Molecular Epidemiology of Cryptosporidiosis in India

描述（由申请人提供）： 本研究将主要在印度韦洛雷基督教医学院与Gagandeep Kang博士合作完成，作为NIH资助RO 1 AI 05786（04/15/03-3/31/08）的扩展。本申请旨在扩展Cpgp 40/15基因及其糖蛋白产物gp 40和gp的功能作用的基础实验室研究！5在介导隐孢子虫-宿主细胞相互作用中的作用，以用于临床分离株中Cpgp 40/15多态性的翻译研究和天然隐孢子虫属物种中对gp 15的免疫应答。在印度南部的儿童感染。韦洛雷CMC隐孢子虫病研究的总体目标是调查隐孢子虫病的分子流行病学和人类对隐孢子虫属的免疫应答。在印度南部，这种寄生虫是儿童腹泻的主要原因。儿童早期感染隐孢子虫可能导致随后的生长、身体健康和认知功能受损。在患有艾滋病的儿童中，这种寄生虫可能会导致严重的，往往是致命的疟疾，对此没有特异性的治疗方法。关于隐孢子虫病的分子流行病学或宿主对这种寄生虫的免疫反应，特别是在发展中国家的背景下，知之甚少。该提案的重点将是基于Cpgp 40/15多态性的隐孢子虫属分离株的分子表征，以及在印度南部城市贫民窟地区正在进行的出生队列研究中招募的0至24个月龄儿童中测定对gp 15的血清抗体应答。这项研究将使未来的研究，以确定是否Cpgp 40/15多态性和抗体反应gp！5可作为研究发展中国家隐孢子虫病流行病学的工具，确定gp的作用！5在人类感染中的作用，并评估对这种蛋白质的免疫应答是否参与疾病的保护。在第一个特定的目标Cpgp 40/15等位基因亚组的隐孢子虫属分离的儿童隐孢子虫病在印度南部将被确定。在第二个具体目标血清IgG，IgM和伊加和粪便分泌伊加水平的gp！将在隐孢子虫属感染的儿童和未检测到隐孢子虫属感染的儿童中测量5，并确定研究期间抗体水平的变化。

DESCRIPTION (provided by applicant): This research will be done primarily at Christian Medical College, Vellore, India in collaboration with Dr. Gagandeep Kang as an extension of NIH grant RO1 AI05786, 04/15/03-3/31/08. This application seeks to extend basic laboratory studies on the functional role of the Cpgp40/15 gene and its glycoprotein products gp40 and gp!5 in mediating Cryptosporidium-host cell interactions to a translational study on Cpgp40/15 polymorphisms in clinical isolates and immune response to gpl5 in natural Cryptosporidium spp. infections in children in southern India. The overall goal of studies on cryptosporidiosis in CMC, Vellore is to investigate the molecular epidemiology of cryptosporidiosis and the human immune response to Cryptosporidium spp. in southern India where this parasite is a major cause of diarrhea in children. Cryptosporidial infection in early childhood may result in subsequent impairment in growth, physical fitness and cognitive function. In children with AIDS, this parasite may cause severe and often fatal diarrheal disease for which there is no specific therapy. Very little is known about the molecular epidemiology of cryptosporidiosis or about host immune responses to this parasite, particularly in the setting of the developing world. The focus of this proposal will be on molecular characterization of Cryptosporidium spp isolates based on Cpgp40/15 polymorphisms and on determination of serum antibody responses to gp 15 in children aged 0 to 24 months of age who are enrolled in an ongoing birth cohort study in an urban slum area of southern India. This study will enable future studies to determine whether Cpgp40/15 polymorphisms and antibody response to gp!5 can be used as tools to study the epidemiology of cryptosporidiosis in developing countries, to determine the role of gp!5 in human infection and to evaluate whether immune responses to this protein is involved in protection from disease. In the first specific aim Cpgp40/15 allelic subgroups of Cryptosporidium spp isolates from children with cryptosporidiosis in southern India will be determined. In the second specific aim serum IgG, IgM and IgA and fecal secretory IgA levels to gp!5 will be measured in Cryptosporidium spp infected children and in children with no detectable Cryptosporidium spp infection and the change in antibody levels during the study period determined.