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Plasmodium falciparum glutamate dehydrogenase is genetically conserved across eight malaria endemic states of India: Exploring new avenues of malaria elimination

机译:在印度的八个疟疾流行州恶性疟原虫谷氨酸脱氢酶的遗传保护作用:探索消除疟疾的新途径

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摘要

Accurate and timely diagnosis is very critical for management, control and elimination of the malaria. Malaria rapid diagnostic tests (RDTs) have improved the diagnosis and management of malaria in remote areas, community and places where microscopy is not available for diagnosis. According to WHO report 2018, Plasmodium falciparum malaria constitutes more than 50% of malaria cases in India. Most of the RDTs used for diagnosis of falciparum malaria today employ HRP2 as a target antigen. However, low density parasitemia and deletion of hrp-2 gene in P. falciparum leads to false negative results and necessitates the development of alternative/ new or improved RDT for malaria diagnosis. We have analysed the genetic diversity and homology modelling of Pfgdh (glutamate dehydrogenase), ldh (lactate dehydrogenase) and aldolase genes in P. falciparum isolates from the eight endemic states of India to assess their potential as antigen for RDT development. We observed negligible sequence diversity in Pfgdh in comparison to the low level of diversity in ldh and aldolase gene. No structural or functional changes were observed in modelling studies and all three genes were under negative purifying selection pressure. The highly conserved nature of pfgdh gene suggests that GDH could be a potential target molecule for Pan/Pf diagnostic test for malaria.
机译:准确及时的诊断对于控制,控制和消除疟疾至关重要。疟疾快速诊断测试(RDT)改善了偏远地区,社区和无法使用显微镜进行诊断的地方的疟疾诊断和管理。根据世界卫生组织2018年报告,恶性疟原虫疟疾占印度疟疾病例的50%以上。如今,用于诊断恶性疟疾的大多数RDT都采用HRP2作为靶抗原。然而,恶性疟原虫的低密度寄生虫病和hrp-2基因的缺失会导致假阴性结果,因此有必要开发替代/新的或改良的RDT来诊断疟疾。我们分析了印度八个流行州恶性疟原虫分离株中Pfgdh(谷氨酸脱氢酶),ldh(乳酸脱氢酶)和醛缩酶基因的遗传多样性和同源性模型,以评估其作为RDT发展抗原的潜力。与ldh和醛缩酶基因的低多样性相比,我们观察到Pfgdh的序列多样性可忽略不计。在建模研究中未观察到结构或功能变化,所有三个基因均处于负纯化选择压力下。 pfgdh基因的高度保守性质表明,GDH可能是Pan / Pf疟疾诊断测试的潜在靶分子。

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