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Sample records for multiplexed foot-and-mouth disease

  1. Multiplexed Molecular Assays for Rapid Rule-Out of Foot-and-Mouth Disease

    SciTech Connect

    Lenhoff, R; Naraghi-Arani, P; Thissen, J; Olivas, J; Carillo, C; Chinn, C; Rasmussen, M; Messenger, S; Suer, L; Smith, S M; Tammero, L; Vitalis, E; Slezak, T R; Hullinger, P J; Hindson, B J; Hietala, S; Crossley, B; Mcbride, M

    2007-06-26

    A nucleic acid-based multiplexed assay was developed that combines detection of foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign animal diseases and four domestic animal diseases that cause vesicular or ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and swine. The FMDV 'look-alike' diagnostic assay panel contains five PCR and twelve reverse transcriptase PCR (RT-PCR) signatures for a total of seventeen simultaneous PCR amplifications for seven diseases plus incorporating four internal assay controls. It was developed and optimized to amplify both DNA and RNA viruses simultaneously in a single tube and employs Luminex{trademark} liquid array technology. Assay development including selection of appropriate controls, a comparison of signature performance in single and multiplex testing against target nucleic acids, as well of limits of detection for each of the individual signatures is presented. While this assay is a prototype and by no means a comprehensive test for FMDV 'look-alike' viruses, an assay of this type is envisioned to have benefit to a laboratory network in routine surveillance and possibly for post-outbreak proof of freedom from foot-and-mouth disease.

  2. Hand, Foot and Mouth Disease

    MedlinePlus

    ... What's this? Submit Button Past Emails CDC Features Hand, Foot & Mouth Disease Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Hand, foot, and mouth disease is common in infants ...

  3. Evaluation of Multiplexed Foot-and-Mouth Disease Nonstructural Protein Antibody Assay Against Standardized Bovine Serum Panel

    SciTech Connect

    Perkins, J; Parida, S; Clavijo, A

    2007-05-14

    Liquid array technology has previously been used to show proof-of-principle of a multiplexed non structural protein serological assay to differentiate foot-and-mouth infected and vaccinated animals. The current multiplexed assay consists of synthetically produced peptide signatures 3A, 3B and 3D and recombinant protein signature 3ABC in combination with four controls. To determine diagnostic specificity of each signature in the multiplex, the assay was evaluated against a naive population (n = 104) and a vaccinated population (n = 94). Subsequently, the multiplexed assay was assessed using a panel of bovine sera generated by the World Reference Laboratory for foot-and-mouth disease in Pirbright, UK. This sera panel has been used to assess the performance of other singleplex ELISA-based non-structural protein antibody assays. The 3ABC signature in the multiplexed assay showed comparative performance to a commercially available non-structural protein 3ABC ELISA (Cedi test{reg_sign}) and additional information pertaining to the relative diagnostic sensitivity of each signature in the multiplex is acquired in one experiment. The encouraging results of the evaluation of the multiplexed assay against a panel of diagnostically relevant samples promotes further assay development and optimization to generate an assay for routine use in foot-and-mouth disease surveillance.

  4. Foot-and-Mouth Disease

    PubMed Central

    Grubman, Marvin J.; Baxt, Barry

    2004-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved. PMID:15084510

  5. Development of a multiplex lateral flow strip test for foot-and-mouth disease virus detection using monoclonal antibodies.

    PubMed

    Yang, Ming; Caterer, Nigel R; Xu, Wanhong; Goolia, Melissa

    2015-09-01

    Foot-and-mouth disease (FMD) is one of the world's most highly contagious animal diseases with tremendous economic consequences. A rapid and specific test for FMD diagnosis at the site of a suspected outbreak is crucial for the implementation of control measures. This project developed a multiplex lateral flow immunochromatographic strip test (multiplex-LFI) for the rapid detection and serotyping of FMD viruses. The monoclonal antibodies (mAbs) against serotypes O, A, and Asia 1 were used as capture mAbs. The mAbs were conjugated with fluorescein, rhodamine or biotin for serotype O, A and Asia 1, respectively. The detection mAbs which consisted of a serotype-independent mAb in combination with one serotype A-specific mAb and one Asia 1-specific mAb, were each colloidal gold-conjugated. The strips used in this study contained one control line and three test lines, which corresponded to one of the three serotypes, O, A or Asia 1. The newly developed multiplex-LFI strip test specifically identified serotype O (n=46), A (n=45) and Asia 1 (n=17) in all tested field isolates. The sensitivity of this strip test was comparable to the double antibody sandwich ELISA for serotypes O and A, but lower than the ELISA for serotype Asia 1. The multiplex-LFI strip test identified all tissue suspensions from animals that were experimentally inoculated with serotypes O, A or Asia 1. FMD viruses were detected in 38% and 50% of the swab samples from the lesion areas of experimentally inoculated sheep for serotypes O and A, respectively. The capability of the multiplex-LFI strip tests to produce rapid results with high specificity for FMD viruses of multiple serotypes makes this test a valuable tool to detect FMD viruses at outbreak sites.

  6. Animal health: foot-and-mouth disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  7. Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth disease virus and look-alike disease viruses

    SciTech Connect

    Hindson, B J; Reid, S M; Baker, B R; Ebert, K; Ferris, N P; Bentley Tammero, L F; Lenhoff, R J; Naraghi-Arani, P; Vitalis, E A; Slezak, T R; Hullinger, P J; King, D P

    2007-07-26

    A high-throughput multiplexed assay was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspect cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRT-PCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.

  8. Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth and look-alike disease viruses

    SciTech Connect

    Hindson, B J; Baker, B R; Bentley Tammero, L F; Lenhoff, R J; Naraghi-Arani, P; Vitalis, E A; Slezak, T R; Hullinger, P J; Reid, S M; Ebert, K; Ferris, N P; King, D P

    2007-09-18

    A high-throughput multiplexed assay (Multiplex Version 1.0) was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspect cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRTPCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.

  9. Diagnostic Evaluation of Multiplexed Reverse Transcription-PCR Microsphere Array Assay for Detection of Foot-and-Mouth and Look-Alike Disease Viruses▿

    PubMed Central

    Hindson, Benjamin J.; Reid, Scott M.; Baker, Brian R.; Ebert, Katja; Ferris, Nigel P.; Tammero, Lance F. Bentley; Lenhoff, Raymond J.; Naraghi-Arani, Pejman; Vitalis, Elizabeth A.; Slezak, Thomas R.; Hullinger, Pamela J.; King, Donald P.

    2008-01-01

    A high-throughput multiplexed assay was developed for the differential laboratory detection of foot-and-mouth disease virus (FMDV) from viruses that cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses by using multiplexed reverse transcription-PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the 17 primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR assay was evaluated using 287 field samples, including 247 samples (213 true-positive samples and 35 true-negative samples) from suspected cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true-negative samples collected from healthy animals. The mRT-PCR assay results were compared to those of two singleplex rRT-PCR assays, using virus isolation with antigen enzyme-linked immunosorbent assays as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% (95% confidence interval [CI], 89.8 to 96.4%), and the sensitivity was 98.1% (95% CI, 95.3 to 99.3%) for the two singleplex rRT-PCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses, such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n = 2) and bovine viral diarrhea virus (n = 2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized by using focused single-target rRT-PCR assays. PMID:18216216

  10. Genomics and outbreaks: foot and mouth disease.

    PubMed

    Freimanis, G L; Di Nardo, A; Bankowska, K; King, D J; Wadsworth, J; Knowles, N J; King, D P

    2016-04-01

    Foot and mouth disease virus (FMDV) is an animal pathogen of global economic significance. Identifying the sources of outbreaks plays an important role in disease control; however, this can be confounded by the ease with which FMDV can spread via movement of infected livestock and animal products, aerosols or fomites, e.g. contaminated persons and objects. As sequencing technologies have advanced, this review highlights the uses of viral genomic data in helping to understand the global distribution and transboundary movements of FMDV, and the role that these approaches have played in control and surveillance programmes. The recent application of next-generation sequencing platforms to address important epidemiological and evolutionary challenges is discussed with particular reference to the advent of 'omics' technologies.

  11. Foot-and-mouth disease virus L peptidase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV), equine rhinitis A virus (ERAV) and bovine rhinitis B virus (BRBV) comprise the genus Aphthovirus of the Picornaviridae family. Seven genera within this family, Aphthoviruses, Cardioviruses, Erboviruses (ERBV), Kobuviruses, Senecaviruses, Sapeloviruses, and Tescho...

  12. Simultaneously typing nine serotypes of enteroviruses associated with hand, foot, and mouth disease by a GeXP analyzer-based multiplex reverse transcription-PCR assay.

    PubMed

    Hu, Xiumei; Zhang, Yong; Zhou, Xiaomian; Xu, Banglao; Yang, Mengjie; Wang, Miao; Zhang, Chen; Li, Jin; Bai, Ruyin; Xu, Wenbo; Ma, Xuejun

    2012-02-01

    Hand, foot, and mouth disease (HFMD) is a contagious enteroviral disease occurring primarily in young children and caused by enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and other serotypes of coxsackievirus and echovirus. In this study, a GeXP analyzer-based multiplex reverse transcription (RT)-PCR assay (GeXP assay) consisting of chimeric primer-based PCR amplification with fluorescent labeling and capillary electrophoresis separation was developed to simultaneously identify nine serotypes of enteroviruses associated with HFMD in China, including EV71, CVA16, CVA4, -5, -9, and -10, and CVB1, -3, and -5. The RNAs extracted from cell cultures of viral isolates and synthetic RNAs via in vitro transcription were used to analyze the specificity and sensitivity of the assay. The GeXP assay detected as little as 0.03 tissue culture infective dose (TCID(50)) of EV71 and CVA16, 10 copies of panenterovirus, EV71, CVA16, CVB1, and CVB5, and 100 copies of 10 (including panenterovirus) premixed RNA templates. A total of 180 stool specimens collected from HFMD patients and persons suspected of having HFMD were used to evaluate the clinical performance of this assay. In comparison with the results of conventional methods, the sensitivities of the GeXP assay for detection of panenterovirus, EV71, and CVA16 were 98.79% (163/165), 91.67% (44/48), and 91.67% (33/36), respectively, and the specificities were 80.00% (12/15), 98.48% (130/132), and 100% (144/144), respectively. The concordance of typing seven other serotypes of enteroviruses with the results of conventional methods was 92.59% (25/27). In conclusion, the GeXP assay is a rapid, cost-effective, and high-throughput method for typing nine serotypes of HFMD-associated enteroviruses.

  13. Foot-and-mouth disease in tropical wildlife.

    PubMed

    Pinto, Aramis Augusto

    2004-10-01

    This review of foot-and-mouth disease in cloven-hoofed, free-living animals, describes the disease, the wide range of the hosts, the carrier state, and the interrelationship between disease in domestic livestock and wildlife. This information becomes even more crucial to the development of control strategies when linked to the process of pathogenesis and the epidemiology of the disease.

  14. Novel approaches to foot-and-mouth disease vaccine development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The need for better Foot-and-mouth disease (FMD) vaccines is not new, a report from the Research Commission on FMD, authored by F. Loeffler and P. Frosch in 1897, highlighted the need for developing a vaccine against FMD and qualified this as a devastating disease causing “severe economic damage to ...

  15. The pathogenesis of Foot-and-Mouth Disease in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental invest...

  16. Airborne spread of foot-and-mouth disease - model intercomparison

    SciTech Connect

    Gloster, J; Jones, A; Redington, A; Burgin, L; Sorensen, J H; Turner, R; Dillon, M; Hullinger, P; Simpson, M; Astrup, P; Garner, G; Stewart, P; D'Amours, R; Sellers, R; Paton, D

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office during 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.

  17. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV

  18. Foot-and-mouth disease: past, present and future

    PubMed Central

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions. PMID:24308718

  19. Modelling vaccination strategies against foot-and-mouth disease

    NASA Astrophysics Data System (ADS)

    Keeling, M. J.; Woolhouse, M. E. J.; May, R. M.; Davies, G.; Grenfell, B. T.

    2003-01-01

    Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, `predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.

  20. Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the GFRA (Global Foot-and-mouth disease Research Alliance) conducted a gap analysis of FMD (Foot-and-Mouth Disease) research. This work has been updated and reported in a series of papers, in this article we report findings in the fields of 1) pathogenesis and 2) molecular biology. The arti...

  1. Foot-and-mouth disease virus modulates cellular vimentin for virus survival

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV), the causative agent of foot-and-mouth disease, is an Apthovirus within the Picornaviridae family. During infection with FMDV, several host cell membrane rearrangements occur to form sites of viral replication. The largest viral protein in the replication complex,...

  2. Foot and mouth disease: a look from the wild side.

    PubMed

    Weaver, Genevieve V; Domenech, Joseph; Thiermann, Alex R; Karesh, William B

    2013-10-01

    We review the literature and discuss control options regarding foot and mouth disease (FMD) in wildlife around the world. There are more than 100 species of wild, feral, laboratory, or domesticated animals that have been infected naturally or experimentally with FMD virus. Apart from the African buffalo (Syncerus caffer) in sub-Saharan Africa, wildlife has not been demonstrated to play a significant role in the maintenance of FMD. More often, wildlife are passively infected when outbreaks of FMD occur in domestic livestock, and, in some wild ungulates, infection results in severe disease. Efforts to control FMD in wildlife may not be successful when the disease is endemic in livestock and may cause more harm to wildlife, human livelihoods, and domestic animals. Currently in sub-Saharan Africa, the complete eradication of FMD on a subcontinental scale in the near term is not possible, given the presence of FMD-infected African buffalo and the existence of weak veterinary infrastructures in some FMD-endemic countries. Therefore efforts to control the disease should be aimed at improved vaccines and improved use of vaccines, improved livestock management practices, and utilization of programs that can help in disease control such as the FMD Progressive Control Program and regulatory frameworks that facilitate trade such zonation, compartmentalization, and commodity-based trade. Though not meeting the definition of wildlife used in this review, feral domestic animals warrant a special concern with regard to FMD control.

  3. Hand, foot and mouth disease--outbreak in Romania?

    PubMed

    Chiriac, Anca; Foia, Liliana; Chiriac, Anca; Nanescu, Sonia; Filip, Florina; Solovan, C; Gorduza, E V

    2013-01-01

    Hand, foot and mouth disease (HFMD) is a viral illness usually occurring during the summer months in children younger than 5 years of age. In the North-East area of Romania the incidence is usually low, each dermatologist reporting 1-2 cases or even less per year. The diagnosis is usually based on the characteristic clinical aspect: vesicles and papules on the hands and feet and superficial oral ulcers. HFMD is typically a benign and self-limiting disease that resolves in approximately 7 days; in Asia there have been few reported severe cases that developed neurological complications and even death, while in certain areas of China this disease is a more and more serious public health problem. In the summer of 2012 in North-East Romania numerous cases of disease have been reported, some with atypical clinical manifestations and most of them with mild or moderate forms of disease. The present article is a discussion on one of these cases. The diagnosis was made based on lesions location and clinical appearance. An outbreak of HFMD should be confirmed by virology tests.

  4. Vaccination: foot-and-mouth disease experience in South America.

    PubMed

    Bergmann, I E; Malirat, V; Neitzert, E; Correa Melo, E

    2004-01-01

    Vaccination against foot-and-mouth disease (FMD) constitutes an important component of the policy for its control and eradication in South America. Considering that immunization may not impair subclinical infection, it became advisable to ally to vaccination campaigns a surveillance instrument to monitor silent viral circulation. Novel approaches for the evaluation of antibodies to FMD non-capsid proteins (NCPs), developed and validated at PANAFTOSA proved valuable for assessing viral circulation in immunized populations. The extensive and coordinated application in South America of vaccination together with this serosurvey tool indicated the effectiveness of systematic vaccination to prevent FMD spread and to restrain silent viral circulation intra- and inter- herds, and gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America. The fitness of NCP tests to assess viral circulation in a population supported the incorporation into the OIE code of the "free of FMD with vaccination" category as a step prior to the recognition of the "free of FMD without vaccination" category. Likewise it released the path to allow animals, vaccinated for protective purposes during emergencies, to live for the term of their productive lives.

  5. Is a multivalent hand, foot, and mouth disease vaccine feasible?

    PubMed

    Klein, Michel; Chong, Pele

    2015-01-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed.

  6. Is a multivalent hand, foot, and mouth disease vaccine feasible?

    PubMed Central

    Klein, Michel; Chong, Pele

    2015-01-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed. PMID:26009802

  7. A practitioner's primer on foot-and-mouth disease.

    PubMed

    Musser, Jeffrey M B

    2004-04-15

    Foot-and-mouth disease (FMD) is caused by an RNA virus of the genus Aphthovirus; 7 immunologically distinct serotypes of the virus have been identified. Susceptible species are mainly domestic and wild even-toed ungulates, such as cattle, sheep, goats, pigs, bison, and deer. All body fluids of infected animals can contain the virus and are considered infective. The primary mode of transmission is animal-to-animal transmission through inhalation or ingestion of aerosols containing the virus. The virus can also be spread mechanically by contaminated organic debris and fomites and can survive for 48 hours on human oral and nasal mucosa and be spread to uninfected animals in this manner. There is a rapid progression of clinical signs after an animal becomes infected, and the virus spreads rapidly throughout a herd. Clinical signs include excessive salivation; fever; vesicles and erosions of the oral and nasal mucosa, coronary band, interdigital area, and teats; lameness; sloughing of claws; reluctance to move; anorexia; mastitis; decreased milk production; and abortion or weak newborns. In mature animals, FMD has high morbidity and low mortality rates. Infected animals can become inapparent carriers of the virus.

  8. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses

  9. The Hampshire epidemic of foot-and-mouth disease, 1967.

    PubMed

    Sellers, R F; Forman, A J

    1973-03-01

    An analysis was made of the spread of foot-and-mouth disease during the epidemic in Hampshire in January and February 1967. To explain the pattern of spread, it had to be postulated that virus was present seven days before the first outbreak was reported. It is suggested that the disease occurred initially in pigs fed on infected meat and that the virus was subsequently disseminated from the local abattoir, where the pigs were killed, to four farms by movement of animals, slaughterhouse waste, people or vehicles, and to fifteen by the airborne route. Subsequent spread from these farms was by movement in two instances and by the airborne route in five. The source and route of infection of the last farm in the outbreak were not determined.The risk of spread through movement was associated more with carriage of infected slaughterhouse waste, movement of animals, people or vehicles carrying animals than through collection of milk, artificial insemination or movement of other types of vehicles. Outbreaks of disease among pigs gave rise to more secondary spread than outbreaks in cattle. Secondary outbreaks attributed to airborne spread occurred only in ruminants. Most airborne spread was into areas of high livestock density and cattle in the larger herds became infected. Airborne spread could be correlated with wind direction and speed but not with rain. The reduction in the number of outbreaks at the end of the epidemic could be attributed to the elimination of the largest sources of virus, the control of movements and the fact that in all instances except two the wind was blowing virus over towns and out to sea, to areas of low stock density and to areas where animals had been killed.

  10. The Epidemiology of Hand, Foot and Mouth Disease in Asia

    PubMed Central

    Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y.; Tan, Chong Yew; Chen, Mark IC; Horby, Peter

    2016-01-01

    Context: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). Objective: This study reports a systematic review of the epidemiology of HFMD in Asia. Data Sources: PubMed, Web of Science and Google Scholar were searched up to December 2014. Study Selection: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. Data Extraction: Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. Results: HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies. The uncertainty in these estimates inhibits their use for further analysis. Limitations: Diversity of study designs complicates attempts to identify features of HFMD epidemiology. Conclusions: Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps. PMID:27273688

  11. Introduction and history of foot-and-mouth disease virus.

    PubMed

    Mahy, B W J

    2005-01-01

    Foot-and-mouth disease (FMD) has been recognized as a significant epidemic disease threatening the cattle industry since the sixteenth century, and in the late nineteenth century it was shown by Loeffler and Frosch to be caused by a submicroscopic, filterable transmissible agent, smaller than any known bacteria. The agent causing FMD was thus the first virus of vertebrates to be discovered, soon after the discovery of tobacco mosaic virus of plants. It was not until 1920 that a convenient animal model for the study of FMD virus was established by Waldmann and Pape, using guinea-pigs, and with the later development of in vitro cell culture systems for the virus, the chemical and physical properties of FMD virus were elucidated during the remainder of the twentieth century, culminating in 1989 with a complete description of the three-dimensional structure of the virion. FMD virus is classified as a species in the Aphthovirus genus of the family Picornaviridae. The virus is acid labile, and the genome RNA contains a characteristic tract of polyC located about 360 nucleotides from the 5' terminus. Seven main serotypes exist throughout the world, as well as numerous subtypes. The World Reference Laboratory for FMD is located at Pirbright, Surrey, UK and undertakes surveillance of FMD epidemics by serotyping as well as by genotyping isolates of the virus. A major epidemic of FMD occurred in the UK in 2001 and was caused by a virulent strain of FMD virus with origins in Asia. The advantages and some disadvantages of controlling FMD outbreaks by vaccination are discussed.

  12. Detection of African swine fever, classical swine fever, and foot-and-mouth disease viruses in swine oral fluids by multiplex reverse transcription real-time polymerase chain reaction.

    PubMed

    Grau, Frederic R; Schroeder, Megan E; Mulhern, Erin L; McIntosh, Michael T; Bounpheng, Mangkey A

    2015-03-01

    African swine fever (ASF), classical swine fever (CSF), and foot-and-mouth disease (FMD) are highly contagious animal diseases of significant economic importance. Pigs infected with ASF and CSF viruses (ASFV and CSFV) develop clinical signs that may be indistinguishable from other diseases. Likewise, various causes of vesicular disease can mimic clinical signs caused by the FMD virus (FMDV). Early detection is critical to limiting the impact and spread of these disease outbreaks, and the ability to perform herd-level surveillance for all 3 diseases rapidly and cost effectively using a single diagnostic sample and test is highly desirable. This study assessed the feasibility of simultaneous ASFV, CSFV, and FMDV detection by multiplex reverse transcription real-time polymerase chain reaction (mRT-qPCR) in swine oral fluids collected through the use of chewing ropes. Animal groups were experimentally infected independently with each virus, observed for clinical signs, and oral fluids collected and tested throughout the course of infection. All animal groups chewed on the ropes readily before and after onset of clinical signs and before onset of lameness or serious clinical signs. ASFV was detected as early as 3 days postinoculation (dpi), 2-3 days before onset of clinical disease; CSFV was detected at 5 dpi, coincident with onset of clinical disease; and FMDV was detected as early as 1 dpi, 1 day before the onset of clinical disease. Equivalent results were observed in 4 independent studies and demonstrate the feasibility of oral fluids and mRT-qPCR for surveillance of ASF, CSF, and FMD in swine populations.

  13. Action of FAO in the control of foot and mouth disease.

    PubMed

    Leforban, Yves; Gerbier, Guillaume; Rweyemamu, Mark

    2002-10-01

    This paper describes the role played by FAO in the control of foot and mouth disease. Since 1954 the FAO European Commission for the control of foot-and-mouth disease co-ordinated the regional programme for eradication of FMD in Europe. One of the major achievements of the Commission has been to prevent the introduction and spread of exotic strains of foot and mouth disease into Europe through the Balkans. FAO also supports the activities of the Foot-and-Mouth Disease World Reference Laboratory located in the Institute of Animal Health, Pirbright, UK. The Infectious Diseases/EMPRES Group of the Animal Health Service, Animal Production and Health Division of FAO, promotes a global approach to the control and eradication of transboundary animal diseases over the world. For foot and mouth disease, the strategy is based on co-ordinated regional programmes. For FAO, no sustainable progress can be achieved in FMD control over the world without addressing and supporting the control of the disease in endemic countries.

  14. Late-onset acute graft-versus-host disease mimicking hand, foot, and mouth disease

    PubMed Central

    Mahabal, Gauri; George, Leni; Bindra, Mandeep; George, Biju

    2016-01-01

    Acute skin graft-versus-host disease (GVHD) classically presents as a pruritic erythematous maculopapular rash. We describe a patient who underwent allogeneic hematopoietic stem cell transplantation and presented with a hand foot and mouth disease like clinical presentation. Histopathology was suggestive of acute GVHD. This case is being reported to make dermatologists aware of this unusual presentation of GVHD. PMID:27990387

  15. Cloned Viral Protein Vaccine for Foot-and-Mouth Disease: Responses in Cattle and Swine

    NASA Astrophysics Data System (ADS)

    Kleid, Dennis G.; Yansura, Daniel; Small, Barbara; Dowbenko, Donald; Moore, Douglas M.; Grubman, Marvin J.; McKercher, Peter D.; Morgan, Donald O.; Robertson, Betty H.; Bachrach, Howard L.

    1981-12-01

    A DNA sequence coding for the immunogenic capsid protein VP3 of foot-and-mouth disease virus A12, prepared from the virion RNA, was ligated to a plasmid designed to express a chimeric protein from the Escherichia coli tryptophan promoter-operator system. When Escherichia coli transformed with this plasmid was grown in tryptophan-depleted media, approximately 17 percent of the total cellular protein was found to be an insoluble and stable chimeric protein. The purified chimeric protein competed equally on a molar basis with VP3 for specific antibodies to foot-and-mouth disease virus. When inoculated into six cattle and two swine, this protein elicited high levels of neutralizing antibody and protection against challenge with foot-and-mouth disease virus.

  16. EV71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines.

    PubMed

    Klein, Michel H

    2015-03-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease in infants and young children. Enterovirus 71 (EV71) and coxsackievirus A16 have emerged as neurotropic viruses responsible for severe neurological complications and a serious public health threat across the Asia-Pacific region. Formalin-inactivated EV71 vaccines have elicited protection against EV71 but not against coxsackievirus A16 infections. The development of a bivalent formalin-inactivated EV71/FI coxsackievirus A16 vaccine should be the next step towards that of multivalent hand, foot and mouth disease vaccines which should ultimately include other prevalent pathogenic coxsackieviruses and echovirus 30. This editorial summarizes the major challenges faced by the development of hand, foot and mouth disease vaccines.

  17. 9 CFR 94.4 - Cured or cooked meat from regions where rinderpest or foot-and-mouth disease exists.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... where rinderpest or foot-and-mouth disease exists. 94.4 Section 94.4 Animals and Animal Products ANIMAL... (INCLUDING POULTRY) AND ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN...-mouth disease exists. (a) The importation of cured meats derived from ruminants or swine, originating...

  18. 75 FR 1697 - Change in Disease Status of the Republic of Korea With Regard to Foot-and-Mouth Disease and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... Foot-and-Mouth Disease and Rinderpest AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... rinderpest and foot-and-mouth disease (FMD) and the list of regions that are subject to certain...

  19. Phylogeographic analysis of the 2000-2002 foot-and-mouth disease epidemic in Argentina

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is a highly transmissible disease of livestock. FMD has been eradicated from many countries and the consequences of FMD epidemics are, in some cases, devastating. That was the case of Argentina in 2000-2002, where within few months, FMD virus spread throughout most of t...

  20. Development of vaccines toward the global control and eradication of foot-and-mouth disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot and mouth disease (FMD) is one of the most economically and socially devastating diseases affecting animal agriculture throughout the world. Although mortality is low, millions of animals have been killed in efforts to rapidly control and eradicate FMD. The causing virus (FMDV) is a highly vari...

  1. Detection of Foot-and-Mouth Disease Virus Infected Cattle Using Infrared Thermography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is a highly infectious viral disease of livestock that has significant economic, social and environmental impacts. One problem hampering the diagnosis, control and eradication efforts is the need for veterinarians to inspect hundreds of animals from suspected case premis...

  2. Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer.

    PubMed

    Gibbs, E P; Herniman, K A; Lawman, M J; Sellers, R F

    1975-06-28

    After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock.

  3. Foot and mouth disease virus non structural protein 2C interacts with Beclin1 modulating virus replication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV), the causative agent of foot-and-mouth disease (FMD), is an Apthovirus within the Picornaviridae family. Replication of the virus occurs in association with replication complexes that are formed by host cell membrane rearrangements. The largest viral protein in th...

  4. Chimeric Foot-and-Mouth Disease Viruses: Evaluation of Their Efficacy as Potential Marker Vaccines in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous work in swine has demonstrated that full protection against Foot-and-Mouth Disease (FMD) can be achieved following vaccination with chimeric Foot-and-Mouth Disease Virus (FMDV) vaccines, whereby the VP1 G-H loop has been substituted with a non-homologous alternative. If proven to be effect...

  5. Global foot-and-mouth disease research update and gap analysis: 3 - vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. In this paper, we report updated findings in the field of FMD vaccine research. This paper consists of the following four sections: 1) Research priorities identified in the 2010 GFRA gap ana...

  6. Hand, foot, and mouth disease caused by coxsackievirus A6, Thailand, 2012.

    PubMed

    Puenpa, Jiratchaya; Chieochansin, Thaweesak; Linsuwanon, Piyada; Korkong, Sumeth; Thongkomplew, Siwanat; Vichaiwattana, Preyaporn; Theamboonlers, Apiradee; Poovorawan, Yong

    2013-04-01

    In Thailand, hand, foot, and mouth disease (HFMD) is usually caused by enterovirus 71 or coxsackievirus A16. To determine the cause of a large outbreak of HFMD in Thailand during June-August 2012, we examined patient specimens. Coxsackievirus A6 was the causative agent. To improve prevention and control, causes of HFMD should be monitored.

  7. Impact of the 2001 Foot-and-Mouth Disease Outbreak in Britain: Implications for Rural Studies

    ERIC Educational Resources Information Center

    Scott, Alister; Christie, Michael; Midmore, Peter

    2004-01-01

    This paper assesses the impact of the 2001 foot-and-mouth disease outbreak in terms of its implications for the discipline of rural studies. In particular, it focuses on the position of agriculture in rural economy and society, the standing of the government after its management of the outbreak, and the performance of the new devolved regional…

  8. A High Explanatory Power Model of Foot and Mouth Disease Spread in Central California

    DTIC Science & Technology

    2013-03-01

    spongiform encephalopathy and Foot and mouth disease in Great Britain. A dissertation presented in partial fulfillment of the requirements for the degree...Kong, Hong Kong retrieved from www.pnas.org/cgi/doi/10.1073/pnas.0913286107 Stevenson, M. (2003). The Spatio-temporal epidemiology of Bovine

  9. Global foot-and-mouth disease research update and gap analysis: 6 - immunology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. This has been updated with findings reported in a series of papers. Here we present findings for FMD immunology research. The paper consists of the following four sections: 1. Research prior...

  10. Global foot-and-mouth disease research update and gap analysis: 5 - biotherapeutics and disinfectants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the Global Foot-and-mouth disease Research Alliance(GFRA)conducted a gap analysis of FMD research. This work has been updated and reported in a series of papers with the focus of this article being (i) biotherapeutics and (ii) disinfectants, including environmental contamination. The paper ...

  11. Global foot-and-mouth disease research update and gap analysis: 4 - diagnostics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the Global Foot-And-Mouth Disease Research Alliance (GFRA) conducted a gap analysis of FMD research. Published as a series of seven papers, in this paper, we report updated findings in the field of diagnostics. The paper consists of the following four sections: 1. Research priorities identi...

  12. The foot-and-mouth disease carrier state divergence in vaccinated and non-vaccinated cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated following simulated-natural virus exposure of 43 cattle that were either naïve or vaccinated using a recombinant, adenovirus-vectored vaccine. Although vaccinated cattle were protected against clinical dise...

  13. Global foot-and-mouth disease research update and gap analysis: 2 - epidemiology, wildlife and economics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2014, the Global Foot-and-mouth disease Research ings in the fields of (i) epidemiology, (ii) wildlife and (iii) Alliance (GFRA) conducted a gap analysis of foot-and- economics. Although the three sections, epidemiology, wildlife and economics are presented as separate entities, the fields are ...

  14. Epididymitis caused by coxsackievirus A6 in association with hand, foot, and mouth disease.

    PubMed

    Vuorinen, Tytti; Osterback, Riikka; Kuisma, Jani; Ylipalosaari, Pekka

    2014-12-01

    Coxsackievirus A6 (CV-A6) caused hand, foot, and mouth disease (HFMD) with a unique manifestation of epididymitis. The patient underwent operation due to suspicion of testicular torsion. Epididymitis was diagnosed by ultrasound examination. Enterovirus was detected from epididymal fluid by PCR and typed by partial sequencing of viral protein 1 as CV-A6.

  15. Mechanisms of foot-and-mouth disease virus tropism inferred from differential tissue gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease virus (FMDV) has a characteristic tropism in terms of primary, secondary, and persistent infection and vesicular lesion sites. The virus targets specific tissues for primary replication. From these tissues, the virus spreads via the blood stream to a few preferred secondary in...

  16. Induction of foot-and-mouth disease virus specific cytotoxic T cell killing by vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus which infects cloven-hoofed animals including large and small ruminants and swine. Current vaccine strategies are...

  17. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular... RINDERPEST, FOOT-AND-MOUTH DISEASE, NEWCASTLE DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER... RESTRICTED IMPORTATIONS § 94.17 Dry-cured pork products from regions where foot-and-mouth disease,...

  18. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER... § 94.17 Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African...

  19. Serotyping of foot and mouth disease virus and Pasteurella multocida from Indian gaurs (Bos gaurus), concurrently infected with foot and mouth disease and haemorrhagic septicaemia.

    PubMed

    Chandranaik, Basavegowdanadoddi Marinaik; Hegde, Raveendra; Shivashankar, Beechagondahalli Papanna; Giridhar, Papanna; Muniyellappa, Handenahally Kaverappa; Kalge, Rajeshwar; Sumathi, Benamanahalli Raju; Nithinprabhu, Kumble; Chandrashekara, Narasimhaiah; Manjunatha, Venkataramanappa; Jaisingh, Nirupama; Mayanna, Asha; Chandrakala, Gowda Kallenahalli; Kanaka, Sermaraja; Venkatesha, Mudalagiri Dasappagupta

    2015-06-01

    We report the serotyping of foot-and-mouth disease virus (FMDV) and Pasteurella multocida from Indian gaurs which were concurrently infected with foot-and-mouth disease (FMD) and haemorrhagic septicaemia. Bannerghatta biological park (BBP), a national park located in the outskirts of Bengaluru city, Karnataka, India, is bordered by several villages. These villages witnessed massive outbreaks of FMD which spread rapidly to the herbivores at BBP. Post-mortem was conducted on carcasses of two Indian gaurs that died with symptoms of FMD. The salient gross findings included extensive vesicular lesions on the tongue, gums, cheeks, upper palate and hooves. Haemorrhagic tracheitis and ecchymotic haemorrhages on the heart were characteristic. The vesicular lesions of oral cavity were positive for 'O' type of FMD virus by sandwich enzyme-linked immuno sorbent assay (ELISA). The heart blood and spleen samples yielded growth of pure cultures of P. multocida. The isolates were typed as P. multocida type B using KTSP61 and KTT72 primers yielding specific amplicons of 620 bp. The phylogenetic analysis of the isolates was carried by sequencing of 1.4-Kbp nucleotides on the 16S ribosomal RNA (rRNA) gene of the isolates.

  20. Current Status and Future Prospects to Achieve Foot-and-Mouth Disease Eradication in South America.

    PubMed

    Clavijo, A; Sanchez-Vazquez, M J; Buzanovsky, L P; Martini, M; Pompei, J C; Cosivi, O

    2017-02-01

    South America has a favourable position with respect to foot-and-mouth disease (FMD) compared with other FMD-affected regions due to the elimination of endemic clinical presentation of the disease. South America has reached the final stage of control and aims to eradicate the disease in the region under the provisions of the Hemispheric Program for the Eradication of FMD 2011-2020 (PHEFA). This programme aims at bringing eradication to completion, thereby eliminating the pool of foot-and-mouth disease genotypes active in South America. This plan includes a regional political agreement that provides strategies and technical guidelines for the eradication of foot-and-mouth disease from South America. It incorporates knowledge and experience regarding the disease's history and its connection with the different production systems, animal movement and trade. The Pan American Foot and Mouth Disease Center has led the control and eradication programmes, providing the framework for designing national and subregional programmes that have led to significant progress in controlling the disease in South America. The current situation is the result of several factors, including the proper implementation of a national control programmes, good veterinary infrastructure in most countries and public-private participation in the process of eradicating the disease. Notwithstanding the favourable health status, there are significant challenges for the goal of eradication. At this stage, South American countries should enhance their surveillance strategies particularly through the use of target or risk-based surveys that contribute to increase the degree of sensitivity in the search for viral circulation in the context of absence of clinical occurrence of FMD.

  1. Adjuvants for foot-and-mouth disease virus vaccines: recent progress.

    PubMed

    Cao, Yimei

    2014-11-01

    Foot-and-mouth disease (FMD) is a highly contagious and rapidly spreading disease of cloven-hoofed animals. In most countries, animals are immunized with inactivated whole virus vaccines to control the spread of foot-and-mouth disease virus (FMDV); however, there are safety and efficacy (especially, cell-mediated immunity) concerns. Many efforts are currently devoted to the development of effective vaccines by combining the application of protective antigens together with the search for specific and targeting adjuvants that maximizes the immunogenicity with a desired immune response. In this review, we outline previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll-like receptors (TLRs) or different cytokines, focusing mostly on their efficacy when used with FMD vaccine, and somewhat on mechanisms by which adjuvants mediate their effects.

  2. Elimination of foot-and-mouth disease in South America: lessons and challenges

    PubMed Central

    Naranjo, José; Cosivi, Ottorino

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988–2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988–2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011–2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable. PMID:23798699

  3. Elimination of foot-and-mouth disease in South America: lessons and challenges.

    PubMed

    Naranjo, José; Cosivi, Ottorino

    2013-08-05

    Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988-2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988-2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011-2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable.

  4. The survival of foot-and-mouth disease virus in open air conditions.

    PubMed Central

    Donaldson, A. I.; Ferris, N. P.

    1975-01-01

    The influence of the Open Air Factor (OAF) and daylight on the survival of foot-and-mouth disease (FMD) virus held as captured aerosols on spider microthreads has been investigated. Virus inactivation due to OAF was slight. Similarly, the effect of daylight on the survival of virus was not marked. The results are discussed in relation to the airborne spread of FMD virus in nature. PMID:168250

  5. The growth and persistence of foot-and-mouth disease virus in the bovine mammary gland

    PubMed Central

    Burrows, R.; Mann, J. A.; Greig, A.; Chapman, W. G.; Goodridge, D.

    1971-01-01

    In animals exposed to foot-and-mouth disease virus by indirect contact, virus was recovered from the blood, milk, pharynx, vagina and rectum for variable periods of time before clinical disease was apparent. Virus instilled into the mammary gland multiplied rapidly and virus concentrations greater than 107 p.f.u./ml. were recorded within 8-32 hr., depending on the virus strain and dose inoculated. Virus multiplication was accompanied by clinical signs of mastitis but the classical signs of foot-and-mouth disease did not appear for 52-117 hr. Dissemination of virus from the mammary gland occurred within 4-24 hr. and in some animals samples taken from the pharynx, mouth, nose and vagina contained virus for periods up to 97 hr. before the appearance of vesicular lesions. Virus production in the udder declined with the appearance of virus neutralizing activity in the blood and the milk but persisted in some animals for periods of 3-7 weeks. The ability of foot-and-mouth disease virus to persist in mammary tissue was confirmed by the demonstration of virus multiplication in the udders of immune animals. PMID:4326249

  6. Quantification of foot-and-mouth disease virus transmission rates using published data.

    PubMed

    Goris, Nesya E; Eblé, Phaedra L; de Jong, Mart C M; De Clercq, Kris

    2009-01-01

    Foot-and-mouth disease is an extremely infectious and devastating disease affecting all species of cloven-hoofed animals. To understand the epidemiology of the causative virus and predict viral transmission dynamics, quantified transmission parameters are essential to decision makers and modellers alike. However, such quantified parameters are scarcely available, and recently a series of animal experiments was set up to obtain such data experimentally. In this communication, however, we report on the use of data from an animal experiment conducted 10 years ago to quantify transmission of foot-and-mouth disease virus between non-vaccinated sheep and from sub-clinically infected sheep to in-contact pigs. This new analysis utilises a state-of-the-art Generalised Linear Model to estimate the transmission rate. From the obtained results it is concluded that meta-analysis of "old" experiments using newly developed techniques can provide useful data to replace, reduce and refine future foot-and-mouth disease transmission experiments, thereby minimising animal suffering for research purposes.

  7. Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins

    SciTech Connect

    Strebel, K.; Beck, E.; Strohmaier, K.; Schaller, H.

    1986-03-01

    Defined segments of the cloned foot-and-mouth disease virus genome corresponding to all parts of the coding region were expressed in Escherichia coli as fusions to the N-terminal part of the MS2-polymerase gene under the control of the inducible lambdaPL promoter. All constructs yielded large amounts of proteins, which were purified and used to raise sequence-specific antisera in rabbits. These antisera were used to identify the corresponding viral gene products in /sup 35/S-labeled extracts from foot-and-mouth disease virus-infected BHK cells. This allowed us to locate unequivocally all mature foot-and-mouth disease virus gene products in the nucleotide sequence, to identify precursor-product relationships, and to detect several foot-and mouth disease virus gene products not previously identified in vivo or in vitro.

  8. New England Foot and Mouth Disease Tabletop Exercise

    SciTech Connect

    Hullinger, P

    2008-09-30

    The Multiscale Epidemiologic/Economic Simulation and Analysis (MESA) Decision Support System (DSS) is the product of investments that began in FY05 by the Department of Homeland Security (DHS) Science and Technology Directorate and continue today with joint funding by both DHS and the US Department of Agriculture (USDA). The DSS consists of a coupled epidemiologic/economic model, a standalone graphical user interface (GUI) that supports both model setup and post-analysis, and a Scenario Bank archive to store all content related to foreign animal disease (FAD) studies (Figure 1). The MESA epi model is an object-oriented, agent-based, stochastic, spatio-temporal simulator that parametrically models FAD outbreaks and response strategies from initial disease introduction to conclusion over local, regional, and national scales. Through its output database, the epi model couples to an economic model that calculates farm-level impacts from animal infections, responsive control strategies and loss of trade. The MESA architecture contains a variety of internal models that implement the major components of the epi simulation, including disease introduction, intra-herd spread, inter-herd spread (direct and indirect), detection, and various control strategies (movement restrictions, culling, vaccination) in a highly configurable and extensible fashion. MESA will produce both overall and daily summary statistics for the outbreak, epidemic curves, and costs associated with the outbreak. This information can be used to reconstruct and analyze the course of the outbreak. Geographical information produced by MESA can be used to produce maps and movies as visual aids to understand the distribution characteristics of a simulated outbreak.

  9. The fencing issue relative to the control of foot-and-mouth disease.

    PubMed

    Sutmoller, Paul

    2002-10-01

    Certain livestock diseases in sub-Saharan Africa, such as foot-and-mouth disease are difficult to control because of the large numbers of infected wildlife hosts. These wildlife disease reservoirs form a continuous hazard of transmittal of the diseases to domestic livestock, which limits the access of livestock products from southern Africa to international markets. The disease reservoirs are often found in border areas between countries with susceptible species and infected reservoir animals continuously crossing the border. A regional approach to disease control is probably the only way to achieve any real progress. Here we review the positive and negative attributes of fencing as a control mechanism for disease transmission.

  10. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 4 - Diagnostics.

    PubMed

    Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed knowledge gaps in foot-and-mouth disease (FMD) research in the field of diagnostics. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from around the world. Findings were used to identify priority areas for future FMD research. Molecular and genetic technologies, including sequencing, are developing at an increasing rate both in terms of capability and affordability. These advances potentiate progress in many other fields of research, from vaccine development to epidemiology. The development of RT-LAMP represents an important breakthrough allowing greater use and access to molecular diagnostics. It is now possible to determine virus serotype using PCR, although only for certain virus pools, continued progress is needed to cover the global spectrum of FMD viruses. Progress has also been made in the development of pen-side rapid diagnostics, some with the ability to determine serotype. However, further advances in pen-side serotype or strain determination would benefit both FMD-free countries and endemic countries with limited access to well-resourced laboratories. Novel sampling methods that show promise include air sampling and baited ropes, the latter may aid sampling in wildlife and swine. Studies of infrared thermography for the early detection of FMD have not been encouraging, although investigations are ongoing. Multiplex tests have been developed that are able to simultaneously screen for multiple pathogens with similar clinical signs. Crucial for assessing FMDV freedom, tests exist to detect animals that have been infected with FMDV regardless of vaccination status; however, limitations exist, particularly when testing previously vaccinated animals. Novel vaccines are being developed with complementary DIVA tests for this purpose. Research is also needed to improve the current imprecise approaches to FMD vaccine matching. The development of simple, affordable

  11. Foot-and-mouth disease: technical and political challenges to eradication.

    PubMed

    Smith, Mark T; Bennett, Anthony M; Grubman, Marvin J; Bundy, Bradley C

    2014-06-30

    Foot-and-mouth disease (FMD) is a highly-contagious livestock disease with global socioeconomic ramifications. The disease negatively impacts both individual farmers through reduced herd viability and nations through trade restrictions of animals and animal derivatives. Vaccines for FMD prevention have existed for over 70 years, yet the disease remains enzootic in a large percentage of the globe. FMD persistence is due in part to technical limitations of historic and current vaccine technologies. There also exist many socioeconomic and political barriers to global FMD eradication. Here we highlight the barriers to eradication and discuss potential avenues toward FMD eradication.

  12. Design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3C protease.

    PubMed

    Roqué Rosell, Núria R; Mokhlesi, Ladan; Milton, Nicholas E; Sweeney, Trevor R; Zunszain, Patricia A; Curry, Stephen; Leatherbarrow, Robin J

    2014-01-15

    Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3C protease, making this enzyme an attractive target for antiviral drugs. A peptide corresponding to an optimal substrate has been modified at the C-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as Michael acceptors with the enzyme active site. Further investigation highlighted key structural determinants for inhibition, with a positively charged P2 being particularly important for potency.

  13. Protection of Cattle against Foot-and-Mouth Disease by a Synthetic Peptide

    NASA Astrophysics Data System (ADS)

    Dimarchi, Richard; Brooke, Gerald; Gale, Charles; Cracknell, Victor; Doel, Timothy; Mowat, Noel

    1986-05-01

    A chemically synthesized peptide consisting essentially of two separate regions (residues 141 to 158 and 200 to 213) of a virus coat protein (VP1) from the 01 Kaufbeuren strain of foot-and-mouth disease virus was prepared free of any carrier protein. It elicited high levels of neutralizing antibody and protected cattle against intradermolingual challenge by inoculation with infectious virus. Comparative evaluation of this peptide with a single-site peptide (residues 141 to 158) in guinea pigs suggests the importance of the VP1 carboxyl terminal residues in enhancing the protective response.

  14. Hypersensitivity in cattle after foot-and-mouth disease vaccination: response to hydroxpropylmethylcellulose.

    PubMed Central

    Black, L.; Menard, F. J.; Beadle, G. G.; Pay, T. W.

    1975-01-01

    Intravenous provocation (IVP) tests demonstrated that hydroxypropylmethylcellulose (MC) was able to elicit anaphylactic signs in cattle vaccinated with foot-and-mouth disease (FMD) vaccine produced at one centre but not with similar vaccine produced at another. The former vaccine also provoked serum reagins which were demonstrated by passive cutaneous anaphylaxis (PCA) tests in goats. Reaginic sera which reacted specifically with MC were used in PCA tests to screen samples taken serially from the vaccine production lines. The reactions observed suggested that a substance with MC or similar specificity was present in the antifoaming agent routinely added to vaccines. Images Plate 1 PMID:168252

  15. A novel Enterovirus 96 circulating in China causes hand, foot, and mouth disease.

    PubMed

    Xu, Yi; Sun, Yisuo; Ma, Jinmin; Zhou, Shuru; Fang, Wei; Ye, Jiawei; Tan, Limei; Ji, Jingkai; Luo, Dan; Li, Liqiang; Li, Jiandong; Fang, Chunxiao; Pei, Na; Shi, Shuo; Liu, Xin; Jiang, Hui; Gong, Sitang; Xu, Xun

    2017-02-07

    Enterovirus 96 (EV-96) is a recently described member of the species Enterovirus C and is associated with paralysis and myelitis. In this study, using metagenomic sequencing, we identified a new enterovirus 96 strain (EV-96-SZ/GD/CHN/2014) as the sole pathogen causing hand, foot, and mouth disease (HFMD). A genomic comparison showed that EV-96-SZ/GD/CHN/2014 is most similar to the EV-96-05517 strain (85% identity), which has also been detected in Guangdong Province. This is the first time that metagenomic sequencing has been used to identify an EV-96 strain shown to be associated with HFMD.

  16. Foot-and-mouth disease: a review of the virus and the symptoms.

    PubMed

    Meyer, R F; Knudsen, R C

    2001-11-01

    Foot-and-mouth disease virus (FMDV) is the etiologic agent of foot-and-mouth disease (FMD), which is a disease of cattle, swine, and other cloven-footed animals. FMD is characterized by the formation of vesicles on the tongue, nose, muzzle, and coronary bands of infected animals. The virus has several unique characteristics that enable it to cause one of the most economically devastating diseases in today's world. The ease with which it may be transmitted by contact and aerosol, combined with its enhanced ability to initiate infections, virtually ensures that most, if not all, animals in a herd will contract FMD. The long-term survival of FMDV in infected animals' tissues and organs, especially when refrigerated, offers an opportunity for its national and international transmission through the food chain. Multiple serotypes and numerous subtypes reduce the effectiveness and reliability of vaccines. The possible development of carriers in vaccinated animals and those that have recovered from FMD provides additional potential sources of new outbreaks. These features create a disease that can have a major economic impact on farmers and entire nations.

  17. Foot-and-mouth disease in Asiatic black bears (Ursus thibetanus).

    PubMed

    Officer, Kirsty; Lan, Nguyen Thi; Wicker, Leanne; Hoa, Nguyen Thi; Weegenaar, Annemarie; Robinson, Jill; Ryoji, Yamaguchi; Loukopoulos, Panayiotis

    2014-09-01

    Foot-and-mouth disease (FMD) is a highly contagious, debilitating, and globally significant viral disease typically affecting cloven-hoofed hosts. The diagnosis of FMD in bears in Vietnam is described. The current study describes a confirmed case of FMD in a bear species, and the clinical signs compatible with FMD in a Malayan sun bear. Thirteen Asiatic black bears (Ursus thibetanus) and 1 Malayan sun bear (Helarctos malayanus) were apparently affected. In August 2011, an adult bear became lethargic, and developed footpad vesicles. Over 15 days, 14 out of 17 bears developed similar signs; the remaining 3 co-housed bears and another 57 resident bears did not. All affected bears developed vesicles on all footpads, and most were lethargic for 24-48 hr. Nasal and oral lesions were noted in 6 and 3 cases, respectively. Within 1 month, all looked normal. Foot-and-mouth disease virus (FMDV) was detected by reverse transcription polymerase chain reaction, classified as serotype O, and isolated by virus isolation techniques. Phylogenetic analysis demonstrated clustering of 3 bear isolates, in a branch distinct from other FMDV type O isolates. The outbreak likely occurred due to indirect contact with livestock, and was facilitated by the high density of captive bears. It showed that Asiatic black bears are capable of contracting FMDV and developing clinical disease, and that the virus spreads easily between bears in close contact.

