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      The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus

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          Abstract

          The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the discordance between the detection of infectious FMDV in carriers and the apparent lack of contagiousness to in-contact animals. Although substantial progress has been made in elucidating the causal mechanisms of persistent FMDV infection, there are still critical knowledge gaps that need to be addressed in order to elucidate, predict, prevent, and model the risks associated with the carrier state. This is further complicated by the occurrence of a distinct form of neoteric subclinical infection, which is indistinguishable from the carrier state in field scenarios, but may have substantially different epidemiological properties. This review summarizes the current state of knowledge of the FMDV carrier state and identifies specific areas of research in need of further attention. Findings from experimental investigations of FMDV pathogenesis are discussed in relation to experience gained from field studies of foot-and-mouth disease.

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          Most cited references153

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          The economic impacts of foot and mouth disease – What are they, how big are they and where do they occur?

          Although a disease of low mortality, the global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animals affected. This impact can be separated into two components: (1) direct losses due to reduced production and changes in herd structure; and (2) indirect losses caused by costs of FMD control, poor access to markets and limited use of improved production technologies. This paper estimates that annual impact of FMD in terms of visible production losses and vaccination in endemic regions alone amount to between US$6.5 and 21 billion. In addition, outbreaks in FMD free countries and zones cause losses of >US$1.5 billion a year. FMD impacts are not the same throughout the world: 1. FMD production losses have a big impact on the world's poorest where more people are directly dependent on livestock. FMD reduces herd fertility leading to less efficient herd structures and discourages the use of FMD susceptible, high productivity breeds. Overall the direct losses limit livestock productivity affecting food security. 2. In countries with ongoing control programmes, FMD control and management creates large costs. These control programmes are often difficult to discontinue due to risks of new FMD incursion. 3. The presence, or even threat, of FMD prevents access to lucrative international markets. 4. In FMD free countries outbreaks occur periodically and the costs involved in regaining free status have been enormous. FMD is highly contagious and the actions of one farmer affect the risk of FMD occurring on other holdings; thus sizeable externalities are generated. Control therefore requires coordination within and between countries. These externalities imply that FMD control produces a significant amount of public goods, justifying the need for national and international public investment. Equipping poor countries with the tools needed to control FMD will involve the long term development of state veterinary services that in turn will deliver wider benefits to a nation including the control of other livestock diseases.
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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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              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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                Author and article information

                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                28 February 2020
                March 2020
                : 9
                : 3
                : 167
                Affiliations
                [1 ]Foreign Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Plum Island animal Disease Center, Orient, NY 11957, USA
                [2 ]Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66506, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-2074-3886
                https://orcid.org/0000-0002-7517-7893
                Article
                pathogens-09-00167
                10.3390/pathogens9030167
                7157498
                32121072
                2f933a19-9860-43bb-b15e-1c9a35546029
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 February 2020
                : 25 February 2020
                Categories
                Review

                foot-and-mouth disease,foot-and-mouth disease virus,fmd,fmdv,virus,carrier,persistent infection,transmission,pathogenesis,cattle

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