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      Parameterization of the Durations of Phases of Foot-And-Mouth Disease in Cattle


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          The objective of the current study was to update parameterization of mathematical simulation models for foot-and-mouth disease (FMD) spread in cattle utilizing recent knowledge of FMD virus (FMDV) pathogenesis and infection dynamics to estimate the duration of distinct phases of FMD. Specifically, the durations of incubation, latent, and infectious periods were estimated for 3 serotypes (O, Asia1, and A) of FMDV, individually and collectively (pan-serotypic). Animal-level data were used in Accelerated Failure Time (AFT) models to estimate the duration of the defined phases of infection, while also investigating the influence of factors related to the experimental design (exposure methods) and virus serotype on disease progression. Substantial influences upon the estimated duration of distinct phases of FMD included the quantity of viral shedding used as a proxy for the onset of infectiousness, virus serotypes, and experimental exposure methods. The use of detection of any viral RNA in nasal secretions as a proxy of infectiousness lengthened the total infectious period compared to use of threshold-based detection. Additionally, the experimental system used to infect the animals also had significant effects on the duration of distinct phases of disease. Overall, the mean [95% Confidence Interval (CI)] durations of pan-serotype disease phases in cattle were estimated to be: incubation phase = 3.6 days (2.7–4.8), latent phase = 1.5 days (1.1–2.1), subclinical infectious phase = 2.2 days (1.5–3.5), clinical infectious phase = 8.5 days (6.2–11.6), and total infectious phase = 10.8 days (8.2–14.2). This study highlights the importance of identifying appropriate proxy measures to define the onset and duration of infectiousness in FMDV-infected cattle in the absence of actual transmission data. Additionally, it is demonstrated herein that factors associated with experimental design, such as virus exposure methods, may significantly affect disease progression in individual animals and should be considered when data is extrapolated from experimental studies. Given limitations in experimental data availability, pan-serotypic parameters which include all routes of exposure and a threshold-defined onset of infectiousness may be the most robust parameters for exploratory disease spread modeling approaches, when information on the specific virus of interest is not available.

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          Most cited references 35

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          Relationship between clinical signs and transmission of an infectious disease and the implications for control.

           Bryan Charleston (corresponding) ,  Bartek Bankowski,  Simon Gubbins (2011)
          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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            The pathogenesis of foot-and-mouth disease II: viral pathways in swine, small ruminants, and wildlife; myotropism, chronic syndromes, and molecular virus-host interactions.

            Investigation into the pathogenesis of foot-and-mouth disease (FMD) has focused on the study of the disease in cattle with less emphasis on pigs, small ruminants and wildlife. 'Atypical' FMD-associated syndromes such as myocarditis, reproductive losses and chronic heat intolerance have also received little attention. Yet, all of these manifestations of FMD are reflections of distinct pathogenesis events. For example, naturally occurring porcinophilic strains and unique virus-host combinations that result in high-mortality outbreaks surely have their basis in molecular-, cellular- and tissue-level interactions between host and virus (i.e. pathogenesis). The goal of this review is to emphasize how the less commonly studied FMD syndromes and host species contribute to the overall understanding of pathogenesis and how extensive in vitro studies have contributed to our understanding of disease processes in live animals. Published 2011. This article is a US Government work and is in the public domain in the USA.
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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.

                Author and article information

                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                09 August 2019
                : 6
                1Foreign Animal Disease Research Unit, Plum Island Animal Disease Center, Agricultural Research Service, United States Department of Agriculture , Greenport, NY, United States
                2Monitoring and Modeling, Center for Epidemiology and Animal Health, Animal and Plant Health Inspection Service, United States Department of Agriculture , Fort Collins, CO, United States
                3Plum Island Animal Disease Center Research Participation Program, Oak Ridge Institute for Science and Education , Oak Ridge, TN, United States
                4Department of Veterinary Population Biology, University of Minnesota , St. Paul, MN, United States
                Author notes

                Edited by: Alejandra Victoria Capozzo, National Council for Scientific and Technical Research (CONICET), Argentina

                Reviewed by: Eva Perez, Pirbright Institute (Biotechnology and Biological Sciences Research Council), United Kingdom; Aldo Dekker, Wageningen University & Research, Netherlands

                This article was submitted to Veterinary Epidemiology and Economics, a section of the journal Frontiers in Veterinary Science

                †Carolina Stenfeldt orcid.org/0000-0002-2074-3886

                Copyright © 2019 Yadav, Stenfeldt, Branan, Moreno-Torres, Holmstrom, Delgado and Arzt.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 8, Equations: 0, References: 44, Pages: 14, Words: 10080
                Veterinary Science
                Original Research


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