  18. Molecular characterisation of foot-and-mouth disease viruses from Pakistan, 2005-2008.

    PubMed

    Waheed, U; Parida, S; Khan, Q M; Hussain, M; Ebert, K; Wadsworth, J; Reid, S M; Hutchings, G H; Mahapatra, M; King, D P; Paton, D J; Knowles, N J

    2011-04-01

    Foot-and-mouth disease (FMD), an economically important disease of cloven-hoofed animals, is endemic in Pakistan where three virus serotypes are present (O, A and Asia 1). Fifty-eight clinical samples collected between 2005 and 2008 from animals with suspected FMD in various locations in Pakistan were subjected to virus isolation on primary cell culture, antigen ELISA and real-time RT-PCR (rRT-PCR). Viruses were isolated from 32 of these samples and identified as FMDV type O (n = 31) or type A (n = 1). Foot-and-mouth disease virus (FMDV) genome was detected in a further 11 samples by real-time RT-PCR. Phylogenetic analyses of the VP1 nucleotide sequences showed that all of the type O viruses belonged to the MIDDLE EAST-SOUTH ASIA topotype with the majority belonging to the PanAsia-2 lineage; a single example of the older PanAsia lineage was identified. The single FMDV type A virus belonged to the ASIA topotype, but did not cluster with known strains that are currently circulating (such as Iran-05) and was not closely related to other type A viruses from the region. These findings demonstrate the widespread distribution of O-PanAsia-2 in Pakistan and the presence of undisclosed novel type A lineages in the region.

  19. Characterization of epitope-tagged foot-and-mouth disease virus.

    PubMed

    Seago, Julian; Jackson, Terry; Doel, Claudia; Fry, Elizabeth; Stuart, David; Harmsen, Michiel M; Charleston, Bryan; Juleff, Nicholas

    2012-11-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals with an almost-worldwide distribution. Conventional FMD vaccines consisting of chemically inactivated viruses have aided in the eradication of FMD from Europe and remain the main tool for control in endemic countries. Although significant steps have been made to improve the quality of vaccines, such as improved methods of antigen concentration and purification, manufacturing processes are technically demanding and expensive. Consequently, there is large variation in the quality of vaccines distributed in FMD-endemic countries compared with those manufactured for emergency use in FMD-free countries. Here, we have used reverse genetics to introduce haemagglutinin (HA) and FLAG tags into the foot-and-mouth disease virus (FMDV) capsid. HA- and FLAG-tagged FMDVs were infectious, with a plaque morphology similar to the non-tagged parental infectious copy virus and the field virus. The tagged viruses utilized integrin-mediated cell entry and retained the tag epitopes over serial passages. In addition, infectious HA- and FLAG-tagged FMDVs were readily purified from small-scale cultures using commercial antibodies. Tagged FMDV offers a feasible alternative to the current methods of vaccine concentration and purification, a potential to develop FMD vaccine conjugates and a unique tool for FMDV research.

  20. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    PubMed

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients.

  1. Thermal inactivation of foot and mouth disease virus in extruded pet food.

    PubMed

    Gubbins, S; Forster, J; Clive, S; Schley, D; Zuber, S; Schaaff, J; Corley, D

    2016-12-01

    The risk of importing foot and mouth disease, a highly contagious viral disease of livestock, severely restricts trade and investment opportunities in many developing countries where the virus is present. This study was designed to investigate the inactivation of foot and mouth disease virus (FMDV) by heat treatments used in extruded commercial pet food manufacture. If extrusion could be shown to reliably inactivate the virus, this could potentially facilitate trade for FMDV-endemic countries. The authors found that there was no detectable virus following: i) treatment of FMDVspiked meat slurry at 68°C for 300 s; ii) treatment of FMDV-spiked slurry and meal mix at 79°C for 10 or 30 s, or iii) treatment of homogenised bovine tongue epithelium, taken from an FMDV-infected animal, at 79°C for 10 s. This corresponds to an estimated 8 log10 reduction in titre (95% credible interval: 6 log10 -13 log10). Furthermore, the authors found that the pH of the slurry and meal mix was sufficient to inactivate FMDV in the absence of heat treatment. This demonstrates that heat treatments used in commercial pet food manufacture are able to substantially reduce the titre of FMDV in infected raw materials.

  2. Failure of vaccination to prevent outbreaks of foot-and-mouth disease.

    PubMed Central

    Woolhouse, M. E.; Haydon, D. T.; Pearson, A.; Kitching, R. P.

    1996-01-01

    Outbreaks of foot-and-mouth disease persist in dairy cattle herds in Saudi Arabia despite revaccination at intervals of 4-6 months. Vaccine trials provide data on antibody responses following vaccination. Using this information we developed a mathematical model of the decay of protective antibodies with which we estimated the fraction of susceptible animals at a given time after vaccination. The model describes the data well, suggesting over 95% take with an antibody half-life of 43 days. Farm records provided data on the time course of five outbreaks. We applied a 'SLIR' epidemiological model to these data, fitting a single parameter representing disease transmission rate. The analysis provides estimates of the basic reproduction number R(0), which may exceed 70 in some cases. We conclude that the critical intervaccination interval which would provide herd immunity against FMDV is unrealistically short, especially for heterologous challenge. We suggest that it may not be possible to prevent foot-and-mouth disease outbreaks on these farms using currently available vaccines. PMID:8666082

  3. Foot-and-Mouth Disease Virus 3C Protease Cleaves NEMO To Impair Innate Immune Signaling

    PubMed Central

    Wang, Dang; Fang, Liurong; Li, Kui; Zhong, Huijuan; Fan, Jinxiu; Ouyang, Chao; Zhang, Huan; Duan, Erzhen; Luo, Rui; Zhang, Zhongming; Liu, Xiangtao; Chen, Huanchun

    2012-01-01

    Foot-and-mouth disease is a highly contagious viral illness of wild and domestic cloven-hoofed animals. The causative agent, foot-and-mouth disease virus (FMDV), replicates rapidly, efficiently disseminating within the infected host and being passed on to susceptible animals via direct contact or the aerosol route. To survive in the host, FMDV has evolved to block the host interferon (IFN) response. Previously, we and others demonstrated that the leader proteinase (Lpro) of FMDV is an IFN antagonist. Here, we report that another FMDV-encoded proteinase, 3Cpro, also inhibits IFN-α/β response and the expression of IFN-stimulated genes. Acting in a proteasome- and caspase-independent manner, the 3Cpro of FMDV proteolytically cleaved nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), a bridging adaptor protein essential for activating both NF-κB and interferon-regulatory factor signaling pathways. 3Cpro specifically targeted NEMO at the Gln 383 residue, cleaving off the C-terminal zinc finger domain from the protein. This cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of 3Cpro abrogated NEMO cleavage and the inhibition of IFN induction. Collectively, our data identify NEMO as a substrate for FMDV 3Cpro and reveal a novel mechanism evolved by a picornavirus to counteract innate immune signaling. PMID:22718831

  4. 5-fluorouracil in lethal mutagenesis of foot-and-mouth disease virus.

    PubMed

    Agudo, Rubén; Arias, Armando; Domingo, Esteban

    2009-06-01

    5-fluorouracil (FU) is a pyrimidine analogue extensively used in cancer chemotherapy. FU can be metabolized into 5-fluorouridine-triphosphate, which can be used as substrate for viral RNA-dependent RNA polymerases. This results in the incorporation of mutations into viral RNA. Accumulation of mutations may lead to loss of virus infectivity, in a process known as lethal mutagenesis. RNA virus pathogens are particularly difficult to control because they are highly mutable, and mutants resistant to antiviral agents are readily selected. Here, we review the basic principles of lethal mutagenesis as an antiviral approach, and the participation of FU in its development. Recent studies with foot-and-mouth disease virus indicate that FU can act both as an inhibitor and as a mutagen during foot-and-mouth disease virus replication. This dual activity renders FU an adequate drug for lethal mutagenesis. We suggest that structural and biochemical studies can contribute to the lead to new design of base or nucleoside analogues targeted specifically to viral polymerases.

  5. Inoculation of swine with foot-and-mouth disease SAP-mutant virus induces early protection against disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) leader proteinase (L^pro) cleaves itself from the viral polyprotein and cleaves the translation initiation factor eIF4G. As a result, host cell translation is inhibited, affecting the host innate immune response. We have demonstrated that L^pro is also associated ...

  6. Accuracy of Herdsmen Reporting versus Serologic Testing for Estimating Foot-and-Mouth Disease Prevalence

    PubMed Central

    Handel, Ian G.; Tanya, Vincent N.; Hamman, Saidou M.; Nfon, Charles; Bergman, Ingrid E.; Malirat, Viviana; Sorensen, Karl J.; Bronsvoort, Barend M. de C.

    2014-01-01

    Herdsman-reported disease prevalence is widely used in veterinary epidemiologic studies, especially for diseases with visible external lesions; however, the accuracy of such reports is rarely validated. Thus, we used latent class analysis in a Bayesian framework to compare sensitivity and specificity of herdsman reporting with virus neutralization testing and use of 3 nonstructural protein ELISAs for estimates of foot-and-mouth disease (FMD) prevalence on the Adamawa plateau of Cameroon in 2000. Herdsman-reported estimates in this FMD-endemic area were comparable to those obtained from serologic testing. To harness to this cost-effective resource of monitoring emerging infectious diseases, we suggest that estimates of the sensitivity and specificity of herdsmen reporting should be done in parallel with serologic surveys of other animal diseases. PMID:25417556

  7. Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli

    NASA Astrophysics Data System (ADS)

    Küpper, Hans; Keller, Walter; Kurz, Christina; Forss, Sonja; Schaller, Heinz

    1981-02-01

    Double-stranded DNA copies of the single-stranded genomic RNA of foot and mouth disease virus have been cloned into the Escherichia coli plasmid pBR322. A restriction map of the viral genome was established and aligned with the biochemical map of foot and mouth disease virus. The coding sequence for structural protein VP1, the major antigen of the virus, was identified and inserted into a plasmid vector where the expression of this sequence is under control of the phage λ PL promoter. In an appropriate host the synthesis of antigenic polypeptide can be demonstrated by radioimmunoassay.

  8. On The Use Of Models To Assess Foot-And-Mouth Disease Transmission And Control

    SciTech Connect

    Kostova-Vassilevska, T

    2004-07-12

    The 2001 outbreaks of foot-and-mouth disease (FMD) in Europe (Ferguson et al. 2001a, 2001b; Bouma et al. 2003) and concern about the possibility of an intentional introduction of a devastating foreign animal disease triggered renewed interest in both theoretical and experimental research related to FMD. Theoretical models of disease transmission, which influenced the tactical decisions of the United Kingdom (UK) government during the epidemic (Taylor 2003), resulted in large numbers of uninfected animals being slaughtered. After the epidemic, the adopted control policies were sharply criticized (Kitching 2004;, Taylor 2003). Still, the role of computationaL modeling for analyzing the scope of the epidemic and devising control strategies was recognized as substantial and necessary.

  9. Capsid coding sequences of foot-and-mouth disease viruses are determinants of pathogenicity in pigs.

    PubMed

    Lohse, Louise; Jackson, Terry; Bøtner, Anette; Belsham, Graham J

    2012-05-24

    The surface exposed capsid proteins, VP1, VP2 and VP3, of foot-and-mouth disease virus (FMDV) determine its antigenicity and the ability of the virus to interact with host-cell receptors. Hence, modification of these structural proteins may alter the properties of the virus.In the present study we compared the pathogenicity of different FMDVs in young pigs. In total 32 pigs, 7-weeks-old, were exposed to virus, either by direct inoculation or through contact with inoculated pigs, using cell culture adapted (O1K B64), chimeric (O1K/A-TUR and O1K/O-UKG) or field strain (O-UKG/34/2001) viruses. The O1K B64 virus and the two chimeric viruses are identical to each other except for the capsid coding region.Animals exposed to O1K B64 did not exhibit signs of disease, while pigs exposed to each of the other viruses showed typical clinical signs of foot-and-mouth disease (FMD). All pigs infected with the O1K/O-UKG chimera or the field strain (O-UKG/34/2001) developed fulminant disease. Furthermore, 3 of 4 in-contact pigs exposed to the O1K/O-UKG virus died in the acute phase of infection, likely from myocardial infection. However, in the group exposed to the O1K/A-TUR chimeric virus, only 1 pig showed symptoms of disease within the time frame of the experiment (10 days). All pigs that developed clinical disease showed a high level of viral RNA in serum and infected pigs that survived the acute phase of infection developed a serotype specific antibody response. It is concluded that the capsid coding sequences are determinants of FMDV pathogenicity in pigs.

  10. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE...

  11. Epidemiological features of hand-foot-and-mouth disease in Shenzhen, China from 2008 to 2010.

    PubMed

    Zheng, S; Cao, C X; Cheng, J Q; Wu, Y S; Xie, X; Xu, M

    2014-08-01

    This study analysed the spatio-temporal distribution and propagation of hand-foot-and-mouth disease (HFMD) in Shenzhen from 2008 to 2010. Specifically, we examined the epidemiological data, temporal distribution and spatial distribution, and then the relationship between meteorological, social factors and the number of reported HFMD cases was analysed using Spearman's rank correlation. Finally, a geographically weighted regression model was constructed for the number of reported HFMD cases in 2009. It was found that three independent variables, i.e. the number of reported HFMD cases in 2008 and, annual average temperature and precipitation, had different spatial impacts on the number of reported HFMD cases in 2009. In addition, these variables accounted for the propagation mechanism of HFMD in the centre and east of Shenzhen, where the high incidence rate areas are located. These results will be of great help in understanding the spatio-temporal distribution of HFMD and developing approaches to prevent this disease.

  12. Effect of foot-and-mouth disease virus on the frequency, phenotype and function of circulating dendritic cells in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms in FMDV-infected animals appear within 2 to 3 days of exposure. Dendritic cells (DC) play an essential role in protective immune responses agai...

  13. Sero-prevalence, risk factors and distribution of foot and mouth disease in Ethiopia.

    PubMed

    Abdela, Nejash

    2017-05-01

    Foot and mouth disease (FMD), world's most important highly infectious and contagious trans-boundary animal diseases, is responsible for huge global losses of livestock production as well as severe impacts on international trade. This vesicular disease is caused by foot and mouth disease virus of the genus Aphthovirus, family Picornaviridae. Currently FMD is major global animal health problem and endemic in Africa including Ethiopia. This paper systematically reviewed the sero-prevalence reports, associated risk factors and distribution of FMD in Ethiopia with the main aim of making compressive document on prevalence, risk factor and distribution of the disease thus helping as a basis for designing effective control strategies. FMD is widely distributed in Ethiopia and its prevalence varies from place to place with seropositivity that ranges from 5.6% to 42.7% in cattle and from 4% to 11% in small ruminant and in 30% in ungulate wildlife. In Ethiopia endemic distributions of five of seven serotypes, namely serotypes O, A, C, SAT1 and SAT2 have been documented. The dominant serotype being reported recently is serotype O and serotype C has not been reported in the country since 1983. However, serotype C specific antibody was detected in cattle indicating that circulation of serotype C viruses in the country may have gone unnoticed. The most common risk factor associated with FMD infection in Ethiopia includes production system, geographic location, species, age of animals, contact with wildlife and season of the year, mixed animal species and Breed. Conclusively, this paper revealed as FMD is posing a major threat in different area of the country thereby causing substantial economic losses through morbidity, mortality and restriction of international trade. Thus, demanding for great attention as its occurrence is may affect the export earnings of the country thereby threaten the livelihood of farmers and economy of the country at large.

  14. Molecular differentiation and phylogenetic analysis of the Egyptian foot-and-mouth disease virus SAT2.

    PubMed

    El-Shehawy, Laila I; Abu-Elnaga, Hany I; Rizk, Sonia A; Abd El-Kreem, Ahmed S; Mohamed, A A; Fawzy, Hossam G

    2014-03-01

    In February 2012, a massive new foot-and-mouth disease (FMD) outbreak struck Egypt. In this work, one-step RT-PCR assays were used for in-house detection and differentiation of foot-and-mouth disease virus (FMDV) in Egypt in this year using pan-serotypic and serotype-targeting sequence primers. FMDV SAT2 was the dominant virus in the examined isolates from the epidemic. The complete VP1 coding regions of two isolates were sequenced. The two isolates had 99.2 % sequence identity to most contemporary Egyptian SAT2 reference viruses, whereas they had 89.7-90.1 % identity to the SAT2/EGY/2/2012 isolate, which was collected from Alexandria, Egypt, and previously sequenced by WRLFMD. Phylogenetic analysis showed that Egypt had one topotype and two lineage of FMDV SAT2 in 2012. The Egyptian and the Palestinian 2012 strains were associated mainly with topotype VII, lineage SAT2/VII/Ghb-12, while the virus isolated from Alexandria Governorate belonged to the SAT2/VII/Alx-12 lineage. Topotype VII also comprised lineages that included strains isolated from Libya in 2012 and 2003. Furthermore, within the same topotype, the Egyptian SAT2/2012 isolates were related to strains from Saudi Arabia, Sudan, Eritrea, Cameroon and Nigeria. Nevertheless, more epidemiological work with neighboring countries is needed to prevent cross-border spread of disease and to reach a precise conclusion about the origin of the 2012 FMDV SAT2 emergency in the Middle East.

  15. Phylogeography of foot-and-mouth disease virus serotype O in Ecuador.

    PubMed

    de Carvalho, Luiz Max Fagundes; Santos, Leonardo Bacelar Lima; Faria, Nuno Rodrigues; de Castro Silveira, Waldemir

    2013-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of the most important disease of domestic cattle, foot-and-mouth disease. In Ecuador, FMDV is maintained at an endemic state, with sporadic outbreaks. To unravel the tempo and mode of FMDV spread within the country we conducted a Bayesian phylogeographic analysis using a continuous time Markov chain (CTMC) to model the diffusion of FMDV between Ecuadorian provinces. We implement this framework through Markov chain Monte Carlo available in the BEAST package to study 90 FMDV serotype O isolates from 17 provinces in the period 2002-2010. The Bayesian approach also allowed us to test hypotheses on the mechanisms of viral spread by incorporating environmental and epidemiological data in our prior distributions and perform Bayesian model selection. Our analyses suggest an intense flow of viral strains throughout the country that is possibly coupled to animal movements and ecological factors, since most of inferred viral spread routes were in Coast and Highland regions. Moreover, our results suggest that both short- and long-range spread occur within Ecuador. The province of Esmeraldas, in the border with Colombia and where most animal commerce is done, was found to be the most probable origin of the circulating strains, pointing to a transboundary behavior of FMDV in South America. These findings suggest that uncontrolled animal movements can create a favorable environment for FMDV maintenance and pose a serious threat to control programmes. Also, we show that phylogeographic modeling can be a powerful tool in unraveling the spatial dynamics of viruses and potentially in controlling the spread of these pathogens.

  16. Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

    PubMed

    Dong, Yan-mei; Zhang, Guo-guang; Huang, Xiao-jun; Chen, Liang; Chen, Hao-tai

    2015-05-01

    Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV.

  17. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71

    PubMed Central

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-01-01

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient’s symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis. PMID:26877620

  18. VP1 sequencing protocol for foot and mouth disease virus molecular epidemiology.

    PubMed

    Knowles, N J; Wadsworth, J; Bachanek-Bankowska, K; King, D P

    2016-12-01

    Nucleotide sequences of field strains of foot and mouth disease virus (FMDV) contribute to our understanding of the distribution and evolution of viral lineages that circulate in different regions of the world. This paper outlines a practical reversetranscription polymerase chain reaction (RT-PCR) and sequencing strategy that can be used to generate RNA sequences encoding the VP1 (1D) region of FMDV. The protocol contains a panel of PCR and sequencing primers that can be selected to characterise genetically diverse isolates representing all seven FMDV serotypes. A list of sequences is also described, comprising prototype sequences for all proposed FMDV topotypes, in order to provide a framework for phylogenetic analysis. The technical details and prototype sequences provided in this paper can be employed by FMD Reference Laboratories and others in an approach to harmonise the molecular epidemiology of FMDV.

  19. Potential of electrolyzed water for disinfection of foot-and-mouth disease virus.

    PubMed

    Bui, Vuong N; Nguyen, Khong V; Pham, Nga T; Bui, Anh N; Dao, Tung D; Nguyen, Thanh T; Nguyen, Hoa T; Trinh, Dai Q; Inui, Kenjiro; Uchiumi, Hiroshi; Ogawa, Haruko; Imai, Kunitoshi

    2017-02-18

    Acidic electrolyzed water (EW) (pH 2.6-5.8) and alkaline EW (pH 11.2-12.1) were examined as potential disinfectants against foot-and-mouth disease virus (FMDV). Using acidic EW with pH 2.6 and alkaline EW with pH>11.7, the viral titer decreased in vitro by >4.0 log values, 2 min after the virus was mixed with EW at a 1:10 dilution. The strong virucidal effect of acidic EW (pH 2.6), but not that of alkaline EW (>11.7), seemed to depend on the chlorine level in the solution. Genetic analysis revealed that viral RNA was substantially reduced, especially by alkaline EW.

  20. Dynamic impacts of a catastrophic production event: the foot-and-mouth disease case.

    PubMed

    Cordier, Alexandre; Gohin, Jean; Krebs, Stephane; Rault, Arnaud

    2013-03-01

    In foot-and-mouth disease (FMD) free countries, the occurrence of an FMD outbreak is a rare event with potentially large economic losses. We explore the dynamic effects of an FMD outbreak on market variables and economic surplus taking into account the largely neglected issue of farm bankruptcy. Simulations are performed on a stylized agricultural economy, which is a net exporter before the outbreak. We find complex dynamic market effects when the farm credit market suffers from information imperfections leading to farm closure. Welfare effects are also dramatically altered. Domestic consumers may lose in the long run from an FMD outbreak because domestic supply contracts. On the other hand, farmers able to resist this event may ultimately gain. Our analysis also shows that these effects are not monotone, making any efficient policy response to this catastrophic event quite challenging.

  1. Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design.

    PubMed

    Kotecha, Abhay; Seago, Julian; Scott, Katherine; Burman, Alison; Loureiro, Silvia; Ren, Jingshan; Porta, Claudine; Ginn, Helen M; Jackson, Terry; Perez-Martin, Eva; Siebert, C Alistair; Paul, Guntram; Huiskonen, Juha T; Jones, Ian M; Esnouf, Robert M; Fry, Elizabeth E; Maree, Francois F; Charleston, Bryan; Stuart, David I

    2015-10-01

    Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids.

  2. The 2001 foot and mouth disease epidemic in the United Kingdom: animal welfare perspectives.

    PubMed

    Crispin, S M; Roger, P A; O'Hare, H; Binns, S H

    2002-12-01

    The management of the foot and mouth disease (FMD) epidemic which occurred in the United Kingdom (UK) in 2001 resulted in widespread animal welfare problems. These problems arose firstly because of the large numbers of animals slaughtered to bring the epidemic under control, which meant that the conditions under which animals were slaughtered and the manner in which this was carried out often breached regulations concerning welfare at slaughter. Secondly, the restrictions imposed on movements, especially animal movements, resulted in what appeared to be readily avoidable difficulties with livestock dying from, for example, food shortages and pregnant animals giving birth under unsuitable conditions. This brief review is based on the personal experiences of the authors as well as relevant observations and reports from a variety of sources.

  3. [Demographic characteristics of patients with hand-foot-and-mouth disease. Atypical cases series].

    PubMed

    Gürkm, Asuman; Acar, Mehtap; Şenel, Saliha

    2015-08-01

    Hand-foot-and-mouth disease (HFMD) is a common childhood exanthem. Various types of lesions and widespread distribution in atypical cases have been described, but data on the predilection of lesion localizations in atypical cases are insufficient. We aimed to describe the demographic features of patients with HFMD, and to characterize lesion localizations in patients with atypical eruptions treated at an outpatient dermatology clinic of a pediatric hospital, between November 2011 and August 2013.The study included 67 patients. Mean age of the patients was 34 months and there was a male predominance (60%). All the patients had eruptions on hands, feet, and mouth. Children aged <24 months had involvement of the diaper area and extremities, which was significantly higher than those aged 24-48 months and >48 months (P < 0.0001 and P= 0.011, respectively). None of the patients had serious systemic complications.

  4. Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus.

    PubMed Central

    Kleina, L G; Grubman, M J

    1992-01-01

    The thiol protease inhibitor E-64 specifically blocks autocatalytic activity of the leader protease of foot-and-mouth disease virus (FMDV) and interferes with cleavage of the structural protein precursor in an in vitro translation assay programmed with virion RNA. Experiments with FMDV-infected cells and E-64 or a membrane-permeable analog, E-64d, have confirmed these results and demonstrated interference in virus assembly, causing a reduction in virus yield. In addition, there is a lag in the appearance of virus-induced cellular morphologic alterations, a delay in cleavage of host cell protein p220 and in shutoff of host protein synthesis, and a decrease in viral protein and RNA synthesis. The implications of using E-64-based compounds as potential antiviral agents for FMDV are discussed. Images PMID:1331517

  5. The stability and potency of vaccines prepared from inactivated foot-and-mouth disease virus concentrates.

    PubMed

    Doel, T R; David, D J

    1984-07-01

    The stability of 146S particles in concentrates of foot-and-mouth disease virus stored at 4 degrees C was similar to that of 146S particles in a conventional virus preparation. Proteolytic degradation of VPl was not observed in the stored conventional virus preparation or inhibitor-supplemented concentrate but was observed in a supplement-free concentrate. The potencies of vaccines made from the conventional and concentrated preparations and stored in parallel at 4 degrees C appeared to decrease after 16 weeks. The vaccines made from the supplement-free concentrate and the Trasylol supplemented concentrate appeared to be at least as potent as the conventional vaccine and were clearly superior to vaccine made from ox serum supplemented concentrate.

  6. Detection of hand, foot and mouth disease in the yucatan peninsula of Mexico.

    PubMed

    Machain-Williams, Carlos; Dzul-Rosado, Alma R; Yeh-Gorocica, Aarón B; Rodriguez-Ruz, Katia G; Noh-Pech, Henry; Talavera-Aguilar, Lourdes; Salazar, Ma Isabel; Castro-Mussot, María Eugenia; Reyes-Solis, Guadalupe; Garcia-Rejon, Julián E; Puerto-Manzano, Fernando I; Blitvich, Bradley J

    2014-11-19

    We report a case of hand, foot and mouth disease (HFMD) in a 5-year-old male from Merida City in the Yucatan Peninsula of Mexico. A clinical and physical examination revealed that the patient had symptoms typical of HFMD, including fever, fatigue, odynophagia, throat edema, hyperemia, lesions on the hands and feet, and blisters in the oral cavity. The patient fully recovered after a convalescence period of almost three weeks. Reverse transcription-polymerase chain reaction and nucleotide sequencing revealed that the etiological agent was enterovirus 71 (EV71). The sequence has greatest (90.4%) nucleotide identity to the corresponding regions of EV71 isolates from the Netherlands and Singapore. Although HFMD is presumably common in Mexico, surprisingly there are no data in the PubMed database to support this. This case report provides the first peer-reviewed evidence of HFMD in Mexico.

  7. Detection of Hand, Foot and Mouth Disease in the Yucatan Peninsula of Mexico

    PubMed Central

    Machain-Williams, Carlos; Dzul-Rosado, Alma R.; Yeh-Gorocica, Aarón B.; Rodriguez-Ruz, Katia G.; Noh-Pech, Henry; Talavera-Aguilar, Lourdes; Salazar, Ma. Isabel; Castro-Mussot, María Eugenia; Reyes-Solis, Guadalupe; Garcia-Rejon, Julián E.; Puerto-Manzano, Fernando I.; Blitvich, Bradley J.

    2014-01-01

    We report a case of hand, foot and mouth disease (HFMD) in a 5-year-old male from Merida City in the Yucatan Peninsula of Mexico. A clinical and physical examination revealed that the patient had symptoms typical of HFMD, including fever, fatigue, odynophagia, throat edema, hyperemia, lesions on the hands and feet, and blisters in the oral cavity. The patient fully recovered after a convalescence period of almost three weeks. Reverse transcription-polymerase chain reaction and nucleotide sequencing revealed that the etiological agent was enterovirus 71 (EV71). The sequence has greatest (90.4%) nucleotide identity to the corresponding regions of EV71 isolates from the Netherlands and Singapore. Although HFMD is presumably common in Mexico, surprisingly there are no data in the PubMed database to support this. This case report provides the first peer-reviewed evidence of HFMD in Mexico. PMID:25568757

  8. Constitutively active IRF7/IRF3 fusion protein completely protects swine against Foot-and-Mouth Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) remains one of the most devastating livestock diseases around the world. Several serotype specific vaccine formulations exist but require about 5-7 days to induce protective immunity. Our previous studies have shown that a constitutively active fusion protein of porcine ...

  9. Suppression of Swine NK Cell Function During Acute Infection with Foot-and-Mouth Disease Virus (FMDV)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and causes an economically devastating disease. This highly acute infection has multiple negative effects on the innate response, presumably contributing to the rapid spread of virus within the host. Understanding the regulation of in...

  10. Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) resea...

  11. Control of foot-and-mouth disease by using replication-defective human adenoviruses to deliver vaccines and biotherapeutics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  12. Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

  13. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FM...

  14. Different public health geographies of the 2001 foot and mouth disease epidemic: 'citizen' versus 'professional' epidemiology.

    PubMed

    Bailey, Cathy; Convery, Ian; Mort, Maggie; Baxter, Josephine

    2006-06-01

    Recently, there have been calls for health geographers to add critical and theoretical debate to 'post-medical' geographies, whilst at the same time informing 'new' public health strategies (Soc. Sci. Med. 50(9)1273; Area 33(4) (2002) 361). In this paper we reflect on how, alongside 'professional epidemiologies', 'citizen epidemiologies' can have credibility in informing public health policy and practice. We do this by drawing on mixed method and participatory research that used a citizens' panel to articulate the health and social outcomes of the 2001 foot and mouth disease disaster. We consider the difficulties of creating dialogue between on the one hand, time-limited, discrete, theoretical, visible and by implication legitimate, 'professional' knowledge and on the other, ongoing, holistic, experiential and often hidden 'citizen' knowledge of the foot and mouth disease epidemic. Despite significant evidence that in disaster and crisis situations, people need to be actively involved in key 'recovery' decisions (see for example At Risk Natural Hazards, People's Vulnerability, and Disasters, Routledge, London; A New Species of Trouble, Norton, New York), lay accounts, which may in themselves provide valuable evidence about the impact of the disaster, are often ignored. If health geographers are to critically inform 'new' public health policy then we need to consider research approaches that give voice to citizens' understanding of health outcomes as well as those of professionals. If 'new' public health is concerned with the material character of health inequalities, with fostering 'healthy' living and working environments, the promotion of community participation and individual empowerment (Area 33(4) (2002) 361), then we argue that situated, negotiated, everyday geographies of lay epidemiologies can and should inform public health policy.

  15. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs.

    PubMed

    Blignaut, Belinda; Visser, Nico; Theron, Jacques; Rieder, Elizabeth; Maree, Francois F

    2011-04-01

    Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of SAT1 virus KNP/196/91. The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and antigenic profiles to the KNP/196/91 parental virus, thus indicating that the functions provided by the capsid can be readily exchanged between serotypes. As these qualities are necessary for vaccine manufacturing, high titres of stable chimeric virus were obtained. Chemically inactivated vaccines, formulated as double-oil-in-water emulsions, were produced from intact 146S virion particles of both the chimeric and parental viruses. Inoculation of guinea pigs with the respective vaccines induced similar antibody responses. In order to show compliance with commercial vaccine requirements, the vaccines were evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralizing antibodies and showed protection against homologous FMDV challenge, albeit not to the same extent as for the vaccine prepared from the parental virus. These results provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and that they induce protective immune responses in FMD host species.

  16. Developing vaccines against foot-and-mouth disease and some other exotic viral diseases of livestock

    PubMed Central

    Paton, David J.; Taylor, Geraldine

    2011-01-01

    Vaccines remain the main tool for the control of livestock viral diseases that pose a serious threat to animal and occasionally human health, reduce food security, distort trade in animals and their products, and undermine agricultural development in poor countries. Globalization and climate change increase the likelihood for new patterns of emergence and spread of livestock viruses. Conventionally attenuated and killed virus products have had spectacular success, and recent examples include the global eradication of rinderpest and the control of bluetongue in the UK and northern Europe. However, in many cases, livestock vaccines could benefit from improvement in some properties (e.g. stability, speed of onset and duration of immunity, and breadth of cross-protection to different serotypes or strains) and in some cases are not available at all. Compared with human vaccines, uptake of livestock products is highly cost-sensitive and their use may also need to be compatible with post-vaccination screening methods to determine whether or not animals continue to be infected. Requirements and prospects for new or improved vaccines are described for some priority viral diseases with potential for transboundary spread, particularly for foot-and-mouth disease. PMID:21893540

  17. Developing vaccines against foot-and-mouth disease and some other exotic viral diseases of livestock.

    PubMed

    Paton, David J; Taylor, Geraldine

    2011-10-12

    Vaccines remain the main tool for the control of livestock viral diseases that pose a serious threat to animal and occasionally human health, reduce food security, distort trade in animals and their products, and undermine agricultural development in poor countries. Globalization and climate change increase the likelihood for new patterns of emergence and spread of livestock viruses. Conventionally attenuated and killed virus products have had spectacular success, and recent examples include the global eradication of rinderpest and the control of bluetongue in the UK and northern Europe. However, in many cases, livestock vaccines could benefit from improvement in some properties (e.g. stability, speed of onset and duration of immunity, and breadth of cross-protection to different serotypes or strains) and in some cases are not available at all. Compared with human vaccines, uptake of livestock products is highly cost-sensitive and their use may also need to be compatible with post-vaccination screening methods to determine whether or not animals continue to be infected. Requirements and prospects for new or improved vaccines are described for some priority viral diseases with potential for transboundary spread, particularly for foot-and-mouth disease.

  18. QS-21 enhances the early antibody response to oil adjuvant foot-and-mouth disease vaccine in cattle

    PubMed Central

    2016-01-01

    Purpose One of the most important tools against foot-and-mouth disease, a highly contagious and variable viral disease of cloven-hoofed animals, is vaccination. However, the effectiveness of foot-and-mouth disease vaccines on slowing the spread of the disease is questionable. In contrast, high potency vaccines providing early protection may solve issues with the spread of the disease, escaping mutants, and persistency. To increase the potency of the vaccine, additives such as saponin and aluminium hydroxide are used. However, the use of saponin with an oil adjuvant is not common and is sometimes linked to toxicity. QS-21, which is less toxic than Quil A, has been presented as an alternative for use with saponin. In this study, the addition of QS-21 to a commercially available foot-and-mouth disease water-in-oil-in-water emulsion vaccine was evaluated in cattle. Materials and Methods After vaccination, serum samples were collected periodically over 3 months. Sera of the QS-21 and normal oil vaccine groups were compared via serum virus neutralization antibody titre and liquid phase blocking enzyme-linked immunosorbent assay antibody titre. Results The results showed that there was a significant early antibody increase in the QS-21 group. Conclusion Strong early virus neutralizing antibody response will be useful for emergency or ring vaccinations against foot-and-mouth disease in target animals. PMID:27489804

  19. Structure-based discovery of foot-and-mouth disease inhibitors that target the 3Dpol RNA-dependent RNA polymerase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease Virus (FMDV) primarily targets cloven-hoofed animals. The FMDV outbreak results in significant economic losses. There are currently no available antiviral drugs for Foot-and-Mouth Disease (FMD) treatment, and vaccination needs at least 7 days to effectively trigger the immune...

  20. Heparan Sulfate-Binding Foot-and-Mouth Disease Virus Enters Cells Via Caveolae-Mediated Endocytosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) utilizes different cell surface macromolecules to facilitate infection of cultured cells. Virus which is virulent for susceptible animals infects cells via four members of the alpha V subclass of cellular integrins. In contrast, tissue culture adaptation of some...

  1. Role of Jumonji c-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) can utilize as many as three distinct groups of receptor molecules to attach and enter a susceptible host cell. Four integrin heterodimers (alphavBeta1, alphavBeta3, alphavBeta6, and alphavBeta8) can function as the primary receptor for FMDV field strains. FMDV ...

  2. Poetic Justice? Rural Policy Clashes with Rural Poetry in the 2001 Outbreak of Foot and Mouth Disease in the UK

    ERIC Educational Resources Information Center

    Nerlich, Brigitte; Doring, Martin

    2005-01-01

    In 2001, the foot and mouth disease epidemic in the UK gave rise to widespread individual and community trauma and has had negative health, economic and social impacts on the people who live in affected rural areas. Many found strength by sharing their experiences with friends and relatives; others expressed their feelings in poems and art. Using…

  3. Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained several positively charged amino acids...

  4. An integrative analysis of foot-and-mouth disease virus carriers in Vietnam achieved through targeted surveillance and molecular epidemiology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A multidisciplinary, molecular and conventional epidemiological approach was applied to an investigation of endemic foot-and-mouth disease in Vietnam. Within the study space, it was found that 22.3 percent of sampled ruminants had previously been infected with FMD virus (FMDV) and that 2.4 percent w...

  5. Characterization of a chimeric foot-and-mouth disease virus bearing bovine rhinitis B virus leader proteinase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our recent study has shown that bovine rhinovirus type 2 (BRV2), a new member of the Aphthovirus genus, shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). Despite low sequence conservation (36percent amino acid identity) and N- and C-terminus folding differences,...

  6. Exploring the role of the lab protein of Foot-and-Mouth Disease Virus (FMDV) during viral infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leader (L) protein of Foot-and-Mouth Disease Virus (FMDV) displays two forms, Lab and Lb, through initiation of translation at two in-frame AUG codons positioned 84 nucleotides apart. The short form (Lb) is the most abundant and functionally well characterized form of L. The presence of these tw...

  7. Differential gene expression in bovine cells infected with wild type and leaderless foot-and-mouth disease virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) plays a critical role in viral pathogenesis. Molecular studies have demonstrated that Lpro inhibits the translation of host capped mRNAs and transcription of some genes involved in the innate immune response to viral infection. Here...

  8. A partial deletion in non-structural protein 3A can attenuate foot-and-mouth disease virus in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of non-structural protein 3A in foot-and-mouth disease virus (FMDV) on the virulence in cattle has received significant attention. Particularly, a characteristic 10–20 amino acid deletion has been implicated as being responsible for virus attenuation in cattle: a 10 amino acid deletion in t...

  9. Pathogenesis of primary foot-and-mouth disease virus infection in the nasopharynx of vaccinated and non-vaccinated cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection in vaccinated and non-vaccinated cattle following simulated-natural virus exposure. FMDV genome and infectious virus were detected during the initial phase of infection from b...

  10. Stress and Stereotypes: Children's Reactions to the Outbreak of Foot and Mouth Disease in the UK in 2001

    ERIC Educational Resources Information Center

    Nerlich, Brigitte; Hillyard, Sam; Wright, Nick

    2005-01-01

    In 2001 foot and mouth disease broke out in the UK and millions of farm animals were slaughtered in order to eradicate it. This affected farmers, town dwellers, adults and children. Based on a small sample of 56 e-mails to a children's BBC (CBBC) message board and using an ethnomethodological approach, this article explores the way in which…

  11. Infection dynamics of foot-and-mouth disease virus in cattle following intra-nasopharyngeal inoculation or contact exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the purpose of developing an improved experimental model for studies of foot-and-mouth disease virus (FMDV) infection in cattle, three different experimental systems based on natural or simulated-natural virus exposure were compared under standardized experimental conditions. Antemortem infecti...

  12. 9 CFR 94.1 - Regions where rinderpest or foot-and-mouth disease exists; importations prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Regions where rinderpest or foot-and-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF...

  13. 9 CFR 94.1 - Regions where rinderpest or foot-and-mouth disease exists; importations prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Regions where rinderpest or foot-and-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF...

  14. 9 CFR 94.1 - Regions where rinderpest or foot-and-mouth disease exists; importations prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Regions where rinderpest or foot-and-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EXPORTATION AND IMPORTATION OF...

  15. Adaptive Responses and Asset Strategies: The Experience of Rural Micro-Firms and Foot and Mouth Disease

    ERIC Educational Resources Information Center

    Phillipson, Jeremy; Bennett, Katy; Lowe, Philip; Raley, Marian

    2004-01-01

    The 2001 Foot and Mouth Disease (FMD) epidemic effectively closed large parts of the UK countryside for several months. Local firms found their operations disrupted and suffered losses of trade. The individual and collective experiences of affected firms provide vivid insights into how rural businesses and the local economies they constitute…

  16. A colorimetric bioassay for high-througput and cost-effectively assessing anti-foot-and-mouth disease virus activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease virus (FMDV) is one of the most contagious animal viruses and has a devastating effect on livestock industries if an outbreaks occurs, especially in FMD-free countries. The virus is very sensitive to inhibition by type I interferons. Currently, a reported assay to measure FM...

  17. Venezuelan Equine Encephalitis Virus replicon particles can induce rapid protection against Foot-and-Mouth Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that swine pretreated with a replication-defective human adenovirus vector (Ad5) containing the porcine type I interferon gene (poIFN-alpha/Beta) are sterilely protected when challenged one day later with Foot-and-Mouth Disease Virus (FMDV), but the dose required is relativ...

  18. Foot-and-mouth disease virus serotype O phylodynamics: genetic variability associated with epidemiological factors in Pakistan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the most challenging aspects of foot-and-mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating ...

  19. SAT2 foot-and-mouth disease virus (FMDV) structurally modified for increased thermostability.

    PubMed

    Scott, Katherine A; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E; Stuart, David I; Charleston, Bryan; Maree, Francois F

    2017-03-15

    Foot-and-mouth disease virus (FMDV) is notoriously unstable, particularly the O and SAT serotypes. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of poor duration immunity and hence require more frequent vaccinations to ensure protection. In-silico calculations predicted residue substitutions that would increase interactions at the inter-pentameric interface supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses for their growth kinetics; antigenicity; plaque morphology; genetic stability; temperature, ionic and pH stability using the thermofluor and inactivation assays, in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutation was the single mutant S2093Y for temperature and pH stability, whilst other promising single mutants were E3198A, L2094V,S2093H and the triple mutant F2062Y-H2087M-H3143V. Although the S2093Y mutant had the greatest stability it exhibited smaller plaques; a reduced growth rate; a change in a monoclonal antibody footprint, and poor genetic stability properties compared to the wild-type virus. However, these factors affecting production can be overcome. The addition of 1M NaCl salt was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilising SAT2 vaccines.IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of serotypes such as SAT2 affects the quality of the vaccine and therefore the duration of immunity. We have shown that by mutating residues at the capsid interface through predictive modelling we can improve the stability of SAT2 viruses. This is an important finding for the potential use of such mutants in improving the

  20. Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs

    PubMed Central

    Stenfeldt, Carolina; Pacheco, Juan M.; Brito, Barbara P.; Moreno-Torres, Karla I.; Branan, Matt A.; Delgado, Amy H.; Rodriguez, Luis L.; Arzt, Jonathan

    2016-01-01

    Understanding the quantitative characteristics of a pathogen’s capability to transmit during distinct phases of infection is important to enable accurate predictions of the spread and impact of a disease outbreak. In the current investigation, the potential for transmission of foot-and-mouth disease virus (FMDV) during the incubation (preclinical) period of infection was investigated in seven groups of pigs that were sequentially exposed to a group of donor pigs that were infected by simulated-natural inoculation. Contact-exposed pigs were comingled with infected donors through successive 8-h time slots spanning from 8 to 64 h post-inoculation (hpi) of the donor pigs. The transition from latent to infectious periods in the donor pigs was clearly defined by successful transmission of foot-and-mouth disease (FMD) to all contact pigs that were exposed to the donors from 24 hpi and later. This onset of infectiousness occurred concurrent with detection of viremia, but approximately 24 h prior to the first appearance of clinical signs of FMD in the donors. Thus, the latent period of infection ended approximately 24 h before the end of the incubation period. There were significant differences between contact-exposed groups in the time elapsed from virus exposure to the first detection of FMDV shedding, viremia, and clinical lesions. Specifically, the onset and progression of clinical FMD were more rapid in pigs that had been exposed to the donor pigs during more advanced phases of disease, suggesting that these animals had received a higher effective challenge dose. These results demonstrate transmission and dissemination of FMD within groups of pigs during the incubation period of infection. Furthermore, these findings suggest that under current conditions, shedding of FMDV in oropharyngeal fluids is a more precise proxy for FMDV infectiousness than clinical signs of infection. These findings may impact modeling of the propagation of FMD outbreaks that initiate

  1. An alternate delivery system improves vaccine performance against foot-and-mouth disease virus (FMDV).

    PubMed

    Pandya, Mital; Pacheco, Juan M; Bishop, Elizabeth; Kenney, Mary; Milward, Francis; Doel, Timothy; Golde, William T

    2012-04-26

    Foot-and-mouth disease virus (FMDV) causes vesicular disease of cloven-hoofed animals with severe agricultural and economic implications. One of the most highly infectious and contagious livestock pathogens known, the disease spreads rapidly in naïve populations making it critical to have rapidly acting vaccines. Needle inoculation of killed virus vaccine is an efficient method of swiftly vaccinating large numbers of animals, either in eradication efforts or in outbreak situations in disease free countries, although, to be efficient, this requires utilizing the same needle with multiple animals. Here we present studies using a needle free system for vaccination with killed virus vaccine, FMDV strain O1 Manisa, as a rapid and consistent delivery platform. Cattle were vaccinated using a commercially available vaccine formulation at the manufacturer's recommended dose as well as four and sixteen fold less antigen load per dose. Animals were challenged intradermalingually (IDL) with live, virulent virus, homologous strain O1 Manisa, at various times following vaccination. All non-vaccinated control cattle exhibited clinical disease, including fever, viremia and lesions, specifically vesicle formation. Cattle vaccinated with the 1/16× and 1/4× doses using the needle free device were protected when challenged at both 7 and 28 days after vaccination. These data suggest that effective protection against disease can be achieved with 1/16 of the recommended vaccine dose when delivered using the needle free, intradermal delivery system, indicating the current vaccine stockpile that can be extended by many fold using this system.

  2. Decision-making for foot-and-mouth disease control: Objectives matter

    USGS Publications Warehouse

    Probert, William J. M.; Shea, Katriona; Fonnesbeck, Christopher J.; Runge, Michael C.; Carpenter, Tim E.; Durr, Salome; Garner, M. Graeme; Harvey, Neil; Stevenson, Mark A.; Webb, Colleen T.; Werkman, Marleen; Tildesley, Michael J.; Ferrari, Matthew J.

    2016-01-01

    Formal decision-analytic methods can be used to frame disease control problems, the first step of which is to define a clear and specific objective. We demonstrate the imperative of framing clearly-defined management objectives in finding optimal control actions for control of disease outbreaks. We illustrate an analysis that can be applied rapidly at the start of an outbreak when there are multiple stakeholders involved with potentially multiple objectives, and when there are also multiple disease models upon which to compare control actions. The output of our analysis frames subsequent discourse between policy-makers, modellers and other stakeholders, by highlighting areas of discord among different management objectives and also among different models used in the analysis. We illustrate this approach in the context of a hypothetical foot-and-mouth disease (FMD) outbreak in Cumbria, UK using outputs from five rigorously-studied simulation models of FMD spread. We present both relative rankings and relative performance of controls within each model and across a range of objectives. Results illustrate how control actions change across both the base metric used to measure management success and across the statistic used to rank control actions according to said metric. This work represents a first step towards reconciling the extensive modelling work on disease control problems with frameworks for structured decision making.

  3. Financial Impacts of Foot-and-Mouth Disease at Village and National Levels in Lao PDR.

    PubMed

    Nampanya, S; Khounsy, S; Abila, R; Young, J R; Bush, R D; Windsor, P A

    2016-10-01

    To assist policies on Foot-and-Mouth Disease (FMD) control in Laos and the Mekong region, the financial impact of recent outbreaks at village and national levels was examined. Village-level impacts were derived from recent research on financial losses due to FMD per smallholder household and number of households with FMD-affected livestock in the village. National-level impacts of FMD were determined from examination of 2011-2013 FMD reported to the Lao Department of Livestock and Fisheries (DLF), with the 2011 epidemic reported separately due to the large number and size of outbreaks of FMD in that year. Estimates of the national financial impact of FMD were based on (i) total FMD financial losses at the village level and (ii) the costs of FMD responses and other related costs at the DLF, provincial and district levels where FMD was reported, but excluding the costs of revenue forgone. A Monte Carlo simulation was utilized to account for likelihood of FMD over- and under-reporting. Foot-and-mouth disease was recorded in four provinces of Phonsaly, Bokeo, Xayyabouli and Champasak in three consecutive years from 2011 to 2013. However, the FMD epidemic in 2011 was more widely distributed and involved 414 villages in 14 provinces, with thousands of cases of morbidity in cattle and buffalo and some mortalities. The estimated financial losses due to FMD in 2011 were USD 30 881(±23 176) at the village level and USD 13 512 291 at the national level based on the number of villages with FMD outbreaks reported. However, when the likelihood of FMD under-reporting was accounted for, the estimated financial losses at the national level could potentially increase to USD 102 094 464 (±52 147 261), being almost 12% of the estimated farm gate value of the national large ruminant herd. These findings confirm that FMD causes substantial financial impacts in villages and to the national economy of Laos, providing justification for sustained investments in FMD control

  4. Control of the deliberate spread of foot-and-mouth disease virus.

    PubMed

    Farsang, Attila; Frentzel, Hendrik; Kulcsár, Gábor; Soós, Tibor

    2013-09-01

    Foot-and-mouth disease (FMD) is one of the most feared of transboundary animal diseases. Accidental or deliberate release of the causative agent can have both direct and indirect effects that result in massive economic losses and disruption. The direct effects of an FMD outbreak include immediate losses to agricultural production and disruption of local economies, while the indirect effects are mainly related to disease control measures such as restriction of market access at local and global levels and the high costs of disease control. To improve the capacity of the European Union (EU) to counter animal bioterrorism threats, AniBioThreat was launched with a special focus on threats to living animals, feed, and food of animal origin. As part of this project, several zoonotic or animal pathogenic agents are considered from different perspectives. FMD virus was selected as one agent to be scrutinized because it is highly contagious and an outbreak can have a severe economic impact. Ways to fight a deliberate outbreak can be demonstrated through the example of FMD. In this article, the virology and epidemiology of FMD virus are discussed with special attention to the related law enforcement aspects.

