Studies of hepatic latency in human ovale malaria
Studies of hepatic latency in human ovale malaria
批准号:
MR/L008661/1
负责人:
Colin Sutherland
金额:
$52.08万
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2014
资助国家:
英国
项目状态:
已结题
起止时间:
2014 至 --
中文摘要
人类的疟疾是由属于疟疾组的几种寄生虫引起的,这些寄生虫从受感染的蚊子进入人的肝脏,在一段时间后,感染出现在血液中,导致发烧和其他症状,我们与疟疾联系在一起。引起人类疟疾的物种之一是卵形疟原虫,它最早发现于1922年。然而,直到2010年,我们才能够提供令人信服的证据,证明这两种寄生虫实际上是两种不同的寄生虫,仅仅通过向下看显微镜就不能相互区分。我们开发了一些简单的DNA测试方法,让卫生工作者能够分辨出这两个物种中的哪一个存在;使用这些方法,现在很明显,这种类型的疟疾实际上比人们想象的更广泛。虽然卵形疟疾通常不会导致一种危及生命的疟疾形式,但有两个特点使其难以控制,并对一些国家彻底消除疟疾的努力构成严重挑战。首先,它通常与其他数量更多的疟疾寄生虫同时出现在人们的血液中,数量相对较少,因此被低估了。其次,它与另一个物种间日疟原虫一样,具有在肝脏阶段“冬眠”数月或数年的能力,在这种休眠阶段对几乎所有已知的疟疾药物都具有抗药性。研究间日疟原虫在肝脏中的这些“睡眠”形式的努力并不是很成功,尽管我们对它们有一些想法,但这些“睡眠”阶段在很大程度上仍然是现代生物学的一个谜。作为英国疟疾参考实验室的主办机构,我们接收来自英国各地疟疾病例的血液样本,其中每年有50多例椭圆形病例。因此,我们预计每周大约有一次,因此有足够的人数来计划对这些寄生虫的新研究。我们已经开发出一种方法,将患者血液中的寄生虫从人类血细胞中提纯出来,我们将寻求将这些寄生虫喂给蚊子,然后感染附近伦敦大学学院同事正在进行的研究工作中获得的肝细胞。如果这项研究成功,我们将有一个研究肝期疟疾的新方法,特别是一个新的窗口,可以了解“昏昏欲睡”的肝期寄生虫的神秘世界。这些信息也应该有助于我们更好地理解间日疟原虫疟疾的这些阶段。
英文摘要
Malaria in humans is caused by several species of parasite belonging to the Plasmodium group, which pass from infected mosquitoes into the person's liver, where after a period of incubation the infection emerges into the blood, causing the fevers and other symptoms we associate with malaria. One of the species causing malaria in humans is Plasmodium ovale, which was first discovered in 1922. It was not until 2010, however, that we were able to provide convincing evidence that these were actually two different parasites which could not be distinguished from each other just by looking down a microscope. We developed some simple DNA testing methods which allow health workers to tell which of these two species is present; using these it is now clear that this type of malaria is actually more widespread than had been thought. Although ovale malaria does not commonly cause a life-threatening form of malaria, two features make it hard to control, and a serious challenge for efforts to eliminate malaria altogether in some countries. Firstly, it is often present in people's blood in relatively small numbers at the same time as other malaria parasites which are more abundant, and so is under-recognised. Secondly, it shares with one other species, Plasmodium vivax, the ability to "hibernate" at the liver stage for months or years, being resistant to almost all known malaria drugs when it is in this resting phase. Efforts to study these "sleeping" forms in the liver for P. vivax malaria have not been very successful, and although we have some ideas about them, these "sleeping" stages remain largely a mystery of modern biology. As host institution for the UK Malaria Reference Laboratory, we receive blood samples from malaria cases across the UK, and each year there are more than fifty ovale cases among them. We thus expect approximately one per week, and therefore have sufficient numbers coming through to plan a new study of these parasites. We have developed a way to purify the parasites in patient blood away from human blood cells, and we will seek to feed these to mosquitoes, and then infect liver cells obtained from the ongoing research work of colleagues at UCL, nearby. If this is successful, we will have a new approach for studying liver-stage malaria, and in particular a new window into the mysterious world of the "sleepy" liver-stage parasites. This information should also help us to better understand these stages in P. vivax malaria, also.
期刊论文(9)
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DOI:
10.1002/anie.201606060
发表时间:
2016-12-05
期刊:
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
影响因子:
16.6
作者:
[Xu, Gaolian, Nolder, Debbie, Reboud, Julien, Oguike, Mary C, van Schalkwyk, Donelly A, Sutherland, Colin J, Cooper, Jonathan M]
通讯作者:
Cooper, Jonathan M
Dimorphism in genes encoding sexual-stage proteins of Plasmodium ovale curtisi and Plasmodium ovale wallikeri.
编码质量卵形柯蒂西和卵子质质质量的基因中的二态性。
DOI:
10.1016/j.ijpara.2015.02.004
发表时间:
2015-06
期刊:
INTERNATIONAL JOURNAL FOR PARASITOLOGY
影响因子:
4
作者:
[Oguike, Mary C., Sutherland, Colin J.]
通讯作者:
Sutherland, Colin J.
DOI:
10.1038/nature21038
发表时间:
2017-02-02
期刊:
Nature
影响因子:
64.8
作者:
[Rutledge GG, Böhme U, Sanders M, Reid AJ, Cotton JA, Maiga-Ascofare O, Djimdé AA, Apinjoh TO, Amenga-Etego L, Manske M, Barnwell JW, Renaud F, Ollomo B, Prugnolle F, Anstey NM, Auburn S, Price RN, McCarthy JS, Kwiatkowski DP, Newbold CI, Berriman M, Otto TD]
通讯作者:
Otto TD
Mosquito and human hepatocyte infections with Plasmodium ovale curtisi and Plasmodium ovale wallikeri.
卵形疟原虫柯蒂西疟原虫和卵形疟原虫沃里克氏疟原虫引起的蚊子和人类肝细胞感染。
DOI:
10.1093/trstmh/trz048
发表时间:
2019
期刊:
Transactions of the Royal Society of Tropical Medicine and Hygiene
影响因子:
2.2
作者:
[Kristan M]
通讯作者:
Kristan M
DOI:
10.1128/mbio.02257-16
发表时间:
2017-02-07
期刊:
mBio
影响因子:
6.4
作者:
[Cowell AN, Loy DE, Sundararaman SA, Valdivia H, Fisch K, Lescano AG, Baldeviano GC, Durand S, Gerbasi V, Sutherland CJ, Nolder D, Vinetz JM, Hahn BH, Winzeler EA]
通讯作者:
Winzeler EA
共 7 条
Evaluating multiple loci modulating susceptibility of African malaria parasites to artemisinin
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批准号:MR/T016124/1
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项目类别:Research Grant
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资助金额:$88.9万
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财政年份:2020
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负责人:Colin Sutherland
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依托单位:
The Structure Theory of Injective Factors
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负责人:Colin Sutherland
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依托单位:
国内基金
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