Semiparametric analysis of the household transmission of cholera

霍乱家庭传播的半参数分析

• 批准号: 9090814
• 负责人: Eben Kenah
• 金额: $ 7.22万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090814
• 关键词: Accounting; Bangladesh; Cholera; Controlled Study; Data; Dose; Effectiveness; Environment; Epidemic; Genetic; Goals; Growth; Haiti; Hospitals; Household; Human; Incidence; Individual; Infection; Intervention; Markov chain Monte Carlo methodology; Methods; Mission; Modeling; Pathway interactions; Patients; Persons; Play; Predisposition; Public Health; Relative Risks; Research; Research Design; Role; Sampling; Site; Statistical Methods; Testing; Time; Vibrio; Vibrio cholerae; Zimbabwe; base; case control; data modeling; design; discrete time; disease transmission; effective intervention; hazard; indexing; infectious disease model; innovation; insight; novel; pathogen; prevent; prospective; public health relevance; semiparametric; simulation; theories; transmission process

 DESCRIPTION (provided by applicant): Cholera has become endemic in multiple sites around the globe and can cause devastating local epidemics, such as Zimbabwe in 2008-2009 and Haiti in 2010-2012. In the last 50 years, the scientific understanding of cholera transmission has emphasized infection from the environment. Recently, evidence has accumulated that person-to-person transmission may play an important role in endemic and epidemic cholera. Vibrio cholerae strains sampled from humans often do not match well with strains sampled from the environment, and Vibrio cholerae excreted from human patients is in a transient hyperinfective state with an infectious dose 10-100 times lower than that not recently passed through humans. An emerging hypothesis is that environmental reservoirs and "slow" human-environment-human transmission pathways maintain cholera reservoirs and spark epidemics but "fast" human-to-human transmission drives the explosive growth of epidemics. If true, this hypothesis would justify increased emphasis on interventions targeted to households or other close contact groups of cholera cases for the control of endemic and epidemic cholera. Despite its potential importance to public health, much of the evidence for this hypothesis is circumstantial. The long-term goal is to test this hypothesis and to understand its implications for cholera control and study design. The goal of the proposed research is to re-analyze longitudinal cholera incidence data from the households of index cases using semiparametric regression models for infectious disease transmission. These models allow the estimation of hazard ratios for infectiousness and susceptibility without making parametric assumptions about the time course of infectiousness in infected individuals. Compared to previous statistical methods for the analysis of household transmission data, these models are more robust, more flexible, and more numerically stable. These methods also have the potential to incorporate pathogen genetic sequence data, which is being collected in several ongoing cholera studies and may allow more precise estimation of transmission parameters. This research is innovative because it applies novel statistical methods to test an important hypothesis in public health. It is significant because understanding the role of person-to-person transmission will be crucial to the effective control of endemic and epidemic cholera.

 描述（由申请人提供）：霍乱已在全球多个地点流行，并可能造成毁灭性的当地流行病，例如 2008-2009 年的津巴布韦和 2010-2012 年的海地。过去 50 年来，人们对霍乱传播的科学认识不断加深 强调来自环境的感染。最近，越来越多的证据表明人际传播可能在地方性和流行性霍乱中发挥重要作用。从人类身上采集的霍乱弧菌菌株往往与从环境中采集的菌株不匹配，从人类患者体内排出的霍乱弧菌处于短暂的高度感染状态，其感染剂量比最近未通过人体的传染剂量低10-100倍。一个新出现的假设是，环境储存库和“缓慢”的人类-环境-人类传播途径维持了霍乱储存库并引发流行病，但“快速”的人际传播推动了流行病的爆炸性增长。如果这一假设成立，则有理由更加重视针对霍乱病例家庭或其他密切接触群体的干预措施，以控制地方性和流行性霍乱。尽管它对公共卫生具有潜在的重要性，但支持这一假设的大部分证据都是间接的。长期目标是检验这一假设并了解其对霍乱控制和研究设计的影响。拟议研究的目标是使用传染病传播的半参数回归模型重新分析来自指示病例家庭的纵向霍乱发病率数据。这些模型可以估计传染性和易感性的风险比，而无需对受感染个体的传染性时间过程做出参数假设。与以前用于分析家庭传输数据的统计方法相比，这些模型更稳健、更灵活且数值更稳定。这些方法还有可能纳入病原体基因序列数据，这些数据是在几项正在进行的霍乱研究中收集的，并且可能允许更精确地估计传播参数。这项研究具有创新性，因为它应用新颖的统计方法来检验公共卫生中的重要假设。这很重要，因为了解人际传播的作用对于有效控制地方性和流行性霍乱至关重要。