  5. Poverty impacts of foot-and-mouth disease and the poverty reduction implications of its control.

    PubMed

    Perry, B D; Rich, K M

    2007-02-17

    Foot-and-mouth disease (FMD) remains one of the most important livestock diseases of the world, given its highly infectious nature, its broad economic impacts on animal wellbeing and productivity, and its implications for successful access to domestic and export markets for livestock and products. The impacts of the disease vary markedly between developed and developing countries, and also within many developing countries. These differences in impact shape some markedly heterogeneous incentives for FMD control and eradication, which become of particular importance when setting priorities for poverty reduction in developing countries. Some consider that the benefits from FMD control accrue only to the better off in such societies and, as such, may not be a priority for investments targeted at poverty reduction. But is that view justified? Others see the control of FMD as a major development opportunity in a globalised environment. In this paper, Brian Perry and Karl Rich summarise the differential impacts of FMD and its control, and link these findings with the growing understanding of how the control of this globally important disease may contribute to the processes of pro-poor growth in certain countries of the developing world.

  6. First isolation and molecular characterization of foot-and-mouth disease virus in Benin.

    PubMed

    Gorna, Kamila; Houndjè, Evelyne; Romey, Aurore; Relmy, Anthony; Blaise-Boisseau, Sandra; Kpodékon, Marc; Saegerman, Claude; Moutou, François; Zientara, Stephan; Bakkali Kassimi, Labib

    2014-06-25

    Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. It is one of the most economically devastating diseases affecting livestock animals. In West Africa, where constant circulation of FMD virus (FMDV) is assumed, very few studies on the characterization of circulating strains have been published. This study describes the first isolation and characterization of FMDV in Benin. FMDV was isolated from 42 samples. Antigen Capture Elisa (Ag-ELISA) and VP1 coding sequence analysis revealed 33 strains of serotype O and 9 strains of serotype A. Phylogenetic analysis of the VP1 sequence revealed two different groups of type O isolates and one group of A isolates. VP1 sequence comparison with the sequences available in the GenBank database revealed a close relationship of the Benin isolates with topotype O of West Africa and with African topotype A of genotype VI. Knowledge of the recent strains circulating in Benin should contribute to better selection of vaccine strains and enable the updating of molecular epidemiology data available for West Africa in general.

  7. Spatio-Temporal Distribution and Hotspots of Hand, Foot and Mouth Disease (HFMD) in Northern Thailand

    PubMed Central

    Samphutthanon, Ratchaphon; Kumar Tripathi, Nitin; Ninsawat, Sarawut; Duboz, Raphael

    2013-01-01

    Hand, Foot and Mouth Disease (HFMD) is an emerging viral disease, and at present, there are no antiviral drugs or vaccines available to control it. Outbreaks have persisted for the past 10 years, particularly in northern Thailand. This study aimed to elucidate the phenomenon of HFMD outbreaks from 2003 to 2012 using general statistics and spatial-temporal analysis employing a GIS-based method. The spatial analysis examined data at the village level to create a map representing the distribution pattern, mean center, standard deviation ellipse and hotspots for each outbreak. A temporal analysis was used to analyze the correlation between monthly case data and meteorological factors. The results indicate that the disease can occur at any time of the year, but appears to peak in the rainy and cold seasons. The distribution of outbreaks exhibited a clustered pattern. Most mean centers and standard deviation ellipses occurred in similar areas. The linear directional mean values of the outbreaks were oriented toward the south. When separated by season, it was found that there was a significant correlation with the direction of the southwest monsoon at the same time. An autocorrelation analysis revealed that hotspots tended to increase even when patient cases subsided. In particular, a new hotspot was found in the recent year in Mae Hong Son province. PMID:24366049

  8. Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong

    PubMed Central

    Yang, Bingyi; Lau, Eric H. Y.; Wu, Peng; Cowling, Benjamin J.

    2016-01-01

    Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (Rt) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with Rt were examined using linear regression. Rt usually started increasing between early spring and summer and peaked in April to May at around 1.1–1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in Rt. We found a negative association between depletion of susceptibles and Rt (coefficients ranged from −0.14 to −0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays. PMID:27271966

  9. Modeling Estimated Personnel Needs for a Potential Foot and Mouth Disease Outbreak

    SciTech Connect

    Simmons, K; Hullinger, P

    2008-01-29

    Foot and Mouth disease (FMD) is a highly infectious and contagious viral disease affecting cloven-hoofed livestock that was last detected in the United States (US) in 1929. The prevalence of FMD in other countries, as well as the current potential for this virus to be used as a form of agroterrorism, has made preparations for a potential FMD outbreak a national priority. To assist in the evaluation of national preparedness, all 50 states were surveyed via e-mail, telephone and web search to obtain emergency response plans for FMD or for foreign animal diseases in general. Information from 33 states was obtained and analyzed for estimates of personnel resources needed to respond to an outbreak. These estimates were consolidated and enhanced to create a tool that could be used by individual states to better understand the personnel that would be needed to complete various tasks over time during an outbreak response. The estimates were then coupled, post-processing, to the output from FMD outbreaks simulated in California using the Multiscale Epidemiological/Economic Simulation and Analysis (MESA) model at Lawrence Livermore National Laboratory to estimate the personnel resource demands, by task, over the course of an outbreak response.

  10. Hand, Foot, and Mouth Disease in China: Critical Community Size and Spatial Vaccination Strategies

    PubMed Central

    Van Boeckel, Thomas P.; Takahashi, Saki; Liao, Qiaohong; Xing, Weijia; Lai, Shengjie; Hsiao, Victor; Liu, Fengfeng; Zheng, Yaming; Chang, Zhaorui; Yuan, Chen; Metcalf, C. Jessica E.; Yu, Hongjie; Grenfell, Bryan T.

    2016-01-01

    Hand Foot and Mouth Disease (HFMD) constitutes a considerable burden for health care systems across China. Yet this burden displays important geographic heterogeneity that directly affects the local persistence and the dynamics of the disease, and thus the ability to control it through vaccination campaigns. Here, we use detailed geographic surveillance data and epidemic models to estimate the critical community size (CCS) of HFMD associated enterovirus serotypes CV-A16 and EV-A71 and we explore what spatial vaccination strategies may best reduce the burden of HFMD. We found CCS ranging from 336,979 (±225,866) to 722,372 (±150,562) with the lowest estimates associated with EV-A71 in the southern region of China where multiple transmission seasons have previously been identified. Our results suggest the existence of a regional immigration-recolonization dynamic driven by urban centers. If EV-A71 vaccines doses are limited, these would be optimally deployed in highly populated urban centers and in high-prevalence areas. If HFMD vaccines are included in China’s National Immunization Program in order to achieve high coverage rates (>85%), routine vaccination of newborns largely outperforms strategies in which the equivalent number of doses is equally divided between routine vaccination of newborns and pulse vaccination of the community at large. PMID:27125917

  11. In vitro anti-foot-and-mouth disease virus activity of magnesium oxide nanoparticles.

    PubMed

    Rafiei, Solmaz; Rezatofighi, Seyedeh Elham; Ardakani, Mohammad Roayaei; Madadgar, Omid

    2015-10-01

    Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven-hoofed animals that can lead to huge economic losses in the livestock production. No antiviral therapies are available for treating FMD virus (FMDV) infections in animals. The antiviral effects of magnesium oxide nanoparticles (MgO NPs) on the FMDV were investigated in cell culture. The viability of the cells after MgO NP treatment was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The direct effects of MgO NPs on the FMDV in extracellular (virucidal assay) and also different stages of virus replication (antiviral assay) were evaluated by plaque reduction assay. The results showed that MgO NPs were safe at concentrations up to 250 µg/ml in the Razi Bovine kidney cell line. The treatments with NPs indicated that the MgO NPs exerted in vitro virucidal and antiviral activities. Plaque reduction assay revealed that MgO NPs can inhibit FMDV by more than 90% at the early stages of infection such as attachment and penetration but not after penetration. The results of this study suggested that NPs might be applied locally as an antiviral agent in early stages of infection in susceptible animals.

  12. The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing

    NASA Astrophysics Data System (ADS)

    Dong, Weihua; Li, Xian’En; Yang, Peng; Liao, Hua; Wang, Xiaoli; Wang, Quanyi

    2016-01-01

    The morbidity and mortality of hand, foot and mouth disease (HFMD) are increasing in Beijing, China. Previous studies have indicated an association between incidents of HFMD and weather factors. However, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (EV71) and Coxsackie virus A16 (CV-A16) viruses are not well documented. We analysed 84,502 HFMD cases from 2008 to 2011 in Beijing to explore the seasonal influence of weather factors (average temperature [AT], average relative humidity [ARH], total precipitation [TP] and average wind speed [AWS]) on incidents of HFMD by using a geographically weighted regression (GWR) model. The results indicated that weather factors differ significantly in their influence on HFMD depending on the season. AT had the greatest effect among the four weather factors, and while the influence of AT and AWS was greater in the summer than in the winter, the influence of TP was positive in the summer and negative in the winter. ARH was negatively correlated with HFMD. Also, we observed more EV71-associated cases than CV-A16 but there is no convincing evidence to show significant differences between the influences of the weather factors on EV71 and CV-A16.

  13. EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD).

    PubMed

    Mao, Qun-ying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-05-01

    On December 3rd 2015, the China Food and Drug Administration (CFDA) approved the first inactivated Enterovirus 71 (EV71) whole virus vaccine for preventing severe hand, foot and mouth disease (HFMD). As one of the few preventive vaccines for children's infectious diseases generated by the developing countries in recent years, EV71 vaccine is a blessing to children's health in China and worldwide. However, there are still a few challenges facing the worldwide use of EV71 vaccine, including the applicability against various EV71 pandemic strains in other countries, international requirements on vaccine production and quality control, standardization and harmonization on different pathogen monitoring and detecting methods, etc. In addition, the affordability of EV71 vaccine in other countries is a factor to be considered in HFMD prevention. Therefore, with EV71 vaccine commercially available, there is still a long way to go before reaching effective protection against severe HFMD after EV71 vaccines enter the market. In this paper, the bottlenecks and prospects for the wide use of EV71 vaccine after its approval are evaluated.

  14. The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing.

    PubMed

    Dong, Weihua; Li, Xian'en; Yang, Peng; Liao, Hua; Wang, Xiaoli; Wang, Quanyi

    2016-01-12

    The morbidity and mortality of hand, foot and mouth disease (HFMD) are increasing in Beijing, China. Previous studies have indicated an association between incidents of HFMD and weather factors. However, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (EV71) and Coxsackie virus A16 (CV-A16) viruses are not well documented. We analysed 84,502 HFMD cases from 2008 to 2011 in Beijing to explore the seasonal influence of weather factors (average temperature [AT], average relative humidity [ARH], total precipitation [TP] and average wind speed [AWS]) on incidents of HFMD by using a geographically weighted regression (GWR) model. The results indicated that weather factors differ significantly in their influence on HFMD depending on the season. AT had the greatest effect among the four weather factors, and while the influence of AT and AWS was greater in the summer than in the winter, the influence of TP was positive in the summer and negative in the winter. ARH was negatively correlated with HFMD. Also, we observed more EV71-associated cases than CV-A16 but there is no convincing evidence to show significant differences between the influences of the weather factors on EV71 and CV-A16.

  15. Molecular investigation of foot-and-mouth disease virus in domestic bovids from Gharbia, Egypt.

    PubMed

    Elhaig, Mahmoud Mohey; Elsheery, Mohamed Nagi

    2014-12-01

    An outbreak of foot-and-mouth disease (FMD) affecting cattle and water buffalo (Bubalus bubalis) occurred in Egypt during 2012/2013. The present study was undertaken to determine the current strains of the FMD virus (FMDV) and the prevalence of FMD among cattle and buffalo in Gharbia, Egypt. The diagnostic sensitivity of two RT-PCR assays for the detection of FMDV was evaluated. The results revealed that SAT2 was the causative agent. The percentage of infected of animals varied with the detection method, ranging from 62.5 % by the untranslated region (UTR) RT-PCR to 75.6 % by SAT2 RT-PCR. The overall prevalence and mortality rates were 100 and 21 %, respectively. The mortality was higher in buffalo (23.3 %) than it was in cattle (17 %). A partial sequence of SAT2 was identical (90-100 %) to Egyptian isolates and was close in similarity to sequences from Sudan and Libya. In conclusion, FMD in Egypt is caused by SAT2. No other serotypes were detected. The results of this study provided the valuable data regarding the epidemiology of SAT2 in cattle and water buffalo from Egypt, which strengthens the need to change the strategies of both control and prevention that help to prevent the spread of the disease.

  16. Normal variation in thermal radiated temperature in cattle: implications for foot-and-mouth disease detection

    PubMed Central

    2011-01-01

    Background Thermal imagers have been used in a number of disciplines to record animal surface temperatures and as a result detect temperature distributions and abnormalities requiring a particular course of action. Some work, with animals infected with foot-and-mouth disease virus, has suggested that the technique might be used to identify animals in the early stages of disease. In this study, images of 19 healthy cattle have been taken over an extended period to determine hoof and especially coronary band temperatures (a common site for the development of FMD lesions) and eye temperatures (as a surrogate for core body temperature) and to examine how these vary with time and ambient conditions. Results The results showed that under UK conditions an animal's hoof temperature varied from 10°C to 36°C and was primarily influenced by the ambient temperature and the animal's activity immediately prior to measurement. Eye temperatures were not affected by ambient temperature and are a useful indicator of core body temperature. Conclusions Given the variation in temperature of the hooves of normal animals under various environmental conditions the use of a single threshold hoof temperature will be at best a modest predictive indicator of early FMD, even if ambient temperature is factored into the evaluation. PMID:22104039

  17. Application of mouse model for effective evaluation of foot-and-mouth disease vaccine.

    PubMed

    Lee, Seo-Yong; Ko, Mi-Kyeong; Lee, Kwang-Nyeong; Choi, Joo-Hyung; You, Su-Hwa; Pyo, Hyun-Mi; Lee, Myoung-Heon; Kim, Byounghan; Lee, Jong-Soo; Park, Jong-Hyeon

    2016-07-19

    Efficacy evaluation of foot-and-mouth disease (FMD) vaccines has been conducted in target animals such as cows and pigs. In particular, handling FMD virus requires a high level of biosafety management and facilities to contain the virulent viruses. The lack of a laboratory animal model has resulted in inconvenience when it comes to using target animals for vaccine evaluation, bringing about increased cost, time and labor for the experiments. The FMD mouse model has been studied, but most FMD virus (FMDV) strains are not known to cause disease in adult mice. In the present study, we created a series of challenge viruses that are lethal to adult C57BL/6 mice. FMDV types O, A, and Asia1, which are related to frequent FMD outbreaks, were adapted for mice and the pathogenesis of each virus was evaluated in the mouse model. Challenge experiments after vaccination using in-house and commercial vaccines demonstrated vaccine-mediated protection in a dose-dependent manner. In conclusion, we propose that FMD vaccine evaluation should be carried out using mouse-adapted challenge viruses as a swift, effective efficacy test of experimental or commercial vaccines.

  18. An integrated model to predict the atmospheric spread of foot-and-mouth disease virus.

    PubMed Central

    Sørensen, J. H.; Mackay, D. K.; Jensen, C. O.; Donaldson, A. I.

    2000-01-01

    The application of a computer model called Rimpuff for simulating the airborne spread of foot-and-mouth disease (FMD) is described. Rimpuff is more sophisticated and accurate than other FMD simulation models previously described. It can be run on a desktop computer and performs analyses very quickly. It can be linked to a geographical information system and so the information generated can be integrated with geographical and demographical data for display in a format that can be easily assimilated and transmitted electronically. The system was validated using historical data from outbreaks of FMD in France and the UK in 1981, and from Denmark and the former German Democratic Republic (GDR) in 1982. A very good fit was obtained between the direction of the plumes of virus simulated by the model and the spread of disease from France to the UK in 1981. Although cattle in the UK were infected during the episode, the concentrations of airborne virus in the plumes simulated by the model were beneath the infectivity threshold for cattle. It was concluded from the analysis that the number of pigs infected in France, and therefore the source concentration of airborne virus, was probably much higher than was recorded at the time of the outbreaks. Analysis of the Denmark/GDR episode pointed to the possibility that the source of virus for the 1982 epidemic in Denmark could have been one or more unreported outbreaks involving pigs in the former GDR. PMID:10982082

  19. Molecular Characterization of Foot-and-Mouth Disease Viruses Collected in Tanzania Between 1967 and 2009.

    PubMed

    Kasanga, C J; Wadsworth, J; Mpelumbe-Ngeleja, C A R; Sallu, R; Kivaria, F; Wambura, P N; Yongolo, M G S; Rweyemamu, M M; Knowles, N J; King, D P

    2015-10-01

    This paper describes the molecular characterization of foot-and-mouth disease viruses (FMDV) recovered from outbreaks in Tanzania that occurred between 1967 and 2009. A total of 44 FMDV isolates, containing representatives of serotypes O, A, SAT 1 and SAT 2 from 13 regions of Tanzania, were selected from the FAO World Reference Laboratory for FMD (WRLFMD) virus collection. VP1 nucleotide sequences were determined for RT-PCR amplicons, and phylogenetic reconstructions were determined by maximum likelihood and neighbour-joining methods. These analyses showed that Tanzanian type O viruses fell into the EAST AFRICA 2 (EA-2) topotype, type A viruses fell into the AFRICA topotype (genotype I), type SAT 1 viruses into topotype I and type SAT 2 viruses into topotype IV. Taken together, these findings reveal that serotypes O, A, SAT 1 and SAT 2 that caused FMD outbreaks in Tanzania were genetically related to lineages and topotypes occurring in the East African region. The close genetic relationship of viruses in Tanzania to those from other countries suggests that animal movements can contribute to virus dispersal in sub-Saharan Africa. This is the first molecular description of viruses circulating in Tanzania and highlights the need for further sampling of representative viruses from the region so as to elucidate the complex epidemiology of FMD in Tanzania and sub-Saharan Africa.

  20. A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease

    PubMed Central

    Zhang, Dingmei; Li, Ruolin; Zhang, Wangjian; Li, Guowei; Ma, Zhanzhong; Chen, Xiashi; Du, Zhicheng; Li, Zhiyuan; Guo, Pi; Lin, Zhuochen; Lu, Jiahai; Hao, Yuantao

    2017-01-01

    The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD. PMID:28084311

  1. Emergence and Distribution of Foot-and-Mouth Disease Virus Serotype A and O in Bangladesh.

    PubMed

    Nandi, S P; Rahman, M Z; Momtaz, S; Sultana, M; Hossain, M A

    2015-06-01

    Foot-and-mouth disease (FMD) is endemic in Bangladesh and is predominantly due to FMDV serotype O. In 2012, FMD outbreaks were identified in five different districts of Bangladesh. Of 56 symptomatic cattle epithelial tissue samples, diagnostic PCR assay based on 5'-URT detected 38 FMDV infections. Viral genotyping targeting VP1-encoding region confirmed emergence of two distinct serotypes, A and O with an abundance of serotype A in Chittagong and Gazipur districts and serotype O in Pabna and Faridpur. Only single lineage of both A and O was retrieved from samples of five different regions. Sequencing and phylogenetic analysis of VP1 sequences revealed that serotype O sequences were closely related to the Ind 2001 sublineage of Middle East-South Asia (ME-SA) topotype that was previously circulating in Bangladesh, and serotype A sequences belonging to the genotype VII that was dominant in India during the last decade. The results suggest that extensive cross-border animal movement from neighbouring countries is the most likely source of FMDV serotypes in Bangladesh.

  2. Foot-and-mouth disease virus low-fidelity polymerase mutants are attenuated.

    PubMed

    Xie, Xiaochun; Wang, Haiwei; Zeng, Jianxiong; Li, Chen; Zhou, Guohui; Yang, Decheng; Yu, Li

    2014-10-01

    Previous studies have shown that RNA viruses can be attenuated by either increased or decreased viral polymerase replication fidelity. Although foot-and-mouth disease virus (FMDV) high-fidelity RNA-dependent RNA polymerase (RdRp) variants with an attenuated phenotype have been isolated using mutagens, no FMDV mutant with a low-fidelity polymerase has been documented to date. Here, we describe the generation of several FMDV RdRp mutants using site-directed mutagenesis via a reverse genetic system. Mutation frequency assays confirmed that five rescued FMDV RdRp mutant populations had lower replication fidelity than the wild-type virus population, which allowed us to assess the effects of the change in replication fidelity on the virus phenotype. These low-fidelity FMDV RdRp mutants showed increased sensitivity to ribavirin or 5-fluorouracil (5-FU) treatment without a loss of growth capacity in cell cultures. In addition, decreased fitness and attenuated virulence were observed for the RdRp mutants with lower fidelity. Importantly, based on a quantitative analysis for fidelity and virulence, we concluded that lower replication fidelity is associated with a more attenuated virus phenotype. These results further contribute to our understanding of the replication fidelity of polymerases of RNA viruses and its relationship to virulence attenuation.

  3. Favipiravir can evoke lethal mutagenesis and extinction of foot-and-mouth disease virus.

    PubMed

    de Avila, Ana Isabel; Moreno, Elena; Perales, Celia; Domingo, Esteban

    2017-03-17

    Antiviral agents are increasingly considered an option for veterinary medicine. An understanding of their mechanism of activity is important to plan their administration either as monotherapy or in combination with other agents. Previous studies have shown that the broad spectrum antiviral agent favipiravir (T-705) and its derivatives T-1105 and T-1106 are efficient inhibitors of foot-and-mouth disease virus (FMDV) replication in cell culture and in vivo. However, no mechanism for their activity against FMDV has been proposed. In the present study we show that favipiravir (T-705) can act as a lethal mutagen for FMDV in cell culture. Evidence includes virus extinction associated with increase in mutation frequency in the mutant spectrum of 860 residues of the 3D (polymerase)-coding region, and a decrease of specific infectivity while the consensus nucleotide sequence of the region analyzed remained invariant. The mutational spectrum evoked by favipiravir differs from that observed with other viruses in that no predominant transition type is observed, indicating that a movement towards A,U- or G,C-rich regions of sequence space is not a prerequisite for virus extinction. We discuss prospects for the use of favipiravir to assist in the control of FMDV, and its possible broader use in veterinary medicine as an extension of its current status as antiviral agent for human influenza virus.

  4. Inhibition of the foot-and-mouth disease virus subgenomic replicon by RNA aptamers

    PubMed Central

    Forrest, Sophie; Lear, Zoe; Herod, Morgan R.; Ryan, Martin; Rowlands, David J.

    2014-01-01

    We have previously documented the inhibitory activity of RNA aptamers to the RNA-dependent RNA polymerase of foot-and-mouth disease virus (3Dpol). Here we report their modification and use with a subgenomic replicon incorporating GFP (pGFP-PAC replicon), allowing replication to be monitored and quantified in real-time. GFP expression in transfected BHK-21 cells reached a maximum at approximately 8 h post-transfection, at which time change in morphology of the cells was consistent with a virus-induced cytopathic effect. However, transfection of replicon-bearing cells with a 3Dpol aptamer RNA resulted in inhibition of GFP expression and maintenance of normal cell morphology, whereas a control aptamer RNA had little effect. The inhibition was correlated with a reduction in 3Dpol (detected by immunoblotting) and shown to be dose dependent. The 3Dpol aptamers appeared to be more effective than 2′-C-methylcytidine (2′CMC). Aptamers to components of the replication complex are therefore useful molecular tools for studying viral replication and also have potential as diagnostic molecules in the future. PMID:25096816

  5. Molecular epidemiological investigation of foot-and-mouth disease virus in Korea in 2000.

    PubMed

    Shin, Jin-Ho; Sohn, Hyun-Joo; Choi, Kang-Seuk; Kwon, Byung-Jun; Ko, Young-Joon; An, Dong-Jun; Cha, Sang-Ho; Park, Jong-Hyeon; Jeong, Woo-Seog; Park, Jee-Yong; Choi, Cheong-Up; Kweon, Chang-Hee; Song, Jae-Young; Kim, Jong-Yeom; An, Soo-Hwan; Kim, Soon-Jae; Joo, Yi-Seok

    2003-01-01

    The genetic relatedness of 7 Korean type O field strains of foot-and-mouth disease virus (FMDV) in clinical specimens collected from 5 different geographic locations in 2000 was investigated. The sequence of 162 nucleotides (nt 478-639) at the 3' end of the 1D (VP1) genes was determined from amplified cDNA fragments, and subjected to the analysis for the sequence identity/divergence and phylogenetic relationship. The overall nucleotide sequence divergence among the 7 field strains was 0 to 3.8%, suggesting that they are closely related to each other. Phylogenetic analysis with the known Middle East-South Asia (ME-SA) topotype strains showed that the 7 Korean field strains formed two distinct clusters within the same lineage of the ME-SA topotype strains. Cluster 1 consisted of the strains of the primary foci of infection (Paju and Hongseong), and closely related to the strains prevailed in the Far East. Cluster 2 comprised those of subsequently affected regions (Boryeong, Yongin, and Chungju), and was further diverged from the Cluster 1. The result of phylogenetic analysis indicated that the Korean strains may have evolved from a common ancestor of the Pan Asia strains, and that at least 2 phylogenetically clustered variants within the same lineage were prevalent during the epidemic. The potential origin and sources of the virus introduction to Korea were discussed.

  6. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    PubMed

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity.

  7. Comparative study of codon substitution patterns in foot-and-mouth disease virus (serotype O)

    PubMed Central

    Ahn, Insung; Bae, Se-Eun

    2011-01-01

    We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 from various region of the world. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogenetic relationships in the same serotype (serotype O). Moreover, while the SSC and EMC values of FMDVs decreased according to phylogenetic distance, G + C composition at the third codon position was strictly conserved. Although there was little variation among the SSC values of 18 amino acids, more dynamic differences were observed in EMC values. The EMC values of 4- and 6-fold degenerate amino acids showed significantly lower values while most 2-fold degenerate amino acids showed no significant difference. Our findings suggest that different EMC patterns among the 18 amino acids might be an important factor in determining the direction of evolution in FMDV. PMID:21825834

  8. Inactivation of foot-and-mouth disease virus by citric acid and sodium carbonate with deicers.

    PubMed

    Hong, Jang-Kwan; Lee, Kwang-Nyeong; You, Su-Hwa; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jong-Hyeon; Kim, Byounghan

    2015-11-01

    Three out of five outbreaks of foot-and-mouth disease (FMD) since 2010 in the Republic of Korea have occurred in the winter. At the freezing temperatures, it was impossible to spray disinfectant on the surfaces of vehicles, roads, and farm premises because the disinfectant would be frozen shortly after discharge and the surfaces of the roads or machines would become slippery in cold weather. In this study, we added chemical deicers (ethylene glycol, propylene glycol, sodium chloride, calcium chloride, ethyl alcohol, and commercial windshield washer fluid) to keep disinfectants (0.2% citric acid and 4% sodium carbonate) from freezing, and we tested their virucidal efficacies under simulated cold temperatures in a tube. The 0.2% citric acid could reduce the virus titer 4 logs at -20°C with all the deicers. On the other hand, 4% sodium carbonate showed little virucidal activity at -20°C within 30 min, although it resisted being frozen with the function of the deicers. In conclusion, for the winter season, we may recommend the use of citric acid (>0.2%) diluted in 30% ethyl alcohol or 25% sodium chloride solvent, depending on its purpose.

  9. Brazilian foot and mouth disease status and meat exportation to the European Union.

    PubMed

    Carvalho, Luiz Felipe Ramos; de Melo, Cristiano Barros; Seixas, Luiza; McManus, Concepta

    2014-03-01

    The aim of this study was to define the differences between the Brazilian states that export and do not export meat to the European Union (EU) and to identify the variables that are important to meet the export requirements. Infrastructure and computerization of the control of animal transit in Brazil that impact on regional health status were evaluated and linked to other variables such as status for foot and mouth disease (FMD) and qualification to export meat to EU. Variables related to transit control of bovines implemented by the state agencies of animal health and inspection in each Brazilian state were evaluated. Using a discriminant analysis, four variables were selected that explained the variation between Brazilian states that were "free" and "not free" of FMD while another four were selected to explain the variation between the zones "approved" and "not approved" to export meat to the EU, including number of official veterinarians, total transit of bovines and buffaloes, total number of animal transit certificates issued for bovine and buffaloes at the state or zone level, and total number of municipalities in the state or zone. It was possible to correctly discriminate between "free" and "not free" FMD states or zones. Variables related to animal transit are important in assessing the state for the classification of animal health situation and for EU approval for the exportation of meat.

  10. Quantitative characteristics of the foot-and-mouth disease carrier state under natural conditions in India.

    PubMed

    Hayer, S S; Ranjan, R; Biswal, J K; Subramaniam, S; Mohapatra, J K; Sharma, G K; Rout, M; Dash, B B; Das, B; Prusty, B R; Sharma, A K; Stenfeldt, C; Perez, A; Rodriguez, L L; Pattnaik, B; VanderWaal, K; Arzt, J

    2017-03-02

    The goal of this study was to characterize the properties and duration of the foot-and-mouth disease (FMD) carrier state and associated serological responses subsequent to vaccination and naturally occurring infection at two farms in northern India. Despite previous vaccination of cattle in these herds, clinical signs of FMD occurred in October 2013 within a subset of animals at the farms containing juvenile-yearling heifers and steers (Farm A) and adult dairy cattle (Farm B). Subsequent to the outbreak, FMD virus (FMDV) asymptomatic carriers were identified in both herds by seroreactivity to FMDV non-structural proteins and detection of FMDV genomic RNA in oropharyngeal fluid. Carriers' seroreactivity and FMDV genome detection status were subsequently monitored monthly for 23 months. The mean extinction time of the carrier state was 13.1 ± 0.2 months, with extinction having occurred significantly faster amongst adult dairy cattle at Farm B compared to younger animals at Farm A. The rate of decrease in the proportion of carrier animals was calculated to be 0.07 per month. Seroprevalence against FMDV non-structural proteins decreased over the course of the study period, but was found to increase transiently following repeated vaccinations. These data provide novel insights into viral and host factors associated with the FMDV carrier state under natural conditions. The findings reported herein may be relevant to field veterinarians and governmental regulatory entities engaged in FMD response and control measures.

  11. Foot-and-Mouth Disease Virus Persists in the Light Zone of Germinal Centres

    PubMed Central

    Juleff, Nicholas; Windsor, Miriam; Reid, Elizabeth; Seago, Julian; Zhang, Zhidong; Monaghan, Paul; Morrison, Ivan W.; Charleston, Bryan

    2008-01-01

    Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV “carrier state” and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. Here we show by laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborate by in situ hybridization that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus. PMID:18941503

  12. Prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases.

    PubMed

    Liu, Chia-Chyi; Chow, Yen-Hung; Chong, Pele; Klein, Michel

    2014-10-29

    Enterovirus 71 (EV71), an emerging neurotropic virus and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth diseases (HFMD). These viruses have become a serious public health threat in the Asia Pacific region. Formalin-inactivated EV71 (FI-EV71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against EV71. Their failure to prevent CVA16 infections could compromise the acceptability of monovalent EV71 vaccines. Bivalent FI-EV71/FI-CVA16 vaccines have been found to elicit strong neutralizing antibody responses against both viruses in animal models but did not protect against CVA6 and CVA10 viral infections in cell culture neutralization assay. In this review, we discuss the critical bottlenecks in the development of multivalent HFMD vaccines, including the selection of vaccine strains, animal models to assess vaccine potency, the definition of end-points for efficacy trials, and the need for improved manufacturing processes to produce affordable vaccines.

  13. Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China

    PubMed Central

    Li, Xinmin

    2016-01-01

    Severe outbreaks of hand, foot and mouth disease (HFMD) have occurred in China for decades. Our understanding of the HFMD transmission process and its determinants is still limited. In this paper, factors that affect the local variation of HFMD transmission process were studied. Three classes of factors, including meteorological, demographic and public health intervention factors, were carefully selected and their effects on HFMD transmission were investigated with Pearson’s correlation coefficient and multiple linear regression models. The determining factors for the variation of HFMD transmission were different for the southeastern and the northwestern regions of China. In the northwest, fadeouts occurred yearly, and the average age at infection and the fadeout were negatively correlated with the population density. In the southeast, HFMD transmission was governed by the combined effects of the birth rate, the relative humidity and the interaction of the Health System Performance and the log of the population density. When the Health System Performance was low, HFMD transmission increased with the population density, but when the Health System Performance was high, the better health performance counteracted the transmission increase due to the higher population density. PMID:27701445

  14. Foot-and-mouth disease virus leader proteinase: structural insights into the mechanism of intermolecular cleavage.

    PubMed

    Steinberger, Jutta; Grishkovskaya, Irina; Cencic, Regina; Juliano, Luiz; Juliano, Maria A; Skern, Tim

    2014-11-01

    Translation of foot-and-mouth disease virus RNA initiates at one of two start codons leading to the synthesis of two forms of leader proteinase L(pro) (Lab(pro) and Lb(pro)). These forms free themselves from the viral polyprotein by intra- and intermolecular self-processing and subsequently cleave the cellular eukaryotic initiation factor (eIF) 4 G. During infection, Lb(pro) removes six residues from its own C-terminus, generating sLb(pro). We present the structure of sLb(pro) bound to the inhibitor E64-R-P-NH2, illustrating how sLb(pro) can cleave between Lys/Gly and Gly/Arg pairs. In intermolecular cleavage on polyprotein substrates, Lb(pro) was unaffected by P1 or P1' substitutions and processed a substrate containing nine eIF4GI cleavage site residues whereas sLb(pro) failed to cleave the eIF4GI containing substrate and cleaved appreciably more slowly on mutated substrates. Introduction of 70 eIF4GI residues bearing the Lb(pro) binding site restored cleavage. These data imply that Lb(pro) and sLb(pro) may have different functions in infected cells.

  15. The threshold effects of meteorological factors on Hand, foot, and mouth disease (HFMD) in China, 2011

    PubMed Central

    Du, Zhicheng; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng; Hao, Yuantao

    2016-01-01

    We explored the threshold effects of meteorological factors on hand, foot and mouth disease (HFMD) in mainland China to improve the prevention and early warning. Using HFMD surveillance and meteorological data in 2011, we identified the threshold effects of predictors on the monthly incidence of HFMD and predicted the high risk months, with classification and regression tree models (CART). The results of the classification tree showed that there was an 82.35% chance for a high risk of HFMD when the temperature was greater than 24.03 °C and the relative humidity was less than 60.9% during non-autumn seasons. According to the heatmap of high risk prediction, the HFMD incidence in most provinces was beyond the normal level during May to August. The results of regression tree showed that when the temperature was greater than 24.85 °C and the relative humidity was between 80.59% and 82.55%, the relative risk (RR) of HFMD was 3.49 relative to monthly average incidence. This study provided quantitative evidence for the threshold effects of meteorological factors on HFMD in China. The conditions of a temperature greater than 24.85 °C and a relative humidity between 80.59% and 82.55% would lead to a higher risk of HFMD. PMID:27848955

  16. Hand-Washing: The Main Strategy for Avoiding Hand, Foot and Mouth Disease

    PubMed Central

    Zhang, Dingmei; Li, Zhiyuan; Zhang, Wangjian; Guo, Pi; Ma, Zhanzhong; Chen, Qian; Du, Shaokun; Peng, Jing; Deng, Yu; Hao, Yuantao

    2016-01-01

    Epidemics of hand, foot and mouth disease (HFMD) among children have caused concern in China since 2007. We have conducted a retrospective study to investigate risk factors associated with HFMD. In this non-matching case-control study, 99 HFMD patients and 126 control from Guangdong Province were enlisted as participants. Data comprising demographic, socio-economic, clinical and behavior factors were collected from children’s parents through face-to-face interviews by trained interviewers using a standardized questionnaire. Results of the primary logistic regression analyses revealed that age, history of cold food consumption, hand-washing routines, and airing out bedding were significantly associated with HFMD cases. Results of further multivariate analysis indicated that older age (OR = 0.44, 95% CI: 0.34–0.56) and hand-washing before meals (OR = 0.3, 95% CI: 0.13–0.70) are protective factors, whereas airing out bedding more than thrice a month (OR = 4.55, 95% CI: 1.19–17.37) was associated with increased risk for HFMD. Therefore, hand-washing should be recommended to prevent HFMD, and the potential threat of airing out bedding should be carefully considered. However, further studies are needed to examine other possible risk factors. PMID:27322307

  17. Enhanced immune response with foot and mouth disease virus VP1 and interleukin-1 fusion genes.

    PubMed

    Park, Jong Hyeon; Kim, Sun Jin; Oem, Jae Ku; Lee, Kwang Nyeong; Kim, Yong Joo; Kye, Soo Jeong; Park, Jee Yong; Joo, Yi Seok

    2006-09-01

    The capsid of the foot and mouth disease (FMD) virus carries the epitopes that are critical for inducing the immune response. In an attempt to enhance the specific immune response, plasmid DNA was constructed to express VP1/interleukin-1alpha (IL-1alpha) and precursor capsid (P1) in combination with 2A (P1-2A)/IL-1alpha under the control of the human cytomegalovirus (HCMV) immediateearly promoter and intron. After DNA transfection into MA104 (monkey kidney) cells, Western blotting and an immunofluorescence assay were used to confirm the expression of VP1 or P1-2A and IL-1alpha. Mice were inoculated with the encoding plasmids via the intradermal route, and the IgG1 and IgG2a levels were used to determine the immune responses. These results show that although the immunized groups did not carry a high level of neutralizing antibodies, the plasmids encoding the VP1/ IL-1alpha, and P1-2A /IL-1alpha fused genes were effective in inducing an enhanced immune response.

  18. Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo

    PubMed Central

    Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

    2015-01-01

    Abstract The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks. PMID:26691487

  19. Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo.

    PubMed

    Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

    2015-01-01

    The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks.

  20. Hand-Washing: The Main Strategy for Avoiding Hand, Foot and Mouth Disease.

    PubMed

    Zhang, Dingmei; Li, Zhiyuan; Zhang, Wangjian; Guo, Pi; Ma, Zhanzhong; Chen, Qian; Du, Shaokun; Peng, Jing; Deng, Yu; Hao, Yuantao

    2016-06-18

    Epidemics of hand, foot and mouth disease (HFMD) among children have caused concern in China since 2007. We have conducted a retrospective study to investigate risk factors associated with HFMD. In this non-matching case-control study, 99 HFMD patients and 126 control from Guangdong Province were enlisted as participants. Data comprising demographic, socio-economic, clinical and behavior factors were collected from children's parents through face-to-face interviews by trained interviewers using a standardized questionnaire. Results of the primary logistic regression analyses revealed that age, history of cold food consumption, hand-washing routines, and airing out bedding were significantly associated with HFMD cases. Results of further multivariate analysis indicated that older age (OR = 0.44, 95% CI: 0.34-0.56) and hand-washing before meals (OR = 0.3, 95% CI: 0.13-0.70) are protective factors, whereas airing out bedding more than thrice a month (OR = 4.55, 95% CI: 1.19-17.37) was associated with increased risk for HFMD. Therefore, hand-washing should be recommended to prevent HFMD, and the potential threat of airing out bedding should be carefully considered. However, further studies are needed to examine other possible risk factors.

  1. Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001.

    PubMed

    Thompson, D; Muriel, P; Russell, D; Osborne, P; Bromley, A; Rowland, M; Creigh-Tyte, S; Brown, C

    2002-12-01

    The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.

  2. Ihalation, persistence and dispersal f foot-and-mouth disease virus by man.

    PubMed

    Sellers, R F; Donaldson, A I; Herniman, K A

    1970-12-01

    Sampling of human subjects, who had been in contact with animals infected with foot-and-mouth disease (FMD) virus, showed that virus could be recovered from the nose, throat, saliva and from air expelled during coughing, sneezing, talking and breathing. The amounts of virus recovered paralleled those collected with a large-volume sampler and multistage impinger and these findings confirmed that the highest recovery of airborne virus was from infected pigs followed by cattle and sheep. More virus was found in the noses of those examining infected animals than in those operating the samplers, but there was variation between the subjects. In the majority there was a 1.8 log fall in titre by 3.5 hr., but virus persisted in the nose of one subject for 28 hr. Nose blowing or washing the nostrils did not remove virus completely, nor were cloth or industrial masks completely effective in preventing inhalation of virus. It was possible to transmit virus from infected subjects to others on one occasion. No clinical cases of FMD in man resulted from exposure, nor was there any rise in antibody. Use was made of these findings in determining sites of aerosol excretion in animals, and the results are discussed in relation to FMD in man and to the spread of respiratory viruses by the airborne route.

  3. The threshold effects of meteorological factors on Hand, foot, and mouth disease (HFMD) in China, 2011

    NASA Astrophysics Data System (ADS)

    Du, Zhicheng; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng; Hao, Yuantao

    2016-11-01

    We explored the threshold effects of meteorological factors on hand, foot and mouth disease (HFMD) in mainland China to improve the prevention and early warning. Using HFMD surveillance and meteorological data in 2011, we identified the threshold effects of predictors on the monthly incidence of HFMD and predicted the high risk months, with classification and regression tree models (CART). The results of the classification tree showed that there was an 82.35% chance for a high risk of HFMD when the temperature was greater than 24.03 °C and the relative humidity was less than 60.9% during non-autumn seasons. According to the heatmap of high risk prediction, the HFMD incidence in most provinces was beyond the normal level during May to August. The results of regression tree showed that when the temperature was greater than 24.85 °C and the relative humidity was between 80.59% and 82.55%, the relative risk (RR) of HFMD was 3.49 relative to monthly average incidence. This study provided quantitative evidence for the threshold effects of meteorological factors on HFMD in China. The conditions of a temperature greater than 24.85 °C and a relative humidity between 80.59% and 82.55% would lead to a higher risk of HFMD.

  4. Changing epidemiology of hand, foot, and mouth disease in Hong Kong, 2001-2009.

    PubMed

    Ma, Edmond; Lam, Terence; Chan, K C; Wong, Christine; Chuang, S K

    2010-11-01

    We report the surveillance findings of hand, foot, and mouth disease (HFMD) collected from a general practitioner-based sentinel surveillance system and outbreaks reported by institutions and a laboratory-based enterovirus surveillance system in Hong Kong from 2001 to 2009. A seasonal peak was detected in the warmer months (May-July), along with a smaller winter peak (October-December) from 2006 onwards. The number of older children (>5 years) infected increased from 25.4% in 2001 to 33.0% in 2009 (P=0.01, Mantel-Haenszel chi-square test). Laboratory surveillance detected a cyclical high enterovirus 71 activity every 3 to 4 years. This activity was associated with a higher average hospitalization rate for HFMD patients in the outbreaks reported in the corresponding year, although the difference was only marginally significant (P=0.09, linear regression test). The changing epidemiology of HFMD warrants continuous surveillance in order to guide preventive public-health actions.

  5. Analysis of neutralizing epitopes on foot-and-mouth disease virus.

    PubMed Central

    Pfaff, E; Thiel, H J; Beck, E; Strohmaier, K; Schaller, H

    1988-01-01

    For the investigation of the antigenic determinant structure of foot-and-mouth disease virus (FMDV), neutralizing monoclonal antibodies (MAbs) against complete virus were characterized by Western blot (immunoblot), enzyme immunoassay, and competition experiments with a synthetic peptide, isolated coat protein VP1, and viral particles as antigens. Two of the four MAbs reacted with each of these antigens, while the other two MAbs recognized only complete viral particles and reacted only very poorly with the peptide. The four MAbs showed different neutralization patterns with a panel of 11 different FMDV strains. cDNA-derived VP1 protein sequences of the different strains were compared to find correlations between the primary structure of the protein and the ability of virus to be neutralized. Based on this analysis, it appears that the first two MAbs recognized overlapping sequential epitopes in the known antigenic site represented by the peptide, whereas the two other MAbs recognized conformational epitopes. These conclusions were supported and extended by structural analyses of FMDV mutants resistant to neutralization by an MAb specific for a conformational epitope. These results demonstrate that no amino acid exchanges had occurred in the primary antigenic site of VP1 but instead in the other coat proteins VP2 and VP3, which by themselves do not induce neutralizing antibodies. Images PMID:2835507

  6. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs.

    PubMed

    Lyons, Nicholas A; Lyoo, Young S; King, Donald P; Paton, David J

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future.

  7. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs

    PubMed Central

    Lyons, Nicholas A.; Lyoo, Young S.; King, Donald P.; Paton, David J.

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future. PMID:27965966

  8. First finding of Southeast Asia topotype of foot-and-mouth disease virus in Kinmen, Taiwan, in the 2012 outbreak.

    PubMed

    Lin, Yeou-Liang; Chang, Chia-Yi; Pan, Chu-Hsiang; Deng, Ming-Chung; Tsai, Hsiang-Jung; Lee, Fan

    2014-11-01

    Foot-and-mouth disease virus, a member of genus Aphthovirus within the family Picornaviridae, affects cloven-hoofed animals, causing foot-and-mouth disease characterized by vesicle development. The Southeast Asia topotype, one of the topotypes within serotype O of the virus, is prevalent in some Asian countries, but had not previously been found in Taiwan. The topotype was first found in pigs in Kinmen Island, Taiwan, in 2012 and identified by nucleotide sequence comparison and phylogenetic analysis. Outbreaks were reported at 4 farms, resulting in the culling of 628 pigs and 1 cattle. Pigs were the only species infected during the outbreak. The incursion of Southeast Asia topotype into Taiwan implies the expansion of the topotype in East Asia.

  9. First Finding of Southeast Asia Topotype of Foot-and-Mouth Disease Virus in Kinmen, Taiwan, in the 2012 Outbreak

    PubMed Central

    LIN, Yeou-Liang; CHANG, Chia-Yi; PAN, Chu-Hsiang; DENG, Ming-Chung; TSAI, Hsiang-Jung; LEE, Fan

    2014-01-01

    ABSTRACT Foot-and-mouth disease virus, a member of genus Aphthovirus within the family Picornaviridae, affects cloven-hoofed animals, causing foot-and-mouth disease characterized by vesicle development. The Southeast Asia topotype, one of the topotypes within serotype O of the virus, is prevalent in some Asian countries, but had not previously been found in Taiwan. The topotype was first found in pigs in Kinmen Island, Taiwan, in 2012 and identified by nucleotide sequence comparison and phylogenetic analysis. Outbreaks were reported at 4 farms, resulting in the culling of 628 pigs and 1 cattle. Pigs were the only species infected during the outbreak. The incursion of Southeast Asia topotype into Taiwan implies the expansion of the topotype in East Asia. PMID:25056674

  10. Engineering viable foot-and-mouth disease viruses with increased thermostability as a step in the development of improved vaccines.

    PubMed

    Mateo, Roberto; Luna, Eva; Rincón, Verónica; Mateu, Mauricio G

    2008-12-01

    We have rationally engineered foot-and-mouth disease virus to increase its stability against thermal dissociation into subunits without disrupting the many biological functions needed for its infectivity. Amino acid side chains located near the capsid intersubunit interfaces and either predicted or found to be dispensable for infectivity were replaced by others that could establish new disulfide bonds or electrostatic interactions between subunits. Two engineered viruses were normally infectious, genetically stable, and antigenically indistinguishable from the natural virus but showed substantially increased stability against irreversible dissociation. Electrostatic interactions mediated this stabilizing effect. For foot-and-mouth disease virus and other viruses, some evidence had suggested that an increase in virion stability could be linked to an impairment of infectivity. The results of the present study show, in fact, that virion thermostability against dissociation into subunits may not be selectively constrained by functional requirements for infectivity. The thermostable viruses obtained, and others similarly engineered, could be used for the production, using current procedures, of foot-and-mouth disease vaccines that are less dependent on a faultless cold chain. In addition, introduction of those stabilizing mutations in empty (nucleic acid-free) capsids could facilitate the production of infection-risk-free vaccines against the disease, one of the economically most important animal diseases worldwide.

  11. Temporal assessment of seroconversion in response to inactivated foot-and-mouth disease vaccine in Arabian oryx (Oryx leucoryx).

    PubMed

    Kilgallon, C P; Bailey, T A; O'Donovan, D; Wernery, U; Alexandersen, S

    2008-12-13

    Ten male Arabian oryx (Oryx leucoryx) were vaccinated with a commercially available standard aqueous foot-and-mouth-disease vaccine containing aluminium hydroxide as an adjuvant, and their antibody titres against serotypes O and A were measured using solid-phase blocking elisa and the virus neutralisation test. Mean elisa antibody titres greater than 1.45 log(10) were recorded for serotype A, but low elisa titres were recorded for serotype 0; low titres were recorded by VNT for both serotypes.

  12. Host microRNA-203a is antagonistic to the progression of foot-and-mouth disease virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR)-203a is a potent regulator of Sam68 expression both in vitro and in vivo. Here, we showed transfection of miR-203a-3p and miR-203a-5p mimics separately and in combination in a ...

  13. [Comparative testing of the quality of foot-and-mouth disease vaccines prepared with different virus inactivators].

    PubMed

    Dilovski, M; Tekerlekov, P

    1983-01-01

    Formalin, glycidaldehyde, and the binary ethyleneimine were tested under laboratory conditions as inactivators of the foot-and-mouth disease virus along with the possibility of using them in the process of vaccine production. Data is presented on the comparative testing for innocuity and immunogenicity for sheep of F. M. D. vaccines produced with such inactivators. Results showed the advantages of the binary ethyleneimine as against formalin and glycidaldehyde as an inactivator of the F. M. D. virus.

  14. Data-Driven Models of Foot-and-Mouth Disease Dynamics: A Review.

    PubMed

    Pomeroy, L W; Bansal, S; Tildesley, M; Moreno-Torres, K I; Moritz, M; Xiao, N; Carpenter, T E; Garabed, R B

    2015-11-18

    Foot-and-mouth disease virus (FMDV) threatens animal health and leads to considerable economic losses worldwide. Progress towards minimizing both veterinary and financial impact of the disease will be made with targeted disease control policies. To move towards targeted control, specific targets and detailed control strategies must be defined. One approach for identifying targets is to use mathematical and simulation models quantified with accurate and fine-scale data to design and evaluate alternative control policies. Nevertheless, published models of FMDV vary in modelling techniques and resolution of data incorporated. In order to determine which models and data sources contain enough detail to represent realistic control policy alternatives, we performed a systematic literature review of all FMDV dynamical models that use host data, disease data or both data types. For the purpose of evaluating modelling methodology, we classified models by control strategy represented, resolution of models and data, and location modelled. We found that modelling methodology has been well developed to the point where multiple methods are available to represent detailed and contact-specific transmission and targeted control. However, detailed host and disease data needed to quantify these models are only available from a few outbreaks. To address existing challenges in data collection, novel data sources should be considered and integrated into models of FMDV transmission and control. We suggest modelling multiple endemic areas to advance local control and global control and better understand FMDV transmission dynamics. With incorporation of additional data, models can assist with both the design of targeted control and identification of transmission drivers across geographic boundaries.

