-resistant infections became 93% and 82%, respectively. Overall, the present results indicate that the pfcrt T76 assay may be used to forecast therapeutic failure caused by CQ resistance. Validation requires exploration of the phenotype classifications based on the results of in-vivo tests, using genetic analyses that distinguish re-infection from recrudescence and detect microscopically subpatent parasitaemias.