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The impact of within-herd genetic variation upon inferred transmission trees for foot-and-mouth disease virus.

ABSTRACT: Full-genome sequences have been used to monitor the fine-scale dynamics of epidemics caused by RNA viruses. However, the ability of this approach to confidently reconstruct transmission trees is limited by the knowledge of the genetic diversity of viruses that exist within different epidemiological units. In order to address this question, this study investigated the variability of 45 foot-and-mouth disease virus (FMDV) genome sequences (from 33 animals) that were collected during 2007 from eight premises (10 different herds) in the United Kingdom. Bayesian and statistical parsimony analysis demonstrated that these sequences exhibited clustering which was consistent with a transmission scenario describing herd-to-herd spread of the virus. As an alternative to analysing all of the available samples in future epidemics, the impact of randomly selecting one sequence from each of these herds was used to assess cost-effective methods that might be used to infer transmission trees during FMD outbreaks. Using these approaches, 85% and 91% of the resulting topologies were either identical or differed by only one edge from a reference tree comprising all of the sequences generated within the outbreak. The sequence distances that accrued during sequential transmission events between epidemiological units was estimated to be 4.6 nucleotides, although the genetic variability between viruses recovered from chronic carrier animals was higher than between viruses from animals with acute-stage infection: an observation which poses challenges for the use of simple approaches to infer transmission trees. This study helps to develop strategies for sampling during FMD outbreaks, and provides data that will guide the development of further models to support control policies in the event of virus incursions into FMD free countries.

SUBMITTER: Valdazo-Gonzalez B

PROVIDER: S-EPMC7106308 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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The impact of within-herd genetic variation upon inferred transmission trees for foot-and-mouth disease virus.

Valdazo-González Begoña B Kim Jan T JT Soubeyrand Samuel S Wadsworth Jemma J Knowles Nick J NJ Haydon Daniel T DT King Donald P DP

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20150408

Full-genome sequences have been used to monitor the fine-scale dynamics of epidemics caused by RNA viruses. However, the ability of this approach to confidently reconstruct transmission trees is limited by the knowledge of the genetic diversity of viruses that exist within different epidemiological units. In order to address this question, this study investigated the variability of 45 foot-and-mouth disease virus (FMDV) genome sequences (from 33 animals) that were collected during 2007 from eigh ...[more]

PMID: 25861750

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Project description:This was a retrospective cohort study using data collected from a large-scale dairy herd in Kenya (n?=?328 female animals), to investigate the effects of foot-and-mouth disease (FMD) on herd fertility performance following a confirmed outbreak in a regularly vaccinated herd. Kaplan-Meier graphs were used to depict differences in survival functions between exposure groups and Cox regression models were used to calculate hazard ratios (HR) for associations between being clinical FMD cases and the following fertility outcomes: age at first calving; fertility failure related culling (not in calf); time to first service; time to conception. Potential confounding variables investigated and controlled for were age, breed, parity, stage of lactation/gestation and eligibility for service. A case control study was nested within the cohort to investigate the effects of disease on conception HR following calving by comparing animals susceptible to fertility suppression at the time of the outbreak (cases) to animals that had conceived prior to the outbreak (controls). The median age of first calving in clinically affected young-stock was 2.7 months higher than non-clinical cases (adjusted HR?=?0.37, 95%CI 0.21-0.67, P?=?0.01). There was no evidence of a difference in fertility related culling and times to first service and conception. Animals susceptible to fertility suppression at the time of the outbreak had a lower hazard of conception compared to animals served prior to the outbreak (HR?=?0.56, 95%CI 0.41-0.75, P?=?0.01). Within the herd, the odds of being a case decreased with parity and age likely related to the lifetime number of vaccination doses received which may reduce the impact among older animals in the herd. Moreover, one would expect the impact to be higher in a non-vaccinating herd to be higher. Notwithstanding these limitations, the results of this study provide evidence that FMD outbreaks in endemic settings impact herd fertility performance. An increased age at first calving is likely to increase rearing costs and reduce an animal's lifetime productivity while poorer conception rates will likely extend calving intervals. Impaired herd fertility and production will incur higher costs to the farmer and society as animals are less productive which for FMD can extend beyond the outbreak period where economic studies tend to focus. These impacts of FMD on herd fertility should be considered when conducting benefit-cost analyses of FMD control to inform resource allocation.

Project description:Foot-and-mouth disease (FMD) has not been reported in the U.S. since 1929. Recent outbreaks in previously FMD-free countries raise concerns about potential FMD introductions in the U.S. Mathematical modeling is the only tool for simulating infectious disease outbreaks in non-endemic territories. In the majority of prior studies, FMD virus (FMDv) transmission on-farm was modeled assuming homogenous animal mixing. This assumption is implausible for U.S. beef feedlots which are divided into multiple home-pens without contact between home-pens except fence line with contiguous home-pens and limited mixing in hospital pens. To project FMDv transmission and clinical manifestation in a feedlot, we developed a meta-population stochastic model reflecting the contact structure. Within a home-pen, the dynamics were represented assuming homogenous animal mixing by a modified SLIR (susceptible-latent-infectious-recovered) model with four additional compartments tracing cattle with subclinical or clinical FMD and infectious status. Virus transmission among home-pens occurred via cattle mixing in hospital-pen(s), cowboy pen rider movements between home-pens, airborne, and for contiguous home-pens fence-line and via shared water-troughs. We modeled feedlots with a one-time capacity of 4,000 (small), 12,000 (medium), and 24,000 (large) cattle. Common cattle demographics, feedlot layout, endemic infectious and non-infectious disease occurrence, and production management were reflected. Projected FMD-outbreak duration on a feedlot ranged from 49 to 82 days. Outbreak peak day (with maximum number of FMD clinical cattle) ranged from 24 (small) to 49 (large feedlot). Detection day was 4-12 post-FMD-introduction with projected 28, 9, or 4% of cattle already infected in a small, medium, or large feedlot, respectively. Depletion of susceptible cattle in a feedlot occurred by day 23-51 post-FMD-introduction. Parameter-value sensitivity analyses were performed for model outputs. Detection occurred sooner if there was a higher initial proportion of latent animals in the index home-pen. Shorter outbreaks were associated with a shorter latent period and higher bovine respiratory disease morbidity (impacting the in-hospital-pen cattle mixing occurrence). This first model of potential FMD dynamics on U.S. beef feedlots shows the importance of capturing within-feedlot cattle contact structure for projecting infectious disease dynamics. Our model provides a tool for evaluating FMD outbreak control strategies.

Dataset Information

The impact of within-herd genetic variation upon inferred transmission trees for foot-and-mouth disease virus.

Publications

The impact of within-herd genetic variation upon inferred transmission trees for foot-and-mouth disease virus.

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