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隐孢子虫的全球负担、新型诊断方法、治疗方法及疫苗靶点综述

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium.

作者信息

Checkley William, White A Clinton, Jaganath Devan, Arrowood Michael J, Chalmers Rachel M, Chen Xian-Ming, Fayer Ronald, Griffiths Jeffrey K, Guerrant Richard L, Hedstrom Lizbeth, Huston Christopher D, Kotloff Karen L, Kang Gagandeep, Mead Jan R, Miller Mark, Petri William A, Priest Jeffrey W, Roos David S, Striepen Boris, Thompson R C Andrew, Ward Honorine D, Van Voorhis Wesley A, Xiao Lihua, Zhu Guan, Houpt Eric R

机构信息

Program in Global Disease Epidemiology and Control, Department of International Health, Johns Hopkins University, Baltimore, MD, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.

Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA.

出版信息

Lancet Infect Dis. 2015 Jan;15(1):85-94. doi: 10.1016/S1473-3099(14)70772-8. Epub 2014 Sep 29.

Abstract

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

摘要

隐孢子虫属被公认为是水源性传染病流行期间及免疫功能低下宿主中腹泻病的病因。研究还提请人们注意全球负担被低估的情况,并表明在最佳诊断、治疗和免疫方面存在重大差距。隐孢子虫病日益被确认为全球发病和死亡的重要原因。在资源匮乏地区和高收入国家开展的研究证实了隐孢子虫作为腹泻和儿童营养不良病因的重要性。隐孢子虫感染的诊断检测并不理想,需要专门的检测方法,而这些方法往往不敏感。抗原检测和聚合酶链反应(PCR)提高了敏感性,多重抗原检测和分子检测方法未得到充分利用。治疗对健康宿主有一定效果,但对艾滋病患者尚无已证实的疗效。利用隐孢子虫基因组有助于确定有前景的治疗靶点,并且有药物正在研发中,但体外和动物体内疗效评估方法尚未得到很好的标准化。接触后产生的部分免疫力表明成功研发疫苗具有潜力,并且有几种疫苗正在研发中;然而,保护的替代指标尚未明确界定。改进该生物体的繁殖和基因操作方法将是重大进展。

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