Epidemiology of Shigellosis in the Peruvian Amazon

说明(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。由于多重耐药菌株的迅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全球范围内增加。在IRSDA支持初期，完成了志贺氏菌病年龄别发病率、疾病发展的危险因素、抗生素耐药性图谱和地区血清型数据的确定，以确定耐药志贺氏菌的负担和高度流行地区分离株的血清型分布。ERIC-PCR与用于部分分离物的分子分型的金标准PFGE进行了比较，发现其具有与PFGE几乎相同的判别指数，并且更简单、更快速、更负担得起，因此更适合在流行区使用。在巢式病例对照研究中，来自接受纵向监测的哨兵儿童及其接触者的分离株受到培养产量低的限制，以确定家庭间传播的方式。在包括苍蝇、饮用水、地表水和洗手水在内的环境来源中，几乎只通过PCR鉴定志贺氏菌，就需要鉴定和评估一种分型方法，这种方法不需要通过培养进行初步分离，就可以完全了解志贺氏菌病的传播动力学。本补充申请将使用一种组合的方法来解决这些来源的相关性，包括聚合酶链式反应检测、对接近这些聚合酶链式反应阳性但培养阴性来源的风险的流行病学分析以及对感染源的时空分析，以便最好地了解这种重要病原体的生态和传播动态。为进行这项研究而组建的合作研究小组是一个由流行病学家、内科医生、生物统计学家和分子生物学家组成的成熟的国际小组，他们在国际环境下培训初级科学家方面有良好的记录。拟议的项目将在继续培训一位有前途的内科医生-科学家的过程中进一步加强这些国际研究联系。

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.