  15. Economic effects of foot and mouth disease outbreaks along the cattle marketing chain in Uganda

    PubMed Central

    Baluka, Sylvia Angubua

    2016-01-01

    Aim: Disease outbreaks increase the cost of animal production; reduce milk and beef yield, cattle sales, farmers’ incomes, and enterprise profitability. The study assessed the economic effects of foot and mouth disease (FMD) outbreaks along the cattle marketing chain in selected study districts in Uganda. Materials and Methods: The study combined qualitative and quantitative study designs. Respondents were selected proportionally using simple random sampling from the sampling frame comprising of 224, 173, 291, and 185 farmers for Nakasongola, Nakaseke, Isingiro, and Rakai, respectively. Key informants were selected purposively. Data analysis combined descriptive, modeling, and regression analysis. Data on the socio-economic characteristics and how they influenced FMD outbreaks, cattle markets revenue losses, and the economic cost of the outbreaks were analyzed using descriptive measures including percentages, means, and frequencies. Results: Farmers with small and medium herds incurred higher control costs, whereas large herds experienced the highest milk losses. Total income earned by the actors per month at the processing level reduced by 23%. In Isingiro, bulls and cows were salvage sold at 83% and 88% less market value, i.e., a loss of $196.1 and $1,552.9 in small and medium herds, respectively. Conclusion: All actors along the cattle marketing chain incur losses during FMD outbreaks, but smallholder farmers are most affected. Control and prevention of FMD should remain the responsibility of the government if Uganda is to achieve a disease-free status that is a prerequisite for free movement and operation of cattle markets throughout the year which will boost cattle marketing. PMID:27397974

  16. Study on the epidemiology of foot and mouth disease in Ethiopia.

    PubMed

    Ayelet, G; Gelaye, E; Negussie, H; Asmare, K

    2012-12-01

    This study was designed to describe the status of foot and mouth disease (FMD) in Ethiopia, through analysis of FMD outbreak reports and the detection of antibodies, to address the possibility of establishing a disease-free zone. Serum samples collected from cattle between 2003 and 2006 for the serosurveillance of rinderpest were used for this study. The records of the Ministry of Agriculture and Rural Development from 2002 to 2006 indicate that FMD outbreaks occurred each year in Ethiopia during this period, with the highest number in 2004, when 134 outbreaks took place. The highest rates were from the North Shoa zones of both the Oromia and Amhara regions. The serum samples were tested using the 3ABC enzyme-linked immunosorbent assay kit, to identify antibodies against FMD. From a total of 4,465 sera, 10.5% (n = 467) tested positive. The highest seroprevalence was detected in samples from the Eastern zone of Rgray with 41.5%; followed by the Guji zone of Oromia and Yeka district of the city of Addis Ababa, with 32.7% and 30%, respectively. Antibodies specific to FMD virus were not detected in Gambella or Benishangul. The effects of cattle, sheep and goat density, both separately and together, were analysed with a spatial regression model, but did not have a significant effect on seroprevalence. This indicates that other factors, such as farming systems and livestock movement, play a significant role in the occurrence of FMD. Based on these study findings, it might be appropriate to establish disease-free zones in Gambella and Benishangul.

  17. FOOT-AND-MOUTH DISEASE IN A SMALL SAMPLE OF EXPERIMENTALLY INFECTED PRONGHORN (ANTILOCAPRA AMERICANA).

    PubMed

    Rhyan, Jack; McCollum, Matthew; Gidlewski, Thomas; Shalev, Moshe; Ward, Gordon; Donahue, Brenda; Arzt, Jonathan; Stenfeldt, Carolina; Mohamed, Fawzi; Nol, Pauline; Deng, Ming; Metwally, Samia; McKenna, Thomas; Salman, Mo

    2016-10-01

    There is limited information on the pathogenesis and epidemiology of foot-and-mouth disease (FMD) in North American wildlife and none concerning pronghorn ( Antilocapra americana ). In an experimental study of 13 pronghorn and six steers ( Bos taurus ), we compared the susceptibility of pronghorn to FMD virus (FMDV) strain O, with that of cattle ( Bos taurus ). We also determined the potential for intra- and interspecies transmission of FMDV strain O in pronghorn and cattle, assessed the application of conventional laboratory tests in their suitability to detect FMDV infection in pronghorn, and evaluated the potential role of pronghorn as efficient long-term carriers of FMDV. After acclimation to containment at Plum Island Animal Disease Center, two pronghorn and one steer were each infected by intraepithelial tongue inoculation with 10,000 bovine tongue infective doses of FMDV, strain O1 Manisa. Inoculated animals were housed with contact animals. When contact-exposed animals developed fever they were placed in rooms with previously unexposed animals. All inoculated and exposed cattle and pronghorn developed clinical disease typical of FMD. Pronghorn developed severe foot lesions and mild to moderate oral lesions, primarily on the tongue. Duration of clinical signs in both species was 2-3 wk with foot abnormalities evident to the end of the study (51 d postexposure). Other lesions included pancreatitis, myositis of the tongue, and secondary lesions including pleuritis, pneumonia, decubital ulcers, and tenosynovitis. Virus transmission occurred between pronghorn, from cattle to pronghorn, and from pronghorn to cattle. Conventional laboratory tests detected virus and antibodies against nonstructural and structural FMDV proteins in pronghorn and cattle. Virus was present in some animals for 1 wk but was not detectable by virus isolation or PCR at 3 wk postinfection or afterward.

  18. Retrospective evaluation of foot-and-mouth disease vaccine effectiveness in Turkey.

    PubMed

    Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

    2014-04-01

    Foot-and-mouth disease (FMD) is present in much of Turkey and its control is largely based on vaccination. The arrival of the FMD Asia-1 serotype in Turkey in 2011 caused particular concern, spreading rapidly westwards across the country towards the FMD free European Union. With no prior natural immunity, control of spread would rely heavily on vaccination. Unlike human vaccines, field protection is rarely evaluated directly for FMD vaccines. Between September 2011 and July 2012 we performed four retrospective outbreak investigations to assess the vaccine effectiveness (VE) of FMD Asia-1 vaccines in Turkey. Vaccine effectiveness is defined as the reduction in risk in vaccinated compared to unvaccinated individuals with similar virus exposure in the field. The four investigations included 12 villages and 1230 cattle >4 months of age. One investigation assessed the FMD Asia-1 Shamir vaccine, the other three evaluated the recently introduced FMD Asia-1 TUR 11 vaccine made using a field isolate of the FMD Asia-1 Sindh-08 lineage that had recently entered Turkey. After adjustment for confounding, the TUR 11 vaccine provided moderate protection against both clinical disease VE=69% [95% CI: 50%-81%] and infection VE=63% [95% CI: 29%-81%]. However, protection was variable with some herds with high vaccine coverage still experiencing high disease incidence. Some of this variability will be the result of the variation in virus challenge and immunity that occurs under field conditions. In the outbreak investigated there was no evidence that the Asia-1 Shamir vaccine provided adequate protection against clinical FMD with an incidence of 89% in single vaccinated cattle and 69% in those vaccinated two to five times. Based on these effectiveness estimates, vaccination alone is unlikely to produce the high levels of herd immunity needed to control FMD without additional control measures.

  19. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3 - Vaccines.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed research knowledge gaps in the field of FMDV (foot-and-mouth disease virus) vaccines. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD vaccine research. Vaccines play a vital role in FMD control, used both to limit the spread of the virus during epidemics in FMD-free countries and as the mainstay of disease management in endemic regions, particularly where sanitary controls are difficult to apply. Improvements in the performance or cost-effectiveness of FMD vaccines will allow more widespread and efficient disease control. FMD vaccines have changed little in recent decades, typically produced by inactivation of whole virus, the quantity and stability of the intact viral capsids in the final preparation being key for immunogenicity. However, these are exciting times and several promising novel FMD vaccine candidates have recently been developed. This includes the first FMD vaccine licensed for manufacture and use in the USA; this adenovirus-vectored FMD vaccine causes in vivo expression of viral capsids in vaccinated animals. Another promising vaccine candidate comprises stabilized empty FMDV capsids produced in vitro in a baculovirus expression system. Recombinant technologies are also being developed to improve otherwise conventionally produced inactivated vaccines, for example, by creating a chimeric vaccine virus to increase capsid stability and by inserting sequences into the vaccine virus for desired antigen expression. Other important areas of ongoing research include enhanced adjuvants, vaccine quality control procedures and predicting vaccine protection from immune correlates, thus reducing dependency on animal challenge studies. Globally, the degree of independent vaccine evaluation is highly variable, and this is essential for vaccine quality. Previously neglected, the

  20. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain

  1. Hand-foot-and-mouth disease and weather factors in Guangzhou, southern China.

    PubMed

    Li, T; Yang, Z; DI, B; Wang, M

    2014-08-01

    Hand-foot-and-mouth disease (HFMD) is becoming one of the common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, we aimed to examine the effect of weather patterns on the incidence of HFMD in the subtropical city of Guangzhou for the period 2009-2012, and assist public health prevention and control measures. A negative binomial multivariable regression was used to identify the relationship between meteorological variables and HFMD. During the study period, a total of 166,770 HFMD-confirmed cases were reported, of which 11 died, yielding a fatality rate of 0·66/10,000. Annual incidence rates from 2009 to 2012 were 132·44, 311·40, 402·76, and 468·59/100,000 respectively. Each 1°C rise in temperature corresponded to an increase of 9·38% (95% CI 8·17-10·51) in the weekly number of HFMD cases, while a 1 hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 6·80% (95% CI -6·99 to -6·65), having an opposite effect. Similarly, a 1% rise in relative humidity corresponded to an increase of 0·67% or 0·51%, a 1 m/h rise in wind velocity corresponded to an increase of 4·01% or 2·65%, and a 1 day addition in the number of windy days corresponded to an increase of 24·73% or 25·87%, in the weekly number of HFMD cases, depending on the variables considered in the model. Our findings revealed that the epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on occurrence and transmission of HFMD.

  2. Review: Evaluation of Foot-and-Mouth Disease Control Using Fault Tree Analysis.

    PubMed

    Isoda, N; Kadohira, M; Sekiguchi, S; Schuppers, M; Stärk, K D C

    2015-06-01

    An outbreak of foot-and-mouth disease (FMD) causes huge economic losses and animal welfare problems. Although much can be learnt from past FMD outbreaks, several countries are not satisfied with their degree of contingency planning and aiming at more assurance that their control measures will be effective. The purpose of the present article was to develop a generic fault tree framework for the control of an FMD outbreak as a basis for systematic improvement and refinement of control activities and general preparedness. Fault trees are typically used in engineering to document pathways that can lead to an undesired event, that is, ineffective FMD control. The fault tree method allows risk managers to identify immature parts of the control system and to analyse the events or steps that will most probably delay rapid and effective disease control during a real outbreak. The present developed fault tree is generic and can be tailored to fit the specific needs of countries. For instance, the specific fault tree for the 2001 FMD outbreak in the UK was refined based on control weaknesses discussed in peer-reviewed articles. Furthermore, the specific fault tree based on the 2001 outbreak was applied to the subsequent FMD outbreak in 2007 to assess the refinement of control measures following the earlier, major outbreak. The FMD fault tree can assist risk managers to develop more refined and adequate control activities against FMD outbreaks and to find optimum strategies for rapid control. Further application using the current tree will be one of the basic measures for FMD control worldwide.

  3. Construction and characterization of 3A-epitope-tagged foot-and-mouth disease virus.

    PubMed

    Ma, Xueqing; Li, Pinghua; Sun, Pu; Bai, Xingwen; Bao, Huifang; Lu, Zengjun; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

    2015-04-01

    Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids (aa) in most FMDVs examined to date. Specific deletion in the FMDV 3A protein has been associated with the inability of FMDV to grow in primary bovine cells and cause disease in cattle. However, the aa residues playing key roles in these processes are poorly understood. In this study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9 aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues 94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses stably maintained and expressed the foreign epitopes even after 10 serial passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties and plaque phenotypes similar to those of the parental virus in BHK-21 cells. However, the epitope-tagged viruses exhibited lower growth rates and smaller plaque size phenotypes than those of the parental virus in primary fetal bovine kidney (FBK) cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the decreased ability of FMDV to replicate in primary bovine cells was not associated with the length of 3A, and the genetic determinant thought to play key role in decreased ability to replicate in primary bovine cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101 in 3A protein.

  4. Investigation of foot-and-mouth disease outbreaks in the Mbala and Kazungula districts of Zambia.

    PubMed

    Banda, Frank; Kasanga, Christopher J; Sallu, Raphael; Sinkala, Yona; Sinkombe, Tingiya W; Mulumba, Misheck; Rweyemamu, Mark M; Wambura, Philemon N

    2014-01-01

    Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. It is known to be endemic in Zambia, with periodic outbreaks occurring in different geographical areas of the country. This study was conducted to investigate the presence of FMD virus (FMDV) in reported FMD-suspected cases in cattle from the Kazungula and Mbala districts of Zambia. Sixty epithelial tissues or oesophageal-pharyngeal (OP) scrapings (probang samples) were collected from Mbala (n = 51) and Kazungula (n = 9) and examined for FMDV. The FMDV viral RNA and serotypes were examined by realtime reverse transcription polymerase chain reaction (qRT-PCR) and antigen Enzyme- linked immunosorbent assay (ELISA), respectively. Twenty-two samples (36.7%) were positive for the FMDV genome by qRT-PCR with Cycle threshold (Ct) values ranging from 13 to 31. The FMDV-positive samples from epithelial tissues showed relatively higher Ct values compared to those obtained from OP scrapings, irrespective of geographical location. Forty percent (40%; n = 4) of epithelial tissues from Mbala were serotyped into SAT 2 serotype by antigen ELISA. Kazungula samples were serotyped into SAT 1. These findings indicated that Mbala and Kazungula districts had FMD outbreaks in 2012 that were ascribed to at least FMDV serotype SAT 2 and SAT 1 field strains. Furthermore, regular interaction between buffalos from the Mosi-o Tunya Park and domestic animals from surrounding areas could contribute to the occurrence of regular FMD outbreaks in Kazungula, whilst the uncontrolled animal movements across borders between Mbala and Nsumbawanga could be responsible for disease outbreaks in Mbala. In-depth molecular biological studies, including sequencing and phylogeny of the viruses, should be conducted to elucidate the complex epidemiology of FMD in Zambia, thereby providing valuable information needed for the rational control strategy of FMD in Zambia and neighbouring countries.

  5. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 2 - Epidemiology, Wildlife and Economics.

    PubMed

    Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed knowledge gaps in foot-and-mouth disease (FMD) research, and in this study, we consider (i) epidemiology, (ii) wildlife and (iii) economics. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. During 2011-2015, modelling studies were dominant in the broad field of epidemiology; however, continued efforts are required to develop robust models for use during outbreaks in FMD-free countries, linking epidemiologic and economics models. More guidance is needed for both the evaluation and the setting of targets for vaccine coverage, population immunity and vaccine field efficacy. Similarly, methods for seroprevalence studies need to be improved to obtain more meaningful outputs that allow comparison across studies. To inform control programmes in endemic countries, field trials assessing the effectiveness of vaccination in extensive smallholder systems should be performed to determine whether FMD can be controlled with quality vaccines in settings where implementing effective biosecurity is challenging. Studies need to go beyond measuring only vaccine effects and should extend our knowledge of the impact of FMD and increase our understanding of how to maximize farmer participation in disease control. Where wildlife reservoirs of virus exist, particularly African Buffalo, we need to better understand when and under what circumstances transmission to domestic animals occurs in order to manage this risk appropriately, considering the impact of control measures on livelihoods and wildlife. For settings where FMD eradication is unfeasible, further ground testing of commodity-based trade is recommended. A thorough review of global FMD control programmes, covering successes and failures, would be extremely valuable and could be used to guide other control programmes.

  6. Antiviral activity of Paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease.

    PubMed

    Ji, Ping; Chen, Changmai; Hu, Yanan; Zhan, Zixuan; Pan, Wei; Li, Rongrong; Li, Erguang; Ge, Hui-Ming; Yang, Guang

    2015-01-01

    The bark, leaves, and flowers of Paulownia trees have been used in traditional Chinese medicine to treat infectious and inflammatory diseases. We investigated the antiviral effects of Paulownia tomentosa flowers, an herbal medicine used in some provinces of P. R. China for the treatment of skin rashes and blisters. Dried flowers of P. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (EV71) and coxsackievirus A16 (CAV16), the predominant etiologic agents of hand, foot, and mouth disease in P. R. China. The extract inhibited EV71 infection, although no effect was detected against CAV16 infection. Bioactivity-guided fractionation was performed to identify apigenin as an active component of the flowers. The EC50 value for apigenin to block EV71 infection was 11.0 µM, with a selectivity index of approximately 9.3. Although it is a common dietary flavonoid, only apigenin, and not similar compounds like naringenin and quercetin, were active against EV71 infection. As an RNA virus, the genome of EV71 has an internal ribosome entry site that interacts with heterogeneous nuclear ribonucleoproteins (hnRNPs) and regulates viral translation. Cross-linking followed by immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that EV71 RNA was associated with hnRNPs A1 and A2. Apigenin treatment disrupted this association, indicating that apigenin suppressed EV71 replication through a novel mechanism by targeting the trans-acting factors. This study therefore validates the effects of Paulownia against EV71 infection. It also yielded mechanistic insights on apigenin as an active compound for the antiviral activity of P. tomentosa against EV71 infection.

  7. Tracking the Antigenic Evolution of Foot-and-Mouth Disease Virus

    PubMed Central

    Upadhyaya, Sasmita; Lukhwareni, Azwidowi; Esterhuysen, Jan J.; Harvey, William T.; Blignaut, Belinda; Fry, Elizabeth E.; Parida, Satya; Paton, David J.; Mahapatra, Mana

    2016-01-01

    Quantifying and predicting the antigenic characteristics of a virus is something of a holy grail for infectious disease research because of its central importance to the emergence of new strains, the severity of outbreaks, and vaccine selection. However, these characteristics are defined by a complex interplay of viral and host factors so that phylogenetic measures of viral similarity are often poorly correlated to antigenic relationships. Here, we generate antigenic phylogenies that track the phenotypic evolution of two serotypes of foot-and-mouth disease virus by combining host serology and viral sequence data to identify sites that are critical to their antigenic evolution. For serotype SAT1, we validate our antigenic phylogeny against monoclonal antibody escape mutants, which match all of the predicted antigenic sites. For serotype O, we validate it against known sites where available, and otherwise directly evaluate the impact on antigenic phenotype of substitutions in predicted sites using reverse genetics and serology. We also highlight a critical and poorly understood problem for vaccine selection by revealing qualitative differences between assays that are often used interchangeably to determine antigenic match between field viruses and vaccine strains. Our approach provides a tool to identify naturally occurring antigenic substitutions, allowing us to track the genetic diversification and associated antigenic evolution of the virus. Despite the hugely important role vaccines have played in enhancing human and animal health, vaccinology remains a conspicuously empirical science. This study advances the field by providing guidance for tuning vaccine strains via site-directed mutagenesis through this high-resolution tracking of antigenic evolution of the virus between rare major shifts in phenotype. PMID:27448206

  8. The Foot-and-Mouth Disease Carrier State Divergence in Cattle

    PubMed Central

    Eschbaumer, Michael; Rekant, Steven I.; Pacheco, Juan M.; Smoliga, George R.; Hartwig, Ethan J.; Rodriguez, Luis L.

    2016-01-01

    ABSTRACT The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis

  9. Electrical Resistivity Monitoring for Leachate Distribution at Two Foot-and-Mouth- Disease (FMD) Burial Sites

    NASA Astrophysics Data System (ADS)

    Lee, S.; Kaown, D.; Lee, K.; Leem, K.; Ko, K.

    2011-12-01

    The main objective of this study was to provide the basic information on leachate distribution with time changes through the electrical resistivity monitoring for a certain period of time in the Foot-and-Mouth-Disease (FMD) burial facilities which is needed to prevent further soil and groundwater contamination and to build an effective plan for stabilization of the burial site. In this study, dipole-dipoles surveys were carried out around two FMD burial sites in Iceon-si, Gyeonggi-do. The FMD burial facility installed at Daewall-myeon is consists of one block but, at Yul-myeon, it is divided into 2 blocks named A and B blocks. Dipole-Dipole surveys with 8 lines at Yul-myeon and 3 lines at Daewall-myeon were carried out. The observed leachate distribution along survey lines was not clearly evident as time passes at Daewall-myeon site, but, at Yul-myeon site, the leachate distribution around the survey lines showed a decrease of resistivity around the burial facility. At and around A and B blocks of Yul-myeon site, interpretations of the survey data show low resistivity zones below 10 Ωm from a depth 3 m to 10 m and such low resistivity zones of the A block are thicker than the B block by about 5~10 m. From the geochemical data and resistivity survey at two FMD burial sites, it is inferred that the groundwater within a 50-meter radius around burial facilities of the Yul-myeon site are contaminated by leachate. The general resistivity distribution around the burial site is seemed affected by the leachate with high electrical conductivity. The detail distribution patterns can be explained by local distributions of soil and weathered rocks and associated leachate flow. This subject is supported by Brain Korea 21 and Korea Ministry of Environment as 'The GAIA Project (173-092-009)'.

  10. Characteristics of leachate in Foot and Mouth Disease Carcass Disposal using Molecular Biology Method

    NASA Astrophysics Data System (ADS)

    Choi, E. J.; Kim, B. J.; Wi, D. W.; Choi, N. C.; Lee, S. J.; Min, J. E.; Park, C. Y.

    2012-04-01

    The Leachate from Foot and Mouth Disease(FMD) carcass disposal by is one of the types of high-concentration contaminated wastewater with the greatest environmental impact. This is due to its pollutants: nitrate nitrogen (NO3--N) and pathogenic microorganisms. Satisfactory treatment of leachate is not an easy task for its high concentrations of nitrate nitrogen and pathogenic microorganisms. Therefore suitable FMD leachate treatment processes should be adopted to improve treatment performance and to reduce overall running costs. The objective of this study was to determine the leachate characteristics through environmental analysis and molecular biology method (bacteria identification and Polymerase Chain Reaction) using FMD leachate samples for optimal FMD leachate treatment processes. The Sixteen FMD leachate samples was obtained from carcass disposal regions in Korea. Results of environmental analysis showed that pH and Eh was observed from 5.57 to 7.40, -134~358mV. This data was exhibited typical early carcass disposal (Neutral pH and Reducing Environment by abundant organic matter). TOC and nitrate nitrogen high concentrations in FMD leachate showed a large variability from 2.3 to 38,730 mg/L(mean - 6,821.93mg/L) and 0.335 ~231.998mg/L(mean - 37.46mg/L), respectively. The result of bacteria identification was observed Bacillus cereus, Pseudomonas putida, Acinetobacter ursingii, Aeromonas hydrophila, Serratia liquefaciens, Brevundimonas naejangsanensis, Serratia liquefaciens, Pseudomonas fluorescens, Pseudomonas aeruginosa, Acinetobacter ursingii. The results of Polymerase Chain Reaction(PCR) using EzTaxon server data revealed Pseudoclavibacter helvolus, Pseudochrobactrum saccharolyticum, Corynebacterium callunae, Paenibacillus lautus, Paenibacillus sp., Bacillus arvi, Brevundimonas bullata, Acinetobacter ursingii, Lysinibacillus sphaericus, Bacillus pumilus, Bacillus sphaericus, Bacillus psychrodurans, Pseudomonas sp.

  11. A Lagrangian particle model to predict the airborne spread of foot-and-mouth disease virus

    NASA Astrophysics Data System (ADS)

    Mayer, D.; Reiczigel, J.; Rubel, F.

    Airborne spread of bioaerosols in the boundary layer over a complex terrain is simulated using a Lagrangian particle model, and applied to modelling the airborne spread of foot-and-mouth disease (FMD) virus. Two case studies are made with study domains located in a hilly region in the northwest of the Styrian capital Graz, the second largest town in Austria. Mountainous terrain as well as inhomogeneous and time varying meteorological conditions prevent from application of so far used Gaussian dispersion models, while the proposed model can handle these realistically. In the model, trajectories of several thousands of particles are computed and the distribution of virus concentration near the ground is calculated. This allows to assess risk of infection areas with respect to animal species of interest, such as cattle, swine or sheep. Meteorological input data like wind field and other variables necessary to compute turbulence were taken from the new pre-operational version of the non-hydrostatic numerical weather prediction model LMK ( Lokal-Modell-Kürzestfrist) running at the German weather service DWD ( Deutscher Wetterdienst). The LMK model provides meteorological parameters with a spatial resolution of about 2.8 km. To account for the spatial resolution of 400 m used by the Lagrangian particle model, the initial wind field is interpolated upon the finer grid by a mass consistent interpolation method. Case studies depict a significant influence of local wind systems on the spread of virus. Higher virus concentrations at the upwind side of the hills and marginal concentrations in the lee are well observable, as well as canalization effects by valleys. The study demonstrates that the Lagrangian particle model is an appropriate tool for risk assessment of airborne spread of virus by taking into account the realistic orographic and meteorological conditions.

  12. Molecular epidemiology of foot-and-mouth disease virus type A in South America.

    PubMed

    Malirat, Viviana; Bergmann, Ingrid Evelyn; de Mendonça Campos, Renata; Conde, Florangel; Quiroga, José Luis; Villamil, Mariluz; Salgado, Gustavo; Ortiz, Salomón

    2012-07-06

    A databank of 78 VP(1) complete sequences of type A foot-and-mouth disease virus (FMDV) from South American isolates was constructed. Forty-nine samples corresponded to FMDV that circulated between the years 1999-2008, mainly in Venezuela, where most type A outbreaks have occurred lately and twenty-nine to strains historically relevant for the continent. The phylogenetic analysis showed that all South American FMDV belonged to the Euro-SA topotype. Sixteen subgenotypes could be identified, based on a 15% nucleotide divergence cut-off criterion: eight are extinguished, three were active until the year 2002 and the remaining five circulated in Venezuela during the years 2001-2007, illustrating the potential for FMDV diversification under appropriate selective pressure. The last emergencies reported in already-free areas of Colombia in 2004 and 2008 were closely related to isolates acting in Venzuela. Evidence of positive selection over codon 170, within the immunogenic site 4 of VP1 protein, was recorded. A codon deletion in amino acid position 142, within the G-H loop, was found in some isolates within subgenotypes 14, 15 and 16. Conversely amino acid deletion 197 was restricted to all isolates within a particular genetic cluster. The present work is the first comprehensive phylogenetic analysis of FMDV type A in South America, filling a gap of knowledge with respect to both, historical and acting viruses. The results provided evidence that supports the ecosystem dynamics in the region, and also served as an input to establish genetic links of emergencies in already-declared free areas, highlighting the need for strengthening control activities.

  13. Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

    PubMed Central

    Diaz-San Segundo, Fayna; Dias, Camila C. A.; Moraes, Mauro P.; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa

    2013-01-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 107 or 108 infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV. PMID:23468490

  14. Risk factors for foot-and-mouth disease in Tanzania, 2001-2006.

    PubMed

    Allepuz, A; Stevenson, M; Kivaria, F; Berkvens, D; Casal, J; Picado, A

    2015-04-01

    We developed a model to quantify the effect of factors influencing the spatio-temporal distribution of foot-and-mouth disease (FMD) in Tanzania. The land area of Tanzania was divided into a regular grid of 20 km × 20 km cells and separate grids constructed for each of the 12-month periods between 2001 and 2006. For each year, a cell was classified as either FMD positive or negative dependent on an outbreak being recorded in any settlement within the cell boundaries. A Bayesian mixed-effects spatial model was developed to assess the association between the risk of FMD occurrence and distance to main roads, railway lines, wildlife parks, international borders and cattle density. Increases in the distance to main roads decreased the risk of FMD every year from 2001 to 2006 (ORs ranged from 0.43 to 0.97). Increases in the distance to railway lines and international borders were, in general, associated with a decreased risk of FMD (ORs ranged from 0.85 to 0.99). Increases in the distance from a national park decreased the risk of FMD in 2001 (OR 0.80; 95% CI 0.68-0.93) but had the opposite effect in 2004 (OR 1.06; 95% CI 1.01-1.12). Cattle population density was, in general, positively associated with the risk of FMD (ORs ranged from 1.01 to 1.30). The spatial distribution of high-risk areas was variable and corresponded to endemic (2001, 2002 and 2005) and epidemic (2003, 2004 and 2006) phases. Roads played a dominant role in both epidemiological situations; we hypothesize that roads are the main driver of FMD expansion in Tanzania. Our results suggest that FMD occurrence in Tanzania is more related to animal movement and human activity via communication networks than transboundary movements or contact with wildlife.

  15. Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

    PubMed

    Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

    2015-02-04

    Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the

  16. Importance of foot and mouth disease vaccine purity in interpreting serological surveys.

    PubMed

    Smitsaart, E; Espinoza, A M; Maradei, E; Cosentino, B; Guinzburg, M; Madonni, G; Cadenazzi, G; Bottini, R; Filippi, J; Bergmann, I

    2015-12-01

    The aim of this study was to determine whether the degree of purity achieved in conventional vaccines against the foot and mouth disease virus in Argentina interferes with the interpretation of seroepidemiological surveys for confirming the absence of viral activity, which are performed to support the recognition of free zones practising vaccination. The evaluation of 168 vaccine series due to be marketed in Argentina (2006-2012) and subjected to official control testing in cattle, as well as repeated vaccination of cattle and other species using vaccines with high antigen concentrations, demonstrated that they did not induce antibodies to non-structural proteins (NSPs). The results show clearly that vaccines with satisfactory potency do not induce a response to NSPs, even by forcing the immune response through more concentrated doses with multiple valences and revaccination protocols at shorter irtervals than in vaccination campaigns. These results confirm that the vaccines used in routine vaccination programmes have a degree of antigen purification consistent with the needs observed on the basis of sampling for serological surveillance. Moreover, serological surveys conducted in 2006-2011 by Argentina's official Veterinary Services--the National Health and Agrifood Quality Service (SENASA)--on more than 23,000 sera per year from cattle included in the vaccination programme, in order to confirm the absence of virus circulation, revealed an average 0.05% of reactive results, consistent with the specificity of the tests. In conclusion, the vaccines produced by conventional methods and with proven potencythat are available in Argentina are sufficiently purified to ensure thatthey do not interfere with the interpretation of sampling for serological surveillance performed to support the recognition of FMD-free zones practising vaccination.

  17. [Immune response against foot-and-mouth disease virus in cattle: effect of vaccination].

    PubMed

    Braun, M; Sigal, L; Mundo, S; Ramayo, L; Jar, A M; Gómez, G; Fontanals, A; Mazzuca, G O

    1989-01-01

    Foot and Mouth Disease Virus (FMDV) is one of the most feared animal virus and vaccination still has to be used in many countries. In previous reports, using a murine model, we studied the cellular basis of immune responses against FMDV and were able to show that they are atypical. In cattle, although complete protection may be attained after only one dose of killed virus vaccine, very little is known about protection against FMDV, except for antibody responses, but practically nothing concerning the cellular basis of their immune response. Moreover, since neutralizing titers do not always correlate with protection, the potency of vaccines in controlled by viral challenge. Our aim is to study cellular immune responses against FMDV, and to search for a correlate to protection. As a first step, 55 virgin cattle from a non endemic area (Patagonia) were divided into three groups: C: non immunized controls; HS: immunized with saponine containing vaccine; and EO: with oil emulsified vaccine. After vaccination, they were carried to an endemic area (Buenos Aires), where they were challenged with live FMDV. Animals were bled immediately before and 7 days after challenge, and their white blood cells and lymphocyte subpopulations were counted. All animals showed a marked neutropenia and eosinophilia, significantly higher in HS than in EO and C groups; both parameters were significantly better in the 2nd assay. Total lymphocyte counts were normal. Lymphocyte subpopulations were assessed by immunofluorescence using monoclonal antibodies: their proportions were normal and did not change during illness in group C. Several factors could have induced the observed eosinophilia and neutropenia: parasites, stress, saponine, others.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The serological response against foot and mouth disease virus elicited by repeated vaccination of dairy cattle.

    PubMed

    Elnekave, Ehud; Dekker, Aldo; Eble, Phaedra; van Hemert-Kluitenberg, Froukje; Gelman, Boris; Storm, Nick; Klement, Eyal

    2016-09-22

    In Israel, cattle are annually vaccinated against foot and mouth disease (FMD). If infections with FMD virus occur in dairy farms it mainly involves heifers and calves, while older dairy cows seldom become infected. We hypothesized that this difference in susceptibility between adult cows and the young heifers and calves is due to stronger and more stable immune response elicited by multiple vaccinations. In order to test this hypothesis, 99 dairy cattle, divided into six groups according to number of prior vaccinations, were annually vaccinated with a trivalent vaccine (A, O and Asia-1) and followed during two consecutive years. In total 988 sera were sampled at 11 time points. Virus neutralization tests (VNT) were performed in order to determine the neutralizing antibody titers (NAT) against the vaccine homologous serotypes: O-4625, O-Manisa, Asia-1-Shamir and the heterologous serotype A-Turkey-20/2006. A similar NAT pattern was observed to all serotypes and therefore statistical analysis was restricted to O-4625 serotype. In the 'high vaccination' groups (cows that were vaccinated at least four times before the study), high NAT were found on the beginning of the trial and no or only a mild increase of NAT was observed following further vaccinations. Additionally, in the 'high vaccination' groups, the percentage of cows that had a NAT higher than 2.0 (log10) by the end of the 1st year was significantly higher than in the 'low vaccination' groups (cows vaccinated only three times or less before the study). We conclude that starting from the 5th vaccination, the NAT increase following vaccination is mild and NAT are persistent, suggesting reduction of the frequency of routine vaccination after multiple vaccinations is possible.

  19. The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination.

    PubMed Central

    Black, L.; Pay, T. W.

    1975-01-01

    The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests. Images Plate 1 PMID:1054725

  20. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia

    PubMed Central

    NikNadia, NMN; Sam, I-Ching; Rampal, Sanjay; WanNorAmalina, WMZ; NurAtifah, Ghazali; Verasahib, Khebir; Ong, Chia Ching; MohdAdib, MohdAidinniza; Chan, Yoke Fun

    2016-01-01

    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24–1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01–1.34 P<0.034). In summary, the 2–3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs. PMID:27010319

  1. Effect of Climatic Factors on Hand, Foot, and Mouth Disease in South Korea, 2010-2013

    PubMed Central

    Kim, Bryan Inho; Ki, Hyunok; Park, Sunhee; Cho, Eunhi

    2016-01-01

    Hand, foot, and mouth disease (HFMD) causes characteristic blisters and sores mainly in infants and children, and has been monitored in South Korea through sentinel surveillance since 2009. We described the patterns of HFMD occurrence and analyzed the effect of climatic factors on national HFMD incidence. Weekly clinically diagnosed HFMD case rates (per 1,000 outpatients) in sentinel sites and weekly climatic factors, such as average temperature, relative humidity, duration of sunshine, precipitation, and wind speed from 2010 to 2013, were used in this study. A generalized additive model with smoothing splines and climatic variables with time lags of up to 2 weeks were considered in the modeling process. To account for long-term trends and seasonality, we controlled for each year and their corresponding weeks. The autocorrelation issue was also adjusted by using autocorrelation variables. At an average temperature below 18°C, the HFMD rate increased by 10.3% for every 1°C rise in average temperature (95% confidence interval (CI): 8.4, 12.3%). We also saw a 6.6% increase in HFMD rate (95% CI: 3.6, 9.7%) with every 1% increase in relative humidity under 65%, with a 1.5% decrease in HFMD rate observed (95% CI: 0.4, 2.7%) with each 1% humidity increase above 65%. Modeling results have shown that average temperature and relative humidity are related to HFMD rate. Additional research on the environmental risk factors of HFMD transmission is required to understand the underlying mechanism between climatic factors and HFMD incidence. PMID:27285850

  2. Aerosol transmission of foot-and-mouth disease virus Asia-1 under experimental conditions.

    PubMed

    Colenutt, C; Gonzales, J L; Paton, D J; Gloster, J; Nelson, N; Sanders, C

    2016-06-30

    Foot-and-mouth disease virus (FMDV) control measures rely on understanding of virus transmission mechanisms. Direct contact between naïve and infected animals or spread by contaminated fomites is prevented by quarantines and rigorous decontamination procedures during outbreaks. Transmission of FMDV by aerosol may not be prevented by these control measures and this route of transmission may allow infection of animals at distance from the infection source. Understanding the potential for aerosol spread of specific FMDV strains is important for informing control strategies in an outbreak. Here, the potential for transmission of an FMDV Asia 1 strain between pigs and cattle by indirect aerosol exposure was evaluated in an experimental setting. Four naïve calves were exposed to aerosols emitted from three infected pigs in an adjacent room for a 10h period. Direct contact between pigs and cattle and fomite transfer between rooms was prevented. Viral titres in aerosols emitted by the infected pigs were measured to estimate the dose that calves were exposed to. One of the calves developed clinical signs of FMD, whilst there was serological evidence for spread to cattle by aerosol transmission in the remaining three calves. This highlights the possibility that this FMDV Asia 1 strain could be spread by aerosol transmission given appropriate environmental conditions should an outbreak occur in pigs. Our estimates suggest the exposure dose required for aerosol transmission was higher than has been previously quantified for other serotypes, implying that aerosols are less likely to play a significant role in transmission and spread of this FMDV strain.

  3. Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study.

    PubMed

    Roche, S E; Garner, M G; Sanson, R L; Cook, C; Birch, C; Backer, J A; Dube, C; Patyk, K A; Stevenson, M A; Yu, Z D; Rawdon, T G; Gauntlett, F

    2015-04-01

    Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

  4. Estimation of the transmission of foot-and-mouth disease virus from infected sheep to cattle

    PubMed Central

    2014-01-01

    The quantitative role of sheep in the transmission of foot-and-mouth disease virus (FMDV) is not well known. To estimate the role of sheep in the transmission of FMDV, a direct contact transmission experiment with 10 groups of animals each consisting of 2 infected lambs and 1 contact calf was performed. Secretions and excretions (oral swabs, blood, urine, faeces and probang samples) from all animals were tested for the presence of FMDV by virus isolation (VI) and/or RT-PCR. Serum was tested for the presence of antibodies against FMDV. To estimate FMDV transmission, the VI, RT-PCR and serology results were used. The partial reproduction ratio R0p i.e. the average number of new infections caused by one infected sheep introduced into a population of susceptible cattle, was estimated using either data of the whole infection chain of the experimental epidemics (the transient state method) or the final sizes of the experimental epidemics (the final size method). Using the transient state method, R0p was estimated as 1.0 (95% CI 0.2 - 6.0) using virus isolation results and 1.4 (95% CI 0.3 - 8.0) using RT-PCR results. Using the final size method, R0p was estimated as 0.9 (95% CI 0.2 - 3.0). Finally, R0p was compared to the R0’s obtained in previous transmission studies with sheep or cattle only. This comparison showed that the infectivity of sheep is lower than that of cattle and that sheep and cattle are similarly susceptible to FMD. These results indicate that in a mixed population of sheep and cattle, sheep play a more limited role in the transmission of FMDV than cattle. PMID:24886222

  5. Efficient rescue of foot-and-mouth disease virus in cultured cells transfected with RNA extracted from clinical samples.

    PubMed

    Bisht, Punam; Mohapatra, Jajati K; Subramaniam, Saravanan; Das, Biswajit; Pande, Veena; Biswal, Jitendra K; Sharma, Gaurav K; Rout, Manoranjan; Ranjan, Rajeev; Dash, Bana B; Sanyal, Aniket; Pattnaik, Bramhadev

    2014-02-01

    In this study, an RNA transfection was used to rescue infectious foot-and-mouth disease (FMD) virus from clinical samples in BHK-21 cell line for diagnosis of FMD. Tissue samples (n=190) were subjected to FMD virus isolation by conventional cell culture and also by RNA transfection. FMD virus was isolated from 62% of the clinical samples by RNA transfection, whereas virus was isolated only from 16% of the clinical samples in conventional cell culture method, suggesting better performance of the RNA transfection. Virus was rescued from 67% and 10% of ELISA negative but multiplex PCR positive samples by RNA transfection and conventional cell culture, respectively. The efficiency of transfection was studied on clinical samples subjected to temperature as high as 37°C and varying pH (pH 4-9). Except up to 1 week of storage at 4°C at pH 7.5, virus isolation was not possible by cell culture. Virus was rescued by transfection from samples stored at 4°C for any of the applied pH up to 4 weeks, and when stored at 37°C virus could be rescued up to 4 weeks at pH 7.5 suggesting the fitness of transfection to isolate virus from clinical samples stored under inappropriate conditions. The sequence data and antigenic relationships with the vaccine strains, between virus rescued by transfection and conventional cell culture, were comparable. The RNA transfection will help to increase the efficiency of virus isolation, diagnosis and molecular epidemiological studies.

  6. Cost-benefit analysis of foot and mouth disease control in Ethiopia.

    PubMed

    Jemberu, Wudu T; Mourits, Monique; Rushton, Jonathan; Hogeveen, Henk

    2016-09-15

    Foot and mouth disease (FMD) occurs endemically in Ethiopia. Quantitative insights on its national economic impact and on the costs and benefits of control options are, however, lacking to support decision making in its control. The objectives of this study were, therefore, to estimate the annual costs of FMD in cattle production systems of Ethiopia, and to conduct an ex ante cost-benefit analysis of potential control alternatives. The annual costs of FMD were assessed based on production losses, export losses and control costs. The total annual costs of FMD under the current status quo of no official control program were estimated at 1354 (90% CR: 864-2042) million birr. The major cost (94%) was due to production losses. The costs and benefits of three potential control strategies: 1) ring vaccination (reactive vaccination around outbreak area supported by animal movement restrictions, 2) targeted vaccination (annual preventive vaccination in high risk areas plus ring vaccination in the rest of the country), and 3) preventive mass vaccination (annual preventive vaccination of the whole national cattle population) were compared with the baseline scenario of no official control program. Experts were elicited to estimate the influence of each of the control strategies on outbreak incidence and number of cases per outbreak. Based on these estimates, the incidence of the disease was simulated stochastically for 10 years. Preventive mass vaccination was epidemiologically the most efficient control strategy by reducing the national outbreak incidence below 5% with a median time interval of 3 years, followed by targeted vaccination strategy with a corresponding median time interval of 5 years. On average, all evaluated control strategies resulted in positive net present values. The ranges in the net present values were, however, very wide, including negative values. The targeted vaccination strategy was the most economic strategy with a median benefit cost ratio of 4

  7. Risk factors for foot and mouth disease outbreaks in grazing beef cattle herds.

    PubMed

    Elnekave, E; Zamir, L; Hamd, F; Even Tov, B; Klement, E

    2015-06-15

    Foot and mouth disease (FMD) is considered one of the most important diseases of cattle. Recurrence of FMD outbreaks in Israel is common, even though routine vaccination of livestock is mandatory and control measures are applied during the outbreaks. Grazing beef herds are occasionally involved in these outbreaks and play an important role in disseminating the disease, due to the large efflux of animals from these herds to feedlots. Nevertheless, the risk factors for the occurrence of FMD among these herds have never been investigated. In 2011, Israel faced a large scale outbreak of serotype O FMD virus, which strongly affected beef cattle. We conducted a case-control study of 44 beef cattle herds grazing in the Golan Heights in order to determine the risk factors for FMDV infection. Data were analyzed using a generalized estimation equation (GEE) with a logit link function. Multivariable analysis was conducted for factors with p-value lower than 0.1 in the univariable analysis. The presence of calves under 6 months of age was found as a significant risk factor for FMDV infection in the univariable analysis (odds ratio (OR)=5.95, confidence intervals of 95% (CI95%)=1.59-22.29, p=0.008). This was also the only variable that remained statistically significant in the multivariable analysis. Herds in which more than 6 months between vaccination of adults and exposure had elapsed were in higher risk, albeit not statistically significant, for the occurrence of FMDV infection (OR=3.29, CI95%=0.83-12.99, p=0.089). The higher probability of infection in herds, which included young calves may be a result of their higher susceptibility due to administration of only one or no vaccine prior to the outbreak. The results of the study thus support increasing the frequency of vaccination of both cows and calves in grazing beef herds. Intensifying surveillance where young calves are abundant may also prove efficient for early detection of infected herds and for mitigating outbreaks

  8. Development of vaccines toward the global control and eradication of foot-and-mouth disease.

    PubMed

    Rodriguez, Luis L; Gay, Cyril G

    2011-03-01

    Foot-and-mouth disease (FMD) is one of the most economically and socially devastating diseases affecting animal agriculture throughout the world. Although mortality is usually low in adult animals, millions of animals have been killed in efforts to rapidly control and eradicate FMD. The causing virus, FMD virus (FMDV), is a highly variable RNA virus occurring in seven serotypes (A, O, C, Asia 1, Sat 1, Sat 2 and Sat 3) and a large number of subtypes. FMDV is one of the most infectious agents known, affecting cloven-hoofed animals with significant variations in infectivity and virus transmission. Although inactivated FMD vaccines have been available for decades, there is little or no cross-protection across serotypes and subtypes, requiring vaccines that are matched to circulating field strains. Current inactivated vaccines require growth of virulent virus, posing a threat of escape from manufacturing sites, have limited shelf life and require re-vaccination every 4-12 months. These vaccines have aided in the eradication of FMD from Europe and the control of clinical disease in many parts of the world, albeit at a very high cost. However, FMDV persists in endemic regions impacting millions of people dependent on livestock for food and their livelihood. Usually associated with developing countries that lack the resources to control it, FMD is a global problem and the World Organization for Animal Health and the United Nations' Food Agriculture Organization have called for its global control and eradication. One of the main limitations to FMDV eradication is the lack of vaccines designed for this purpose, vaccines that not only protect against clinical signs but that can actually prevent infection and effectively interrupt the natural transmission cycle. These vaccines should be safely and inexpensively produced, be easy to deliver, and also be capable of inducing lifelong immunity against multiple serotypes and subtypes. Furthermore, there is a need for better

  9. Foot-and-Mouth disease control using vaccination: the Dutch experience in 2001.

    PubMed

    Pluimers, F H

    2004-01-01

    A first case of foot-and-mouth disease (FMD) was confirmed on a farm in Oene on 21 March 2001. The Dutch eradication strategy for the area which is densely populated with susceptible animals was immediately applied: stamping out the infected herd and pre-emptive culling of all susceptible animals on farms within a radius of 1 km around an infected farm. If the organisation was unable to cull infected herds within 24 hours after detection and the neighbouring farms within four days, emergency ring vaccination would be applied. By 26 March it was clear that capacity problems prevented the required rapid culling and therefore the decision to apply emergency vaccination was taken. On 28 March vaccination of all susceptible animals was started in 2 km zones around infected farms. In the area where the first outbreak occurred, by 1 April 11 farms were found to be infected. Tracing the links between these infections was difficult, the farms being at a greater distance than 4 km from each other and fear increased that the disease could not be contained in this area. It was therefore decided to vaccinate a larger area: "Vaccination area Noord Veluwe". Suppressive vaccination was chosen. This implied that all vaccinated animals should be killed and destroyed. Vaccination rapidly reduced the number of new infections. In total 26 farms became infected with FMD. The last affected farm was confirmed on 22 April 2001. The last vaccinated animal was culled on 25 May 2001. EU rules also gave the option of choosing protective vaccination. The consequence was that only vaccinated cattle could stay alive. The status 'FMD-free without vaccination' however would then be recovered 12 months after the last outbreak. This consequence was too damaging to the export interests of the country. The killing of healthy vaccinated animals became the predominant factor in the discussion of farmers, politicians and the general public. The need for adjustments in the FMD eradication strategy and in

  10. Farmers' Intentions to Implement Foot and Mouth Disease Control Measures in Ethiopia.

    PubMed

    Jemberu, Wudu T; Mourits, M C M; Hogeveen, H

    2015-01-01

    The objectives of this study were to explore farmers' intentions to implement foot and mouth disease (FMD) control in Ethiopia, and to identify perceptions about the disease and its control measures that influence these intentions using the Health Belief Model (HBM) framework. Data were collected using questionnaires from 293 farmers in three different production systems. The influence of perceptions on the intentions to implement control measures were analyzed using binary logistic regression. The effect of socio-demographic and husbandry variables on perceptions that were found to significantly influence the intentions were analyzed using ordinal logistic regression. Almost all farmers (99%) intended to implement FMD vaccination free of charge. The majority of farmers in the pastoral (94%) and market oriented (92%) systems also had the intention to implement vaccination with charge but only 42% of the crop-livestock mixed farmers had the intention to do so. Only 2% of pastoral and 18% of crop-livestock mixed farmers had the intention to implement herd isolation and animal movement restriction continuously. These proportions increased to 11% for pastoral and 50% for crop-livestock mixed farmers when the measure is applied only during an outbreak. The majority of farmers in the market oriented system (>80%) had the intention to implement herd isolation and animal movement restriction measure, both continuously and during an outbreak. Among the HBM perception constructs, perceived barrier was found to be the only significant predictor of the intention to implement vaccination. Perceived susceptibility, perceived benefit and perceived barrier were the significant predictors of the intention for herd isolation and animal movement restriction measure. In turn, the predicting perceived barrier on vaccination control varied significantly with the production system and the age of farmers. The significant HBM perception predictors on herd isolation and animal movement

  11. Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

    PubMed

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-03-01

    Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature and respiratory rate were significantly different among 3 groups. But no statistical difference of amplitude in temperature and respiratory rate was observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was significantly different in 3 groups. However, amplitude and acrophase revealed no statistical difference in circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for

  12. Foot and mouth disease risk assessment in Mongolia--local expertise to support national policy.

    PubMed

    Wieland, B; Batsukh, B; Enktuvshin, S; Odontsetseg, N; Schuppers, M

    2015-06-01

    To address weaknesses in the current foot and mouth disease (FMD) control system and to inform the formulation of a national control strategy, Mongolia conducted two separate risk assessments, one for the Eastern region which in the past has seen re-current introductions of infection, and one for the Western region, where freedom from disease had been demonstrated over several years until FMD was re-introduced in 2013. The risk assessment was conducted in three stages: first local experts developed entry, exposure and consequence pathways during separate workshops in both regions, then data was collected, compiled and analysed, and finally, during a second workshop local experts provided risk estimations for both regions and identified recommendations for risk management. Risk estimates for each pathway were individually recorded, which ensured that views of all experts were equally represented in the risk estimation and which allowed assessing possible impact of different factors related to the background of participating local experts on risk estimates. Entry risk pathways with highest risk estimates were related to livestock movements and in the consequence assessment due to direct contacts. Uncertainty, for which disagreement between participants acted as a proxy, was high in entry pathways and in the assessment of effectiveness of control measures. The risk assessment was conducted with local experts who had no previous risk assessment experience. Through their involvement in the whole process however, they assumed a high level of ownership and despite lively discussions for some risk pathways, a high level of agreement was achieved and credible results were communicated to decision makers. Especially valuable were the derived recommendations. Through the risk assessment the local experts gained a thorough understanding of the FMD risk which resulted in sensible and realistic recommendations, which, if implemented, can lead to a sustainable strengthening of

