Duraisingh M T, Drakeley C J, Muller O, Bailey R, Snounou G, Targett G A, Greenwood B M, Warhurst D C
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.
Parasitology. 1997 Mar;114 ( Pt 3):205-11. doi: 10.1017/s0031182096008487.
The 4-aminoquinolines chloroquine (CQ) and amodiaquine (AM) were used to treat Gambian children with uncomplicated falciparum malaria in a randomized drug trial. Blood samples were taken immediately before treatment (day 0), and at day 7 and day 28 after treatment. Samples from those parasitologically positive at day 7 following treatment ('early positives') and those positive at day 28 but negative at day 7 ('late positives') have been studied by PCR followed by restriction enzyme digestion to determine the allelic status of the pfmdr 1 locus at the codon-86 position (asparagine or tyrosine), previously associated with resistance to CQ. A significantly higher prevalence of the tyr-86 allele was observed in samples taken immediately before treatment (day 0) in the early positives group when compared with the late positives group. This suggests the tyr-86 allele contributes to drug resistance in the early positives group. This association remained significant for both CQ and AM groups, implying a common genetic basis of resistance. Predominance of the allele at day 7 is consistent with a strong selection in the first week following treatment. In the late positives group, a significantly higher prevalence of the tyr-86 allele was observed in the samples at day 28 when compared with those at day 0, suggestive of selection during the period day 7 to day 28. Differences were observed in the extent of this selection in the CQ and AM groups. The samples were genotyped at 3 unlinked polymorphic loci. These analyses suggested that most parasites observed at day 7 were probably recrudescences whereas most of those at day 28 were reinfections.
在一项随机药物试验中，使用4-氨基喹啉类药物氯喹（CQ）和阿莫地喹（AM）治疗冈比亚患单纯性恶性疟的儿童。在治疗前（第0天）、治疗后第7天和第28天采集血样。对治疗后第7天寄生虫学检测呈阳性的患者（“早期阳性者”）以及第28天呈阳性但第7天呈阴性的患者（“晚期阳性者”）的样本进行聚合酶链反应（PCR），随后进行限制性内切酶消化，以确定恶性疟原虫多重耐药基因1（pfmdr 1）位点第86密码子位置（天冬酰胺或酪氨酸）的等位基因状态，该位点先前与对CQ的耐药性相关。与晚期阳性者组相比，早期阳性者组在治疗前即刻（第0天）采集的样本中，tyr-86等位基因的患病率显著更高。这表明tyr-86等位基因在早期阳性者组中导致了耐药性。这种关联在CQ组和AM组中均仍然显著，这意味着存在共同的耐药遗传基础。第7天该等位基因占优势与治疗后第一周的强烈选择一致。在晚期阳性者组中，与第0天的样本相比，第28天的样本中tyr-86等位基因的患病率显著更高，这表明在第7天至第28天期间存在选择。在CQ组和AM组中，这种选择的程度存在差异。对样本在3个不连锁的多态性位点进行基因分型。这些分析表明，在第7天观察到的大多数寄生虫可能是复发，而在第28天观察到的大多数寄生虫是再感染。
