氯喹耐药性与巴西亚马逊地区间日疟原虫多拷贝 pvcrt-o 基因有关。
Chloroquine resistance is associated to multi-copy pvcrt-o gene in Plasmodium vivax malaria in the Brazilian Amazon.
机构信息
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, 69040-000, Brazil.
Universidade do Estado do Amazonas (UEA), Manaus, Amazonas, 69040-000, Brazil.
出版信息
Malar J. 2018 Jul 16;17(1):267. doi: 10.1186/s12936-018-2411-5.
BACKGROUND
The resistance of Plasmodium vivax to chloroquine has become an obstacle to control strategies based on the use of anti-malarials. The current study investigated the association between P. vivax CQ-resistance in vivo with copy number variation and mutations in the promoter region in pvcrt-o and pvmdr1 genes.
METHODS
The study included patients with P. vivax that received supervised treatment with chloroquine and primaquine. Recurrences were actively recorded during this period.
RESULTS
Among the 60 patients with P. vivax, 25 were CQ-resistant and 35 CQ-susceptible. A frequency of 7.1% of multi-copy pvcrt-o was observed in CQ-susceptible samples and 7.7% in CQ-resistant at D0 (P > 0.05) and 33.3% in CQ-resistant at DR (P < 0.05). For pvmdr1, 10.7% of the CQ-susceptible samples presented multiple copies compared to 11.1% in CQ-resistant at D0 and 0.0% in CQ-resistant at DR (P > 0.05). A deletion of 19 bp was found in 11/23 (47.6%) of the patients with CQ-susceptible P. vivax and 3/10 (23.1%) of the samples with in CQRPv at D0. At day DR, 55.5% of the samples with CQRPv had the 19 bp deletion. For the pvmdr-1 gene, was no variation in the analysed gene compared to the P. vivax reference Sal-1.
CONCLUSIONS
This was the first study with 42-day clinical follow-up to evaluate the variation of the number of copies and polymorphisms in the promoter region of the pvcrt-o and pvmdr1 genes in relation to treatment outcomes. Significantly higher frequency of multi-copy pvcrt-o was found in CQRPv samples at DR compared to CQ-susceptible, indicating parasite selection of this genotype after CQ treatment and its association with CQ-resistance in vivo.
背景
恶性疟原虫对氯喹的耐药性已成为基于抗疟药物使用的疟疾控制策略的障碍。本研究调查了体内恶性疟原虫对氯喹的耐药性与 pvcrt-o 和 pvmdr1 基因启动子区的拷贝数变异和突变之间的关联。
方法
该研究纳入了接受氯喹和伯氨喹规范治疗的恶性疟原虫患者。在此期间，积极记录复发情况。
结果
在 60 例恶性疟原虫患者中，25 例为氯喹耐药，35 例为氯喹敏感。在氯喹敏感样本中，D0 时多拷贝 pvcrt-o 的频率为 7.1%，氯喹耐药时为 7.7%（P>0.05），DR 时为 33.3%（P<0.05）。对于 pvmdr1，10.7%的氯喹敏感样本呈现多个拷贝，而 D0 时氯喹耐药样本为 11.1%，DR 时为 0.0%（P>0.05）。在 23 例氯喹敏感的恶性疟原虫患者中，有 11 例（47.6%）发现 19 个碱基缺失，10 例（23.1%）的样本在 D0 时存在 CQRPv。在 DR 时，55.5%的 CQRPv 样本存在 19 个碱基缺失。对于 pvmdr-1 基因，与恶性疟原虫参考品 Sal-1 相比，该基因没有变异。
结论
这是第一项对 42 天临床随访的研究，评估了 pvcrt-o 和 pvmdr1 基因启动子区的拷贝数变异和多态性与治疗结果的关系。在 CQRPv 样本中，DR 时的多拷贝 pvcrt-o 频率明显高于氯喹敏感样本，表明 CQ 治疗后这种基因型的寄生虫选择及其与体内氯喹耐药性的相关性。
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