  13. Prevalence and risk factors for foot and mouth disease infection in cattle in Israel.

    PubMed

    Elnekave, Ehud; van Maanen, Kees; Shilo, Hila; Gelman, Boris; Storm, Nick; Abed El Khaliq, Mohamad; Sharir, Beni; Berke, Olaf; Klement, Eyal

    2016-08-01

    Foot and mouth disease (FMD) is a highly contagious viral disease with major economic consequences. In Israel, FMD epidemics recur almost every year and mostly affect cattle. The highest number of outbreaks occurs among beef cattle farms, followed by feedlot farms and dairy farms. We performed several cross-sectional serological studies in Israel during 2006-2014, aimed to reveal if the virus is endemic among cattle and to determine the sero-prevalence of antibodies directed against non-structural proteins (NSP) of FMD virus. Additionally we aimed to determine the risk factors for such sero-positivity. A risk based sampling was performed and the presence of anti-NSP antibodies was estimated using the PrioCHECK(®) ELISA kit. Beef cattle showed the highest sero-prevalence (13.2%, CI95%=10.8-15.8%). Higher FMD sero-prevalence in beef cattle sampled in 2014 was associated with previous FMD outbreaks in the farm and with age (adult cows versus calves (p<0.05)). Sero-prevalence in feedlot calves was significantly lower with only one sero-positive calf out of 256 (0.4%, CI95%=0-2.2%). Sero-prevalence among dairy cattle was 2.7% (CI95%=2-3.6%) with location of up to 3km from FMD outbreaks in multiple farms and location of up to 5km from the nearest border standing out as significant (p<0.05) risk factors for sero-positivity. The extremely low sero-prevalence of FMD in feedlot cattle and the significant association of infection in beef cattle with previous outbreaks suggest absence of virus circulation between these two populations during the study period, although previous data show that during outbreaks such transmission can occur. Low sero-prevalence in dairy cattle located in areas adjacent to previous FMD outbreaks may be attributed to intense routine vaccination and stringent control measures that were applied during outbreaks such as emergency vaccination and strict quarantine. Early detection of FMD outbreaks among grazing beef herds as well as the implementation

  14. Early Decision Indicators for Foot-and-Mouth Disease Outbreaks in Non-Endemic Countries

    PubMed Central

    Garner, Michael G.; East, Iain J.; Stevenson, Mark A.; Sanson, Robert L.; Rawdon, Thomas G.; Bradhurst, Richard A.; Roche, Sharon E.; Van Ha, Pham; Kompas, Tom

    2016-01-01

    Disease managers face many challenges when deciding on the most effective control strategy to manage an outbreak of foot-and-mouth disease (FMD). Decisions have to be made under conditions of uncertainty and where the situation is continually evolving. In addition, resources for control are often limited. A modeling study was carried out to identify characteristics measurable during the early phase of a FMD outbreak that might be useful as predictors of the total number of infected places, outbreak duration, and the total area under control (AUC). The study involved two modeling platforms in two countries (Australia and New Zealand) and encompassed a large number of incursion scenarios. Linear regression, classification and regression tree, and boosted regression tree analyses were used to quantify the predictive value of a set of parameters on three outcome variables of interest: the total number of infected places, outbreak duration, and the total AUC. The number of infected premises (IPs), number of pending culls, AUC, estimated dissemination ratio, and cattle density around the index herd at days 7, 14, and 21 following first detection were associated with each of the outcome variables. Regression models for the size of the AUC had the highest predictive value (R2 = 0.51–0.9) followed by the number of IPs (R2 = 0.3–0.75) and outbreak duration (R2 = 0.28–0.57). Predictability improved at later time points in the outbreak. Predictive regression models using various cut-points at day 14 to define small and large outbreaks had positive predictive values of 0.85–0.98 and negative predictive values of 0.52–0.91, with 79–97% of outbreaks correctly classified. On the strict assumption that each of the simulation models used in this study provide a realistic indication of the spread of FMD in animal populations. Our conclusion is that relatively simple metrics available early in a control program can be used to indicate the likely magnitude of an FMD

  15. Is Hiding Foot and Mouth Disease Sensitive Behavior for Farmers? A Survey Study in Sri Lanka

    PubMed Central

    Gunarathne, Anoma; Kubota, Satoko; Kumarawadu, Pradeep; Karunagoda, Kamal; Kon, Hiroichi

    2016-01-01

    Foot and mouth disease (FMD) has a long history in Sri Lanka and was found to be endemic in various parts of the country and constitutes a constant threat to farmers. In Sri Lanka, currently there is no regular, nationwide vaccination programme devised to control FMD. Therefore, improving farmers’ knowledge regarding distinguishing FMD from other diseases and ensuring prompt reporting of any suspicion of FMD as well as restricting movement of animals are critical activities for an effective FMD response effort. Therefore, the main purpose of this study was to clarify the relationship between farmers’ knowledge levels and their behaviors to establish a strategy to control FMD. In our study, item count technique was applied to estimate the number of farmers that under-report and sell FMD-infected animals, although to do so is prohibited by law. The following findings were observed: about 63% of farmers have very poor knowledge of routes of FMD transmission; ‘under-reporting’ was found to be a sensitive behavior and nearly 23% of the farmers were reluctant to report FMD-infected animals; and ‘selling FMD-infected animals’ is a sensitive behavior among high-level knowledge group while it is a non-sensitive behavior among the low-level knowledge group. If farmers would understand the importance of prompt reporting, they may report any suspected cases of FMD to veterinary officials. However, even if farmers report honestly, they do not want to cull FMD-infected animals. Thus, education programs should be conducted not only on FMD introduction and transmission, but also its impact. Furthermore, consumers may criticize the farmers for culling their infected animals. Hence, not only farmers, but also consumers need to be educated on the economic impact of FMD and the importance of controlling an outbreak. If farmers have a high knowledge of FMD transmission, they consider selling FMD-infected animals as a sensitive behavior. Therefore, severe punishment should

  16. Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam

    PubMed Central

    Kühnert, Denise; Halpin, Rebecca A.; Lin, Xudong; Simenauer, Ari; Akopov, Asmik; Das, Suman R.; Stockwell, Timothy B.; Shrivastava, Susmita; Ngoc, Nghiem My; Uyen, Le Thi Tam; Tuyen, Nguyen Thi Kim; Thanh, Tran Tan; Hang, Vu Thi Ty; Qui, Phan Tu; Hung, Nguyen Thanh; Khanh, Truong Huu; Thinh, Le Quoc; Nhan, Le Nguyen Thanh; Van, Hoang Minh Tu; Viet, Do Chau; Tuan, Ha Manh; Viet, Ho Lu; Hien, Tran Tinh; Chau, Nguyen Van Vinh; Thwaites, Guy; Grenfell, Bryan T.; Stadler, Tanja; Wentworth, David E.; Holmes, Edward C.; Van Doorn, H. Rogier

    2015-01-01

    ABSTRACT Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a

  17. Herd Immunity Against Foot-and-Mouth Disease Under Different Vaccination Practices in India.

    PubMed

    Sharma, G K; Mahajan, S; Matura, R; Biswal, J K; Ranjan, R; Subramaniam, S; Misri, J; Bambal, R G; Pattnaik, B

    2016-02-26

    A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot-and-mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi-annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group-D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log10 1.93 (95% CI 1.92-1.93), 2.02 (2.02-2.02) and 2.02 (2.02-2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log10 1.68 (95% CI 1.67-1.69), 1.77 (1.76-1.78) and 1.85 (1.84-1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme.

  18. Review of the status and control of foot and mouth disease in sub-Saharan Africa.

    PubMed

    Vosloo, W; Bastos, A D S; Sangare, O; Hargreaves, S K; Thomson, G R

    2002-12-01

    Six of the seven serotypes of foot and mouth disease (FMD) virus (i.e. all but Asia 1) are prevalent in Africa although there are marked regional differences in distribution. Three of these serotypes are unique to Africa, namely the three South African Territories (SAT) serotypes. Serotype C may also now be confined to Africa because it has not been reported elsewhere recently. In southern Africa at least, the SAT serotypes have an intimate and probably ancient association with African buffalo (Syncerus caffer) that is instrumental in their maintenance. Within each of the six prevalent serotypes, with the possible exception of C, there are a number of different lineages with more or less defined distributions (i.e. topotypes) that in some cases are sufficiently immunologically different from one another to require specific vaccines to ensure efficient control. This immunological diversity in prevalent serotypes and topotypes, in addition to uncontrolled animal movement in most parts of the continent, render FMD difficult to control in present circumstances. This fact, together with poorly developed intercontinental trade in animals and animal products has resulted in the control of FMD being afforded a low priority in most parts of the continent, although the northern and southern regions of the continent are an exception. As a consequence, eradication of FMD from Africa as a whole is not a prospect within the foreseeable future. In southern Africa, the use of fencing and other means to strictly control the movement of wildlife and livestock as well as judicious application of vaccine has resulted in countries of the region being able to access beef and other livestock markets in Europe and elsewhere in the developed world. Significant marketing of livestock and livestock products from Africa outside the continent is unlikely to be achieved unless similar approaches can be developed for other regions of Africa. This will result in continuing under-exploitation of a

  19. Recombinant Adeno-Vaccine Expressing Enterovirus 71-Like Particles against Hand, Foot, and Mouth Disease

    PubMed Central

    Tsou, Yueh-Liang; Lin, Yi-Wen; Shao, Hsiao-Yun; Yu, Shu-Ling; Wu, Shang-Rung; Lin, Hsiao-Yu; Liu, Chia-Chyi; Huang, Chieh; Chong, Pele; Chow, Yen-Hung

    2015-01-01

    Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-γ T cells associated with Th1/Th2-balanced IFN-ɣ, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-γ T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune

  20. Seroprevalence of Foot-and-Mouth Disease in Susceptible Wildlife in Israel

    PubMed Central

    Elnekave, Ehud; King, Roni; van Maanen, Kees; Shilo, Hila; Gelman, Boris; Storm, Nick; Klement, Eyal

    2016-01-01

    Foot-and-mouth disease (FMD) epidemics recur in Israel almost every year. Wild even-toed ungulates are seldom affected during these epidemics. The seroprevalence of FMD in wild ungulates during 2000 and 2005–2013 was estimated using anti-non-structural proteins ELISA. Overall, 209 samples were tested, comprising sera of 120 wild boar (Sus scrofa lybicus), 64 mountain gazelles (Gazella gazella gazella), 6 water buffaloes (Bubalus bubalis), and 19 Persian fallow deer (Dama dama mesopotamica). None of the tested animals presented clinical signs of FMD during blood collection. Sixteen samples [7.7% (95% confidence interval (CI95%) = 4.4–12.1%)] were found to be seropositive. Fifteen out of 120 samples (12.5%) from wild boar were seropositive, compared with only 1 out of 89 samples (1.1%) from all other species combined (Fisher’s exact test: p = 0.003). Most of the positive samples obtained from wild boar [13/15 (86.7%)] were collected during 2007, and analysis was restricted to that year and species only. The seroprevalence of FMD in this species during 2007 was estimated at 54.2% (CI95% = 32.8–74.5%; n = 24). A significant infection cluster, comprising nine seropositive samples collected in three different locations, was identified in the north-eastern part of Israel. These findings indicate that wild boar was affected during the 2007 FMD epidemic, even though wild boar presenting FMD typical clinical signs were not observed during that year. The actual role of wild boar in the spread of FMD virus in this epidemic, however, could not be determined. The negligible seroprevalence of FMD found for all other surveillance years indicates that ongoing circulation of FMD among wildlife in Israel is unlikely. It is concluded that while the role of wildlife species in the dynamics of FMD in Israel is usually limited, there might be occasions, in which wildlife plays a part in the spread of the virus. PMID:27200364

  1. Foot-and-Mouth Disease in Red Deer - Experimental Infection and Test Methods Performance.

    PubMed

    Kittelberger, R; Nfon, C; Swekla, K; Zhang, Z; Hole, K; Bittner, H; Salo, T; Goolia, M; Embury-Hyatt, C; Bueno, R; Hannah, M; Swainsbury, R; O'Sullivan, C; Spence, R; Clough, R; McFadden, A; Rawdon, T; Alexandersen, S

    2017-02-01

    The aim of this study was to evaluate a number of foot-and-mouth disease (FMD) test methods for use in red deer. Ten animals were intranasally inoculated with the FMD virus (FMDV) O UKG 11/2001, monitored for clinical signs, and samples taken regularly (blood, serum, oral swabs, nasal swabs, probang samples and lesion swabs, if present) over a 4-week period. Only one animal, deer 1103, developed clinical signs (lesions under the tongue and at the coronary band of the right hind hoof). It tested positive by 3D and IRES real-time reverse transcription polymerase chain reaction (rRT-PCR) in various swabs, lesion materials and serum. In a non-structural protein (NSP) in-house ELISA (NSP-ELISA-IH), one commercial ELISA (NSP-ELISA-PR) and a commercial antibody NSP pen side test, only deer 1103 showed positive results from day post-inoculation (dpi) 14 onwards. Two other NSP-ELISAs detected anti-NSP serum antibodies with lower sensitivity. It also showed rising antibody levels in the virus neutralization test (VNT), the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR at dpi 9, and in another two commercial SPO-ELISAs at dpi 12 (SPO-ELISA-IV) and dpi 19 (SPO-ELISA-IZ), respectively. Six of the red deer that had been rRT-PCR and antibody negative were re-inoculated intramuscularly with the same O-serotype FMDV at dpi 14. None of these animals became rRT-PCR or NSP-ELISA positive, but all six animals became positive in the VNT, the in-house SPO-ELISA-IH and the commercial SPO-ELISA-PR. Two other commercial SPO-ELISAs were less sensitive or failed to detect animals as positive. The rRT-PCRs and the four most sensitive commercial ELISAs that had been used for the experimentally inoculated deer were further evaluated for diagnostic specificity (DSP) using 950 serum samples and 200 nasal swabs from non-infected animals. DSPs were 100% for the rRT-PCRs and between 99.8 and 100% for the ELISAs.

  2. Prevalence and risk factors for foot and mouth disease infection in small ruminants in Israel.

    PubMed

    Elnekave, Ehud; van Maanen, Kees; Shilo, Hila; Gelman, Boris; Storm, Nick; Berdenstain, Svetlane; Berke, Olaf; Klement, Eyal

    2016-03-01

    During the last decade, 27% of the foot and mouth disease (FMD) outbreaks in Israel affected small ruminant (SR) farms. FMD outbreaks reoccur in Israel despite vaccination of all livestock and application of control measures. We performed a cross-sectional serological study, aimed at estimating the prevalence of FMD infection in SR in Israel and the possible risk factors for infection. Overall, 2305 samples of adult sheep (n=1948) and goats (n=357) were collected during 2011-14 in two separate surveys. One survey was based on random sampling of intensive management system farms and the other was originally aimed at the detection of Brucella melitensis at extensive and semi-intensive management system farms. Sera were tested by NS blocking ELISA (PrioCHECK(®)). The serological prevalence of antibodies against non structural proteins (NSP) of FMD virus was estimated at 3.7% (95% confidence interval (CI95%)=3.0% -4.5%). Additionally, a significantly lower infection prevalence (p value=0.049) of 1.0% (CI95%=0.1%-3.6%) was found in a small sample (197 sera) of young SR, collected during 2012. The positive samples from adult SR were scattered all over Israel, though two significant infection clusters were found by the spatial scan statistic. Occurrence of an outbreak on a non-SR farm within 5km distance was associated with a fifteen times increase in the risk of FMD infection of SR in the univariable analysis. Yet, this variable was not included in the multivariable analysis due to collinearities with the other independent variables. Multivariable logistic regression modeling found significantly negative associations (P value<0.05) of grazing and being in a herd larger than 500 animals with risk of infection. Grazing herds and herds larger than 500 animals, both represent farms that are intensively or semi-intensively managed. Higher maintenance of bio-safety, fewer introductions of new animals and higher vaccination compliance in these farms may explain their lower

  3. Seroprevalence of Foot-and-Mouth Disease in Susceptible Wildlife in Israel.

    PubMed

    Elnekave, Ehud; King, Roni; van Maanen, Kees; Shilo, Hila; Gelman, Boris; Storm, Nick; Klement, Eyal

    2016-01-01

    Foot-and-mouth disease (FMD) epidemics recur in Israel almost every year. Wild even-toed ungulates are seldom affected during these epidemics. The seroprevalence of FMD in wild ungulates during 2000 and 2005-2013 was estimated using anti-non-structural proteins ELISA. Overall, 209 samples were tested, comprising sera of 120 wild boar (Sus scrofa lybicus), 64 mountain gazelles (Gazella gazella gazella), 6 water buffaloes (Bubalus bubalis), and 19 Persian fallow deer (Dama dama mesopotamica). None of the tested animals presented clinical signs of FMD during blood collection. Sixteen samples [7.7% (95% confidence interval (CI95%) = 4.4-12.1%)] were found to be seropositive. Fifteen out of 120 samples (12.5%) from wild boar were seropositive, compared with only 1 out of 89 samples (1.1%) from all other species combined (Fisher's exact test: p = 0.003). Most of the positive samples obtained from wild boar [13/15 (86.7%)] were collected during 2007, and analysis was restricted to that year and species only. The seroprevalence of FMD in this species during 2007 was estimated at 54.2% (CI95% = 32.8-74.5%; n = 24). A significant infection cluster, comprising nine seropositive samples collected in three different locations, was identified in the north-eastern part of Israel. These findings indicate that wild boar was affected during the 2007 FMD epidemic, even though wild boar presenting FMD typical clinical signs were not observed during that year. The actual role of wild boar in the spread of FMD virus in this epidemic, however, could not be determined. The negligible seroprevalence of FMD found for all other surveillance years indicates that ongoing circulation of FMD among wildlife in Israel is unlikely. It is concluded that while the role of wildlife species in the dynamics of FMD in Israel is usually limited, there might be occasions, in which wildlife plays a part in the spread of the virus.

  4. Genotypes of the Enterovirus Causing Hand Foot and Mouth Disease in Shanghai, China, 2012-2013.

    PubMed

    Xu, Menghua; Su, Liyun; Cao, Lingfeng; Zhong, Huaqing; Dong, Niuniu; Dong, Zuoquan; Xu, Jin

    2015-01-01

    Sporadic HFMD (hand foot and mouth disease, HFMD) cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9%) with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%), EV71 (30.6%), CA16 (8.8%) and CA10 (7.5%). Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection.

  5. Exposure of in vitro-produced bovine embryos to foot-and-mouth disease virus.

    PubMed

    Marguant-Le Guienne, B; Rémond, M; Cosquer, R; Humblot, P; Kaiser, C; Lebreton, F; Crucière, C; Guerin, B; Laporte, J; Thibier, M

    1998-07-01

    The aim of this study was to investigate whether foot and mouth disease virus (FMDV) interacts with in vitro produced (IVP) bovine embryos. One milliliter of a suspension of FMDV (2 x 10(7) TCID50/mL) was added to several batches of these embryos 7 d after in vitro fertilization, by which time they had either developed to the morula/blastocyst stage (n = 256) or degenerated (n = 260). Six experiments were performed in which developed or degenerated batches of embryos were incubated with FMDV for periods of 1 h (3), 2 h (2) or 4h (1). After this, the embryos were washed 10 times according to the International Embryo Transfer Society (IETS), then pooled and ground up to form a suspension, and assayed on cell cultures for FMDV. The cell cultures were observed daily for cytopathic effects for 3 d post exposure. In addition to the cell culture method, the polymerase chain reaction (PCR) technique was used to assay for the presence of the virus in the washing fluids. Assays for FMDV were also conducted on the first and second wash and on the pooled sample constituting the eight, ninth and tenth wash. With the exception of the second wash from a batch of embryos exposed to FMDV for 2 h, all samples of the first and second wash produced FMDV cytopathic effects, but none occurred with the pooled samples of the 8th, 9th and 10th wash. FMDV was also isolated from all but 1 of the batches of embryos after 1 h of incubation, from 1 of 4 batches after 2 h of incubation and from all batches after 4 h incubation. By contrast, the presence of virus could not be demonstrated by PCR based on the technique used here. These results show that 7 d old IVP bovine embryos can retain FMDV after washing, unlike in vivo-derived embryos, which do not appear to carry risks of FMDV transmission when washed according to IETS recommendations. Stricter controls are, therefore, necessary when using IVP embryos from cattle in a non-FMD-free zone in domestic or international trade.

  6. Protection induced by a commercial bivalent vaccine against Foot-and-Mouth Disease 2010 field virus from Ecuador.

    PubMed

    Duque, Hernando; Naranjo, Jose; Carrillo, Consuelo; Burbano, Alexandra; Vargas, Javier; Pauszek, Lisa; Olesen, Ian; Sanchez-Vazquez, Manuel J; Cosivi, Ottorino; Allende, Rossana M

    2016-07-29

    Foot-and-Mouth Disease serotype O circulated endemically in Ecuador for many years, with an upsurge occurring in 2009. This manuscript describes retrospectively in vitro and in vivo laboratory studies to predict the field effectiveness of a commercial FMD vaccine to protect against the field strain, and explains the key actions and epidemiological strategies followed by the country to control the disease. The results established that the use of a good quality oil vaccine, manufactured with strains that were isolated long ago: O1 Campos Br/58 and A24 Cruzeiro Br/55; combined with the correct epidemiological strategies, are useful to control field strains when used in periodic biannual vaccination campaigns.

  7. The foot and mouth disease network in the southern cone of South America: an example of regional governance.

    PubMed

    Corrales Irrazábal, H A

    2012-08-01

    The fact that foot and mouth disease is highly contagious, easily spread and of major commercial importance makes it a redoubtable challenge for animal health in South American countries and the world over. A number of factors impact directly on the effectiveness of national programmes to eradicate foot and mouth disease. Therefore, in order to meet the challenges posed by today's globalised world, it is of the utmost importance that national level eradication programmes be considered state policies and that they be the subject of broad political agreement at the highest level and consolidated as regional programmes between national Veterinary Services. The programmes, agreements and technical cooperation projects established jointly by Member Countries of the Southern Common Market (MERCOSUR) were a key factor in building management capacity to control foot and mouth disease in the area. Another key factor has been a partnership with one of the most sensitive sectors--the private production sector. Its active and responsible participation in operational functions has done much to strengthen and ensure the competitive development of South American countries and consolidate their role as global beef exporters. However, to prevent further outbreaks it is essential to maintain and reinforce the structure of national programmes and to have strong and highly trained Veterinary Services and sufficient funding to ensure efficient and sustainable plans. These plans must enable Veterinary Services, by means of good governance, to implement effective measures in the areas of animal health and international trade in animals and animal products/by-products, thereby achieving rapid and more equitable social and economic development.

  8. Identification of a novel cell culture adaptation site on the capsid of foot-and-mouth disease virus.

    PubMed

    Chamberlain, Kyle; Fowler, Veronica L; Barnett, Paul V; Gold, Sarah; Wadsworth, Jemma; Knowles, Nick J; Jackson, Terry

    2015-09-01

    Vaccination remains the most effective tool for control of foot-and-mouth disease both in endemic countries and as an emergency preparedness for new outbreaks. Foot-and-mouth disease vaccines are chemically inactivated virus preparations and the production of new vaccines is critically dependent upon cell culture adaptation of field viruses, which can prove problematic. A major driver of cell culture adaptation is receptor availability. Field isolates of foot-and-mouth disease virus (FMDV) use RGD-dependent integrins as receptors, whereas cell culture adaptation often selects for variants with altered receptor preferences. Previously, two independent sites on the capsid have been identified where mutations are associated with improved cell culture growth. One is a shallow depression formed by the three major structural proteins (VP1-VP3) where mutations create a heparan sulphate (HS)-binding site (the canonical HS-binding site). The other involves residues of VP1 and is located at the fivefold symmetry axis. For some viruses, changes at this site result in HS binding; for others, the receptors are unknown. Here, we report the identification of a novel site on VP2 where mutations resulted in an expanded cell tropism of a vaccine variant of A/IRN/87 (called A - ). Furthermore, we show that introducing the same mutations into a different type A field virus (A/TUR/2/2006) resulted in the same expanded cell culture tropism as the A/IRN/87 A -  vaccine variant. These observations add to the evidence for multiple cell attachment mechanisms for FMDV and may be useful for vaccine manufacture when cell culture adaptation proves difficult.

  9. Development of a peptide based latex agglutination assay for serotype identification of foot and mouth disease virus.

    PubMed

    Kaur, Dilpreet; Kaur, Gurpreet; Chandra, Mudit; Saxena, Hari M; Dwivedi, Padam N

    2013-02-01

    Out of 200 serum samples collected from cattle (142) and buffaloes (58) of various ages and sexand subjected to latex agglutination test (LAT) using serotype specific peptides (O, A, Asia 1) and also with peptide for non-structural protein 2B (NSP-2B), 114 (70%) samples were positive against FMDV type 'O', 102 (51%) against serotype 'A' and 104 (52%) against serotype 'Asia 1'. With NSP-2B peptide a total of 71 (35.5%) samples were positive. The results suggest that LAT could be used for the diagnosis of foot and mouth disease virus as it is easy, cheap and effective test.

  10. Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA.

    PubMed

    Ma, X X; Feng, Y P; Gu, Y X; Zhou, J H; Ma, Z R

    2016-06-01

    As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA.

  11. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014.

    PubMed

    Sinclair, C; Gaunt, E; Simmonds, P; Broomfield, D; Nwafor, N; Wellington, L; Templeton, K; Willocks, L; Schofield, O; Harvala, H

    2014-03-27

    In January to February 2014, 16 hand, foot and mouth disease (HFMD) cases were identified in Edinburgh, United Kingdom. All presented with atypical features, with most (n=13) resembling eczema herpeticum or chickenpox. Coxsackievirus A6 (CV-A6) was identified in all the typed cases (n=11). As atypical forms of HFMD associated with CV-A6 are likely to emerge throughout Europe, clinicians should be alert to unusual clinical presentations of HFMD and virologists aware of effective diagnostic testing and enterovirus typing methods.

  12. Dietary germanium biotite supplementation enhances the induction of antibody responses to foot-and-mouth disease virus vaccine in pigs.

    PubMed

    Lee, Jin-A; Jung, Bock-Gie; Jung, Myunghwan; Kim, Tae-Hoon; Yoo, Han Sang; Lee, Bong-Joo

    2014-01-01

    We evaluated the potential ability of germanium biotite (GB) to stimulate the production of antibodies specific for foot-and-mouth disease virus (FMDV). To this aim, we measured the total FMDV-specific antibody responses and IgM production after vaccination against FMD both experimentally and in the field. GB supplementation with FMDV vaccination stimulated the production of anti-FMDV antibodies, and effectively increased IFN-γ and TNF-α levels. These results suggest that GB may be a novel alternative feed supplement that can serve as a boosting agent and an immunostimulator for increasing the efficacy of FMDV vaccination in pigs.

  13. Scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases.

    PubMed

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2012-01-01

    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Infection with EV71 is occasionally associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. Because cellular receptors for viruses play an important role in cell, tissue, and species tropism, it is important to identify and characterize the receptor molecule. Recently, cellular receptors and host factors that stimulate EV71 infection have been identified. Several lines of evidence suggest that scavenger receptor class B, member 2 (SCARB2) plays critical roles in efficient EV71 infection and the development of disease in humans. In this review, we will summarize the findings of recent studies on EV71 infection and on the roles of SCARB2.

  14. Bioinformatics and Molecular Analysis of the Evolutionary Relationship between Bovine Rhinitis A Viruses and Foot-And-Mouth Disease Virus.

    PubMed

    Rai, Devendra K; Lawrence, Paul; Pauszek, Steve J; Piccone, Maria E; Knowles, Nick J; Rieder, Elizabeth

    2015-01-01

    Bovine rhinitis viruses (BRVs) cause mild respiratory disease of cattle. In this study, a near full-length genome sequence of a virus named RS3X (formerly classified as bovine rhinovirus type 1), isolated from infected cattle from the UK in the 1960s, was obtained and analyzed. Compared to other closely related Aphthoviruses, major differences were detected in the leader protease (L(pro)), P1, 2B, and 3A proteins. Phylogenetic analysis revealed that RS3X was a member of the species bovine rhinitis A virus (BRAV). Using different codon-based and branch-site selection models for Aphthoviruses, including BRAV RS3X and foot-and-mouth disease virus, we observed no clear evidence for genomic regions undergoing positive selection. However, within each of the BRV species, multiple sites under positive selection were detected. The results also suggest that the probability (determined by Recombination Detection Program) for recombination events between BRVs and other Aphthoviruses, including foot-and-mouth disease virus was not significant. In contrast, within BRVs, the probability of recombination increases. The data reported here provide genetic information to assist in the identification of diagnostic signatures and research tools for BRAV.

  15. Simple and rapid lateral-flow assay for the detection of foot-and-mouth disease virus.

    PubMed

    Oem, Jae Ku; Ferris, Nigel P; Lee, Kwang-Nyeong; Joo, Yi-Seok; Hyun, Bang-Hun; Park, Jong-Hyeon

    2009-11-01

    A simple lateral-flow assay (LFA) based on a monoclonal antibody (MAb 70-17) was developed for the detection of foot-and-mouth disease virus (FMDV) under nonlaboratory conditions. The LFA was evaluated with epithelial suspensions (n = 704) prepared from current and historical field samples which had been submitted to the Pirbright Laboratory (United Kingdom) and from negative samples (n = 100) collected from naïve animals in Korea. Four FMDV serotypes (type O, A, Asia 1, and C) were detected in the LFA, but not the remaining three FMDV serotypes (SAT 1, SAT 2, and SAT 3). The diagnostic sensitivity of the LFA for FMDV types O, A, C, and Asia 1 was similar, at approximately 87.3%, to that of 87.7% obtained with antigen enzyme-linked immunosorbent assay (Ag-ELISA). The diagnostic specificity of the LFA was 98.8%, compared to 100% for the Ag-ELISA. These results demonstrate that the LFA using the FMDV MAb 70-17 to detect FMDV is a supportive method for taking rapid measurements at the site of a suspected foot-and-mouth disease outbreak in Asia before diagnosing the disease in the laboratory, thereby offering the possibility of implementing control procedures more rapidly.

  16. Recovery of viral RNA and infectious foot-and-mouth disease virus from positive lateral-flow devices.

    PubMed

    Fowler, Veronica L; Bankowski, Bartlomiej M; Armson, Bryony; Di Nardo, Antonello; Valdazo-Gonzalez, Begoña; Reid, Scott M; Barnett, Paul V; Wadsworth, Jemma; Ferris, Nigel P; Mioulet, Valérie; King, Donald P

    2014-01-01

    Foot-and-mouth disease Virus (FMDV) is an economically important, highly contagious picornavirus that affects both wild and domesticated cloven hooved animals. In developing countries, the effective laboratory diagnosis of foot-and-mouth disease (FMD) is often hindered by inadequate sample preservation due to difficulties in the transportation and storage of clinical material. These factors can compromise the ability to detect and characterise FMD virus in countries where the disease is endemic. Furthermore, the high cost of sending infectious virus material and the biosecurity risk it presents emphasises the need for a thermo-stable, non-infectious mode of transporting diagnostic samples. This paper investigates the potential of using FMDV lateral-flow devices (LFDs) for dry transportation of clinical samples for subsequent nucleic acid amplification, sequencing and recovery of infectious virus by electroporation. FMDV positive samples (epithelial suspensions and cell culture isolates) representing four FMDV serotypes were applied to antigen LFDs: after which it was possible to recover viral RNA that could be detected using real-time RT-PCR. Using this nucleic acid, it was also possible to recover VP1 sequences and also successfully utilise protocols for amplification of complete FMD virus genomes. It was not possible to recover infectious FMDV directly from the LFDs, however following electroporation into BHK-21 cells and subsequent cell passage, infectious virus could be recovered. Therefore, these results support the use of the antigen LFD for the dry, non-hazardous transportation of samples from FMD endemic countries to international reference laboratories.

  17. Foot and mouth disease (FMD) virus: quantification of whole virus particles during the vaccine manufacturing process by size exclusion chromatography.

    PubMed

    Spitteler, Marcelo A; Fernández, Ignacio; Schabes, Erika; Krimer, Alejandro; Régulier, Emmanuel G; Guinzburg, Mariela; Smitsaart, Eliana; Levy, M Susana

    2011-09-22

    Foot and mouth disease (FMD) is a highly infectious viral disease that affects cattle, sheep, goats and swine causing severe economic losses worldwide. The efficacy of inactivated vaccines is critically dependent on the integrity of foot and mouth disease virus (FMDV) particles. The recommended method to quantify the active ingredient of vaccines is the 140S quantitative sucrose density gradient analysis. This method has been an immensely valuable tool over the past three decades but it is highly operator dependent and difficult to automate. We developed a method to quantify FMDV particles during the vaccine manufacturing process that is based on separation of components by size-exclusion chromatography and measurement of virus by absorption at 254nm. The method is linear in the 5-70μg/mL range, it is applicable to different FMDV strains, and has a good correlation with the 140S test. The proposed method uses standard chromatographic media and it is amenable to automation. The method has potential as a process analytical technology and for control of final product by manufacturers, international vaccine banks and regulatory agencies.

  18. Psychosocial effects of the 2001 UK foot and mouth disease epidemic in a rural population: qualitative diary based study

    PubMed Central

    Mort, Maggie; Convery, Ian; Baxter, Josephine; Bailey, Cathy

    2005-01-01

    Objectives To understand the health and social consequences of the 2001 foot and mouth disease epidemic for a rural population. Design Longitudinal qualitative analysis. Setting North Cumbria, the worst affected area in Britain. Sample Purposive sample of 54 respondents divided in six demographically balanced rural occupational and population groups. Main outcome measures 3071 weekly diaries contributed over 18 months; 72 semistructured interviews (with the 54 diarists and 18 others); 12 group discussions with diarists Results The disease epidemic was a human tragedy, not just an animal one. Respondents' reports showed that life after the foot and mouth disease epidemic was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Distress was experienced across diverse groups well beyond the farming community. Many of these effects continued to feature in the diaries throughout the 18 month period. Conclusions The use of a rural citizens' panel allowed data capture from a wide spectrum of the rural population and showed that a greater number of workers and residents had traumatic experiences than has previously been reported. Recommendations for future disaster management include joint service reviews of what counts as a disaster, regular NHS and voluntary sector sharing of intelligence, debriefing and peer support for front line workers, increased community involvement in disposal site or disaster management, and wider, more flexible access to regeneration funding and rural health outreach work. PMID:16214809

  19. Bioinformatics and Molecular Analysis of the Evolutionary Relationship between Bovine Rhinitis A Viruses and Foot-And-Mouth Disease Virus

    PubMed Central

    Rai, Devendra K.; Lawrence, Paul; Pauszek, Steve J.; Piccone, Maria E.; Knowles, Nick J.; Rieder, Elizabeth

    2015-01-01

    Bovine rhinitis viruses (BRVs) cause mild respiratory disease of cattle. In this study, a near full-length genome sequence of a virus named RS3X (formerly classified as bovine rhinovirus type 1), isolated from infected cattle from the UK in the 1960s, was obtained and analyzed. Compared to other closely related Aphthoviruses, major differences were detected in the leader protease (Lpro), P1, 2B, and 3A proteins. Phylogenetic analysis revealed that RS3X was a member of the species bovine rhinitis A virus (BRAV). Using different codon-based and branch-site selection models for Aphthoviruses, including BRAV RS3X and foot-and-mouth disease virus, we observed no clear evidence for genomic regions undergoing positive selection. However, within each of the BRV species, multiple sites under positive selection were detected. The results also suggest that the probability (determined by Recombination Detection Program) for recombination events between BRVs and other Aphthoviruses, including foot-and-mouth disease virus was not significant. In contrast, within BRVs, the probability of recombination increases. The data reported here provide genetic information to assist in the identification of diagnostic signatures and research tools for BRAV. PMID:27081310

  20. Efficacy of synthetic peptide candidate vaccines against serotype-A foot-and-mouth disease virus in cattle.

    PubMed

    Zhang, Zhongwang; Pan, Li; Ding, Yaozhong; Zhou, Peng; Lv, Jianliang; Chen, Haotai; Fang, Yuzhen; Liu, Xinsheng; Chang, Huiyun; Zhang, Jie; Shao, Junjun; Lin, Tong; Zhao, Furong; Zhang, Yongguang; Wang, Yonglu

    2015-02-01

    Foot-and-mouth disease (FMD) remains a major threat to livestock worldwide, especially in developing countries. To improve the efficacy of vaccination against FMD, various types of vaccines have been developed, including synthetic peptide vaccines. We designed three synthetic peptide vaccines, 59 to 87 aa in size, based on immunogenic epitopes in the VP1, 3A, and 3D proteins of the A/HuBWH/CHA/2009 strain of the foot-and-mouth disease virus (FMDV), corresponding to amino acid positions 129 to 169 of VP1, 21 to 35 of 3A, and 346 to 370 of 3D. The efficacies of the vaccines were evaluated in cattle and guinea pigs challenged with serotype-A FMDV. All of the vaccines elicited the production of virus-neutralizing antibodies. The PB peptide, which contained sequences corresponding to positions 129 to 169 of V P1 and 346 to 370 of 3D, demonstrated the highest levels of immunogenicity and immunoprotection against FMDV. Two doses of 50 μg of the synthetic PB peptide vaccine provided 100% protection against FMDV infection in guinea pigs, and a single dose of 100 μg provided 60% protection in cattle. These findings provide empirical data for facilitating the development of synthetic peptide vaccines against FMD.

  1. Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus.

    PubMed

    Li, Wenting; Wang, Kejun; Kang, Shimeng; Deng, Shoulong; Han, Hongbing; Lian, Ling; Lian, Zhengxing

    2015-12-16

    Foot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats' cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene, and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV.

  2. Chimeric foot-and-mouth disease viruses: evaluation of their efficacy as potential marker vaccines in cattle.

    PubMed

    Fowler, V L; Paton, D J; Rieder, E; Barnett, P V

    2008-04-07

    Previous work in pigs, has demonstrated that full protection against foot-and-mouth disease (FMD) can be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. If proven to be effective in other economically important species such as cattle, such vaccine constructs could be trialed as potential marker vaccines. Here, we determine if G-H loop chimera FMDV vaccines can: (i) protect cattle from virus challenge and (ii) induce an antibody response that would enable the identification of infection, regardless of vaccination status. Inactivated, oil adjuvanated, chimeric vaccine constructs, based on the backbone sequence of the A(12)119 serotype virus, fully protected cattle from challenge 21 days post-vaccination. Differentiation assays developed for use in this study were able to identify sub-clinical infection, which in one vaccinated animal, persisted beyond day 32 post-challenge. This paper emphasises the importance of epitopes outside of the VP1 G-H loop for protective immunity in cattle, and demonstrates that chimeric FMDV vaccines could prove to be useful marker vaccines for the future.

  3. Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus

    PubMed Central

    Li, Wenting; Wang, Kejun; Kang, Shimeng; Deng, Shoulong; Han, Hongbing; Lian, Ling; Lian, Zhengxing

    2015-01-01

    Foot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats’ cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene, and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV. PMID:26671568

  4. Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response

    PubMed Central

    Diaz-San Segundo, Fayna; Medina, Gisselle N.; Ramirez-Medina, Elizabeth; Velazquez-Salinas, Lauro; Koster, Marla; Grubman, Marvin J.

    2015-01-01

    ABSTRACT Codon bias deoptimization has been previously used to successfully attenuate human pathogens, including poliovirus, respiratory syncytial virus, and influenza virus. We have applied a similar technology to deoptimize the capsid-coding region (P1) of foot-and-mouth disease virus (FMDV). Despite the introduction of 489 nucleotide changes (19%), synonymous deoptimization of the P1 region rendered a viable FMDV progeny. The resulting strain was stable and reached cell culture titers similar to those obtained for wild-type (WT) virus, but at reduced specific infectivity. Studies in mice showed that 100% of animals inoculated with the FMDV A12 P1 deoptimized mutant (A12-P1 deopt) survived, even when the animals were infected at doses 100 times higher than the dose required to cause death by WT virus. All mice inoculated with the A12-P1 deopt mutant developed a strong antibody response and were protected against subsequent lethal challenge with WT virus at 21 days postinoculation. Remarkably, the vaccine safety margin was at least 1,000-fold higher for A12-P1 deopt than for WT virus. Similar patterns of attenuation were observed in swine, in which animals inoculated with A12-P1 deopt virus did not develop clinical disease until doses reached 1,000 to 10,000 times the dose required to cause severe disease in 2 days with WT A12. Consistently, high levels of antibody titers were induced, even at the lowest dose tested. These results highlight the potential use of synonymous codon pair deoptimization as a strategy to safely attenuate FMDV and further develop live attenuated vaccine candidates to control such a feared livestock disease. IMPORTANCE Foot-and-mouth disease (FMD) is one of the most feared viral diseases that can affect livestock. Although this disease appeared to be contained in developed nations by the end of the last century, recent outbreaks in Europe, Japan, Taiwan, South Korea, etc., have demonstrated that infection can spread rapidly, causing

  5. Effects of Meteorological Parameters and PM10 on the Incidence of Hand, Foot, and Mouth Disease in Children in China

    PubMed Central

    Huang, Ruixue; Bian, Guolin; He, Tianfeng; Chen, Lv; Xu, Guozhang

    2016-01-01

    Hand, foot, and mouth disease (HFMD) is a globally-prevalent infectious disease. However, few data are available on prevention measures for HFMD. The purpose of this investigation was to evaluate the impacts of temperature, humidity, and air pollution, particularly levels of particulate matter with an aerodynamic diameter 10 micrometers (PM10), on the incidence of HFMD in a city in Eastern China. Daily morbidity, meteorological, and air pollution data for Ningbo City were collected for the period from January 2012 to December 2014. A total of 86,695 HFMD cases were enrolled in this study. We used a distributed lag nonlinear model (DLNM) with Poisson distribution to analyze the nonlinear lag effects of daily mean temperature, daily humidity, and found significant relationships with the incidence of HFMD; in contrast, PM10 level showed no relationship to the incidence of HFMD. Our findings will facilitate the development of effective preventive measures and early forecasting of HFMD outbreaks. PMID:27171104

  6. Detection of foot-and-mouth disease virus RNA by reverse transcription loop-mediated isothermal amplification.

    PubMed

    Chen, Hao-tai; Zhang, Jie; Liu, Yong-sheng; Liu, Xiang-tao

    2011-11-09

    A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for foot-and-mouth disease virus (FMDV) RNA. The amplification was able to finish in 45 min under isothermal condition at 64°C by employing a set of four primers targeting FMDV 2B. The assay showed higher sensitivity than RT-PCR. No cross reactivity was observed from other RNA viruses including classical swine fever virus, swine vesicular disease, porcine reproductive and respiratory syndrome virus, Japanese encephalitis virus. Furthermore, the assay correctly detected 84 FMDV positive samples but not 65 FMDV negative specimens. The result indicated the potential usefulness of the technique as a simple and rapid procedure for the detection of FMDV infection.

  7. Description of recent foot and mouth disease outbreaks in nonendemic areas: Exploring the relationship between early detection and epidemic size

    PubMed Central

    McLaws, Melissa; Ribble, Carl

    2007-01-01

    The objective of this investigation was to describe the detection of foot and mouth disease (FMD) outbreaks in nonendemic areas, and to consider how events early in an epidemic influence the epidemic’s course. We identified 24 epidemics that occurred between 1992 and 2003 in areas officially considered free of FMD. We obtained information about these epidemics from many sources, including the scientific literature, the grey (non peer-reviewed) literature, and individuals involved with the outbreaks. While most of the epidemics consisted of fewer than 150 infected premises, there were 4 extremely large epidemics, each consisting of more than 2000 infected premises. There was no direct relationship between the time to detection and either the total number of infected premises or the number of animals killed for disease control purposes. We believe that the movement of infected animals through markets was the most critical factor that contributed to the unusual magnitude of the very large epidemics. PMID:17987967

  8. Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of Foot-and-Mouth Disease Virus in host cells.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-Mouth Disease (FMD) is a highly contagious disease of livestock caused by a highly variable RNA virus that has seven serotypes and more than sixty subtypes. Both prophylactic and post-infection means of controlling the disease outbreak, including universally applicable vaccines and emergenc...

  9. Systemic foot-and-mouth disease vaccination in cattle promotes specific antibody secreting cells at the respiratory tract and triggers local anamnestic-compatible responses upon aerosol infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot and mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated whole FMD virus (FMDV) particles, are regularly used worldwide in regions recognized as free from the disease. Here, we studied the generation of antibody ...

  10. Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence

    PubMed Central

    Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Juleff, Nicholas

    2016-01-01

    ABSTRACT Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly

  11. Review of the foot and mouth disease situation in North Africa and the risk of introducing the disease into Europe.

    PubMed

    Bouguedour, R; Ripani, A

    2016-12-01

    Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, including cattle, pigs, sheep, goats, and certain wildlife species. The disease can cause massive economic losses when introduced into countries that were free from the infection, generating negative effects due to reduced animal productivity and restrictions on international livestock trade. Following 15 years of FMD absence, Tunisia and Algeria experienced an incursion of the disease in 2014. The epidemiological situation and disease control measures in operation for FMD in the North African region are not homogeneous. The FMD virus detected in Tunisia and Algeria during the epidemic in 2014 showed 99% identity with a strain isolated in Libya in 2013. Morocco was not affected by the 2014 epidemic but it started a preventive vaccination campaign for cattle in August of that year. The relatively short distance between the North African continent and southern Europe may facilitate the introduction of pathogens, including FMD virus. The history of infectious diseases demonstrates that the Mediterranean Sea is not a sufficient barrier to viral infections. Considering the geography and the FMD situation in North African countries, strong and coordinated intervention strategies are required, including economic, political and disease control aspects, to prevent the spread of FMD to other countries in North Africa or to other regions, e.g. southern Europe. Regional platforms such as the Mediterranean Animal Health Network (REMESA) could play a crucial role in coordinating and managing animal health crises, such as the 2014 FMD epidemic.

  12. Non-capsid proteins to identify foot-and-mouth disease viral circulation in cattle irrespective of vaccination.

    PubMed

    Bergmann, I E; Malirat, V; Neitzert, E

    2005-12-01

    The ability of foot-and-mouth disease virus (FMDV) to establish subclinical and even persistent infection, the so called carrier state, imposes the need to reliably demonstrate absence of viral circulation, to monitor the progress of control measures, either during eradication programs or after reintroduction of virus in free areas. This demonstration becomes critical in immunized populations, because of the concern that silent viral circulation could be hidden by immunization. This concern originates from the fact that vaccination against foot-and-mouth disease (FMD) protects against clinical disease, but not necessarily against subclinical infection or establishment of the carrier state in cattle. A novel approach, developed and validated at PANAFTOSA during the 1990s, based on an immunoenzymatic system for detection of antibodies against non-capsid proteins (NCP) has proven valuable for monitoring viral circulation within and between herds, irrespective of the vaccination status. Antibodies against NCP are induced during infection but, in principle, not upon vaccination. The validation of this system led to its international recognition as the OIE index test. The fitness of this serosurvey tool to assess viral circulation in systematically vaccinated populations was demonstrated through its extensive application in most regions in South America. The experience attained in these regions supported the incorporation of the "free of FMD with vaccination" provisions into the OIE code. Likewise, it opened the way to alternatives to the "stamping out" policy. The results gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America, and supported the development of recommendations and guidelines that are being implemented for serosurveys that go with control measures in vaccinated populations.

  13. Evolutionary analysis of serotype A foot-and-mouth disease viruses circulating in Pakistan and Afghanistan during 2002-2009.

    PubMed

    Jamal, Syed M; Ferrari, Giancarlo; Ahmed, Safia; Normann, Preben; Curry, Stephen; Belsham, Graham J

    2011-12-01

    Foot-and-mouth disease (FMD) is endemic in Pakistan and Afghanistan. Three different serotypes of the virus, namely O, A and Asia-1, are responsible for the outbreaks of this disease in these countries. In the present study, the nucleotide-coding sequences for the VP1 capsid protein (69 samples) or for all four capsid proteins (P1, seven representative samples) of the serotype A FMD viruses circulating in Pakistan and Afghanistan were determined. Phylogenetic analysis of the foot-and-mouth disease virus (FMDV) VP1-coding sequences from these countries collected between 2002 and 2009 revealed the presence of at least four lineages within two distinct genotypes, all belonging to the Asia topotype, within serotype A. The predominant lineage observed was A-Iran05 but three other lineages (a new one is named here A-Pak09) were also identified. The A-Iran05 lineage is still evolving as revealed by the presence of seven distinct variants, the dominant being the A-Iran05AFG-07 and A-Iran05BAR-08 sublineages. The rate of evolution of the A-Iran05 lineage was found to be about 1.2×10(-2) substitutions per nucleotide per year. This high rate of change is consistent with the rapid appearance of new variants of FMDV serotype A in the region. The A22/Iraq FMDV vaccine is antigenically distinct from the A-Iran05BAR-08 viruses. Mapping of the amino acid changes between the capsid proteins of the A22/Iraq vaccine strain and the A-Iran05BAR-08 viruses onto the A22/Iraq capsid structure identified candidate amino acid substitutions, exposed on the virus surface, which may explain this antigenic difference.

  14. Quantitative estimates of the risk of new outbreaks of foot-and-mouth disease as a result of burning pyres.

    PubMed

    Jones, R; Kelly, L; French, N; England, T; Livesey, C; Wooldridge, M

    2004-02-07

    The risk of dispersing foot-and-mouth disease virus into the atmosphere, and spreading it to susceptible holdings as a result of burning large numbers of carcases together on open pyres, has been estimated for six selected pyres burned during the 2001 outbreak in the UK. The probability of an animal or holding becoming infected was dependent on the estimated level of exposure to the virus predicted from the concentrations of virus calculated by the Met Office, Bracknell. In general, the probability of infection per animal and per holding decreased as their distance from the pyre increased. In the case of two of the pyres, a holding under the pyre plumes became infected on a date consistent with when the pyre was lit. However, by calculating their estimated probability of infection from the pyres it was concluded that it was unlikely that in either case the pyre was the source of infection.

