Semiparametric analysis of the household transmission of cholera



 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.