Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes
Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes
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DOI：
10.4269/ajtmh.2002.67.578
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发表时间：
2002-12-01
影响因子：
3.3
通讯作者：
Targett, GAT
中科院分区：
文献类型：
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作者：
Sutherland, CJ;Alloueche, A;Targett, GAT
恶性疟原虫多药耐药1（P.falciparummultidrugresistance1，pfmdr 1）和氯喹耐药转运蛋白（P. falciparumchloroquineresistancetransporter，pfcrt）基因多态性与氯喹治疗失败有关。我们发现这些位点在有症状的冈比亚儿童分离株之间存在显著的连锁不平衡（P = 0.026），并且在治疗后随访期间，在持续存在或重新出现恶性疟原虫滋养体的儿童中，耐药相关等位基因pfmdr 1 - 86 Tyr和pfcrt-76 Thr具有强选择性（P = 1.9 × 10（-7））。因此，这种基因型是我们研究人群中耐药感染的特征。由于携带这种耐药基因型的寄生虫对公共卫生的长期影响取决于其可传播性，我们研究了冈比亚儿童在治疗后随访期间携带性阶段寄生虫的pfmdr 1 - 86 Tyr和pfcrt-76 Thr的患病率。CQ成功处理后出现的配子体比其他处理后出现的配子体更有可能是这种基因型（P = 4.83 x 10（-4）），并且对按蚊具有感染性。因此，治疗的成功可能伴随着公共卫生的失败，因为治愈的儿童以更快的速度将抗性基因传给蚊子。
Polymorphisms in two genes of Plasmodium falciparum (P. falciparum multidrug resistance 1 [pfmdr1] and P. falciparum chloroquine [CQ] resistance transporter [pfcrt]) are associated with CQ treatment failure. We found significant linkage disequilibrium between these loci among isolates from symptomatic Gambian children (P = 0.026) and strong selection for the resistance-associated alleles pfmdr1-86Tyr and pfcrt-76Thr in children with persistent or re-emerging P. falciparum trophozoites during post-treatment follow-up (P = 1.9 X 10(-7)). Therefore, this genotype is characteristic of resistant infections among our study population. Since the long-term public health impact of parasites carrying such resistant genotypes depends upon their transmissibility, we examined the prevalence of pfmdr1-86Tyr and pfcrt-76Thr among Gambian children harboring sexual stage parasites during post-treatment follow-up. Gametocytes that emerged after successful treatment with CQ were significantly more likely to be of this genotype than were those emerging after other treatments (P = 4.83 x 10(-4)), and were infective to Anopheles mosquitoes. Therapeutic success may thus be accompanied by public health failure as cured children pass resistance genes on to mosquitoes at an enhanced rate.