  15. Use of ethnoveterinary remedies in the management of foot and mouth disease lesions in a diary herd.

    PubMed

    Gakuya, D W; Mulei, C M; Wekesa, S B

    2011-01-01

    An outbreak of Foot and Mouth Disease (FMD) affecting 95 (57.2%) out of 166 cattle occurred in a medium-scale dairy farm in Kikuyu district, Kenya. Ethnoveterinary remedies of natural Soda ash solution (97% sodium bicarbonate), honey and finger millet flour were used to manage the FMD lesions. The lesions were washed with soda ash solution to remove the necrotic tissue after which raw honey and finger millet flour were applied to the cleaned lesions. The lesions were examined daily and those with necrotic material washed again with the Soda ash solution. Honey and finger millet flour were applied daily for three days. There was rapid healing of the lesions with the animals resuming feeding after three days. The fast healing of the lesions vindicates the use of these cheap, locally available and easy to apply products in the management of FMD lesions. However, more studies are needed to evaluate further their potencies.

  16. Beyond policy networks: policy framing and the politics of expertise in the 2001 Foot and Mouth Disease crisis.

    PubMed

    Wilkinson, Katy; Lowe, Philip; Donaldson, Andrew

    2010-01-01

    For the past decade, the policy community/issue network typology of pressure group interaction has been used to explain policy outcomes and the policy-making process. To re-examine the validity of this typology, the paper focuses on the UK government's response to the 2001 Foot and Mouth Disease (FMD) crisis, and in particular the decision to pursue contiguous culling rather than vaccination to overcome the epidemic. Rather than illustrating the emergence of an issue network in agricultural policy, the decision-making process of the FMD outbreak demonstrates continuity with prior crises. In addition, the politicization of scientific expertise is identified as an emerging trend in crisis management. Policy framing is used to explain the impetus behind the contiguous cull decision, concluding that the legacy of previous policy choices conditioned the crisis response to a far greater degree than contemporaneous pressure group action.

  17. Screwworms, Cochliomyia hominivorax, reared for mass release do not carry and spread foot-and-mouth disease virus and classical swine fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transporting live screwworms Cochliomyia hominivorax Coquerel for developing new strains from countries where foot-and-mouth disease (FMD) and classical swine fever (CSF) are endemic, to the mass rearing facilities in Mexico and Panama may introduce these exotic diseases. This study was conducted to...

  18. Disinfection of foot-and-mouth disease and African swine fever viruses with citric acid and sodium hypochlorite on birch wood carriers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transboundary animal disease viruses such as foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV) are highly contagious and cause severe morbidity and mortality in livestock. Proper disinfection during an outbreak can help prevent virus spread and will shorten the time for contam...

  19. The pathogenesis of foot-and-mouth disease II; viral pathways in swine, small ruminants, and wildlife, myotropism, chronic syndromes, and molecular virus-host interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Investigation of the pathogenesis of foot-and-mouth disease (FMD) has focused on 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 lit...

  20. Sero-prevalence of foot-and-mouth disease (FMD) in large ruminants at peri urban dairy farms near Islamabad, Pakistan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is an important, endemic, trans-boundary viral disease affecting livestock in Pakistan and associated with high economic losses. This survey was conducted to estimate sero-prevalence of FMD in large ruminants from peri-urban dairy farms near Islamabad. Serum samples were...

  1. The position of the Dutch Farmers' Union on lessons learned and future prevention and control of foot and mouth disease.

    PubMed

    Cuijpers, M P; Osinga, K J

    2002-12-01

    Foot and mouth disease (FMD) has devastated animal husbandry in The Netherlands frequently in the past and still constitutes a threat. The use of vaccination reduced the number of outbreaks in The Netherlands in the 20th Century. However, the desire of some member states of the European Community not to use vaccination led to a new strategy based on stamping-out of infected and contagious farms and to strict transportation regulations. In 2001, this proved very disruptive to the wider rural economy, such as the recreational and tourism sectors. The policy also caused severe animal welfare problems and psychological problems among farmers and their families. This raised questions about the wider, and not only veterinary or agricultural, implications of control strategies of foot and mouth disease virus (FMDV). The technology seems to be in place for a return to the use of protective vaccination against FMDV during an outbreak, provided the Office International des Epizooties (OIE: World organisation for animal health) and European Commission (EC) receive data that substantiate the reliability of differentiating tests such as the 3ABC enzyme-linked immunosorbent assay (ELISA) for use in individual animals. Research is in progress but may not be able to produce these data until 2003 or 2004. High potency vaccines should be used to elicit sufficient immunity within three to four days. During an FMD crisis, farmers should be assisted to find markets for products from areas affected by FMDV. The human dimension of any FMD outbreak must be dealt with sufficiently in any contingency plan.

  2. Adenovirus-vectored foot-and-mouth disease vaccine confers early and full protection against FMDV O1 Manisa in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A human adenovirus (Ad5) vectored foot-and-mouth disease virus (FMDV) sero-type O1-Manisa subunit vaccine (Ad5-O1Man) was engineered to deliver FMDV O1-Manisa empty capsids. Swine inoculated with Ad5-O1Man developed an FMDV-specific neutralizing antibody response as compared to animals inoculated wi...

  3. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

  4. Serotype diversity of foot-and-mouth-disease virus in livestock without history of vaccination in the far north region of Cameroon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little information is available about the natural cycle of foot-and-mouth disease (FMD) in the absence of control measures such as vaccination. Cameroon presents a unique opportunity for epidemiological studies because FMD vaccination is not practiced. We carried out a prospective study including se...

  5. Role of the Arg56 of the structural protein VP3 of foot-and-mouth disease virus (FMDV) 01 campos in virus virulence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) is an extremely infectious and antigenically diverse picornavirus that causes high incidences of morbidity within naive livestock populations. Several reports indicate that FMDV O1 subtype strains undergo antigenic variation under diverse growth conditions. Of par...

  6. Domain disruptions of individual 3B proteins for foot-and-mouth disease virus do not alter growth in cell culture nor virulence in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Picornavirus RNA replication is initiated by a small viral protein primer, 3B (also known as VPg), that is covalently linked to the 5’RNA of the viral genome. In contrast to other picornaviruses that encode a single copy of 3B, foot-and-mouth disease virus (FMDV) encodes three copies of 3B that are ...

  7. Synonymous deoptimization of the foot-and-mouth disease virus P1 coding region causes attenuation in vivo while inducing a strong neutralizing antibody response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Codon bias deoptimization has been previously used to successfully attenuate human pathogens including polio, respiratory syncytial and influenza viruses. We have applied a similar technology to deoptimize the capsid coding region (P1 region) of the cDNA infectious clone of foot-and-mouth disease vi...

  8. A Reverse Genetic System Provides a Powerful Tool in the Design of Foot-and-Mouth Disease Viruses with Enhanced Properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fact that the foot-and-mouth disease viral (FMDV) RNA can be made infectious in the absence of other components of the virion allows the recovery of genetically engineered new viruses from in vitro-generated RNA molecules. We utilize infectious cDNA technology to produce recombinant FMDV, retain...

  9. Introduction of tag epitopes in the inter-AUG region of foot and mouth disease virus: effect on the L protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) initiates translation from two in–frame AUG codons producing two forms of the leader (L) proteinase, termed Lab (starting at the first AUG) and Lb (starting at second AUG). In a previous study, we have demonstrated that acDNA-derived mutant FMDV (A24-L1123) conta...

  10. A Conserved Domain in the Leader Proteinase of Foot-and-Mouth Disease Virus is Required for Proper Sub-Cellular Localization and Function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) is involved in antagonizing the innate immune response by blocking the expression of interferon (IFN) protein and by reducing the immediate-early induction of IFN beta mRNA and IFN stimulated genes. In addition to its role in shutti...

  11. Predicting antigenic sites on the foot-and-mouth disease virus capsid of the South African Territories (SAT) types using virus neutralization data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) outer capsid proteins 1B, 1C and 1D contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. This study presents a phylogenetic, genetic and antigenic analysis of the South African Territories (SAT) seroty...

  12. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of jumonji C-domain containing protein 6 in RHA demethylation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported that RNA Helicase A (RHA) re-localized from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells, coincident with a reduction in methylation of arginine residues in the RHA C-terminus. To further define the mechanism of RHA demethylation in FMDV-...

  13. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Non-structural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids in most FMDVs examined to date. The role of 3A in virus growth and virulence within the natural host is not well understood. Using a yeast two-hybrid approach, we identified cellular ...

  14. Analysis of SAT type foot-and-mouth disease virus capsid proteins and the identification of putative amino acid residues in virus stability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) initiates infection by adhering to integrin receptors on target cells, followed by cell entry and disassembly of the virion through acidification within endosomes. Mild heating of the virions also leads to irreversible dissociation into pentamers, a characteristic...

  15. Transcriptomic analysis of persistent infection with foot-and-mouth disease virus in cattle suggests impairment of cell-mediated immunity in the nasopharynx

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vac...

  16. Innate Immune Defenses Induced by CpG do not Promote Vaccine-Induced Protection Against Foot-and-Mouth Disease in Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Emergency vaccination as part of the control strategies against Foot-and-Mouth Disease (FMD) epidemics has the potential not only to limit the spread of the virus but also to reduce large-scale culling of affected herds. With the aim to reduce the time between vaccination and the onset of immunity, ...

  17. Persistent foot-and-mouth disease virus infection in the nasopharynx of cattle: tissue-specific distribution and local cytokine expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 st...

  18. Combination of Adt-O1MANISA AND Ad5-boIFN induces early protective immunity against foot-and-mouth diseases in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth-disease (FMD) remains one of the most important economic concerns for the agricultural industry worldwide. Although vaccination with a commercially available inactivated whole virus formulation, or a recently developed replication-defective human adenovirus 5 vector-based subunit vacc...

  19. Analysis of sat type foot-and-mouth disease virus capsid proteins: influence of receptor usage on the properties of virus particles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The viral mechanism involved in foot-and-mouth disease (FMD) tissue tropism, host range and the events during viral entry into susceptible cells is not well understood. Using infectious cDNA clones of the three South African Territories (SAT) type viruses prevalent in sub-Saharan Africa, the biologi...

  20. Detection of Foot-and-Mouth Disease Virus RNA and capsid protein in lymphoid tissues of convalescent pigs does not indicate existence of a carrier state

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A systematic study was performed to investigate the potential of pigs to maintain persistent Foot-and-Mouth Disease Virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal- or oropharyngeal fluids obtained after resolution of clinical infection with FMDV serotypes A, O...

  1. Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

  2. Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection; however the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mono...

  3. Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural killer (NK) cells play a role in innate antiviral immunity by directly lysing virus-infected cells and producing antiviral cytokines such as interferon gamma (IFNgamma). We developed a system for characterizing the bovine NK response to foot-and-mouth disease virus (FMDV), which causes a dis...

  4. STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH DISEASE : II. CATAPHORESIS AND FILTRATION.

    PubMed

    Olitsky, P K; Boëz, L

    1927-03-31

    Cataphoresis experiments show that the virus of foot-and-mouth disease carries, under ordinary conditions, an electropositive charge. Its isoelectric range is at the high point of pH = about 8. Although cultivable bacteria are, as a rule, electronegative, yet certain protozoa, such as trypanosomes and spirochetes are also electropositive. In respect to charge, then, the virus is different from ordinary bacteria, but there is nothing in this finding to indicate an inanimate character of the incitant. A knowledge of the charge, however, aids in the interpretation of certain filtration phenomena, and indirectly in delimiting the size of the virus. In addition, it serves to explain its remarkable resistance to certain chemicals-a subject to be dealt with in the next paper of this series. Finally, cataphoresis indicates the possible separation of the virus from protein particles. Filtration experiments were made with different types of filters: Seitz, Berkefeld V and N, and Chamberland, of practically all sizes, collodion membranes, and Bechhold's ultrafilter. The results confirm the electropositive charge of the virus, as well as the minuteness of its size. Filtration was effected through the Seitz, Berkefeld, and Chamberland filters. In regard to the latter, the active agent passed through the L 11 only when its charge was shifted to negative: under ordinary conditions, carrying an electropositive charge, it failed to traverse this more dense wall, and was completely adsorbed in the oppositely charged barrier. Filtrations through electronegative collodion membranes, prepared in different ways and of varying thicknesses, resulted, as a rule, in failure, unless the thinnest and most permeable membranes were employed. But in these, the complication of microscopic holes was to be considered. Hence this method was regarded as impracticable. Success, however, was obtained with Bechhold's ultrafilter membranes of the most permeable type, and with these it was possible to

  5. Atmospheric Spread of Foot-and-mouth Disease During The Early Phase of The Uk Epidemic 2001

    NASA Astrophysics Data System (ADS)

    Sørensen, J. H.; Mikkelsen, T.; Astrup, P.; Alexandersen, S.; Donaldson, A. I.

    Foot-and-mouth disease (FMD) is a highly contagious viral disease in cloven-hoofed domesticated and wild animals. The highly contagious nature of FMD is a reflection of the wide range of species which are susceptible, the enormous quantities of virus liberated by infected animals, the range of excretions and secretions which can be infectious, the stability of the virus in the environment, the multiplicity of routes of infection and the very small doses of virus that can initiate infection in susceptible hosts. One of the routes for the spread of the disease is the atmospheric dispersion of virus exhaled by infected animals. Such spread can be rapid and extensive, and it is known in certain circumstances to have occurred over a distance of several hundred kilometres. For the FMD epidemic in UK in 2001, atmospheric dispersion models were applied in real time in order to describe the atmospheric dispersion of virus for the larger outbreaks of the disease. The operational value of such modelling is first of all to identify risk zones, which is helpful to the emergency management. The paper addresses the modelling techniques and presents results related with the epidemic in UK in 2001.

  6. The impact of seasonal variability in wildlife populations on the predicted spread of foot and mouth disease

    PubMed Central

    Highfield, Linda D.; Ward, Michael P.; Laffan, Shawn W.; Norby, Bo; Wagner, Gale

    2009-01-01

    Modeling potential disease spread in wildlife populations is important for predicting, responding to and recovering from a foreign animal disease incursion such as foot and mouth disease (FMD). We conducted a series of simulation experiments to determine how seasonal estimates of the spatial distribution of white-tailed deer impact the predicted magnitude and distribution of potential FMD outbreaks. Outbreaks were simulated in a study area comprising two distinct ecoregions in South Texas, USA, using a susceptible-latent-infectious-resistant geographic automata model (Sirca). Seasonal deer distributions were estimated by spatial autoregressive lag models and the normalized difference vegetation index. Significant (P < 0.0001) differences in both the median predicted number of deer infected and number of herds infected were found both between seasons and between ecoregions. Larger outbreaks occurred in winter within the higher deer-density ecoregion, whereas larger outbreaks occurred in summer and fall within the lower deer-density ecoregion. Results of this simulation study suggest that the outcome of an FMD incursion in a population of wildlife would depend on the density of the population infected and when during the year the incursion occurs. It is likely that such effects would be seen for FMD incursions in other regions and countries, and for other diseases, in cases in which a potential wildlife reservoir exists. Study findings indicate that the design of a mitigation strategy needs to take into account population and seasonal characteristics. PMID:19134466

  7. Seasonal modeling of hand, foot, and mouth disease as a function of meteorological variations in Chongqing, China

    NASA Astrophysics Data System (ADS)

    Wang, Pin; Zhao, Han; You, Fangxin; Zhou, Hailong; Goggins, William B.

    2017-02-01

    Hand, foot, and mouth disease (HFMD) is an enterovirus-induced infectious disease, mainly affecting children under 5 years old. Outbreaks of HFMD in recent years indicate the disease interacts with both the weather and season. This study aimed to investigate the seasonal association between HFMD and weather variation in Chongqing, China. Generalized additive models and distributed lag non-linear models based on a maximum lag of 14 days, with negative binomial distribution assumed to account for overdispersion, were constructed to model the association between reporting HFMD cases from 2009 to 2014 and daily mean temperature, relative humidity, total rainfall and sun duration, adjusting for trend, season, and day of the week. The year-round temperature and relative humidity, rainfall in summer, and sun duration in winter were all significantly associated with HFMD. An inverted-U relationship was found between mean temperature and HFMD above 19 °C in summer, with a maximum morbidity at 27 °C, while the risk increased linearly with the temperature in winter. A hockey-stick association was found for relative humidity in summer with increasing risks over 60%. Heavy rainfall, relative to no rain, was found to be associated with reduced HFMD risk in summer and 2 h of sunshine could decrease the risk by 21% in winter. The present study showed meteorological variables were differentially associated with HFMD incidence in two seasons. Short-term weather variation surveillance and forecasting could be employed as an early indicator for potential HFMD outbreaks.

  8. Genetic characterization and molecular epidemiology of foot-and-mouth disease viruses isolated from Afghanistan in 2003-2005.

    PubMed

    Schumann, Kate R; Knowles, Nick J; Davies, Paul R; Midgley, Rebecca J; Valarcher, Jean-Francois; Raoufi, Abdul Quader; McKenna, Thomas S; Hurtle, William; Burans, James P; Martin, Barbara M; Rodriguez, Luis L; Beckham, Tammy R

    2008-04-01

    Foot-and-mouth disease virus (FMDV) isolates collected from various geographic locations in Afghanistan between 2003 and 2005 were genetically characterized, and their phylogeny was reconstructed utilizing nucleotide sequences of the complete VP1 coding region. Three serotypes of FMDV (types A, O, and Asia 1) were identified as causing clinical disease in Afghanistan during this period. Phylogenetic analysis revealed that the type A viruses were most closely related to isolates collected in Iran during 2002-2004. This is the first published report of serotype A in Afghanistan since 1975, therefore indicating the need for inclusion of serotype A in vaccine formulations that will be used to control disease outbreaks in this country. Serotype O virus isolates were closely related to PanAsia strains, including those that originated from Bhutan and Nepal during 2003-2004. The Asia 1 viruses, collected along the northern and eastern borders of Afghanistan, were most closely related to FMDV isolates collected in Pakistan during 2003 and 2004. Data obtained from this study provide valuable information on the FMDV serotypes circulating in Afghanistan and their genetic relationship with strains causing FMD in neighboring countries.

  9. Hand, Foot and Mouth Disease in Hong Kong: A Time-Series Analysis on Its Relationship with Weather

    PubMed Central

    Wang, Pin; Goggins, William B.; Chan, Emily Y. Y.

    2016-01-01

    Background Hand, foot and mouth disease (HFMD) is an emerging enterovirus-induced infectious disease for which the environmental risk factors promoting disease circulation remain inconclusive. This study aims to quantify the association of daily weather variation with hospitalizations for HFMD in Hong Kong, a subtropical city in China. Methods A time series of daily counts of HFMD public hospital admissions from 2008 through 2011 in Hong Kong was regressed on daily mean temperature, relative humidity, wind speed, solar radiation and total rainfall, using a combination of negative binomial generalized additive models and distributed lag non-linear models, adjusting for trend, season, and day of week. Results There was a positive association between temperature and HFMD, with increasing trends from 8 to 20°C and above 25°C with a plateau in between. A hockey-stick relationship of relative humidity with HFMD was found, with markedly increasing risks over 80%. Moderate rainfall and stronger wind and solar radiation were also found to be associated with more admissions. Conclusions The present study provides quantitative evidence that short-term meteorological variations could be used as early indicators for potential HFMD outbreaks. Climate change is likely to lead to a substantial increase in severe HFMD cases in this subtropical city in the absence of further interventions. PMID:27532865

  10. A portable reverse transcription recombinase polymerase amplification assay for rapid detection of foot-and-mouth disease virus.

    PubMed

    Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A; Hufert, Frank T; Weidmann, Manfred

    2013-01-01

    Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4-10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection.

  11. Economic Impacts of Potential Foot and Mouth Disease Agro-terrorism in the United States: A Computable General Equilibrium Analysis

    SciTech Connect

    Oladosu, Gbadebo A; Rose, Adam; Bumsoo, Lee

    2013-01-01

    The foot and mouth disease (FMD) virus has high agro-terrorism potential because it is contagious, can be easily transmitted via inanimate objects and can be spread by wind. An outbreak of FMD in developed countries results in massive slaughtering of animals (for disease control) and disruptions in meat supply chains and trade, with potentially large economic losses. Although the United States has been FMD-free since 1929, the potential of FMD as a deliberate terrorist weapon calls for estimates of the physical and economic damage that could result from an outbreak. This paper estimates the economic impacts of three alternative scenarios of potential FMD attacks using a computable general equilibrium (CGE) model of the US economy. The three scenarios range from a small outbreak successfully contained within a state to a large multi-state attack resulting in slaughtering of 30 percent of the national livestock. Overall, the value of total output losses in our simulations range between $37 billion (0.15% of 2006 baseline economic output) and $228 billion (0.92%). Major impacts stem from the supply constraint on livestock due to massive animal slaughtering. As expected, the economic losses are heavily concentrated in agriculture and food manufacturing sectors, with losses ranging from $23 billion to $61 billion in the two industries.

  12. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide.

    PubMed

    Blanco, Esther; Guerra, Beatriz; de la Torre, Beatriz G; Defaus, Sira; Dekker, Aldo; Andreu, David; Sobrino, Francisco

    2016-05-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136-154)] linked through thioether bonds to a T-cell epitope [3A(21-35)] of FMDV [B4T(thi)] elicits potent B- and T-cell specific responses and confers solid protection in pigs to type C FMDV challenge. Herein we show that downsized versions of this peptide bearing two copies of a B-cell epitope from a type O isolate and using thioether [B2T(thi)] or maleimide [B2T(mal)] conjugation chemistries for their synthesis elicited in swine similar or higher B and T-cell specific responses than tetravalent B4T(thi). Moreover, while partial protection was observed in animals immunized with B4T(thi) (60%) and B2T(thi) (80%), B2T(mal) conferred full (100%) protection against FMDV challenge, associated to high levels of circulating IgG2 and mucosal IgGA, and entirely prevented virus shedding. Interestingly, B2T(mal) is also the most advantageous option in terms of synthetic practicality. Taken together, the results reported here point out to B2T(mal) as a highly valuable, cost-effective FMDV candidate vaccine.

  13. Foot-and-mouth disease virus serotype O phylodynamics: genetic variability associated with epidemiological factors in Pakistan.

    PubMed

    Brito, B P; Perez, A M; Jamal, S M; Belsham, G J; Pauszek, S J; Ahmed, Z; Rodriguez, L L

    2013-12-01

    One of the most challenging aspects of foot-and-mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating outbreaks in disease-free areas. In countries trying to control and eradicate FMD using vaccination strategies, the constantly evolving and wide diversity of field FMDV strains is an obstacle for identifying vaccine strains that are successful in conferring protection against infection with field viruses. Consequently, quantitative knowledge on the factors that are associated with variability of the FMDV is prerequisite for preventing and controlling FMD in the Indian subcontinent. A hierarchical linear model was used to assess the association between time, space, host species and the genetic variability of serotype O FMDV using viruses collected in Pakistan from 2005 to 2011. Significant (P<0.05) amino acid and nucleotide variations were associated with spatial distance, but not with differences in host species, which is consistent with the frequent multi-species infection of this serotype O FMDV. Results from this study will contribute to the understanding of FMDV variability and to the design of FMD control strategies in Pakistan. Viruses sequenced here also provide the earliest reported isolate from the Pan Asia II(ANT-10) sublineage, which has caused several outbreaks in the Middle East and spread into Europe (Bulgaria) and Africa (Libya).

  14. Immunoreactivity and trypsin sensitivity of recombinant virus-like particles of foot-and-mouth disease virus.

    PubMed

    Basagoudanavar, S H; Hosamani, M; Tamil, R P; Sreenivasa, B P; Chandrasekhar, B K; Venkataramanan, R

    2015-03-01

    Foot-and-mouth disease (FMD) is an important infection affecting the health and productivity of cloven-hoofed livestock. Development of improved vaccines and diagnostic reagents is being explored to facilitate the disease control. There is an emerging interest in virus-like particles (VLPs), as their constituent structural proteins are the major immunogens. The VLPs are similar to natural virus particles but lack viral nucleic acid. The objective of the present study was to express the VLPs of FMD virus (FMDV) serotype Asia-1 (IND 63/72), using baculovirus system and characterize them for antigenic structure. The VLPs expressed in insect cells showed immunoreactivity similar to inactivated cell culture FMDV. Further they possess similar sensitivity to trypsin as the inactivated cell culture FMDV, suggesting that trypsin-sensitive antigenic sites could be similarly arranged. Our findings suggest that the FMD VLPs have similar antigenic conformational feature like the wild type virus, thus supporting their utility in development of non-infectious FMD vaccines and/or diagnostic assays.

  15. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine.

    PubMed

    Diaz-San Segundo, Fayna; Dias, Camila C; Moraes, Mauro P; Weiss, Marcelo; Perez-Martin, Eva; Salazar, Andres M; Grubman, Marvin J; de los Santos, Teresa

    2014-11-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FMDV challenge by 7 days post-vaccination. However, since relatively large amounts of Ad5-CI-A24-2B are required to induce protection this strategy could be costly for livestock production. Poly ICLC is a synthetic double stranded RNA that activates multiple innate and adaptive immune pathways. In this study, we have tested for the first time, the adjuvant effect of poly ICLC in combination with Ad5-CI-A24-2B in swine. We found that the combination resulted in a reduction of the vaccine protective dose by 80-fold. Interestingly, the lowest dose of Ad5-CI-A24-2B plus 1mg of poly ICLC protected animals against challenge even in the absence of detectable FMDV-specific neutralizing antibodies at the time of challenge.

  16. Foot and mouth disease in Zambia: spatial and temporal distributions of outbreaks, assessment of clusters and implications for control.

    PubMed

    Sinkala, Yona; Simuunza, Martin; Muma, John B; Pfeiffer, Dirk U; Kasanga, Christopher J; Mweene, Aaron

    2014-04-23

    Zambia has been experiencing low livestock productivity as well as trade restrictions owing to the occurrence of foot and mouth disease (FMD), but little is known about the epidemiology of the disease in these endemic settings. The fundamental questions relate to the spatio-temporal distribution of FMD cases and what determines their occurrence. A retrospective review of FMD cases in Zambia from 1981 to 2012 was conducted using geographical information systems and the SaTScan software package. Information was collected from peer-reviewed journal articles, conference proceedings, laboratory reports, unpublished scientific reports and grey literature. A space-time permutation probability model using a varying time window of one year was used to scan for areas with high infection rates. The spatial scan statistic detected a significant purely spatial cluster around the Mbala-Isoka area between 2009 and 2012, with secondary clusters in Sesheke-Kazungula in 2007 and 2008, the Kafue flats in 2004 and 2005 and Livingstone in 2012. This study provides evidence of the existence of statistically significant FMD clusters and an increase in occurrence in Zambia between 2004 and 2012. The identified clusters agree with areas known to be at high risk of FMD. The FMD virus transmission dynamics and the heterogeneous variability in risk within these locations may need further investigation.

  17. Identification and isolation of foot-and-mouth disease virus from primary suspect cases in Korea in 2000.

    PubMed

    Shin, Jin-Ho; Sohn, Hyun-Joo; Choi, Kang-Seuk; Kwon, Byung-Jun; Choi, Cheong-Up; Kim, Jae-Hoon; Hwang, Eui-Kyung; Park, Jong-Hyeon; Kim, Jong-Yeom; Choi, Sang-Ho; Kim, Ok-Kyung

    2003-01-01

    The Republic of Korea had been free from foot and mouth disease (FMD) since 1934, until a recent outbreak in 2000. From March to April 2000, a total of 15 FMD outbreaks due to the serotype O virus were recorded. Coincidental outbreaks of FMD in cattle or pigs by the serotype O virus were reported in the region, including Taiwan, China, Japan, Russia and Mongolia. In this report, the results of emergency investigations of FMD cases on a dairy farm located approximately 5-km from the demilitarized zone in Korea are described. The causative agent of the disease was identified as the FMD virus O by reverse transcription-polymerase chain reaction (RT-PCR) assays using primers derived from the 3D polymerase, internal ribosome entry site (IRES), 1D/2B regions, enzyme-linked immunosorbent assay (ELISA) for antigen detection and typing. Sequence data of the partial 1D/2B region obtained from vesicular fluid showed close similarity (98% sequence identity) to the Kinmen isolate of the FMD virus O in Taiwan. The causative virus was isolated using black goat fetal lung cells following propagation in unweaned mice.

  18. Genetic characterization of vaccine and field strains of serotype A foot-and-mouth disease virus from India.

    PubMed

    Mohapatra, J K; Pawar, S S; Tosh, C; Subramaniam, S; Palsamy, R; Sanyal, A; Hemadri, D; Pattnaik, B

    2011-01-01

    Extreme antigenic and genetic heterogeneity of serotype A foot-and-mouth disease virus (FMDV) population has resulted in change of vaccine strains in India twice in the last decade. In such a situation, complete characterization of the vaccine strains is imperative. With regard to the frequent outbreaks of this disease, FMDV field strains are also of interest. Therefore three vaccine strains and two field strains of type A FMDV from India were completely sequenced and the obtained sequences were subjected to sequence and phylogenetic analyses. Based on the complete coding region, all the Indian strains clustered in the Asia topotype and exhibited a more than 11% nt divergence from the other Asian strains. The 5'-UTR of some Indian strains revealed block deletions of 43 and 86 nt corresponding to the pseudoknot region. Amino acids S44 in VP2 and F164 in VP1 were found to be the exclusive signatures for the Asia topotype. The vaccine strains differed at 65 aa positions in the capsid region, 13 of them antigenically critical. Variability at such positions is likely to affect the antigenic profile of these strains. Complete genome sequences of the vaccine strains presented here could serve as the reference for any comparative genomics in future.

  19. Epidemiologic Features of Enterovirus 71-Associated Hand-Foot-and-Mouth Disease from 2009 to 2013 in Zhejiang, China

    PubMed Central

    Wang, Zhifang; Lv, Huakun; Zhu, Wenming; Mo, Zhe; Mao, Guangming; Wang, Xiaofeng; Lou, Xiaoming; Chen, Yongdi

    2016-01-01

    Enterovirus 71 (EV71) usually causes hand-foot-and-mouth disease (HFMD) with severe clinical symptoms and even deaths in China. There is no efficient antiviral drug to protect against severe EV71-associated HFMD, making the development of EV71 vaccines therefore a priority. However, the potential target subject population(s) to be immunized with EV71 vaccine are not well understood. In this study, we characterized the epidemiology regarding EV71-associated HFMD on the basis of provincial-level surveillance. We extracted data on EV71-associated HFMD from the National Notifiable Disease Reporting System in Zhejiang Province, China between 1 January 2009 and 31 December 2013 (n = 7650). The higher incidence rate of EV71 cases occurred in those children aged 12–23 months, with boys being predominant. Interestingly, different peaks activities of EV71 infection was observed in different calendar year, with one peak in 2009 and 2013 and two peaks in 2010–2012. However, EV71 infection seemed to predominately occur in warm season and a distinguished cyclic peak that seemed to be of about 12 months. Children aged 12–23 months are thus identified as an important target population for public health intervention, for example, it is recommended that these key subjects immunized with EV71 vaccine. In addition, an enhanced surveillance system for EV71-associated with HFMD needs to focus on generic and phylogenetic analysis. PMID:28042848

  20. Evolutionary analysis of structural protein gene VP1 of foot-and-mouth disease virus serotype Asia 1.

    PubMed

    Zhang, Qingxun; Liu, Xinsheng; Fang, Yuzhen; Pan, Li; Lv, Jianliang; Zhang, Zhongwang; Zhou, Peng; Ding, Yaozhong; Chen, Haotai; Shao, Junjun; Zhao, Furong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Wang, Yonglu; Zhang, Yongguang

    2015-01-01

    Foot-and-mouth disease virus (FMDV) serotype Asia 1 was mostly endemic in Asia and then was responsible for economically important viral disease of cloven-hoofed animals, but the study on its selection and evolutionary process is comparatively rare. In this study, we characterized 377 isolates from Asia collected up until 2012, including four vaccine strains. Maximum likelihood analysis suggested that the strains circulating in Asia were classified into 8 different groups (groups I-VIII) or were unclassified (viruses collected before 2000). On the basis of divergence time analyses, we infer that the TMRCA of Asia 1 virus existed approximately 86.29 years ago. The result suggested that the virus had a high mutation rate (5.745 × 10(-3) substitutions/site/year) in comparison to the other serotypes of FMDV VP1 gene. Furthermore, the structural protein VP1 was under lower selection pressure and the positive selection occurred at many sites, and four codons (positions 141, 146, 151, and 169) were located in known critical antigenic residues. The remaining sites were not located in known functional regions and were moderately conserved, and the reason for supporting all sites under positive selection remains to be elucidated because the power of these analyses was largely unknown.

  1. Identification of health risks of hand, foot and mouth disease in China using the geographical detector technique.

    PubMed

    Huang, Jixia; Wang, Jinfeng; Bo, Yanchen; Xu, Chengdong; Hu, Maogui; Huang, Dacang

    2014-03-21

    Hand, foot and mouth disease (HFMD) is a common infectious disease, causing thousands of deaths among children in China over the past two decades. Environmental risk factors such as meteorological factors, population factors and economic factors may affect the incidence of HFMD. In the current paper, we used a novel model-geographical detector technique to analyze the effect of these factors on the incidence of HFMD in China. We collected HFMD cases from 2,309 counties during May 2008 in China. The monthly cumulative incidence of HFMD was calculated for children aged 0-9 years. Potential risk factors included meteorological factors, economic factors, and population density factors. Four geographical detectors (risk detector, factor detector, ecological detector, and interaction detector) were used to analyze the effects of some potential risk factors on the incidence of HFMD in China. We found that tertiary industry and children exert more influence than first industry and middle school students on the incidence of HFMD. The interactive effect of any two risk factors increases the hazard for HFMD transmission.

  2. Development of foot-and-mouth disease virus (FMDV) serotype O virus-like-particles (VLPs) vaccine and evaluation of its potency.

    PubMed

    Mohana Subramanian, B; Madhanmohan, M; Sriraman, Rajan; Chandrasekhar Reddy, R V; Yuvaraj, S; Manikumar, Kankipati; Rajalakshmi, S; Nagendrakumar, S B; Rana, Samir Kumar; Srinivasan, V A

    2012-12-01

    Foot-and-mouth disease (FMD) is an economically significant viral disease that rampage dairy and other livestock industries in many countries. The disease is being controlled by the use of an inactivated vaccine. However, a recombinant marker vaccine, which avoids the use of live virus, may be an option for the unambiguous differentiation of infected animals from vaccinated animals. A recombinant baculovirus clone containing P1-2A-3C coding sequences of foot-and-mouth disease virus (FMDV) serotype O(1) Manisa was generated. The FMDV structural proteins along with the 3C protease were expressed in Sf9 cells and the generation of virus like particles (VLP) was studied. The recombinant protein was formulated as vaccine using an oil adjuvant, ISA 206 and potency of the vaccine was tested in cattle. The vaccine had a potency value (PD(50)) of 5.01 and most of the vaccinated animals exhibited neutralizing antibody titers after two immunizations.

  3. Vaccination against foot-and-mouth disease virus confers complete clinical protection in 7 days and partial protection in 4 days: Use in emergency outbreak response.

    PubMed

    Golde, William T; Pacheco, Juan M; Duque, Hernando; Doel, Timothy; Penfold, Barry; Ferman, Geoffrey S; Gregg, Douglas R; Rodriguez, Luis L

    2005-12-30

    Recent outbreaks of foot-and-mouth disease virus (FMDV) demonstrate that this highly contagious viral infection of cloven hoofed animals continues to be a significant economic problem worldwide. Debate about the most effective way to respond to outbreaks of FMDV in disease free countries continues to center on the use of vaccines. In this report, we present data showing that a commercially available, standard dose vaccine formulation can fully protect cattle against direct challenge with the virus in as little as 7 days with no carrier transmission to naïve animals. Cattle challenged 4 days after vaccination have reduced disease severity, no detectable virus in blood and little virus shedding from nasal secretions. These significant effects at 4 days post vaccination, confirmed in two separate trials, support the value of using currently available vaccines as a first line of defense against foot-and-mouth disease (FMD) outbreaks.

  4. A computational study of the interaction of the foot and mouth disease virus VP1 with monoclonal antibodies.

    PubMed

    Marrero, Ruben; Limardo, Ramiro Rodríguez; Carrillo, Elisa; König, Guido A; Turjanski, Adrián G

    2015-10-01

    Foot and mouth disease is caused by a non-enveloped virus (FMDV), which disposes several antigenic sites at the surface of their capsid proteins. The most relevant and immunodominant antigenic site of FMDV (site A or AnSA) includes a key virus-cell interaction element (RGD motif) located in the Viral Protein 1 (VP1), more precisely at the GH loop. AnSA includes a set of overlapped and mainly linear epitopes, which are the main targets of the humoral immune response. Taking advantage over specific structural features of the GH loop, we have evaluated the influence of every amino acid residue at AnSA in the interaction with 2 neutralizing antibodies by molecular modeling techniques. Additionally, we constructed diverse interaction complexes with multiple site A mutants and discussed about the structural influence of amino acidic insertions in such relevant antigenic site of FMDV. Our approach is in agreement with previous ELISA experiments and allows the understanding of how FMDV mutations may alter the interaction with different antibodies, as we can estimate the contribution of each amino acid to the interaction. Overall, our work contributes to the development of specific vaccination strategies for FMD control.

  5. Characterization of enterovirus 71 infection and associated outbreak of Hand, Foot, and Mouth Disease in Shawo of China in 2012

    PubMed Central

    Liu, Michelle Y.; Liu, Jin; Lai, Weijian; Luo, Jun; Liu, Yingle; Vu, Gia-Phong; Yang, Zhu; Trang, Phong; Li, Hongjian; Wu, Jianguo

    2016-01-01

    Infection of enterovirus 71 (EV71) and associated hand, foot, and mouth disease (HFMD) are recognized as emerging public health issues worldwide. Hundreds of thousands of children are annually infected with EV71 and develop HFMD in China alone. Studies of EV71 infection are critical to the treatment and prevention of the associated HFMD outbreaks. In this report, we studied an outbreak of 105 HFMD cases in Shawo Township of China between September to October 2012. More than 90% of cases were children younger than 9 years old, with over 50% of cases aged 3–6 years old. Laboratory studies detected a high prevalence of EV71 and suggested EV71 as the most common enterovirus causing HFMD in Shawo. Sequencing analysis showed that the EV71 strains from Shawo belong to the C4 subgenotype, and are phylogenetically more related to those from the distant city of Nanchang than those from the nearby city of Wuhan with distinct variations. More girls were found to be associated with EV71 in Shawo whereas more boys were associated with EV71 in Wuhan and Nanchang. Our studies further the understanding of the molecular epidemiological features of HFMD and infection by enteroviruses in China. PMID:27941929

  6. B epitope multiplicity and B/T epitope orientation influence immunogenicity of foot-and-mouth disease peptide vaccines.

    PubMed

    Blanco, Esther; Cubillos, Carolina; Moreno, Noelia; Bárcena, Juan; de la Torre, Beatriz G; Andreu, David; Sobrino, Francisco

    2013-01-01

    Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFN γ . Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

  7. Genome variability of foot-and-mouth disease virus during the short period of the 2010 epidemic in Japan.

    PubMed

    Nishi, Tatsuya; Yamada, Manabu; Fukai, Katsuhiko; Shimada, Nobuaki; Morioka, Kazuki; Yoshida, Kazuo; Sakamoto, Kenichi; Kanno, Toru; Yamakawa, Makoto

    2017-02-01

    Foot-and-mouth disease virus (FMDV) is highly contagious and has a high mutation rate, leading to extensive genetic variation. To investigate how FMDV genetically evolves over a short period of an epidemic after initial introduction into an FMD-free area, whole L-fragment sequences of 104 FMDVs isolated from the 2010 epidemic in Japan, which continued for less than three months were determined and phylogenetically and comparatively analyzed. Phylogenetic analysis of whole L-fragment sequences showed that these isolates were classified into a single group, indicating that FMDV was introduced into Japan in the epidemic via a single introduction. Nucleotide sequences of 104 virus isolates showed more than 99.56% pairwise identity rates without any genetic deletion or insertion, although no sequences were completely identical with each other. These results indicate that genetic substitutions of FMDV occurred gradually and constantly during the epidemic and generation of an extensive mutant virus could have been prevented by rapid eradication strategy. From comparative analysis of variability of each FMDV protein coding region, VP4 and 2C regions showed the highest average identity rates and invariant rates, and were confirmed as highly conserved. In contrast, the protein coding regions VP2 and VP1 were confirmed to be highly variable regions with the lowest average identity rates and invariant rates, respectively. Our data demonstrate the importance of rapid eradication strategy in an FMD epidemic and provide valuable information on the genome variability of FMDV during the short period of an epidemic.

  8. Genetic and antigenic characterization of foot-and-mouth disease viruses isolated in Taiwan between 1998 and 2009.

    PubMed

    Lin, Yeou-Liang; Jong, Ming-Hwa; Huang, Chin-Cheng; Shieh, Happy K; Chang, Poa-Chun

    2010-09-28

    A devastating outbreak of foot-and-mouth disease (FMD), caused by a porcinophilic serotype O virus, occurred in Taiwan in March 1997. This outbreak was brought under control by means of a stamping-out policy and vaccination. Although mandatory vaccination was conducted in Taiwan between 1997 and 2007, sporadic outbreaks of FMD occurred between 1998 and 2009; however, the viruses that caused these outbreaks remain uncharacterized. This article reports the genetic and antigenic characterization of FMD viruses isolated in Taiwan during this period. Sequence analysis of the VP1 coding region showed that the viruses isolated in Taiwan between 1998 and 2009 were most similar to viruses isolated in Taiwan in 1997 and to viruses isolated from Hong Kong and Vietnam in 1991-1996. The results of phylogenetic analysis suggested that the viruses isolated in Taiwan in 1998-2009 were derived from the viruses isolated in Taiwan in 1997. However, substantial mutations were found in the viruses isolated in 2009, and some of these changes may have resulted from vaccine pressure in the field. Serum neutralization tests confirmed that viruses isolated in 2009 showed a significant change in antigenicity. This is the first report of changes in the VP1 sequence and antigenicity of porcinophilic FMD viruses isolated from an area in which long-term mandatory vaccination against FMD was practiced.

  9. Characterization of the recent outbreak of foot-and-mouth disease virus serotype SAT2 in Egypt.

    PubMed

    Kandeil, Ahmed; El-Shesheny, Rabeh; Kayali, Ghazi; Moatasim, Yassmin; Bagato, Ola; Darwish, Mohamed; Gaffar, Alkhateib; Younes, Abdelgayed; Farag, Tarek; Kutkat, Mohamed A; Ali, Mohamed A

    2013-03-01

    An outbreak of foot-and-mouth disease (FMD) in Egypt affected approximately 40,000 cattle and water buffaloes and killed more than 4,600 animals during February-March 2012. To investigate the etiology of the 2012 outbreak, specimens were collected from six governorates and analyzed using universal primers to amplify the 5' untranslated region (UTR) by reverse-transcription polymerase chain reaction. Only FMDV-SAT2 was detected, with an overall detection rate of 80.3 %. Complete VP1- and leader-proteinase-coding sequences, obtained from three isolates from three different governorates, were compared with previously reported sequences. Phylogenetic analysis of these sequences indicated that the circulating viruses were homogeneous and were closely related to topotype VII. Importantly, the newly emerged viruses were genetically closely related to strains isolated from Saudi Arabia, Sudan, Eritrea and Cameroon between 2000 and 2010, suggesting the dominant nature of this virus and underscoring the need for worldwide intensive surveillance to minimize its devastating consequences.

  10. Role of Jumonji C-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus.

    PubMed

    Lawrence, Paul; Rai, Devendra; Conderino, Joseph S; Uddowla, Sabena; Rieder, Elizabeth

    2016-05-01

    Foot-and-mouth disease virus (FMDV) utilizes four integrins (αvβ1, αvβ3, αvβ6, and αvβ8) as its primary cell receptor. During cell culture propagation, FMDV frequently adapts to use heparan sulfate (HS), and rarely utilizes an unidentified third receptor. Capsid mutations acquired by a soluble integrin resistant FMDV cause (i) adaptation to CHO-677 cells (ii) increased affinity to membrane-bound Jumonji C-domain containing protein 6 (JMJD6) (iii) induced JMJD6 re-localization from the cell surface and cytoplasm to the nucleus. Interestingly, pre-treatment of cells with N- and C-terminal JMJD6 antibodies or by simultaneous incubation of mutant virus with soluble JMJD6 (but not by treatment with HS or αvβ6) impaired virus infectivity in cultured cells. JMJD6 and mutant virus co-purified by reciprocal co-immunoprecipitation. Molecular docking predictions suggested JMJD6 C-terminus interacts with mutated VP1 capsid protein. We conclude when specific VP1 mutations are displayed, JMJD6 contributes to FMDV infectivity and may be a previously unidentified FMDV receptor.

  11. Characterization of a chimeric foot-and-mouth disease virus bearing a bovine rhinitis B virus leader proteinase.

    PubMed

    Uddowla, Sabena; Pacheco, Juan M; Larson, Christopher; Bishop, Elizabeth; Rodriguez, Luis L; Rai, Devendra K; Arzt, Jonathan; Rieder, Elizabeth

    2013-12-01

    Bovine rhinitis B virus (BRBV) shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). This study examined if the BRBV leader proteinase (L(pro) ) could functionally replace that of FMDV. A mutant A24LBRV3DYR FMDV engineered with the BRBV L(pro) and an antigenic marker in the 3D polymerase exhibited growth properties and eIF4G cleavage similar to parental A24WT virus. The A24LBRV3DYR type I interferon activity in infected bovine cells resembled that of A24LL virus that lacks L(pro), but this effect was less pronounced for A24LBRV3DYR infected porcine cells. In vivo studies showed that the A24LBRV3DYR virus was attenuated in cattle, and exhibited low virulence in pigs exposed by direct contact. The mutant virus induced protective immunity in cattle against challenge with parental A24WT. These results provide evidence that L(pro) of different Aphthoviruses are not fully functionally interchangeable and have roles that may depend on the nature of the infected host.

  12. Time Clustered Sampling Can Inflate the Inferred Substitution Rate in Foot-And-Mouth Disease Virus Analyses.

    PubMed

    Pedersen, Casper-Emil T; Frandsen, Peter; Wekesa, Sabenzia N; Heller, Rasmus; Sangula, Abraham K; Wadsworth, Jemma; Knowles, Nick J; Muwanika, Vincent B; Siegismund, Hans R

    2015-01-01

    With the emergence of analytical software for the inference of viral evolution, a number of studies have focused on estimating important parameters such as the substitution rate and the time to the most recent common ancestor (tMRCA) for rapidly evolving viruses. Coupled with an increasing abundance of sequence data sampled under widely different schemes, an effort to keep results consistent and comparable is needed. This study emphasizes commonly disregarded problems in the inference of evolutionary rates in viral sequence data when sampling is unevenly distributed on a temporal scale through a study of the foot-and-mouth (FMD) disease virus serotypes SAT 1 and SAT 2. Our study shows that clustered temporal sampling in phylogenetic analyses of FMD viruses will strongly bias the inferences of substitution rates and tMRCA because the inferred rates in such data sets reflect a rate closer to the mutation rate rather than the substitution rate. Estimating evolutionary parameters from viral sequences should be performed with due consideration of the differences in short-term and longer-term evolutionary processes occurring within sets of temporally sampled viruses, and studies should carefully consider how samples are combined.

  13. Genetic and antigenic analysis of foot-and-mouth disease virus serotype O responsible for outbreaks in India during 2013.

    PubMed

    Subramaniam, Saravanan; Mohapatra, Jajati K; Das, Biswajit; Sanyal, Aniket; Pattnaik, Bramhadev

    2015-03-01

    In recent times, majority of the foot-and-mouth disease (FMD) outbreaks in India are caused by serotype O Ind2001 lineage. The lineage has diverged into four sub-lineages (Ind2001a, b, c and d). We report here the genetic and antigenic analyses of nine Ind2001d isolates that caused outbreaks during April 2013-March 2014 in India. The length of the genomes of outbreak viruses varied between 8153 and 8181 nucleotides without any insertion or deletion in the coding region. Of the nine isolates analyzed antigenically against the currently used Indian vaccine strain INDR2/1975, eight showed good cross serological match (>0.3) indicating optimal antigenic coverage by the vaccine strain. An unprecedented deletion of 22 nucleotides between position 57 and 78 was observed in the 3' untranslated region of one of the isolates without compromising the virus viability, which imply that partial distortion in SL2 of 3'UTR may not have influence on virus viability at least under in-vitro conditions. Recently the Ind2001 lineage has been reported from several countries including Libya and spread of this lineage across a wide geographical area needs to be monitored carefully to avoid any future pandemic.

  14. An increased replication fidelity mutant of foot-and-mouth disease virus retains fitness in vitro and virulence in vivo.

    PubMed

    Zeng, Jianxiong; Wang, Haiwei; Xie, Xiaochun; Yang, Decheng; Zhou, Guohui; Yu, Li

    2013-10-01

    In a screen for RNA mutagen-resistant foot-and-mouth disease virus (FMDV) strains, we isolated an FMDV mutant with RNA-dependent RNA polymerase (RdRp) R84H substitution. This mutant, selected under the mutagenic pressure of 5-fluorouracil (5-FU), is resistant not only to 5-FU but also to other two RNA mutagens, 5-azacytidine and ribavirin, suggesting that the RdRp R84H mutant is a high fidelity variant. Subsequently, the increased fidelity of this mutant was verified through analysis of mutation frequency, which revealed a 1.4-fold enhancement in RdRp fidelity compared with the wild-type virus. Further studies indicated that the R84H mutant exhibited slightly increased fitness in vitro, and its virulence was not reduced in suckling mice. These results indicated that an increase in RdRp fidelity does not always correlate with reduced virus fitness and virus attenuation. Thus, this isolated R84H mutant provides a new platform to examine the evolutionary dynamics of fidelity-changing RNA viruses, such as mutagen resistance, fitness and virulence.

  15. Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

    PubMed

    Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

    2015-10-28

    Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

  16. The rescue and evaluation of FLAG and HIS epitope-tagged Asia 1 type foot-and-mouth disease viruses.

    PubMed

    Yang, Bo; Yang, Fan; Zhang, Yan; Liu, Huanan; Jin, Ye; Cao, Weijun; Zhu, Zixiang; Zheng, Haixue; Yin, Hong

    2016-02-02

    The VP1 G-H loop of the foot-and-mouth disease virus (FMDV) contains the primary antigenic site, as well as an Arg-Gly-Asp (RGD) binding motif for the αv-integrin family of cell surface receptors. We anticipated that introducing a foreign epitope tag sequence downstream of the RGD motif would be tolerated by the viral capsid and would not destroy the antigenic site of FMDV. In this study, we have designed, generated, and characterized two recombinant FMDVs with a FLAG tag or histidine (HIS) inserted in the VP1 G-H loop downstream of the RGD motif +9 position. The tagged viruses were genetically stable and exhibited similar growth properties with their parental virus. What is more, the recombinant viruses rFMDV-FLAG and rFMDV-HIS showed neutralization sensitivity to FMDV type Asia1-specific mAbs, as well as to polyclonal antibodies. Additionally, the r1 values of the recombinant viruses were similar to that of the parental virus, indicating that the insertion of FLAG or HIS tag sequences downstream of the RGD motif +9 position do not eradicate the antigenic site of FMDV and do not affect its antigenicity. These results indicated that the G-H loop of Asia1 FMDV is able to effectively display the foreign epitopes, making this a potential approach for novel FMDV vaccines development.

