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      Virus Excretion from Foot-And-Mouth Disease Virus Carrier Cattle and Their Potential Role in Causing New Outbreaks

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          Abstract

          The role of foot-and-mouth disease virus (FMDV) carrier cattle in causing new outbreaks is still a matter of debate and it is important to find out these carrier animals by post-outbreak serosurveillance to declare freedom from FMDV infection. In this study we explore the differences in viral shedding between carrier and non-carrier animals, quantify the transmission rate of FMDV infection from carriers to susceptible animals and identify potential viral determinants of viral persistence. We collected nasal and saliva samples from 32 vaccinated and 7 unvaccinated FMDV carrier cattle and 48 vaccinated and 13 unvaccinated non-carrier cattle (total n=100) during the acute phase of infection (up to 28 days post-challenge) and then from limited number of animals up to a maximum 168 days post-challenge. We demonstrate that unvaccinated cattle excrete significantly higher levels of virus for longer periods compared with vaccinated cattle and this is independent of whether or not they subsequently become carriers. By introducing naïve cattle in to the FMDV carrier population we show the risk of new outbreaks is clearly very low in controlled conditions, although there could still be a potential threat of these carrier animals causing new outbreaks in the field situation. Finally, we compared the complete genome sequences of viruses from carrier cattle with the challenge virus and found no evidence for viral determinants of the carrier state.

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          Most cited references27

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          Vaccination against foot-and-mouth disease virus: strategies and effectiveness.

          Although present conventional foot-and-mouth disease (FMD) vaccines can prevent clinical disease, protection is short lived ( approximately 6 months), often requiring frequent revaccination for prophylactic control, and vaccination does not induce rapid protection against challenge or prevent the development of the carrier state. Furthermore, it is clear that the clinical protection depends upon the length of immunization and the duration of exposure/challenge methods. This review summarizes the present and future strategies for FMD control in endemic and FMD-free countries, the effectiveness of FMD vaccines in cattle, sheep and pigs, new methods for selecting vaccine strains, suggestions for alternative methods of vaccine testing, suggestions for the development of new-generation efficacious vaccines and their companion tests to differentiate infection in vaccinated animals.
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            Relationship between clinical signs and transmission of an infectious disease and the implications for control.

            Control of many infectious diseases relies on the detection of clinical cases and the isolation, removal, or treatment of cases and their contacts. The success of such "reactive" strategies is influenced by the fraction of transmission occurring before signs appear. We performed experimental studies of foot-and-mouth disease transmission in cattle and estimated this fraction at less than half the value expected from detecting virus in body fluids, the standard proxy measure of infectiousness. This is because the infectious period is shorter (mean 1.7 days) than currently realized, and animals are not infectious until, on average, 0.5 days after clinical signs appear. These results imply that controversial preemptive control measures may be unnecessary; instead, efforts should be directed at early detection of infection and rapid intervention.
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              Studies of quantitative parameters of virus excretion and transmission in pigs and cattle experimentally infected with foot-and-mouth disease virus.

              Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms and the rate of spread, the incubation period and the severity of disease depend on a multitude of parameters, including the strain of virus, the dose received, the route of introduction, the animal species and the husbandry conditions. More knowledge with regard to these parameters is urgently needed to improve resource-efficient disease control. This report describes detailed studies of FMDV load, excretion and transmission in pigs infected with FMDV O UKG 2001, O TAW 1997 and C Noville virus and in cattle infected with the O UKG 2001 virus to facilitate use of a "FMDV load framework" for the assessment of transmission risks. Virus replicated rapidly in pigs and cattle exposed by direct contact. The mean incubation period was around 3-4 days for cattle-to-cattle and 1-3 days for pig-to-pig transmission, depending on the intensity of contact. The results confirmed that a strong relation exists between dose and length of incubation period. Clinical disease was severe in pigs but relatively mild in inoculated cattle; contact infection of cattle appeared to increase the severity of lesions. FMDV RNA was recovered in nasal and mouth swabs from inoculated animals soon after they developed a viraemia and probably reflected the early production and excretion of virus. FMDV RNA in nasal and mouth swabs from contact animals could be detected several days before they showed other signs of infection, indicating the possibility of detecting exposed animals during the incubation period. FMDV RNA could also be detected in swab samples after the viraemic phase. This may have represented background environmental virus that had been trapped in the respiratory tract and mouth. Alternatively, it may have indicated a somewhat slower clearance or half-life of viral RNA or an extended low level of FMDV replication at these sites. The pattern of FMDV RNA concentrations in pigs was closely similar to that in cattle, but the amounts of FMDV RNA were higher.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 June 2015
                2015
                : 10
                : 6
                : e0128815
                Affiliations
                [001]The Pirbright Institute, Ash Road, Pirbright, Surrey GU24 0NF, United Kingdom
                Institut National de la Santé et de la Recherche Médicale (INSERM), FRANCE
                Author notes

                Competing Interests: Simon Gubbins is an academic editor for PLoS ONE.

                Conceived and designed the experiments: SP. Performed the experiments: ARP SP MM. Analyzed the data: ARP MM SG SP. Contributed reagents/materials/analysis tools: ARP MM SG SP. Wrote the paper: SP ARP MM SG.

                Article
                PONE-D-15-13607
                10.1371/journal.pone.0128815
                4482020
                26110772
                b4081de9-54bc-4cf2-9f0c-53b1bd82652f
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 31 March 2015
                : 30 April 2015
                Page count
                Figures: 4, Tables: 3, Pages: 13
                Funding
                This work was funded by the Department for Environment, Food and Rural Affairs (Defra) (grant numbers: SE1122 and SE1125) and carried out in facilities funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
                Categories
                Research Article
                Custom metadata
                All relevant data, including accession numbers, are available as part of the manuscript and its Supporting Information.

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