Statistical and agent-based modeling of complex microbial systems: a means for..

肠道感染仍然是全球儿童腹泻发病率和死亡率的第二大原因，尽管在疾病负担高的国家，获得厕所和安全水源的情况有了显著改善。我们之前的研究已经证明，“肠道病变”-即由人类和动物粪便在环境中传播的病毒，细菌和原生动物病原体的社区-由生活在肯尼亚低收入城市社区的儿童摄入的分类学复杂，并因暴露途径而异。我们的初步数据表明，在那些6个月大的肯尼亚婴儿中，多病原体感染的风险增加，这些婴儿喂养牛奶，生活在城市家庭中，地面是泥土，共用厕所，与家畜同居。这表明，在高负担国家，除了厕所和水源之外，还需要社会发展的多个方面来降低病原体传播的复杂性。我们假设，代表城市社会发展对比的家庭和社区的肠道致病因子的联合建模将表明，发展导致致病因子从复杂到简单的社区结构演变，从而降低单个病原体分类群的检测频率。理解由社会发展引起的病理组复杂性的演变并随后确定有效的干预策略是具有挑战性的，因为现场实验实施起来很昂贵，难以推广到其他环境，仅通过现有的有限的观察数据进行通知，并且目前还没有足够复杂的统计和数学病理组建模工具。我们的建议旨在（1）开发时空和轨迹统计模型，以了解婴儿从肠道致病菌群的复杂暴露风险;（2）收集环境，行为，空间，经济和微生物数据，以表征肠道致病菌群沿着疾病扩散途径以及人类和动物与这些途径的交叉点;以及（3）开发和验证基于代理的模型（ABM），用于预测哪些社会和环境城市发展干预措施（例如，动物围栏，建造厕所或排水沟，混凝土地板）最好地预防高疾病负担国家的婴儿多病原体传播，使用已建立的肯尼亚研究地点作为模型。我们的跨学科团队包括生物统计学家，传染病流行病学家，微生物学家，计算科学家，行为研究员和城市发展地理学家。

Enteric infections remain the second leading cause of diarrheal morbidity and mortality globally in children, despite significant improvements in access to latrines and safe water sources in high disease burden countries. Our prior research has demonstrated that the “enteric pathome” - i.e. the communities of viral, bacterial, and protozoan pathogens transmitted by human and animal feces in the environment - ingested by children living in low-income urban neighborhoods of Kenya is taxonomically complex and varies by exposure pathway. Our preliminary data indicates that the risk of multi-pathogen infection is elevated among those 6- month old Kenyan infants fed cow’s milk and living in urban households with dirt floors, shared latrines, and cohabitating domestic animals. This suggests multiple aspects of societal development beyond latrines and water sources are required to reduce complexity in pathogen transmission in high burden countries. We hypothesize that joint modeling of enteric pathome agents across households and neighborhoods that represent contrasts in urban societal development will show that development leads to pathome evolution from complex to simple community structures, and thus lower detection frequencies for individual pathogen taxa. Understanding the evolution in pathome complexity induced by societal development and subsequently identifying effective intervention strategies is challenging since field experiments are expensive to implement, difficult to generalize to other settings, are only informed by existing, limited observational data, and sufficiently sophisticated statistical and mathematical pathome modeling tools are not currently available. Our proposal aims to (1) develop spatiotemporal and trajectory statistical models to understand the complex exposure risks for infants from the enteric pathome; (2) collect environmental, behavioral, spatial, economic, and microbial data to characterize the enteric pathome along pathways for disease diffusion and the intersection of humans and animals with these pathways; and (3) develop and validate agent-based models (ABMs) for predicting which social and environmental urban developmental interventions (e.g. animal penning, building latrines or drains, concrete floors) best prevent multipathogen transmission to infants in high disease burden countries using established Kenyan study sites as a model. Our interdisciplinary team includes a biostatistician, infectious disease epidemiologists, microbiologist, computational scientist, behavioral researcher, and urban development geographer.