  17. Construction of a bovine enterovirus-based vector expressing a foot-and-mouth disease virus epitope.

    PubMed

    Chu, Jia-Qi; Lee, Yeo-Joo; Park, Jeong-Nam; Kim, Su-Mi; Lee, Kwang-Nyeong; Ko, Young-Joon; Lee, Hyang-Sim; Cho, In-Soo; Kim, Byounghan; Park, Jong-Hyeon

    2013-04-01

    A recombinant infectious bovine enterovirus (BEV) vector was constructed to express a foot-and-mouth disease virus (FMDV) capsid protein (VP1) epitope. Sequences encoding the VP1 epitope (amino acid residues 141-160) of FMDV (vaccine strain O1/Manisa/Turkey/69) were inserted into pBLUBEV at the VP1/2A junction. The growth characteristics of the parental virus and viruses derived from recombinant plasmids (pBLUBEV, pBLUBEV-Manisa-epi) were determined by plaque assay and one-step growth curve analysis. There were no significant differences in the growth kinetics and plaque morphologies between transfectant viruses and their parental virus. The expressed VP1 epitope was detected successfully by using indirect immunofluorescence assay with a polyclonal antibody against the FMDV VP1 epitope from Madin Darby bovine kidney (MDBK) cells infected with BEV-Manisa-epi transfectant virus. This study demonstrated a novel alternative live viral vector that may be utilized as a candidate vaccine vector for veterinary applications.

  18. Evolution of serotype A foot-and-mouth disease virus capsid under neutralizing antibody pressure in vitro.

    PubMed

    Pandey, Laxmi K; Mohapatra, Jajati K; Subramaniam, Saravanan; Sanyal, Aniket; Pande, Veena; Pattnaik, Bramhadev

    2014-03-06

    In this study, the Indian foot-and-mouth disease virus (FMDV) vaccine strain (A IND 40/2000) was passaged under homologous bovine convalescent serum (BCS) pressure to gain insight into the evolutionary dynamics of the antigenic sites. A considerable drop in the neutralization titres of the BCS for the isolated variants as compared to the parental population in either virus neutralization or plaque reduction neutralization test was observed. T143K substitution preceding the integrin binding 'RGD'-motif in the βG-βH loop of VP1 was found to be selected consistently and exclusively under immune pressure. By virtue of its location within an immunodominant site, sequence heterogeneity observed in the field viruses and residues already mapped in the neutralizing monoclonal antibody resistant mutants, position 143 in VP1 was predicted to be a critical residue of an important neutralizing epitope in serotype A FMDV. Using next-generation sequencing approach, the gradual overtaking of the originally dominating major variant by a minor one under a selective environment could be demonstrated. In the control passage regimen, VP2 E131K substitution was fixed within the heparan sulfate binding pocket probably as a result of adaptation to use alternative cellular receptors. But at the same time, these substitutions arising under selection forces other than immune pressure changed the antigenic behaviour of the virus inadvertently.

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

    PubMed

    Parthiban, Aravindh Babu R; Mahapatra, Mana; Gubbins, Simon; Parida, Satya

    2015-01-01

    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.

  20. Different functional sensitivity to mutation at intersubunit interfaces involved in consecutive stages of foot-and-mouth disease virus assembly.

    PubMed

    Rincón, Verónica; Rodríguez-Huete, Alicia; Mateu, Mauricio G

    2015-09-01

    Small spherical viruses are paradigms of supramolecular self-assembly. Identifying the specific structural determinants for virus assembly provides guidelines to develop new antiviral drugs or engineer modified viral particles for medical or technological applications. However, very few systematic studies have been carried out so far to identify those chemical groups at interfaces between virus capsid subunits that are important for viral assembly and function. Foot-and-mouth disease virus (FMDV) and other picornaviruses are assembled in a stepwise process in which different protein-protein interfaces are formed: 5 protomeric subunits oligomerize to form a pentameric intermediate, and 12 of these stable pentameric building blocks associate to form a labile capsid. In this study, a systematic mutational analysis revealed that very few amino acid side chains involved in substantial interactions between protomers within each pentamer are individually required for virus infectivity. This result contrasts sharply with the previous finding that most amino acid side chains involved in interactions between pentamers during the next assembly step are individually required for infectivity. The dramatic difference in sensitivity to single mutations between the two types of protein-protein interfaces in FMDV is discussed in terms of possible structural strategies for achieving self-assembly and genome uncoating in the face of diverse selective constraints.

  1. Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus.

    PubMed

    King, David J; Freimanis, Graham L; Orton, Richard J; Waters, Ryan A; Haydon, Daniel T; King, Donald P

    2016-10-01

    Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT-PCR method was developed to amplify a 7.6kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal.

  2. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle.

    PubMed Central

    Gebauer, F; de la Torre, J C; Gomes, I; Mateu, M G; Barahona, H; Tiraboschi, B; Bergmann, I; de Mello, P A; Domingo, E

    1988-01-01

    Rapid evolution of foot-and-mouth disease virus (FMDV) is documented during persistent infections of cattle. The carrier state was established experimentally with plaque-purified FMDV of serotype C3. Virus was recovered from the esophageal pharyngeal area of the animals up to 539 days postinfection. Analysis of capsid proteins by electrofocusing and by electrophoretic mobility of the genomic poly(C)-rich tract suggested heterogeneity in several isolates and sequential dominance of viral subpopulations. Nucleotide sequences of the VP1-coding region of the parental FMDV C3 clones and of seven isolates from the carrier cattle showed point mutations that represented rates of fixation of mutations of 0.9 X 10(-2) to 7.4 X 10(-2) substitutions per nucleotide per year; 59% of the base changes led to amino acid substitutions, some of which were located within residues 135 to 151, a region involved in neutralization of FMDV. In the esophageal pharyngeal fluid samples, FMDV C3-neutralizing activity was present. Antigenic variation was demonstrated with monoclonal antibodies raised against FMDV C3. Two isolates from carrier cattle differed from the parental virus by 10(2)- or 10(3)-fold decreased reactivity with neutralizing monoclonal antibodies. We suggest that persistent, inapparent infections of ruminants, in addition to being a reservoir of virus, may promote the rapid selection of antigenically variant FMDVs. Images PMID:2835508

  3. Response to foot-and-mouth disease vaccines in newborn calves. Influence of age, colostral antibodies and adjuvants.

    PubMed Central

    Sadir, A. M.; Schudel, A. A.; Laporte, O.; Braun, M.; Margni, R. A.

    1988-01-01

    Oil-emulsified (OE) and aqueous (Aq) vaccines were prepared with the same batch of inactivated A24 8345 foot and mouth disease virus (FMDV). Calves born to vaccinated dams did not respond to the Aq vaccine 30 or 90 days post partum. When the OE vaccine was used on a similar group of calves, no responses were elicited up to 21 days post partum. However, calves 30 or more days old responded like adult cattle to the OE vaccine. When the OE vaccine was used in colostral antibody-free calves 3-30 days old, all animals showed good antibody responses but, in calves vaccinated 3 or 7 days post partum, antibodies were detectable only after a considerable period of time. Our results show that both passively acquired colostral antibodies and age are important in the response of very young calves to FMDV oil vaccines. From a practical point of view, in endemic areas where adult cattle are periodically vaccinated, vaccination of calves between 30 and 60 days post partum with OE vaccines would lead to high levels of herd protection. PMID:2828089

  4. Influence of antibodies transferred by colostrum in the immune responses of calves to current foot-and-mouth disease vaccines.

    PubMed

    Bucafusco, Danilo; Di Giacomo, Sebastián; Pega, Juan; Juncos, María Sol; Schammas, Juan Manuel; Pérez-Filgueira, Mariano; Capozzo, Alejandra Victoria

    2014-11-12

    Immunity to currently used oil-adjuvanted inactivated vaccines against foot-and-mouth disease virus (FMDV) has been studied in detail in adult animals; however, the influence of maternally derived antibodies transferred through colostrum (Mat-Abs) in the immune responses of vaccinated calves is less clear. Here, we report the anti-FMDV humoral responses elicited in calves with or without Mat-Abs that received one or two doses of the current tetravalent oil-adjuvanted commercial vaccine used in Argentina. Anti-FMDV (O1/Campos strain) antibodies (Abs) were evaluated by Liquid Phase Blocking ELISA (LPB-ELISA), virus neutralization test (VNT), isotype ELISA (IgG1, IgG2 and IgM) and avidity ELISA, to allow for the first time a more detailed description of the humoral responses elicited. Our results show that primary IgM responses to FMDV vaccination only became evident as Mat-Abs titers decreased. Likewise, prime and boost vaccination schedules, applied 35 days apart to groups of calves with high or low levels of Mat-Abs, showed that the levels of preexisting neutralizing Mat-Abs prevented the loss of total Abs measured by LPB-ELISA but negatively interfered with the induction of virus neutralizing responses. Altogether, these findings indicate that comprehensive serological characterization of immune responses generated after vaccination in calves may reveal important information on the actual effectiveness of vaccination strategies for young animals, particularly in endemic settings.

  5. Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease.

    PubMed

    Long, Lili; Xu, Lin; Xiao, Zhenghui; Hu, Shixiong; Luo, Ruping; Wang, Hua; Lu, Xiulan; Xu, Zhiyue; Yao, Xu; Zhou, Luo; Long, Hongyu; Gong, Jiaoe; Song, Yanmin; Zhao, Li; Luo, Kaiwei; Zhang, Mengqi; Feng, Li; Yang, Liming; Sheng, Xiaoqi; Fan, Xuegong; Xiao, Bo

    2016-03-22

    From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible.

  6. Genetic variation of foot-and-mouth disease virus isolates recovered from persistently infected water buffalo (Bubalus bubalis).

    PubMed

    Barros, José Júnior F; Malirat, Viviana; Rebello, Moacyr A; Costa, Eliane V; Bergmann, Ingrid E

    2007-02-25

    Genetic variation of foot-and-mouth disease virus (FMDV) isolates, serotype O, recovered serially over a 1-year period from persistently infected buffalos was assessed. The persistent state was established experimentally with plaque-purified FMDV, strain O(1)Campos, in five buffalos (Bubalus bubalis). Viral isolates collected from esophageal-pharyngeal (EP) fluids for up to 71 weeks after infection were analyzed at different times by nucleotide sequencing and T(1) RNase oligonucleotide fingerprinting to assess variability in the VP1-coding region and in the complete genome, respectively. Genetic variation increased, although irregularly, with time after infection. The highest values observed for the VP1-coding region and for the whole genome were 2.5% and 1.8%, respectively. High rates of fixation of mutations were observed using both methodologies, reaching values of 0.65 substitutions per nucleotide per year (s/nt/y) and 0.44s/nt/y for nucleotide sequencing and oligonucleotide fingerprinting, respectively, when selected samples recovered at close time periods were analyzed. The data herein indicate that complex mixtures of genotypes may arise during FMDV type O persistent infection in water buffalos, which can act as viral reservoirs and also represent a potential source of viral variants. These results fit within the quasi-species dynamics described for FMDV, in which viral populations are constituted by related, non-identical genomes that evolve independently from each other, and may predominate at a given time.

  7. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    PubMed Central

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  8. Managing compensation for economic losses in areas surrounding foot and mouth disease outbreaks: the response of France.

    PubMed

    Cassagne, M H

    2002-12-01

    This article describes the French scheme for providing compensation to stock farmers located in the prevention and surveillance zones in the vicinity of foot and mouth disease (FMD) outbreak sites and for economic losses suffered as a result of restrictions on animal and animal product movement. As early as 1991, the Groupements de Defense Sanitaire (GDS: Animal Health Groups--associations of stock farmers dealing with health issues, recognised under French law) set up a Compensation Fund that was put to use during the FMD episode of 2001. The Fund paid out FRF6,488,000 (Euro989,000) to stockbreeders in the five affected departments (French local administrative divisions). Based on the principle of a national mutual benefit society, the Compensation Fund is the first instance of a system of private compensation, outside of conventional insurance schemes, based on a convention between French stock farmers. With decentralised management and speed of implementation, the Compensation Fund has proved its worth. The Fund now needs to be adjusted on the basis of changes introduced in FMD control policy in France and possibly the European Union.

  9. Genetic basis of antigenic variation in foot-and-mouth disease serotype A viruses from the Middle East.

    PubMed

    Upadhyaya, Sasmita; Ayelet, Gelagay; Paul, Guntram; King, Donald P; Paton, David J; Mahapatra, Mana

    2014-01-23

    Foot-and-mouth disease viruses (FMDV) from serotype A exhibit high antigenic diversity. Within the Middle East, a strain called A-Iran-05 emerged in 2003, and subsequently replaced the A-Iran-96 and A-Iran-99 strains that were previously circulating in the region. Viruses from this strain did not serologically match with the established A/Iran/96 vaccine, although most early samples matched with the older A22/Iraq vaccine. However, many viruses from this strain collected after 2006 had poor serological match with the A22/Iraq vaccine necessitating the development of a new vaccine strain (A/TUR/2006). More recently, viruses from the region now exhibit lower cross-reactivity with the A/TUR/2006 antisera highlighting the inadequacy of the serotype A vaccines used in the region. In order to understand the genetic basis of these antigenic phenotypes, we have determined the full capsid sequence for 57 Middle Eastern viruses isolated between 1996 and 2011 and analysed these data in context of antigenic relationship (r1) values that were generated using antisera to A22/Iraq and A/TUR/2006. Comparisons of capsid sequences identified substitutions in neutralising antigenic sites (1, 2 and 4), which either individually or together underpin these observed antigenic phenotypes.

  10. Correlation between efficacy and structure of recombinant epitope vaccines against bovine type O foot and mouth disease virus.

    PubMed

    Fang, Mingli; Li, Jianli; Wang, Hua; Yang, Ming; Zhang, Yongsheng; Zhou, Lei; Wei, Hongfei; Yang, Guang; Yu, Yue; Wei, Xuefeng; Yu, Yongli; Wang, Liying; Wan, Min

    2012-05-01

    To develop recombinant epitope vaccines against foot-and-mouth disease virus (FMDV), genes coding for six recombinant proteins (rP1–rP6) consisting of different combinations of B cell and T cell epitope from VP1 capsid protein (VP1) of type O FMDV were constructed and the 3D structure of these proteins analyzed. This revealed a surface-exposed RGD sequence of B cell epitopes in all six recombinant proteins as that in VP1 of FMDV and rP1, rP2 and rP4 globally mimicked the backbone conformation of the VP1. rP1, rP2 and rP4 stimulated guinea pigs to produce higher level of neutralizing antibodies capable of protecting suckling mice against FMDV challenge. rP1 stimulated cattle to produce FMDV-neutralizing antibody. The data suggest that an efficient recombinant epitope vaccine against FMDV should share local similarities with the natural VP1 of FMDV.

  11. Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot-and-mouth disease virus (FMDV) in mice.

    PubMed

    Borrego, Belén; Rodríguez-Pulido, Miguel; Mateos, Francisco; de la Losa, Nuria; Sobrino, Francisco; Sáiz, Margarita

    2013-09-13

    We have recently described the antiviral effect in mice of in vitro-transcribed RNAs mimicking structural domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome RNA. These small, synthetic and non-infectious RNA molecules (ncRNAs) are potent type-I interferon (IFN) inducers in vivo. In this work, the immunomodulatory effect of the ncRNA corresponding to the internal ribosome entry site (IRES) on immunization with two different FMD vaccine formulations, both based on inactivated virus, including or not a commercial adjuvant, was analyzed in the mice model. The effect of the time interval between RNA inoculation and immunization was also studied. RNA delivery consistently increased the titers of specific anti-FMDV antibodies, including neutralizing antibodies, elicited after vaccination. Moreover, at day 2 after immunization, significant differences in mean antibody titers could be detected between the groups of mice receiving either vaccine co-administered with the RNA and the control group, unlike those immunized with the vaccine alone. When vaccinated mice were challenged with FMDV, the mean values of viral load were lower in the groups receiving the RNA together with the vaccine. Our results show the enhancing effect of the IRES RNA on the immune response elicited after vaccination and suggest the potential of this molecule as an adjuvant for new FMD vaccine design.

  12. Promising multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O in swine.

    PubMed

    Shao, Jun-Jun; Wong, Chung Kai; Lin, Tong; Lee, Shuk Kwan; Cong, Guo-Zheng; Sin, Fion Wai Yee; Du, Jun-Zheng; Gao, Shan-Dian; Liu, Xiang-Tao; Cai, Xue-Peng; Xie, Yong; Chang, Hui-Yun; Liu, Ji-Xing

    2011-01-01

    In order to develop a completely safe immunogen to replace the traditional inactivated vaccine, a tandem-repeat multiple-epitope recombinant vaccine against foot-and-mouth disease (FMD) virus (FMDV) type O was developed. It contained three copies each of residues 141 to 160 and 200 to 213 of VP1 of the O/China/99 strain of FMDV coupled with a swine immunoglobulin G heavy-chain constant region (scIgG). The data showed that the multiple-epitope recombinant vaccine elicited high titers of anti-FMDV specific antibodies in swine at 30 days postvaccination (dpv) and conferred complete protection against a challenge with 10³ 50% swine infective doses of the O/China/99 strain. The anti-FMDV specific antibody titers were not significantly different between the multiple-epitope recombinant vaccine and the traditional vaccine (t test, P > 0.05). The number of 50% pig protective doses was 6.47, which is higher than the number recommended by the World Organization for Animal Health. The multiple-epitope recombinant vaccine resulted in a duration of immunity of at least 6 months. We speculate that the multiple-epitope recombinant vaccine is a promising vaccine that may replace the traditional inactivated vaccine for the prevention and control of FMD in swine in the future.

  13. Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge.

    PubMed

    Maree, Francois F; Nsamba, Peninah; Mutowembwa, Paidamwoyo; Rotherham, Lia S; Esterhuysen, Jan; Scott, Katherine

    2015-06-09

    The genetic diversity of the three Southern African Territories (SAT) types of foot-and-mouth disease virus (FMDV) reflects high antigenic variation, and indications are that vaccines targeting each SAT-specific topotype may be needed. This has serious implications for control of FMD using vaccines as well as the choice of strains to include in regional antigen banks. Here, we investigated an intra-serotype chimeric virus, vSAT2(ZIM14)-SAT2, which was engineered by replacing the surface-exposed capsid-coding region (1B-1D/2A) of a SAT2 genome-length clone, pSAT2, with that of the field isolate, SAT2/ZIM/14/90. The chimeric FMDV produced by this technique was viable, grew to high titres and stably maintained the 1B-1D/2A sequence upon passage. Chemically inactivated, oil adjuvanted vaccines of both the chimeric and parental immunogens were used to vaccinate cattle. The serological response to vaccination showed the production of strong neutralizing antibody titres that correlated with protection against homologous FMDV challenge. We also predicted a good likelihood that cattle vaccinated with an intra-serotype chimeric vaccine would be protected against challenge with viruses that caused recent outbreaks in southern Africa. These results provide support that chimeric vaccines containing the external capsid of field isolates induce protective immune responses in FMD host species similar to the parental vaccine.

  14. Proper quality control of formulated foot-and-mouth disease vaccines in countries with prophylactic vaccination is necessary.

    PubMed

    Jamal, S M; Shah, S I; Ali, Q; Mehmood, A; Afzal, M; Afzal, M; Dekker, A

    2014-12-01

    Vaccination is considered as an important tool to control foot-and-mouth disease (FMD). A good quality vaccine containing relevant serotypes and matching strains is a pre-requisite for vaccination to be effective. The present study investigated the quality of different brands of FMD vaccine available in Pakistan, including three locally produced and two imported products. All the vaccines were found free of bacterial or fungal contamination. No adverse effects were noted in suckling mice and buffalo calves inoculated with the vaccines, showing that the vaccines were sterile and safe. The humoral immune response to the FMD vaccines was determined in buffalo calves for 234 days post-vaccination. Very low humoral immune responses against FMD serotypes O, A and Asia 1 viruses were detected to the locally produced vaccines. The imported vaccines, however, elicited a higher antibody response which persisted for a long period in one of the 2 vaccines. The present study highlights the need of assessing an independent vaccine quality control of finished FMD vaccine products.

  15. Interferon-alpha production by swine dendritic cells is inhibited during acute infection with foot-and-mouth disease virus.

    PubMed

    Nfon, Charles K; Ferman, Geoffrey S; Toka, Felix N; Gregg, Douglas A; Golde, William T

    2008-03-01

    Viruses have evolved multiple mechanisms to evade the innate immune response, particularly the actions of interferons (IFNs). We have previously reported that exposure of dendritic cells (DCs) to foot-and-mouth disease virus (FMDV) in vitro yields no infection and induces a strong type I IFN (IFN-alpha and IFN-beta) response, indicating that DCs may play a critical role in the innate response to the virus. In vivo, FMDV induces lymphopenia and reduced T-cell proliferative responses to mitogen, viral effects that may contribute to evasion of early immune responses. In this study we analyzed the in vivo effects of FMDV infection on the IFN-alpha response of two populations of dendritic cells. During the acute phase of infection of swine, production of IFN-alpha from monocyte-derived DCs (MoDCs) and skin-derived DCs (skin DCs) is inhibited. This effect occurs concurrently with rising viral titers in the blood; however, these cells are not productively infected. Interestingly, there are no changes in the capability of these DCs to take up particles and process antigens, indicating that antigen-presenting cell function is normal. These data indicate that inhibition of the IFN-alpha response of dendritic cell populations from blood and skin by FMDV enhances viral pathogenesis in infected animals.

  16. Development of synthetic peptide ELISA based on nonstructural protein 2C of foot and mouth disease virus.

    PubMed

    Oem, Jae Ku; Kye, Soo Jeong; Lee, Kwang Nyeong; Park, Jong Hyeon; Kim, Yong Joo; Song, Hee Jong; Yeh, Max

    2005-12-01

    It was reported that the sera of convalescent animals contain antibodies to foot and mouth disease (FMD) virus (FMDV) 2C, highly conserved nonstructural protein (NSP), whereas the sera of vaccinated animals do not. But ELISA methods using this protein were not reported and developed until recently. In this study, NSP 2C peptides were synthesized within the amino acid sequence of the conserved 2C nonstructural region of FMDV according to the sequences from Genbank database and used for identifying antigenic determinants. One of the synthesized thirteen peptides gave strong positive reactivity with most of the sera from 13 FMD infected farms, but not with sera from vaccinated and non-infected animals. Moreover, with the sera collected through serial bleedings from four cattle and five goats infected with FMDV O/SKR/2000 experimentally, positive results were obtained in two species after 10 days post infection (DPI). Therefore, we tried to develop and evaluate this ELISA based on 2C peptides. In comparison with the commercial NSP ELISA, the 2C peptide based ELISA method showed good specificity and sensitivity. These results demonstrate that the synthetic 2C peptide ELISA can be a complementary marker to differentiate FMDV-infected from vaccinated on a herd basis.

  17. The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China

    PubMed Central

    Zeng, Hanri; Lu, Jing; Zheng, Huanying; Yi, Lina; Guo, Xue; Liu, Leng; Rutherford, Shannon; Sun, Limei; Tan, Xiaohua; Li, Hui; Ke, Changwen; Lin, Jinyan

    2015-01-01

    Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trendsofCVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China. PMID:25993899

  18. Aspects of heat inactivation of foot-and-mouth disease virus in milk from intramammarily infected susceptible cows.

    PubMed Central

    de Leeuw, P. W.; Tiessink, J. W.; van Bekkum, J. G.

    1980-01-01

    In skim milk obtained from susceptible cows after intramammary and intravenous inoculation (primary infected milk), foot-and-mouth disease (FMD) virus type O1 was slower inactivated by heat treatment than virus that had been added to pre-exposure skim milk. Residual virus infectivity in heated primary infected milk was more efficiently detected in bovine thyroid cell cultures than in secondary pig kidney (PK2) cell cultures. Untreated primary infected milk was found to inhibit both FMD-virus and vesicular stomatitis virus plaque formation in PK2 cells, suggesting the presence of interferon. The results of further tests confirmed that the interfering activity in unheated primary infected milk was indeed caused by an interferon. Interferon excretion in primary infected milk was investigated using a series of milk samples from three cows. Maximum interferon titres were found after 24 h, coinciding with or shortly after the first virus excretion peak. The results are discussed with particular reference to the use of primary infected milk in studies of the thermal inactivation of FMD-virus. PMID:6244342

  19. Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

    PubMed

    Li, Renjun; Ma, Yanfen; Zhai, Lijuan; Lu, Yisong; Chi, Xiaoqing; Wu, Jiusheng; Hu, Songhua

    2016-08-01

    Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals.

  20. Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease

    PubMed Central

    Long, Lili; Xu, Lin; Xiao, Zhenghui; Hu, Shixiong; Luo, Ruping; Wang, Hua; Lu, Xiulan; Xu, Zhiyue; Yao, Xu; Zhou, Luo; Long, Hongyu; Gong, Jiaoe; Song, Yanmin; Zhao, Li; Luo, Kaiwei; Zhang, Mengqi; Feng, Li; Yang, Liming; Sheng, Xiaoqi; Fan, Xuegong; Xiao, Bo

    2016-01-01

    From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible. PMID:27001010

  1. Experimental infection of giraffe (Giraffa camelopardalis) with SAT-1 and SAT-2 foot-and-mouth disease virus.

    PubMed

    Vosloo, W; Swanepoel, S P; Bauman, M; Botha, B; Esterhuysen, J J; Boshoff, C I; Keet, D F; Dekker, A

    2011-04-01

    The potential role of giraffe (Giraffa camelopardalis) in the epidemiology and spread of foot-and-mouth disease (FMD) SAT types was investigated by experimental infection and detection of virus in excretions using virus isolation on primary pig kidney cell cultures. In two experiments separated by a period of 24 months, groups of four animals were needle infected with a SAT-1 or SAT-2 virus, respectively and two in-contact controls were kept with each group. Viraemia was detected 3-9 days post-infection and virus isolated from mouth washes and faeces only occasionally up to day 13. The SAT-1 virus was transmitted to only one in-contact control animal, probably via saliva that contained virus from vesicles in the mouth of a needle-infected animal. None of the animals infected with the SAT-2 virus had any vesicles in the mouth, and there was no evidence of transmission to the in-contact controls. No virus was detected in probang samples for the duration of the experiments (60 days post-infection), indicating that persistent infection probably did not establish with either of these isolates. Giraffe most likely do not play an important role in FMD dissemination. Transmission of infection would possibly occur only during close contact with other animals when mouth vesicles are evident.

  2. Foot-and-Mouth Disease Virus Replicates Only Transiently in Well-Differentiated Porcine Nasal Epithelial Cells▿

    PubMed Central

    Dash, Pradyot; Barnett, Paul V.; Denyer, Michael S.; Jackson, Terry; Stirling, Catrina M. A.; Hawes, Philippa C.; Simpson, Jennifer L.; Monaghan, Paul; Takamatsu, Haru-H.

    2010-01-01

    Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin αvβ6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-β) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-β mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-α mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response. PMID:20592089

  3. A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease

    PubMed Central

    Chen, Xiaoqing; Wang, Chunyang; Xu, Lanfang; Chen, Xiaoshuang; Wang, Wei; Yang, Guang; Tan, Ren Xiang; Li, Erguang; Jin, Yu

    2013-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC50 (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC50 value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD. PMID:23554831

  4. A colorimetric bioassay for high-throughput and cost-effectively assessing anti-foot-and-mouth disease virus activity.

    PubMed

    Ramanathan, Palaniappan; Zhu, James J; Bishop, Elizabeth A; Puckette, Michael C; Hartwig, Ethan; Grubman, Marvin J; Rodriguez, Luis L

    2015-03-15

    Foot-and-mouth disease virus (FMDV) is one of the most contagious animal viruses. This virus is very sensitive to inhibition by type I interferons. Currently, a bioassay based on plaque reduction is used to measure anti-FMDV activity of porcine IFNs. The plaque reduction assay is tedious and difficult to utilize for high-throughput analysis. Using available FMDV susceptible bovine and porcine cells, we developed and tested a colorimetric assay based on cytopathic effect reduction for its ability to quantify FMDV-specific antiviral activity of bovine and porcine type I interferons. Our results show that this new method has significant advantages over other assays in terms of labor intensity, cost, high-throughput capability and/or anti-FMDV specific activity because of simpler procedures and direct measurement of antiviral activity. Several assay conditions were tested to optimize the procedures. The test results show that the assay can be standardized with fixed conditions and a standard or a reference for measuring antiviral activity as units. This is an excellent assay in terms of sensitivity and accuracy based on a statistical evaluation. The results obtained with this assay were highly correlated with a conventional virus titration method.

  5. Molecular epidemiology of the enteroviruses associated with hand, foot and mouth disease/herpangina in Dongguan, China, 2015.

    PubMed

    Peng, Qi; Xie, Mingyu; Zhang, Yinghong; Liu, Qian; Li, Wenrui; Li, Siping; Ma, Qiang; Lu, Xiaomei; Zhong, Baimao

    2016-12-01

    Enteroviruses (EVs) are the etiological agents involved in most cases of hand, foot and mouth disease (HFMD) and herpangina (HA). Information on the epidemiology profiles of EVs in China is very limited, as the present surveillance system of China focuses on CAV16 and EV71, and no published data are available in Dongguan. The aim of this study is to determine the prevalence of EVs among patients with HFMD and HA in Dongguan, China, during 2015. A total of 271 clinical stool specimens that were clinically determined to be positive for enteroviruses were genotyped by semi-nested polymerase chain reaction (PCR) for the VP1 genes of EVs. The results showed that a total of 14 enterovirus genotypes were identified among HFMD and HA patients in this study. CVA6 was the most common genotype for HFMD, and CVA2 accounted for the majority of HA cases in this study. Sequence and phylogenetic analysis showed that all of the CVA6 and CVA2 strains identified in our study displayed a close genetic relationship to strains identified in other cities in China. This study also demonstrates that there are associations between particular causative enterovirus genotypes and some clinical symptoms, which may provide useful information for improving case prevention, diagnosis and treatment of HFMD and HA.

  6. Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008

    PubMed Central

    Yang, Qian; Zhang, Yong; Yan, Dongmei; Zhu, Shuangli; Wang, Dongyan; Ji, Tianjiao; Li, Xiaolei; Song, Yang; Gu, Xinrui; Xu, Wenbo

    2016-01-01

    Coxsackievirus A2 (CV-A2) has been frequently detected and commonly associated with hand, foot, and mouth disease (HFMD) in China since 2008. However, limited sequences of CV-A2 are currently available. As a result, we have been focusing on the genetic characteristics of CV-A2 in the mainland of China during 2008–2015 based on national HFMD surveillance. In this study, 20 CV-A2 strains were isolated and phylogenetic analyses of the VP1 sequences were performed. Full-length genome sequences of two representative CV-A2 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CV-A2 strains could be divided into four genotypes (Genotypes A–D). The CV-A2 prototype strain (Fleetwood) was the sole member of genotype A. From 2008 to 2015, the CV-A2 strains isolated in China dispersed into two different genotypes (B and D). And the genotype D became the dominant circulating strains in China. Strains isolated in Russia and India from 2005 to 2011 converged into genotype C. Intertypic recombination occurred between the Chinese CV-A2 strains and other enterovirus-A donor sequences. This result reconfirmed that recombination is a common phenomenon among enteroviruses. This study helps expand the numbers of whole virus genome sequence and entire VP1 sequence of CV-A2 in the GenBank database for further researcher. PMID:28030650

  7. Assessment using ELISA of the herd immunity levels induced in cattle by foot-and-mouth disease oil vaccines.

    PubMed

    Smitsaart, E N; Zanelli, M; Rivera, I; Fondevila, N; Compaired, D; Maradei, E; Bianchi, T; O'Donnell, V; Schudel, A A

    1998-01-01

    The development of a liquid-phase blocking sandwich ELISA (LPBE) to measure antibodies (Ab) produced in cattle with the O, A and C foot-and-mouth disease virus (FMDV) types of commercial vaccines used in Argentina is described. The test was specific: 99% of naïve cattle sera (n = 130) gave titres below log10 = 1.2, and none had a titre above log10 = 1.5. Comparative studies with serum neutralization test (SNT) using sera from cattle which received one or more vaccine doses is reported. The overall rank correlation coefficient (Spearman's rho, rs) between SNT and LPBE were highly significant (rs > 0.67, P < 0.0001) for all vaccine strains. LBPE Ab titres on sera collected 90 days post vaccination were compared with results of cattle protection tests by applying a logistic regression. The minimum Ab titres at which 85% and 75% of the cattle were protected for each FMDV type were determined in order to interpret field Ab data in terms of protection. Application of this method allows large scale serological examinations to monitor antibody levels in vaccinated animals as an indirect indicator of the FMD control program status in the field. Its use in the evaluation of commercial batches of FMD vaccine is discussed.

  8. Genetic basis of antigenic variation in foot-and-mouth disease serotype A viruses from the Middle East☆

    PubMed Central

    Upadhyaya, Sasmita; Ayelet, Gelagay; Paul, Guntram; King, Donald P.; Paton, David J.; Mahapatra, Mana

    2014-01-01

    Foot-and-mouth disease viruses (FMDV) from serotype A exhibit high antigenic diversity. Within the Middle East, a strain called A-Iran-05 emerged in 2003, and subsequently replaced the A-Iran-96 and A-Iran-99 strains that were previously circulating in the region. Viruses from this strain did not serologically match with the established A/Iran/96 vaccine, although most early samples matched with the older A22/Iraq vaccine. However, many viruses from this strain collected after 2006 had poor serological match with the A22/Iraq vaccine necessitating the development of a new vaccine strain (A/TUR/2006). More recently, viruses from the region now exhibit lower cross-reactivity with the A/TUR/2006 antisera highlighting the inadequacy of the serotype A vaccines used in the region. In order to understand the genetic basis of these antigenic phenotypes, we have determined the full capsid sequence for 57 Middle Eastern viruses isolated between 1996 and 2011 and analysed these data in context of antigenic relationship (r1) values that were generated using antisera to A22/Iraq and A/TUR/2006. Comparisons of capsid sequences identified substitutions in neutralising antigenic sites (1, 2 and 4), which either individually or together underpin these observed antigenic phenotypes. PMID:24035435

  9. Importation of beef from countries infected with foot and mouth disease: a review of risk mitigation measures.

    PubMed

    Sutmoller, P

    2001-12-01

    Risk mitigation measures to reduce the risks associated with importing beef from countries affected by foot and mouth disease (FMD) consist of controls at the farm of origin, inspection of slaughterhouses and maturation and deboning of carcasses. This assessment evaluates the effect of these measures on the mitigation of the risks presented by meat from cattle with FMD, for each of the different stages of the disease. The four disease stages considered are the incubation period, the period of clinical signs, convalescence and the carrier stage. Efficient animal health systems, disease surveillance, and ante-mortem and post-mortem inspection of all cattle effectively reduce the risk of FMD transmission from cattle slaughtered during the period of clinical signs or convalescence. These measures fail if the cattle are slaughtered during the incubation period, because of the absence of clinical signs. Cattle in this stage of the infection are likely to be viraemic, with FMD virus present in the skeletal muscles. Maturation of the carcasses of viraemic cattle reduces the risk of virus presence in the beef. In addition, deboning and removal of the principal lymph nodes and large blood vessels eliminate a source of FMD contamination of the beef. However, the slaughter of viraemic cattle creates an additional hazard of gross environmental viral contamination of the slaughterhouse facilities. Therefore, the maturation process may create a false sense of security, and the emphasis should instead be placed on disease surveillance within the infected zone and on the farms of origin, to prevent the slaughter of herds that are incubating FMD. Cattle slaughtered during the carrier stage do not pose a risk for the international beef trade.

  10. The effect of vaccination on undetected persistence of foot-and-mouth disease virus in cattle herds and sheep flocks.

    PubMed

    Schley, D; Paton, D J; Cox, S J; Parida, S; Gubbins, S

    2009-10-01

    The importance of carrier animals (those in whom virus persists after recovery from disease or acute infection) and their potential role in the spread of disease remain open questions within foot-and-mouth disease epidemiology. Using simple probabilistic models we attempt to quantify the effect of emergency vaccination--and especially the time of application--on the likely number of such animals, using data from challenge experiments on both cattle and sheep to determine the probability of persistence in diseased and subclinically infected animals. We show that the number of persistently infected animals in a group is predominantly determined by the number of animals initially infected on premises--the high variability of which ultimately limits the accuracy of any predictions of carrier numbers based upon transmission models. Furthermore, results suggest that, within a cattle herd, carrier numbers may be increased if challenge occurs shortly after vaccination. We show that the quality of inspection is the principal factor influencing whether or not carrier herds occur and that, by reducing clinical signs, the application of vaccination in regularly checked stock also results in an increase in undetected persistently infected animals. Where clinical detection would be poor regardless of the use of vaccination (i.e. particularly in sheep), vaccination will result in a reduction in the probability of a group containing undetected carriers: otherwise there is a benefit only if vaccination is applied sufficiently far in advance of any challenge. The implications of the results for serosurveillance are discussed, including the requisite test sensitivity and practices for successful implementation.

  11. An evaluation of Foot-and-Mouth Disease outbreak reporting in mainland South-East Asia from 2000 to 2010.

    PubMed

    Madin, Ben

    2011-12-01

    Foot and Mouth Disease (FMD) is considered to be endemic throughout mainland South-East Asia (SEA). The South-East Asia and China FMD (SEACFMD) campaign is a regional control programme which has been ongoing since 1997. The programme encourages countries to submit reports of outbreaks regularly. This paper evolved from a collaboration with SEACFMD to evaluate 10 years worth of reporting. All publicly available outbreak reports (5237) were extracted from the ASEAN Region Animal Health Information System (ARAHIS) for the period from 2000 to mid 2010. These reports included date, outbreak location (at the province and district level) and serotype (if known) plus information on the outbreak size and affected species. Not all records had complete information on the population at-risk or the number of animals affected. This data was transferred into a spatially enabled database (along with data from other sources) and analysed using R and SaTScan. Outbreak serotype was unknown in 2264 (43%) of reports and some countries had very few laboratory confirmed cases (range <1-86%). Outbreak reports were standardised by number of villages in each province. Outbreak intensity varied however there did not appear to be a consistent pattern, nor was there any seasonal trend in outbreaks. Spatial and spatio-temporal cluster detection methods were applied. These identified significant clusters of disease reports. FMD is endemic across the region but is not uniformly present. ARAHIS reports can be regarded as indicators of disease reporting: there may be reports in which laboratory confirmation has not occurred, and in some cases clinical signs are inconsistent with FMD. This raises questions about the specificity of the data. Advances in decentralised testing techniques offer hope for improved verification of FMD as the cause of disease outbreaks. Advances in molecular typing may provide a substantial leap forward in understanding the circulation of FMD in South East Asia.

  12. Outbreak of foot and mouth disease and peste des petits ruminants in sheep flock imported for immediate slaughter in Riyadh

    PubMed Central

    Mahmoud, M. A.; Galbat, S. A.

    2017-01-01

    Aim: To detect and identify the causative agent or agents of the following clinical symptoms which were fever, lack of appetite, salivation, vesiculation, erosions of the buccal mucosa, nose, and feet. The signs vary from mild to severe. The mortality rate of the disease is high. The morbidity rate reaches up to 100%. Sheep also show bloody diarrhea and rapid respiration. Sheep flock resident in El-Kharje Governorate. Materials and Methods: A total of 50 serum samples and 50 buffy coat samples were collected from Marino sheep flock suffered from high mortalities, fever, lameness, diarrhea, stomatitis, and respiratory distress. PrioCHECK® foot and mouth disease virus (FMDV) nonstructural (NS) (marketable enzyme-linked immunosorbent assay [ELISA] kit) was used for revealing of the NS antibodies and liquid phase blocking enzyme immunoassay (LPBE) for identifying the FMD serotype and examined by competitive ELISA (cELISA) for detection of peste des petits ruminants (PPR) antibodies. The buffy coat samples were examined by immunocapture ELISA (Ic ELISA) for detection of PPR antigen. Results: Using PrioCHECK® FMDV NS: Commercial ELISA kit: 38/50 (76%) of the serum samples were positive for the presence of FMD NS viral proteins. In addition, using LPBE the positive samples were identified as FMD serotype O. Examination of the serum sample by cELISA for detection of PPR antibodies gave positive results in 32/50 (64%). While the Ic ELISA identified 32 (64%) positive reactors for PPR antigen. Conclusion: This study reflected high susceptibility of the imported sheep flocks to the infection with FMD and PPR viruses, which are endemic in the Kingdom of Saudi Arabia (KSA). Hence, the imported flocks that prepared for slaughter must be vaccinated with the used vaccine in KSA in the quarantine for the control of FMD especially when importation occurs from counters that are free from these diseases. PMID:28344409

  13. Hand, Foot, and Mouth Disease in Hunan Province, China, 2009-2014: Epidemiology and Death Risk Factors

    PubMed Central

    Luo, Kai-Wei; Gao, Li-Dong; Hu, Shi-Xiong; Zhang, Hong; Deng, Zhi-Hong; Huang, Wei; Sun, Qian-Lai; Zhang, Fan; Zhang, Si-Yu; Chen, Yu

    2016-01-01

    Hand, foot, and mouth disease (HFMD) is an arising public health problem in Asia, including China. Epidemiological data is necessary to enable judicious public health responses and interventions. We analyzed the epidemiological and laboratory data of 759,301 HFMD cases reported to the Hunan Provincial Center for Disease Control and Prevention from 1 January 2009 to 31 December 2014. Univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatality in HFMD. The incidence of HFMD was highest among children aged 1–3 years, compared with other age groups. Of the total HFMD cases, 7,222 (0.95%) were considered severe and 338 (0.04%) were fatal. Enterovirus-A71 was the major cause of severe and fatal cases (65.75% and 88.78%, respectively). For severe cases, the median time from symptom onset to diagnosis was 0.5 days (interquartile range [IQR] 0–1.5 days); the median time from diagnosis to severe illness was 2 days (IQR 1–3 days). For fatal cases, the median time from symptom onset to diagnosis was 0.5 days (IQR 0–1.5 days); the median time from diagnosis to death was 1.5 days (IQR 0.5–2.5 days). In multivariable analysis, the abuse of antibiotic, glucocorticoid and pyrazolone in village clinics at basic medical institutions were identified as independent risk factors for HFMD fatal cases. In conclusion, our results suggest that the future direction to control and respond to HFMD is intensive surveillance of enterovirus-A71 and improving the ability to diagnose disease and treat patients, especially in basic medical institutions. PMID:27898715

  14. Pathogenic characteristics of the Korean 2002 isolate of foot-and-mouth disease virus serotype O in pigs and cattle.

    PubMed

    Oem, J K; Yeh, M T; McKenna, T S; Hayes, J R; Rieder, E; Giuffre, A C; Robida, J M; Lee, K N; Cho, I S; Fang, X; Joo, Y S; Park, J H

    2008-05-01

    Experimental infection of susceptible cattle and pigs showed that the O/SKR/AS/2002 pig strain of foot-and-mouth disease virus (FMDV) causes an infection that is highly virulent and contagious in pigs but very limited in cattle. Pigs directly inoculated with, or exposed to swine infected with, strain O/SKR/AS/2002 showed typical clinical signs, including gross vesicular lesions in mouth and pedal sites. In addition, FMDV was isolated from, and FMDV genomic RNA was detected in, blood, serum, nasal swabs and oesophageal-pharyngeal (OP) fluid early in the course of infection. Antibodies against the non-structural protein (NSP) 3ABC were detected in both directly inoculated and contact pigs, indicating active virus replication. In contrast, the disease in cattle was atypical. After inoculation, lesions were confined to the infection site. A transient viraemia occurred 1 and 2 days after inoculation, and this was followed by the production of antibodies to NSP 3ABC, indicating subclinical infection. No clinical disease was seen, and no antibodies to NSP 3ABC were present in contact cattle. Additionally, no virus or viral nucleic acid was detected in blood, nasal swab and OP fluid samples from contact cattle. Thus, the virus appeared not to be transmitted from infected cattle to contact cattle. In its behaviour in pigs and cattle, strain O/SKR/AS/2002 resembled the porcinophilic FMDV strain of Cathay origin, O/TAW/97. However, the latter, unlike O/SKR/AS/2002, has reduced ability to grow in bovine-derived cells. The porcinophilic character of O/TAW/97 has been attributed to a deletion in the 3A coding region of the viral genome. However, O/SKR/AS/2002 has an intact 3A coding region.

  15. Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa.

    PubMed

    Ferguson, Kenneth J; Cleaveland, Sarah; Haydon, Daniel Thomas; Caron, Alexandre; Kock, Richard A; Lembo, Tiziana; Hopcraft, J Grant C; Chardonnet, Bertrand; Nyariki, Thomas; Keyyu, Julius; Paton, David James; Kivaria, Fredrick Mathias

    2013-09-01

    Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that trans frontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface.

  16. Early Adaptive Immune Responses in the Respiratory Tract of Foot-and-Mouth Disease Virus-Infected Cattle

    PubMed Central

    Pega, J.; Bucafusco, D.; Di Giacomo, S.; Schammas, J. M.; Malacari, D.; Capozzo, A. V.; Arzt, J.; Pérez-Beascoechea, C.; Maradei, E.; Rodríguez, L. L.; Borca, M. V.

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious viral disease which affects both domestic and wild biungulate species. This acute disease, caused by the FMD virus (FMDV), usually includes an active replication phase in the respiratory tract for up to 72 h postinfection, followed by hematogenous dissemination and vesicular lesions at oral and foot epithelia. The role of the early local adaptive immunity of the host in the outcome of the infection is not well understood. Here we report the kinetics of appearance of FMDV-specific antibody-secreting cells (ASC) in lymphoid organs along the respiratory tract and the spleen in cattle infected by aerosol exposure. While no responses were observed for up to 3 days postinfection (dpi), all animals developed FMDV-ASC in all the lymphoid organs studied at 4 dpi. Tracheobronchial lymph nodes were the most reactive organs at this time, and IgM was the predominant isotype, followed by IgG1. Numbers of FMDV-ASC were further augmented at 5 and 6 dpi, with an increasing prevalence in upper respiratory organs. Systemic antibody responses were slightly delayed compared with the local reaction. Also, IgM was the dominant isotype in serum at 5 dpi, coinciding with a sharp decrease of viral RNA detection in peripheral blood. These results indicate that following aerogenous administration, cattle develop a rapid and vigorous genuine local antibody response throughout the respiratory tract. Time course and isotype profiles indicate the presence of an efficient T cell-independent antibody response which drives the IgM-mediated virus clearance in cattle infected by FMDV aerosol exposure. PMID:23255811

  17. Heterogeneity in a communal cattle-farming system in a zone endemic for foot and mouth disease in South Africa.

    PubMed

    Van Schalkwyk, Ockert Louis; De Clercq, Eva M; De Pus, Claudia; Hendrickx, Guy; Van den Bossche, Peter; Knobel, Darryn L

    2016-05-31

    In South Africa, communal livestock farming is predominant in the foot and mouth disease control zone adjacent to the Greater Kruger National Park (KNP), where infected African buffaloes are common. During routine veterinary inspections of cattle in this area, a large amount of production and demographic parameters were being recorded. These data were collated for a five-year period (2003-2007) in three study sites to better understand the temporal dynamics and spatial heterogeneity in this system. A decreasing gradient from South to North with respect to both human and cattle population densities was observed. Rainfall and human population density alone could explain 71% of the variation in cattle density. Northern and central sites showed an overall decrease in total cattle numbers (15.1 and 2.9%, respectively), whereas a 28.6% increase was recorded in the South. The number of cattle owners in relation to cattle numbers remained stable during the study period. Only 4.0% of households in the South own cattle, compared to 13.7 and 12.7% in the North and Centre. The overall annual calving rate was 23.8%. Annual mortality rates ranged from 2.4 to 3.2%. Low calf mortality (2.1%) was recorded in the North compared to the South (11.6%). Annual off-take in the form of slaughter averaged 0.2, 11.7, and 11.0% in the North, Central and South sites, respectively. These figures provide valuable baseline data and demonstrate considerable spatial heterogeneity in cattle demography and production at this wildlife-livestock interface, which should be taken into consideration when performing disease risk assessments or designing disease control systems.

  18. Predicting the incidence of hand, foot and mouth disease in Sichuan province, China using the ARIMA model.

    PubMed

    Liu, L; Luan, R S; Yin, F; Zhu, X P; Lü, Q

    2016-01-01

    Hand, foot and mouth disease (HFMD) is an infectious disease caused by enteroviruses, which usually occurs in children aged <5 years. In China, the HFMD situation is worsening, with increasing number of cases nationwide. Therefore, monitoring and predicting HFMD incidence are urgently needed to make control measures more effective. In this study, we applied an autoregressive integrated moving average (ARIMA) model to forecast HFMD incidence in Sichuan province, China. HFMD infection data from January 2010 to June 2014 were used to fit the ARIMA model. The coefficient of determination (R 2), normalized Bayesian Information Criterion (BIC) and mean absolute percentage of error (MAPE) were used to evaluate the goodness-of-fit of the constructed models. The fitted ARIMA model was applied to forecast the incidence of HMFD from April to June 2014. The goodness-of-fit test generated the optimum general multiplicative seasonal ARIMA (1,0,1) × (0,1,0)12 model (R 2 = 0·692, MAPE = 15·982, BIC = 5·265), which also showed non-significant autocorrelations in the residuals of the model (P = 0·893). The forecast incidence values of the ARIMA (1,0,1) × (0,1,0)12 model from July to December 2014 were 4103-9987, which were proximate forecasts. The ARIMA model could be applied to forecast HMFD incidence trend and provide support for HMFD prevention and control. Further observations should be carried out continually into the time sequence, and the parameters of the models could be adjusted because HMFD incidence will not be absolutely stationary in the future.

  19. Children’s Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease

    NASA Astrophysics Data System (ADS)

    Li, Pengyuan; Li, Tao; Gu, Qiuyun; Chen, Xiaomin; Li, Jiahui; Chen, Xiashi; Chen, Yan; Zhang, Danwei; Gao, Rong; He, Zhenjian; Zhu, Xun; Zhang, Wangjian; Hao, Yuantao; Zhang, Dingmei

    2016-11-01

    Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children’s caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children’s 257 samples (98 children’s caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children’s caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children’s caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities.

