Genetic sequences from pathogens can provide information about infectious disease dynamics that may supplement or replace information from other epidemiological observations. Most currently available methods first estimate phylogenetic trees from sequence data, then estimate a transmission model conditional on these phylogenies. Outside limited classes of models, existing methods are unable to enforce logical consistency between the model of transmission and that underlying the phylogenetic reconstruction. Such conflicts in assumptions can lead to bias in the resulting inferences. Here, we develop a general, statistically efficient, plug-and-play method to jointly estimate both disease transmission and phylogeny using genetic data and, if desired, other epidemiological observations. This method explicitly connects the model of transmission and the model of phylogeny so as to avoid the aforementioned inconsistency. We demonstrate the feasibility of our approach through simulation and apply it to estimate stage-specific infectiousness in a subepidemic of human immunodeficiency virus in Detroit, Michigan. In a supplement, we prove that our approach is a valid sequential Monte Carlo algorithm. While we focus on how these methods may be applied to population-level models of infectious disease, their scope is more general. These methods may be applied in other biological systems where one seeks to infer population dynamics from genetic sequences, and they may also find application for evolutionary models with phenotypic rather than genotypic data.
Background: While live attenuated monovalent human rotavirus vaccine (Rotarix) efficacy has been characterized through randomized studies, its effectiveness, especially in non-clinical settings, is unclear. In this study, we estimate direct, indirect, and overall effectiveness of Rotarix vaccination. Methods:We analyze 29 months of all-cause diarrhea surveillance from a child cohort (n=376) and ten years of serial population-based case-control lab-confirmed rotavirus data (n=2489) from rural Ecuador during which Rotarix vaccination was introduced. We estimate: 1) the direct effect of vaccination from a cohort of children born from 2008-2013 using Cox regression to compare time to first all-cause diarrhea case by vaccine status; and 2) the overall effect on all-cause diarrheal and symptomatic and asymptomatic rotavirus infection for all age groups, including indirect effects on adults, from the case-control data using weighted logistic regression.Results: Rotarix vaccination provided direct protection against all-cause diarrhea among children 0.5 -2 years (All-cause diarrhea reduction for receipt of 2 doses of Rotarix=57.1%, 95% CI: 16.6, 77.9%). Overall effectiveness against rotavirus infection was strong (Exposure to 100% coverage of Rotarix vaccination was associated with an 85.5% reduction, 95% CI: 61.1-94.6%) compared to 0% coverage. Indirect effects were observed among older, vaccine-ineligible children and adults (84.5% reduction, 95% CI: 48.2-95.4%). Vaccine effectiveness was high against both symptomatic (48.3% reduction,95% CI: 0.03-73.1%) and asymptomatic infection (90.1% reduction, 95% CI: 56.9-97.7%). Rotavirus vaccine effectiveness in Ecuador 3Conclusions: Rotarix vaccination suppresses overall transmission. It is highly effective among children in a rural community setting and provides population-level benefits through indirect protection among adults.
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