Epidemiology of Shigellosis in the Peruvian Amazon

描述（申请人提供）：志贺氏菌病是临床痢疾的主要原因，也是贫困地区儿童发病和死亡的常见原因。由于多种抗生素耐药菌株的快速传播和缺乏可用的疫苗，志贺氏菌病的发病率和死亡率可能在世界范围内增加。在IRSDA支持的初始阶段，完成了志贺氏菌病年龄特异性发病率、疾病发展的风险因素、抗生素耐药性概况和区域血清型数据的确定，以确定高度流行地区的耐药性志贺氏菌负担和分离株的血清型分布。ERIC-PCR相比，金标准PFGE的一个子集的分离株的分子分型，并被发现有一个几乎相同的歧视指数PFGE，更简单，更快，更实惠，因此更适合在流行地区使用。在一项巢式病例对照研究中，从纵向监测的哨点儿童及其接触者中分离的菌株受到培养物产量低的限制，该研究旨在确定家族间传播的模式。在包括苍蝇、饮用水、地表沃茨和洗手液在内的环境来源中，几乎完全通过PCR鉴定志贺菌，因此有必要鉴定和评价一种分型方法，该方法不需要通过培养进行初步分离，以充分了解志贺菌病的传播动力学。本补充申请将使用包括PCR检测、接近这些PCR阳性但培养阴性来源的风险的流行病学分析和感染源的时空分析的组合方法来解决这些来源的相关性，以便最佳地理解这种重要病原体的生态学和传播动力学。进行这项研究的合作研究小组是一个由流行病学家、医生、生物统计学家和分子生物学家组成的国际小组，在国际环境中培训初级科学家方面有着良好的记录。拟议的项目将进一步加强这些国际研究联系，继续培训有前途的医生和科学家。

DESCRIPTION (provided by applicant): Shigellosis is the principal cause of clinical dysentery and a frequent cause of morbidity and mortality in children in impoverished regions. Due to the rapid spread of multiple antibiotic resistant strains and the lack of an available vaccine the morbidity and mortality from shigellosis is likely to increase worldwide. In the initial period of IRSDA support the determination of age-specific incidence rates of shigellosis, risk factors for disease development, antibiotic resistance profiles and regional serotype data to define the burden of drug resistant Shigella and serotype distribution of isolates in a highly endemic area was completed. ERIC-PCR was compared to the gold standard PFGE for the molecular typing of a subset of isolates and was found to be have a nearly equal discriminatory index to PFGE and was simpler, faster, and more affordable therefore more appropriate for use in endemic areas. Isolates from sentinel children under longitudinal surveillance and their contacts studied in a nested case control study to determine the mode of interfamilial spread was limited by the low yield of cultures. The identification of Shigella nearly exclusively by PCR in environmental sources including flies, drinking water, surface waters, and hand washings necessitate the identification and evaluation of a typing method that does not require primary isolation by culture to fully understand the transmission dynamics of shigellosis. The present supplemental application will address the relevance of these sources using a combined approach including PCR detection, epidemiologic analysis of the risk of proximity to these PCR positive but culture negative sources and a space-time analysis of sources of infection in order to optimally understand the ecology and transmission dynamics of this important pathogen. The collaborative research group that is assembled to conduct this study is an established international group of epidemiologists, physicians, biostatisticians, and molecular biologists with a proven track record in the training of junior scientists in an international setting. The proposed project will further strengthen these international research ties in the process of the continued training of a promising physician-scientist.