Extinction dynamics of the foot-and-mouth disease virus carrier state under natural conditions

Authors: BERTRAM, MIRANDA - Oak Ridge Institute For Science And Education (ORISE); YADAV, SHANKAR - Oak Ridge Institute For Science And Education (ORISE); DELGADO, AMY - Animal And Plant Health Inspection Service (APHIS); Arzt, Jonathan

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2020
Publication Date: 5/20/2020
Citation: Bertram, M.R., Yadav, S., Delgado, A., Arzt, J. 2020. Extinction dynamics of the foot-and-mouth disease virus carrier state under natural conditions. Frontiers in Veterinary Science. https://doi.org/10.3389/fvets.2020.00276.
DOI: https://doi.org/10.3389/fvets.2020.00276

Interpretive Summary: Foot-and-mouth disease (FMD) is one of the most economically important livestock diseases worldwide. Following the typical phase of FMD, a large proportion of cattle and buffalo become carriers, meaning the virus is maintained in their tissues, for up to three years. FMD control and trade policies have to account for the possibility than an animal is a carrier. Animals eventually recover from the carrier state, however the length of time required to clear the infection varies greatly. Statistical models can be used to assess the probability of an animal being a carrier, however these types of models have not been validated for the sake of guiding FMD control and trade policies. The goal of the current study was to develop and assess statistical models to describe recovery from the carrier state using data from studies of naturally infected cattle and Asian buffalo in Vietnam and India. Two different statistical models were developed to predict the probability of an individual animal being a carrier at sequential times after an outbreak. We analyzed the studies separately and combined using each statistical model. The two statistical models gave similar results, and both predicted higher probabilities of an animal being a carrier than previously published. This study demonstrated that statistical models are useful to assess the probability of an animal being a carrier at some time after an outbreak. This study also demonstrated that combining data from several small studies improves the results from the statistical models. Results of this study will inform policy decisions regarding FMDV carriers and contribute to protection of USA livestock herds from exotic diseases.

Technical Abstract: Foot-and-mouth disease (FMD) is one of the most economically important livestock diseases worldwide. Following the clinical phase of FMD, a large proportion of ruminants remain persistently infected for up to three years. Although extinction of this carrier state occurs continuously at the animal and population levels, models have not been validated to capture the dynamics of persistent infection for the sake of guiding FMD control and trade policies. The goal of the current study was to develop and assess statistical models to describe the extinction of FMD virus (FMDV) persistent infection using data from primary longitudinal studies of naturally infected cattle and Asian buffalo in Vietnam and India. Specifically, an accelerated failure time (AFT) model and a generalized linear mixed model (GLMM) were developed to predict the probability of persistent infection at the individual animal level at sequential time points after outbreaks. The primary studies were analyzed separately by country and combined using an individual-participant data meta-analysis approach . The models estimated similar trends in the duration of persistent infection for the study/species groups included in the analyses, however the significance of the trends differed between the models. The overall probabilities of persistent infection were similar as predicted by the AFT and GLMM models: 6 months: 99% (AFT) /80% (GLMM), 12 months: 51% (AFT) /32% (GLMM), 18 months: 6% (AFT) /5% (GLMM), 24 months: 0.8% (AFT) /0.6% (GLMM ). These models utilizing diverse and robust data sets predict higher probabilities of persistence than previously published, suggesting greater endurance of carriers subsequent to an outbreak. This study demonstrates the utility of statistical models to investigate the dynamics of persistent infection and the importance of large datasets, which can be achieved by combining data from several smaller studies in meta-analyses. Results of this study will inform policy decisions regarding FMDV persistent infection.