Extinction Dynamics of the Foot-and-Mouth Disease Virus Carrier State Under Natural Conditions.

Miranda R Bertram,Jonathan Arzt,Amy Delgado,Carolina Stenfeldt,Shankar Yadav

doi:10.3389/fvets.2020.00276

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 extended periods. Although extinction of this carrier state occurs continuously at the animal and population levels, studies vary widely in their estimates of the duration of persistent infection. There is a need for robust statistical models 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, accelerated failure time (AFT) models and generalized linear mixed models (GLMM) were developed to predict the probability of persistent infection in seropositive animals and identified carriers at the individual animal level at sequential time points after outbreaks. The primary studies were analyzed 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 enhance current knowledge of the FMDV carrier state and may inform policy decisions regarding FMDV persistent infection.

Highlights

Foot-and-mouth disease virus (FMDV; Aphthovirus, Picornaviridae) is the causative agent of foot-and-mouth disease (FMD), one of the most economically important diseases of livestock worldwide
The goals of the current study were to assess the utility of two distinct statistical models for predicting the probability of persistent FMDV infection post-outbreak at the individual animal level, and to compare different analytical methods to assess extinction of the carrier state
Animals from which FMDV RNA was detected in oropharyngeal fluid (OPF) during the study were considered persistently infected

Summary

Introduction

Foot-and-mouth disease virus (FMDV; Aphthovirus, Picornaviridae) is the causative agent of foot-and-mouth disease (FMD), one of the most economically important diseases of livestock worldwide. The existence of prolonged asymptomatic persistent infection (carrier state) in ruminants has practical implications in FMDV-endemic regions that are distinct from management practices in regions striving to regain FMD-free status after an outbreak [5]. Transmission from persistently infected cattle to naïve animals via direct contact has not been demonstrated [10, 13, 14], deposition of oropharyngeal fluid from persistently infected cattle into the nasopharynx of naïve cattle has been demonstrated to cause disease [15]. Transmission via direct contact in the persistent phase has only been demonstrated to occur from African Cape buffalo (Syncerus caffer) [16, 17], and the role of persistently infected animals in FMDV epidemiology remains unclear. Concerns over the potential risk of transmission from persistently infected animals have prompted authorities to implement trade restrictions for animals and animal products for extended periods following FMD outbreaks and from FMD-endemic regions [18]

Objectives

Methods

Results

Discussion

Conclusion