  20. Hand-foot-and-mouth disease epidemiological status and relationship with meteorological variables in Guangzhou, southern China, 2008-2012.

    PubMed

    Li, Tiegang; Yang, Zhicong; Liu, Xiangyi; Kang, Yan; Wang, Ming

    2014-01-01

    Hand-foot-and-mouth disease (HFMD) is becoming one of the extremely common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, it was used an ecological study plus the negative binomial regression to identify the epidemic status of HFMD and its relationship with meteorological variables. During 2008-2012, a total of 173,524 HFMD confirmed cases were reported, 12 cases of death, yielding a fatality rate of 0.69 per 10,000. The annual incidence rates from 2008 to 2012 were 60.56, 132.44, 311.40, 402.76, and 468.59 (per 100,000), respectively, showing a rapid increasing trend. Each 1 °C rise in temperature corresponded to an increase of 9.47% (95% CI 9.36% to 9.58%) in the weekly number of HFMD cases, while a one hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 7.53% (95% CI -7.60% to -7.45%). Similarly, each one percent rise in relative humidity corresponded to an increase of 1.48% or 3.3%, and a one meter per hour rise in wind speed corresponded to an increase of 2.18% or 4.57%, in the weekly number of HFMD cases, depending on the variables considered in the model. These findings revealed that epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on the incidence of HFMD.

  1. The impact of importation of live ruminants on the epizootiology of foot and mouth disease in Saudi Arabia.

    PubMed

    Abd El-Rahim, I H A; Asghar, A H; Mohamed, A M; Fat'hi, S M

    2016-12-01

    Approximately five million live ruminants are imported annually into Saudi Arabia. The majority of these animals are imported shortly before the pilgrimage season from Sudan and the Horn of Africa, where foot and mouth disease (FMD) is known to be enzootic. This study was designed to investigate the impact of the importation of these live ruminants on the epizootiology of FMD in Saudi Arabia. The authors carried out antibody testing on a total of 480 sheep and 233 cattle from the sacrificial livestock yards of the Saudi Project for Utilization of Hajj Meat, which performs ritual slaughter on behalf of pilgrims in the Holy City of Makkah. The results revealed that 136 (28.3%) of the 480 sheep tested were serologically positive for FMD, using an indirect enzymelinked immunosorbent assay (ELISA) (3ABC FMD ELISA). This included 17.7% of Sawakani sheep (imported from Sudan) and 40.9% of Barbari sheep (imported from the Horn of Africa). Among the cattle, 120 (51.5%) of 233 animals tested positive for FMD virus (FMDV) antibodies. The 120 seropositive cattle included all clinically suspected cattle and 62 (35.4%) symptom-free, in-contact cattle. The findings highlight the risks associated with the annual importation of live ruminants from FMD-enzootic areas. The risks include the possible introduction of new exotic FMDV serotypes, particularly when potential carriers or subclinically infected animals are considered. An understanding of the epidemiology of different strains and the ability to track their movement between geographical regions is essential for the development of efficient control strategies for the disease. Therefore, genotyping of FMDV strains isolated from imported and local animals is recommended.

  2. Household Financial Status and Gender Perspectives in Determining the Financial Impact of Foot and Mouth Disease in Lao PDR.

    PubMed

    Nampanya, S; Khounsy, S; Abila, R; Dy, C; Windsor, P A

    2016-08-01

    The socioeconomic impacts of foot and mouth disease (FMD) during 2011-12 outbreaks on large ruminant smallholders in Laos were investigated, including examination of data on gender, household financial status and farmer husbandry practices. A mix of participatory tools and survey questionnaires at the village and household level, respectively, were conducted, involving individual farmer interviews (n = 124) and group meetings with village elders to establish criteria for classification of household financial status as being 'poor, medium or well off' according to rice sufficiency, assets and household incomes. FMD-attributable financial losses were determined by inclusion of losses due to: mortality, morbidity and costs of treatments. The estimated mean financial losses due to FMD were USD 436 (±92) in the 'poor' and USD 949 (±76) in the 'well off' household categories (P < 0.001), being 128% and 49% of income from the sale of large ruminants, respectively. Variation in financial losses reflected differences in morbidity, farmer husbandry practices including frequency of observation of animals and thus recognition of FMD and choice of treatments. Of concern were adverse financial impacts of treatment especially where antibiotics were used; delays in reporting of FMD cases after observation of signs (mean of 2 days); admission that 10% of farmers had sold FMD-affected livestock; and that 22% of respondents claimed their large ruminants were cared for by females. The findings confirm that FMD has the most severe financial impact on poorer households and that females have a significant role in large ruminant production. It is recommended that livestock extension activities promote the benefits of prevention rather than treatment for FMD and encourage participation of women in biosecurity and disease risk management interventions including rapid reporting and regulatory compliance, particularly with animal movement controls and other biosecurity practices that

  3. The field effectiveness of routine and emergency vaccination with an inactivated vaccine against foot and mouth disease.

    PubMed

    Elnekave, E; Li, Y; Zamir, L; Even-Tov, B; Hamblin, P; Gelman, B; Hammond, J; Klement, E

    2013-01-30

    High potency, inactivated foot and mouth disease (FMD) vaccines may be used in non endemic countries for emergency vaccination during outbreaks in order to prevent virus spread. In endemic countries either standard or high potency vaccines are used for routine vaccination. Despite their wide use there is a shortage of data on the field effectiveness of inactivated FMD vaccines. Epidemics of FMD caused by viruses of serotype O occur frequently in Israel, where a high potency (≥6PD(50)) vaccine is used for both routine and emergency vaccination. We investigated an outbreak of FMD caused by a virus of serotype O, which took place during 2011 in a feedlot and an adjacent dairy herd. Post outbreak testing of antibodies against non-structural protein demonstrated that infection occurred in 96% of the calves that received two doses of vaccine at least three months prior to the outbreak and more than 50% showed clinical signs consistent with FMD. Replacement heifers that had been vaccinated 3-5 times with the last vaccination administered 7 months prior to the outbreak were all infected and 18% showed clinical signs. Testing of cattle sera of the same vaccination status as the affected cattle demonstrated low neutralizing antibody (NA) titers against the field virus strain and an r(1) value of 0.37 compared to the vaccine strain. In contrast, cattle vaccinated only once but up to two weeks before the outbreak, were almost all protected from clinical disease and to a lesser extent, protected from FMD virus infection, despite low NA titers. We conclude that emergency vaccination was highly effective due to a mechanism not associated with NA, whereas routine vaccination with the same vaccine formulation provided only limited protection due to poor longevity of the elicited immunity and low matching with the field strain (despite an r(1) higher than 0.3).

  4. Children’s Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease

    PubMed Central

    Li, Pengyuan; Li, Tao; Gu, Qiuyun; Chen, Xiaomin; Li, Jiahui; Chen, Xiashi; Chen, Yan; Zhang, Danwei; Gao, Rong; He, Zhenjian; Zhu, Xun; Zhang, Wangjian; Hao, Yuantao; Zhang, Dingmei

    2016-01-01

    Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children’s caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children’s 257 samples (98 children’s caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children’s caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children’s caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities. PMID:27819276

  5. Predictive spatial modelling of alternative control strategies for the foot-and-mouth disease epidemic in Great Britain, 2001.

    PubMed

    Morris, R S; Wilesmith, J W; Stern, M W; Sanson, R L; Stevenson, M A

    2001-08-04

    A spatial simulation model of foot-and-mouth disease was used in March and early April 2001 to evaluate alternative control policies for the 2001 epidemic in Great Britain. Control policies were those in operation from March 20, 2001, and comprised a ban on all animal movements from February 23, 2001, and a stamping-out policy. Each simulation commenced with the known population of infected farms on April 10, 2001, and ran for 200 days. For the control policy which best approximated that actually implemented from late March, the model predicted an epidemic of approximately 1800 to 1900 affected farms, and estimated that the epidemic would be eradicated between July and October 2001, with a low probability of continuing beyond October 2001. This policy included the slaughter-out of infected farms within 24 hours, slaughter of about 1.3 of the surrounding farms per infected farm within a further 48 hours, and minimal interfarm movements of susceptible animals. Delays in the slaughter of animals on infected farms beyond 24 hours after diagnosis slightly increased the epidemic size, and failure to achieve pre-emptive slaughter on an adequate number of at-risk farms substantially increased the expected size of the epidemic. Vaccination of up to three of the most outbreak-dense areas carried out in conjunction with the adopted control policy reduced the predicted size of the epidemic by less than 100 farms. Vaccination of buffer zones (designed to apply available vaccine and manpower as effectively as possible) carried out in place of the adopted control policy allowed the disease to spread out of control, producing an epidemic involving over 6000 farms by October 2001, with no prospect of immediate eradication.

  6. Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

    PubMed Central

    Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan; Singh, Karam Pal; Stenfeldt, Carolina; Rodriguez, Luis L.; Pattnaik, Bramhadev; Arzt, Jonathan

    2016-01-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genome detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle. PMID:27977708

  7. Exploiting serological data to understand the epidemiology of foot-and-mouth disease virus serotypes circulating in Libya

    PubMed Central

    Eldaghayes, Ibrahim; Dayhum, Abdunaser; Kammon, Abdulwahab; Sharif, Monier; Ferrari, Giancarlo; Bartels, Christianus; Sumption, Keith; King, Donald P.; Grazioli, Santina; Brocchi, Emiliana

    2017-01-01

    Sporadic outbreaks of foot-and-mouth disease (FMD) have occurred in Libya for almost fifty years. During the spring of 2013, a countrywide serosurvey was undertaken to assess the level of FMD virus circulation and identify FMD virus serotypes in the country. A total of 4221 sera were collected, comprising samples from large ruminants (LR; n=1428 samples from 357 farms) and small ruminants (SR; n=2793 samples from 141 farms). FMD sero-prevalence of NSP antibodies determined by ELISA were 19.0% (271/1428) with 95% CI (16.9 – 21.0) and 13.5% (378/2793) with 95% CI (12.3 – 14.8) for LR and SR samples, respectively. The sero-prevalence of NSP antibodies in LR was 12.3% and 19.8% for age group < 1 year and ≥ 1 year, respectively (X2= 4.95, P= 0.026), while in SR was 3.7%, 13.6% and 21.3% for age group < 1 year, 1-2 year and > 2 year, respectively (X2= 118.1, P= 0.000). These observed NSP serologic profiles support the hypothesis of an endemic level of FMD circulation in Libya. All positive sera were tested for SP antibodies for O, A and SAT-2 FMD virus serotypes. Serotype O was the dominant circulating serotype followed by serotype A, while evidence of SAT-2 was not found. These data provide an insight into the wider epidemiology of FMD in Libya, and contribute to field and laboratory investigations that during 2013 serotype O (O/ME-SA/Ind-2001 lineage) was isolated from clinical samples collected from the country. PMID:28180094

  8. Proper Timing of Foot-and-Mouth Disease Vaccination of Piglets with Maternally Derived Antibodies Will Maximize Expected Protection Levels

    PubMed Central

    Dekker, Aldo; Chénard, Gilles; Stockhofe, Norbert; Eblé, Phaedra L.

    2016-01-01

    We investigated to what extent maternally derived antibodies interfere with foot-and-mouth disease (FMD) vaccination in order to determine the factors that influence the correct vaccination for piglets. Groups of piglets with maternally derived antibodies were vaccinated at different time points following birth, and the antibody titers to FMD virus (FMDV) were measured using virus neutralization tests (VNT). We used 50 piglets from 5 sows that had been vaccinated 3 times intramuscularly in the neck during pregnancy with FMD vaccine containing strains of FMDV serotypes O, A, and Asia-1. Four groups of 10 piglets were vaccinated intramuscularly in the neck at 3, 5, 7, or 9 weeks of age using a monovalent Cedivac-FMD vaccine (serotype A TUR/14/98). One group of 10 piglets with maternally derived antibodies was not vaccinated, and another group of 10 piglets without maternally derived antibodies was vaccinated at 3 weeks of age and served as a control group. Sera samples were collected, and antibody titers were determined using VNT. In our study, the antibody responses of piglets with maternally derived antibodies vaccinated at 7 or 9 weeks of age were similar to the responses of piglets without maternally derived antibodies vaccinated at 3 weeks of age. The maternally derived antibody levels in piglets depended very strongly on the antibody titer in the sow, so the optimal time for vaccination of piglets will depend on the vaccination scheme and quality of vaccine used in the sows and should, therefore, be monitored and reviewed on regular basis in countries that use FMD prophylactic vaccination. PMID:27446940

  9. Exploiting serological data to understand the epidemiology of foot-and-mouth disease virus serotypes circulating in Libya.

    PubMed

    Eldaghayes, Ibrahim; Dayhum, Abdunaser; Kammon, Abdulwahab; Sharif, Monier; Ferrari, Giancarlo; Bartels, Christianus; Sumption, Keith; King, Donald P; Grazioli, Santina; Brocchi, Emiliana

    2017-01-01

    Sporadic outbreaks of foot-and-mouth disease (FMD) have occurred in Libya for almost fifty years. During the spring of 2013, a countrywide serosurvey was undertaken to assess the level of FMD virus circulation and identify FMD virus serotypes in the country. A total of 4221 sera were collected, comprising samples from large ruminants (LR; n=1428 samples from 357 farms) and small ruminants (SR; n=2793 samples from 141 farms). FMD sero-prevalence of NSP antibodies determined by ELISA were 19.0% (271/1428) with 95% CI (16.9 - 21.0) and 13.5% (378/2793) with 95% CI (12.3 - 14.8) for LR and SR samples, respectively. The sero-prevalence of NSP antibodies in LR was 12.3% and 19.8% for age group < 1 year and ≥ 1 year, respectively (X(2)= 4.95, P= 0.026), while in SR was 3.7%, 13.6% and 21.3% for age group < 1 year, 1-2 year and > 2 year, respectively (X(2)= 118.1, P= 0.000). These observed NSP serologic profiles support the hypothesis of an endemic level of FMD circulation in Libya. All positive sera were tested for SP antibodies for O, A and SAT-2 FMD virus serotypes. Serotype O was the dominant circulating serotype followed by serotype A, while evidence of SAT-2 was not found. These data provide an insight into the wider epidemiology of FMD in Libya, and contribute to field and laboratory investigations that during 2013 serotype O (O/ME-SA/Ind-2001 lineage) was isolated from clinical samples collected from the country.

  10. Multiple introductions of serotype O foot-and-mouth disease viruses into East Asia in 2010-2011.

    PubMed

    Valdazo-González, Begoña; Timina, Anna; Scherbakov, Alexey; Abdul-Hamid, Nor Faizah; Knowles, Nick J; King, Donald P

    2013-09-05

    Foot-and-mouth disease virus (FMDV) is a highly contagious and genetically variable virus. Sporadic introductions of this virus into FMD-free countries may cause outbreaks with devastating consequences. In 2010 and 2011, incursions of the FMDV O/SEA/Mya-98 strain, normally restricted to countries in mainland Southeast Asia, caused extensive outbreaks across East Asia. In this study, 12 full genome FMDV sequences for representative samples collected from the People's Republic of China (PR China) including the Hong Kong Special Administrative Region (SAR), the Republic of Korea, the Democratic People's Republic of Korea, Japan, Mongolia and The Russian Federation were generated and compared with additional contemporary sequences from viruses within this lineage. These complete genomes were 8119 to 8193 nucleotides in length and differed at 1181 sites, sharing a nucleotide identity ≥ 91.0% and an amino acid identity ≥ 96.6%. An unexpected deletion of 70 nucleotides within the 5'-untranslated region which resulted in a shorter predicted RNA stem-loop for the S-fragment was revealed in two sequences from PR China and Hong Kong SAR and five additional related samples from the region. Statistical parsimony and Bayesian phylogenetic analysis provide evidence that these outbreaks in East Asia were generated by two independent introductions of the O/SEA/Mya-98 lineage sometime between August 2008 and March 2010. The rapid emergence of these viruses from Southeast Asia highlights the importance of adopting approaches to closely monitor the spread of this lineage that now poses a threat to livestock industries in other regions.

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

    PubMed

    Valdazo-González, Begoña; Kim, Jan T; Soubeyrand, Samuel; Wadsworth, Jemma; Knowles, Nick J; Haydon, Daniel T; King, Donald P

    2015-06-01

    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.

  12. Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in Spain.

    PubMed

    Cabrerizo, M; Tarragó, D; Muñoz-Almagro, C; Del Amo, E; Domínguez-Gil, M; Eiros, J M; López-Miragaya, I; Pérez, C; Reina, J; Otero, A; González, I; Echevarría, J E; Trallero, G

    2014-03-01

    Hand, foot and mouth disease (HFMD) is a childhood illness frequently caused by genotypes belonging to the enterovirus A species, including coxsackievirus (CV)-A16 and enterovirus (EV)-71. Between 2010 and 2012, several outbreaks and sporadic cases of HFMD occurred in different regions of Spain. The objective of the present study was to describe the enterovirus epidemiology associated with HFMD in the country. A total of 80 patients with HFMD or atypical rash were included. Detection and typing of the enteroviruses were performed directly in clinical samples using molecular methods. Enteroviruses were detected in 53 of the patients (66%). CV-A6 was the most frequent genotype, followed by CV-A16 and EV-71, but other minority types were also identified. Interestingly, during almost all of 2010, CV-A16 was the only causative agent of HFMD but by the end of the year and during 2011, CV-A6 became predominant, while CV-A16 was not detected. In 2012, however, both CV-A6 and CV-A16 circulated. EV-71 was associated with HFMD symptoms only in three cases during 2012. All Spanish CV-A6 sequences segregated into one major genetic cluster together with other European and Asian strains isolated between 2008 and 2011, most forming a particular clade. Spanish EV-71 strains belonged to subgenogroup C2, as did most of the European sequences circulated. In conclusion, the recent increase of HFMD cases in Spain and other European countries has been due to a larger incidence of circulating species A enteroviruses, mainly CV-A6 and CV-A16, and the emergence of new genetic variants of these viruses.

  13. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle

    PubMed Central

    Medina, Gisselle N.; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J.

    2015-01-01

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+ and CD8+ gamma interferon (IFN-γ)+ cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle. PMID:26607309

  14. Effect of vaccination against foot-and-mouth disease on growth performance of Korean native goat (Capra hircus coreanae).

    PubMed

    Jo, N C; Jung, J; Kim, J N; Lee, J; Jeong, S Y; Kim, W; Sung, H G; Seo, S

    2014-06-01

    The objectives of this study were 1) to evaluate the effects of vaccination against foot-and-mouth disease (FMD) on growth performance, nutrient digestibility, hematological parameters, and behavior in a ruminant animal and 2) to investigate a possible strategy for reducing its adverse effect. A total of 12 Korean native goats (Capra hircus coreanae; 19.8 ± 2.9 kg) were used in a crossover design with 3 experimental periods and 3 treatments, randomized and balanced for counteracting possible carry-over effects. The treatments were 1) control, 2) co-injection with a commercially available dipyrone (CADI), and 3) supplementation with γ-amino butyric acid (GABA) at 10 g/kg in concentrate mix. Each period lasted 4 wk, and the vaccination against FMD was performed at 2 wk after the start of each period. The goats were individually housed in a metabolic cage and fed ad libitum with a diet consisting of bermuda grass and commercial concentrate mix (6:4, wt/wt). Dry matter intake, ADG, nutrients digestibility, hematological parameters, and behavioral activities of the goats were measured before and after vaccination. Although DMI was not decreased (P > 0.05), ADG was decreased by the vaccination to the goats (P < 0.01). The total number of leukocytes was increased while that of erythrocytes was decreased by the FMD vaccination (P < 0.01). The vaccination shortened standing time while extended lying time and the time spent in drinking (P < 0.05). The treatment by CADI reduced the adverse effect of vaccination on ADG and goat behavior compared with control and GABA treatment (P < 0.05). We concluded that the FMD vaccination decreased ADG of the goats without depression of diet intake, and CADI may attenuate the adverse effect of the FMD vaccination.

  15. Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2)

    PubMed Central

    Daoud, Hind M.; Soliman, Eman M.

    2015-01-01

    Aim: This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Materials and Methods: Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. Results: The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. Conclusion: This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis. PMID:27047027

  16. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle.

    PubMed

    Medina, Gisselle N; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J; de los Santos, Teresa

    2015-11-25

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4(+) and CD8(+) gamma interferon (IFN-γ)(+) cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle.

  17. Identification and antigenic site analysis of foot-and-mouth disease virus from pigs and cattle in Korea.

    PubMed

    Oem, Jae Ku; Lee, Kwang Nyeong; Cho, In Soo; Kye, Soo Jeong; Park, Jee Yong; Park, Jong Hyeon; Kim, Yong Joo; Joo, Yi Seok; Song, Hee Jong

    2005-06-01

    From May to June 2002, a total of 16 foot-and mouth disease (FMD) outbreaks due to the serotype O virus, Pan Asia strain, were recorded in Korea. The viruses were identified by antigen ELISA, RT-PCR and sequence analysis. The overall nucleotide sequence divergence of the VP1 region among the 4 isolates in 2002 was 0 to 1.4%, but between O/SKR/2002 and O/SKR/2000 isolates was 1.9-4.9%. Phylogenetic analysis with the some known strains from East Asian countries showed that the 4 Korean isolates in 2002 formed one distinct cluster, which different from clusters of Korean isolates in 2000, with in the same lineage of the ME-SA topotype strains. Deduced amino acid sequences around neutralizable antigenic site on VP1 site of O/SKR/2002 isolates were aligned and compared with other strains. At the antigenic site 1, the replacements of the critical amino acid residues at position 144 from V to L and at position 152 from A to T were observed in O/SKR/2002 viruses. For antigenic site 2 and 4, there were not significant variations in general. At the antigenic site 3, the substitutions of amino acid residues were present at positions 54 and 56 in O/SKR/2002 isolates and an alternative residue I at position 54 are observed only at the sequence of O/SKR/AS/2002 (cow) virus. And the substitution (L-->P) of significant residue at position 144 was detected at the amino acid sequence of the O/SKR/2002 (cow) virus.

  18. Evidence of recombination in a new isolate of foot-and-mouth disease virus serotype Asia 1.

    PubMed

    Lee, Kwang-Nyeong; Oem, Jae-Ku; Park, Jong-Hyeon; Kim, Su-Mi; Lee, Seo-Yong; Tserendorj, Sh; Sodnomdarjaa, R; Joo, Yi-Seok; Kim, Heebal

    2009-01-01

    Phylogenetic analysis of the nucleotide sequence of VP1 revealed that a new isolate of foot-and-mouth disease virus (FMDV) serotype Asia 1 identified in Mongolia in 2005 was related to Chinese and Russian strains isolated during the same year. In this study, these strains were defined as East Asian strains having a common geographical origin, and the complete genomic sequence of the Mongolian strain (As1/MOG/05) was determined and compared to other strains of serotype Asia 1. As1/MOG/05 showed 100% identity with an East Asian strain from China (As1/Qinghai/CHA/05) in terms of its VP1 nucleotide sequence. However, the Mongolian strain has a four-amino acid extension in 3D that is missing from all other strains of serotype Asia 1, and which is not due to an insertion. A full genomic scan revealed that the Mongolian strain is closer to the East Asian strain As1/JS/CHA/05 than to all other strains of serotype Asia 1 in nearly all genomic regions. Within the narrow region of low similarity between the two sequences, As1/JS/CHA/05 was found to have a mosaic structure with a partial 2C fragment supposedly transferred from Hong Kong strain As1/HNK/CHA/05. The genomic mosaicism and extension detected in non-structural protein-coding regions in this study may be used to trace the origins and evolution of problematic strains of serotype Asia 1 that have arisen in East Asia since 2005.

  19. Antigenic site variation in foot-and-mouth disease virus serotype O grown under vaccinal serum antibodies in vitro.

    PubMed

    Sarangi, Laxmi N; Mohapatra, Jajati K; Subramaniam, Saravanan; Sanyal, Aniket; Pattnaik, Bramhadev

    2013-09-01

    Foot-and-mouth disease virus (FMDV) is constantly evolving under neutralizing antibody pressure in either naturally infected or vaccinated animals. This study was carried out to understand the dynamics of evolution of antigenic sites. Neutralizing antibody-resistant populations of three strains of FMDV serotype O (INDR2/1975, IND120/2002 and IND271/2001) were isolated by serial propagation in BHK-21 cells in the presence of sub-neutralizing level of bovine vaccinal sera (BVS). In the partial neutralization escape variants, fixation of aa substitutions were observed at critical residues of all established antigenic sites of serotype O {144 of VP1 (site 1), 45 and 48 of VP1 (site 3), 72 and 134 of VP2 (Site 2)} except site 4 and 5. In majority of the variant populations, site 3 was found to be substituted and therefore immunodominance may not be associated with a particular site, rather it appears to be a virus strain and infected host specific affair. Substitutions were also observed in proximity to the identified residues {41 and 51 (βB-βC loop), 133, 140 and 143 (βG-βH loop), 201, 204 and 209 (C terminus) of VP1, 71 and 75 (βB-βC loop), 131 (βE-αB region), 174 and 179 (βG-βH loop) and 219 (C terminus) of VP3} within antigenic sites of serotype O or other serotypes which could be significant in terms of neutralizing antibody binding and immune escape. Presence of similar residues in the Indian field viruses as selected in the variants supports the importance of these sites in antigenic diversification of serotype O FMD virus.

  20. Evolution of foot-and-mouth disease virus intra-sample sequence diversity during serial transmission in bovine hosts

    PubMed Central

    2013-01-01

    RNA virus populations within samples are highly heterogeneous, containing a large number of minority sequence variants which can potentially be transmitted to other susceptible hosts. Consequently, consensus genome sequences provide an incomplete picture of the within- and between-host viral evolutionary dynamics during transmission. Foot-and-mouth disease virus (FMDV) is an RNA virus that can spread from primary sites of replication, via the systemic circulation, to found distinct sites of local infection at epithelial surfaces. Viral evolution in these different tissues occurs independently, each of them potentially providing a source of virus to seed subsequent transmission events. This study employed the Illumina Genome Analyzer platform to sequence 18 FMDV samples collected from a chain of sequentially infected cattle. These data generated snap-shots of the evolving viral population structures within different animals and tissues. Analyses of the mutation spectra revealed polymorphisms at frequencies >0.5% at between 21 and 146 sites across the genome for these samples, while 13 sites acquired mutations in excess of consensus frequency (50%). Analysis of polymorphism frequency revealed that a number of minority variants were transmitted during host-to-host infection events, while the size of the intra-host founder populations appeared to be smaller. These data indicate that viral population complexity is influenced by small intra-host bottlenecks and relatively large inter-host bottlenecks. The dynamics of minority variants are consistent with the actions of genetic drift rather than strong selection. These results provide novel insights into the evolution of FMDV that can be applied to reconstruct both intra- and inter-host transmission routes. PMID:23452550

  1. Induction of a Cross-Reactive CD8+ T Cell Response following Foot-and-Mouth Disease Virus Vaccination▿

    PubMed Central

    Guzman, Efrain; Taylor, Geraldine; Charleston, Bryan; Ellis, Shirley A.

    2010-01-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. Current inactivated FMDV vaccines generate short-term, serotype-specific protection, mainly through neutralizing antibody. An improved understanding of the mechanisms of protective immunity would aid design of more effective vaccines. We have previously reported the presence of virus-specific CD8+ T cells in FMDV-vaccinated and -infected cattle. In the current study, we aimed to identify CD8+ T cell epitopes in FMDV recognized by cattle vaccinated with inactivated FMDV serotype O. Analysis of gamma interferon (IFN-γ)-producing CD8+ T cells responding to stimulation with FMDV-derived peptides revealed one putative CD8+ T cell epitope present within the structural protein P1D, comprising residues 795 to 803 of FMDV serotype O UKG/2001. The restricting major histocompatibility complex (MHC) class I allele was N*02201, expressed by the A31 haplotype. This epitope induced IFN-γ release, proliferation, and target cell killing by αβ CD8+ T cells, but not CD4+ T cells. A protein alignment of representative samples from each of the 7 FMDV serotypes showed that the putative epitope is highly conserved. CD8+ T cells from FMDV serotype O-vaccinated A31+ cattle recognized antigen-presenting cells (APCs) loaded with peptides derived from all 7 FMDV serotypes, suggesting that CD8+ T cells recognizing the defined epitope are cross-reactive to equivalent peptides derived from all of the other FMDV serotypes. PMID:20861264

  2. Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

    PubMed Central

    Asfor, Amin S.; Upadhyaya, Sasmita; Knowles, Nick J.; King, Donald P.; Paton, David J.

    2014-01-01

    Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design. PMID:24584474

  3. Spatio-Temporal Clustering of Hand, Foot, and Mouth Disease at the County Level in Guangxi, China

    PubMed Central

    Xie, Yi-hong; Chongsuvivatwong, Virasakdi; Tang, Zhenzhu; McNeil, Edward B.; Tan, Yi

    2014-01-01

    Background Amid numerous outbreaks of hand, foot and mouth disease (HFMD) in Asia over the past decade, studies on spatio-temporal clustering are limited. Without this information the distribution of severe cases assumed to be sporadic. We analyzed surveillance data with onset dates between 1 May 2008 to 31 October 2013 with the aim to document the spatio-temporal clustering of HFMD cases and severe cases at the county level. Methods Purely temporal and purely spatial descriptive analyses were done. These were followed by a space-time scan statistic for the whole study period and by year to detect the high risk clusters based on a discrete Poisson model. Results The annual incidence rate of HFMD in Guangxi increased whereas the severe cases peaked in 2010 and 2012. EV71 and CoxA16 were alternating viruses. Both HFMD cases and severe cases had a seasonal peak in April to July. The spatio-temporal cluster of HFMD cases were mainly detected in the northeastern, central and southwestern regions, among which three clusters were observed in Nanning, Liuzhou, Guilin city and their neighbouring areas lasting from 1.2 to 2.5 years. The clusters of severe cases were less consistent in location and included around 40–70% of all severe cases in each year. Conclusions Both HFMD cases and severe cases occur in spatio-temporal clusters. The continuous epidemic in Nanning, Liuzhou, Guilin cities and their neighbouring areas and the clusters of severe cases indicate the need for further intensive surveillance. PMID:24505378

  4. 77 FR 46016 - Notice of Determination of the Foot-and-Mouth Disease Status of Japan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-02

    ... restricted because of shared land borders or trading practices with regions that have one or both of these... referenced by the commenter was intended as a description of general practices rather than as a statement of... infrastructure, biosecurity measures, livestock demographics, marketing practices, disease surveillance,...

  5. The Vulnerability of U.S. Agriculture to Foot and Mouth Disease

    DTIC Science & Technology

    2015-06-01

    Pitt, “ Bird Flu Could Cost Nearly $1 Billion in Minnesota and Iowa,” Washington Post, May 18, 2015, http://www.washingtonpost.com/national/health...science/ bird -flu-could-cost-nearly- 1-billion-in-minnesota-and-iowa/2015/05/18/2ef0fe48-fda6-11e4-8c77-bf274685e1df_story.html. 3 U.S. Department of...from the 2008 version.45 In 2011, disaster assistance programs expired leaving farmers impacted by disease or adverse weather situations without aid

  6. Global situation of foot-and-mouth disease (FMD)--a short review.

    PubMed

    Kesy, A

    2002-01-01

    This article reviews the actual world FMD situation. In 2000, fifty nine countries officially reported outbreaks of FMD. The disease occurred in Europe (Greece), Asia (Russia, Mongolia, Bangladesh, Cambodia, China, Japan, Laos, Nepal, Pakistan, Philippines, Republic of Korea, Taiwan, Thailand, Vietnam, Iran, Iraq, Turkey, in Caucasian region--Georgia, Azerbaijan and Armenia as well as in Kazakhstan, Kyrgyzstan, Turkmenistan and Tajikistan), Africa (Egypt, Kenya, Mauritania, South Africa, Tanzania, Uganda, Malawi, Namibia, Zambia and Zimbabwe) and in South America (Brazil, Colombia, Uruguay, Bolivia, Peru, Ecuador and Venezuela). In 2001, FMD was still spreading throughout the endemic regions and appeared in some of the west European countries--Great Britain, The Netherlands, France and Ireland. In South America, FMD occurred in Argentina, Uruguay, Brazil and Colombia. In Asia the FMD spread in Turkey, Iran, Afghanistan, Georgia, Azerbaijan, Mongolia, Kuwait, Bahrain, Yemen, Qatar, United Arab Emirates, Oman, Iran, Bhutan, Nepal, Malaysia, Philippines, Thailand and Taiwan. The FMD situation in Africa was unclear, but probably most countries in West, East and South Africa were affected. The most recent data of the OIE from May 2002 confirmed FMD outbreaks in population of pigs in Republic of Korea.

  7. Impact of foot-and-mouth disease on milk production on a large-scale dairy farm in Kenya.

    PubMed

    Lyons, Nicholas A; Alexander, Neal; Stärk, Katharina D C; Dulu, Thomas D; Sumption, Keith J; James, Andrew D; Rushton, Jonathan; Fine, Paul E M

    2015-06-15

    The economic impact of foot-and-mouth disease (FMD) has been poorly characterised particularly in endemic settings where such knowledge is important for decision-making on disease control with limited resources. In order to address this, a study was designed using individual animal data from a large-scale dairy farm in Kenya to estimate the impact of an FMD outbreak due to serotype SAT2 virus on milk yield. Daily milk yields from 218 mainly European-breed cattle that were lactating during the 29-day outbreak period were considered in the analysis. At the herd level, the average daily yields decreased from around 20 to 13kg per cow, recovering approximately 2 months after the commencement of the outbreak. Generalised estimating equations (GEE) and an autoregressive correlation matrix were used to compare yields of reported clinical FMD cases and non-cases. No difference was found between reported clinical and non-clinical cases suggesting inaccurate case recording, poor sensitivity of the case definition and subclinical infections being present. To further investigate the impact of FMD, yields were predicted for each individual animal based on historic data from the same herd using a similar GEE approach. For cattle lactating during the outbreak, comparisons were made between actual and predicted yields from the commencement of the outbreak to 305 days lactation using a linear regression model. Animals produced significantly less than predicted if in parity 2 or greater and between 0 and 50 days in milk (DIM) at the start of the outbreak period. The maximum effect was seen among animals in parity ≥4 and between 0 and 50 DIM at the start of the outbreak, producing on average 688.7kg (95%CI 395.5, 981.8) less milk than predicted for their remaining lactation, representing an average 15% reduction in the 305 day production for these animals. Generalisation of the results requires caution as the majority of Kenyan milk is produced in smallholder farms. However, such

  8. A safe foot-and-mouth disease vaccine platform with two negative markers for differentiating infected from vaccinated animals.

    PubMed

    Uddowla, Sabena; Hollister, Jason; Pacheco, Juan M; Rodriguez, Luis L; Rieder, Elizabeth

    2012-11-01

    Vaccination of domestic animals with chemically inactivated foot-and-mouth disease virus (FMDV) is widely practiced to control FMD. Currently, FMD vaccine manufacturing requires the growth of large volumes of virulent FMDV in biocontainment-level facilities. Here, two marker FMDV vaccine candidates (A(24)LL3D(YR) and A(24)LL3B(PVKV)3D(YR)) featuring the deletion of the leader coding region (L(pro)) and one of the 3B proteins were constructed and evaluated. These vaccine candidates also contain either one or two sets of mutations to create negative antigenic markers in the 3D polymerase (3D(pol)) and 3B nonstructural proteins. Two mutations in 3D(pol), H(27)Y and N(31)R, as well as RQKP(9-12)→PVKV substitutions, in 3B(2) abolish reactivity with monoclonal antibodies targeting the respective sequences in 3D(pol) and 3B. Infectious cDNA clones encoding the marker viruses also contain unique restriction endonuclease sites flanking the capsid-coding region that allow for easy derivation of custom designed vaccine candidates. In contrast to the parental A(24)WT virus, single A(24)LL3D(YR) and double A(24)LL3B(PVKV)3D(YR) mutant viruses were markedly attenuated upon inoculation of cattle using the natural aerosol or direct tongue inoculation. Likewise, pigs inoculated with live A(24)LL3D(YR) virus in the heel bulbs showed no clinical signs of disease, no fever, and no FMD transmission to in-contact animals. Immunization of cattle with chemically inactivated A(24)LL3D(YR) and A(24)LL3B(PVKV)3D(YR) vaccines provided 100% protection from challenge with parental wild-type virus. These attenuated, antigenically marked viruses provide a safe alternative to virulent strains for FMD vaccine manufacturing. In addition, a competitive enzyme-linked immunosorbent assay targeted to the negative markers provides a suitable companion test for differentiating infected from vaccinated animals.

  9. Pathogenesis of Primary Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Vaccinated and Non-Vaccinated Cattle.

    PubMed

    Stenfeldt, Carolina; Eschbaumer, Michael; Pacheco, Juan M; Rekant, Steven I; Rodriguez, Luis L; Arzt, Jonathan

    2015-01-01

    A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection following simulated-natural (intra-nasopharyngeal) virus exposure of cattle that were non-vaccinated or vaccinated using a recombinant adenovirus-vectored FMDV vaccine. FMDV genome and infectious virus were detected during the initial phase of infection in both categories of animals with consistent predilection for the nasopharyngeal mucosa. A rapid progression of infection with viremia and widespread dissemination of virus occurred in non-vaccinated animals whilst vaccinated cattle were protected from viremia and clinical FMD. Analysis of micro-anatomic distribution of virus during early infection by lasercapture microdissection localized FMDV RNA to follicle-associated epithelium of the nasopharyngeal mucosa in both groups of animals, with concurrent detection of viral genome in nasopharyngeal MALT follicles in vaccinated cattle only. FMDV structural and non-structural proteins were detected in epithelial cells of the nasopharyngeal mucosa by immunomicroscopy 24 hours after inoculation in both non-vaccinated and vaccinated steers. Co-localization of CD11c+/MHC II+ cells with viral protein occurred early at primary infection sites in vaccinated steers while similar host-virus interactions were observed at later time points in non-vaccinated steers. Additionally, numerous CD8+/CD3- host cells, representing presumptive natural killer cells, were observed in association with foci of primary FMDV infection in the nasopharyngeal mucosa of vaccinated steers but were absent in non-vaccinated steers. Immunomicroscopic evidence of an activated antiviral response at primary infection sites of vaccinated cattle was corroborated by a relative induction of interferon -α, -β, -γ and -λ mRNA in micro-dissected samples of nasopharyngeal mucosa. Although vaccination protected cattle from viremia and clinical FMD, there was subclinical infection of

  10. Human adenovirus-vectored foot-and-mouth disease vaccines: establishment of a vaccine product profile through in vitro testing.

    PubMed

    Brake, D A; McIlhaney, M; Miller, T; Christianson, K; Keene, A; Lohnas, G; Purcell, C; Neilan, J; Schutta, C; Barrera, J; Burrage, T; Brough, D E; Butman, B T

    2012-01-01

    Next generation, foot-and-mouth disease (FMD) molecular vaccines based on replication deficient human adenovirus serotype 5 viral vectored delivery of FMD capsid genes (AdFMD) are being developed by the United States Dept. of Homeland Security and industry partners. The strategic goal of this program is to develop AdFMD licensed vaccines for the USA National Veterinary Stockpile for use, if needed, as emergency response tools during an FMD outbreak. This vaccine platform provides a unique opportunity to develop a set of in vitro analytical parameters to generate an AdFMD vaccine product profile to replace the current lot release test for traditional, inactivated FMD vaccines that requires FMDV challenge in livestock. The possibility of an indirect FMD vaccine potency test based on a serological alternative was initially investigated for a lead vaccine candidate, Adt.A24. Results show that serum virus neutralization (SVN) based serology testing for Adt.A24 vaccine lot release is not feasible, at least not in the context of vaccine potency assessment at one week post-vaccination. Thus, an in vitro infectious titer assay (tissue culture infectious dose 50, TCID50) which measures FMD infectious (protein expression) titer was established. Pre-validation results show acceptable assay variability and linearity and these data support further studies to validate the TCID50 assay as a potential potency release test. In addition, a quantitative physiochemical assay (HPLC) and three immunochemical assays (Fluorescent Focus-Forming Unit (FFU); tissue culture expression dose 50 (TCED50); Western blot) were developed for potential use as in vitro assays to monitor AdFMD vaccine lot-to-lot consistency and other potential applications. These results demonstrate the feasibility of using a traditional modified-live vaccine virus infectivity assay in combination with a set of physiochemical and immunochemical tests to build a vaccine product profile that will ensure the each Ad

  11. Complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in Thailand, 2012-2014.

    PubMed

    Mauleekoonphairoj, John; Vongpunsawad, Sompong; Puenpa, Jiratchaya; Korkong, Sumeth; Poovorawan, Yong

    2015-10-01

    The complete genomic sequences of 14 enterovirus 71 (EV71) strains isolated from children with hand, foot, and mouth disease in Thailand from 2012 to 2014 were determined and compared to enterovirus group A prototypes. Phylogenetic analysis revealed that 13 strains resembled the B5 subgroup, while one strain from a fatal case designated THA_1219 belonged to the C4 subgroup. Similarity plot and bootscan analyses suggested that THA_1219 underwent recombination in the P2 and P3 regions. Full-genome data from this work will contribute to the study of evolution dynamics of EV71.

  12. Outbreaks of Foot-and-Mouth Disease in Libya and Saudi Arabia During 2013 Due to an Exotic O/ME-SA/Ind-2001 Lineage Virus.

    PubMed

    Knowles, N J; Bachanek-Bankowska, K; Wadsworth, J; Mioulet, V; Valdazo-González, B; Eldaghayes, I M; Dayhum, A S; Kammon, A M; Sharif, M A; Waight, S; Shamia, A M; Tenzin, S; Wernery, U; Grazioli, S; Brocchi, E; Subramaniam, S; Pattnaik, B; King, D P

    2016-10-01

    Foot-and-mouth disease viruses are often restricted to specific geographical regions and spread to new areas may lead to significant epidemics. Phylogenetic analysis of sequences of the VP1 genome region of recent outbreak viruses from Libya and Saudi Arabia has revealed a lineage, O-Ind-2001, normally found in the Indian subcontinent. This paper describes the characterization of field viruses collected from these cases and provides information about a new real-time RT-PCR assay that can be used to detect viruses from this lineage and discriminate them from other endemic FMD viruses that are co-circulating in North Africa and western Eurasia.

  13. Neutralizing antibody responses to foot-and-mouth disease quadrivalent (type O, A, C and Asia 1) vaccines in growing calves with pre-existing maternal antibodies.

    PubMed

    Patil, Prasanna K; Sajjanar, Channabasavaraj M; Natarajan, Chitattor; Bayry, Jagadeesh

    2014-03-14

    The presence of maternal antibodies is a major obstacle for eliciting protective immune responses to foot-and-mouth disease (FMD) vaccines in young, growing animals. In this report, we analyzed the ability of inactivated quadrivalent oil emulsified and aluminium hydroxide adjuvanted FMD vaccines to elicit neutralizing antibody responses in growing calves that had maternal antibodies. Our results demonstrate that oil emulsified vaccines but not aluminium hydroxide adjuvanted FMD vaccines could surmount maternal antibodies to elicit strong and significant levels of neutralizing antibody responses in growing claves.

  14. Summary of foot-and-mouth disease outbreaks reported in and around the Kruger National Park, South Africa, between 1970 and 2009.

    PubMed

    Dyason, E

    2010-12-01

    Information with regard to foot-and-mouth disease (FMD) outbreaks that occurred in the Kruger National Park (KNP) and adjacent areas of South Africa between 1970 and 2009 was collected from reports and files of various government departments and collated into one report. The collected data were summarised in a table and assessed for patterns. Fifty-one FMD outbreaks occurred during this period in the target area, of which 16 were SAT 1, 31 were SAT 2,4 were SAT 3 and 3 were not serotyped. No pattern could be discerned although SAT 1 outbreaks occurred more frequently in the summer months while more SAT 2 outbreaks occurred in winter.

  15. Increased humoral antibody response of foot-and-mouth disease virus vaccine in growing pigs pre-treated with poly-γ-glutamic acid

    PubMed Central

    Lee, Jee-Hoon; Kang, Ik-Jae; Kim, A-Reum; Noh, You-Sun; Chung, Hee-Chun

    2016-01-01

    This study was conducted to determine if humoral antibody response of foot-and-mouth disease (FMD) vaccine improved in 8-week-old growing pigs born to well-vaccinated sows pre-treated with 60 mg of poly-γ-glutamic acid (γ-PGA) three days before vaccination. Antibody against FMD virus serotype O was measured 0, 2, 4 and 6 weeks post-vaccination, using a PrioCHECK FMDV type O ELISA kit. The results showed that positive antibody reactions against FMDV serotype O antigen among a component of the vaccine significantly increased in response to pre-injection with γ-PGA. PMID:26645341

  16. Role of the international organisation for animal health (Office International des Epizooties: OIE) in the control of foot and mouth disease.

    PubMed

    Vallat, B

    2002-10-01

    The author describes activities conducted by the International Organisation for Animal Health (OIE: Office International des Epizooties) to control foot and mouth disease (FMD) world-wide. These activities fall within the framework of the principal missions of the OIE. The first of these missions is the collection and dissemination of epidemiological information and of scientific knowledge on animal diseases, the socio-economic or disease implications of which can be particularly serious. The implementation of the measures required to control the disease and to protect countries threatened by FMD depends on the quality and rapidity of the transmission of this information. The co-ordination of studies, research and control programmes against FMD is equally important for the OIE. This work is based, in particular, on work conducted by the OlE foot and mouth disease and other epizootics Commission. OIE Member Countries not only have access to the most recent data on the diagnosis, surveillance and control of FMD but also have recourse to the official recognition procedure for disease-free status provided by this Commission. Finally, through the standardisation of health recommendations, diagnostic tests, manufacture protocols and the control of biological products, made available by the OIE International Animal Health Code Commission in regard to the former and by the OIE Standards Commission in regard to the latter, the OIE provides the reference for international trade in animals and animal products, and is recognised in this role by the World Trade Organization.

  17. Epidemiological Characteristics and Spatial-Temporal Clusters of Hand, Foot, and Mouth Disease in Zhejiang Province, China, 2008-2012.

    PubMed

    Gui, Juanjuan; Liu, Zhifang; Zhang, Tianfang; Hua, Qihang; Jiang, Zhenggang; Chen, Bin; Gu, Hua; Lv, Huakun; Dong, Changzheng

    2015-01-01

    Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008-2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen's serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens' serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008-2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children

  18. Rational design and efficacy of a multi-epitope recombinant protein vaccine against foot-and-mouth disease virus serotype A in pigs.

    PubMed

    Cao, Yimei; Li, Dong; Fu, Yuanfang; Bai, Qifeng; Chen, Yingli; Bai, Xingwen; Jing, Zhizhong; Sun, Pu; Bao, Huifang; Li, Pinghua; Zhang, Jing; Ma, Xueqing; Lu, Zengjun; Liu, Zaixin

    2017-04-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and outbreaks of this disease are often economically catastrophic. Recently, a series of outbreaks of foot-and-mouth disease virus (FMDV) serotype A occurred in many countries, including China. Therefore, it is necessary to develop safe and effective vaccines. We designed multi-epitope recombinant proteins A6, A7, and A8 with different three-dimensional structures and compared their immunogenicity in pigs. The results indicated that A8 conferred the greatest protection against FMDV serotype A challenge in pigs, and A8 was selected as the vaccine antigen. We further tested the adjuvant activity of CpG DNA in conjunction with the A8 vaccine, and the results showed significantly increased antigen-specific IFN-γ responses in pigs co-administered A8 with CpG compared to those vaccinated with A8 alone. A vaccine potency test showed that the CpG-adjuvanted A8 vaccine contained a 10.81 protective dose 50% (PD50) per dose for pigs, suggesting the potential for this vaccine to be used in emergency vaccination campaigns for the prevention of FMDV serotype A infection in pigs.

  19. Epidemiology of foot-and-mouth disease in Landhi Dairy Colony, Pakistan, the world largest Buffalo colony

    PubMed Central

    Klein, Joern; Hussain, Manzoor; Ahmad, Munir; Afzal, Muhammad; Alexandersen, Soren

    2008-01-01

    Background Foot-and-mouth disease (FMD) is endemic in Pakistan and causes huge economic losses. This work focus on the Landhi Dairy Colony (LDC), located in the suburbs of Karachi. LDC is the largest Buffalo colony in the world, with more than 300,000 animals (around 95% buffaloes and 5% cattle, as well as an unknown number of sheep and goats). Each month from April 2006 to April 2007 we collected mouth-swabs from apparently healthy buffaloes and cattle, applying a convenient sampling based on a two-stage random sampling scheme, in conjunction with participatory information from each selected farm. Furthermore, we also collected epithelium samples from animals with clinical disease, as well as mouth-swabs samples from those farms. In addition, we analysed a total of 180 serum samples randomly collecting 30 samples each month at the local slaughterhouse, from October 2006 to March 2007. Samples have been screened for FMDV by real-time RT-PCR and the partial or full 1D coding region of selected isolates has been sequenced. Serum samples have been analysed by applying serotype-specific antibody ELISA and non-structural proteins (NSP) antibody ELISA. Results FMDV infection prevalence at aggregate level shows an endemic occurrence of FMDV in the colony, with peaks in August 2006, December 2006 and February 2007 to March 2007. A significant association of prevalence peaks to the rainy seasons, which includes the coldest time of the year and the muslimic Eid-festival, has been demonstrated. Participatory information indicated that 88% of all questioned farmers vaccinate their animals. Analysis of the serum samples showed high levels of antibodies for serotypes O, A, Asia 1 and C. The median endpoint-titre for all tested serotypes, except serotype C, in VNT titration is at a serum dilution of equal or above 1/100. All 180 serum samples collected have been tested for antibodies against the non-structural proteins and all but four have been found positive. Out of the 106

  20. [Epidemiological features and pathogenic characteristics of hand, foot and mouth disease in Gansu Province, China during 2008-2012].

    PubMed

    Yu, De-Shan; Zhang, Yong; Chen, Jian-Hua; Duan, Li-Ping; Zhao, Xiao-Hong; Li, Xiao-Lei; Sun, Qiang; Chen, Xiao; Liu, Jian-Feng; Zheng, Yun-He; Meng, Lei

    2014-01-01

    This study aims to analyze the epidemiological features and pathogenic characteristics of hand, foot and mouth disease (HFMD) in Gansu Province, China and to provide a basis for the development of effective prevention and control measures. The descriptive epidemiological analysis was used to analyse the data of HFMD cases in Gansu. The specimens collected from hospitals were subjected to RT-PCR or real-time PCR to detect human enterovirus (HEV) nucleic acid, and HEV strains were isolated using human rhabdomyosarcoma cells and human laryngeal carcinoma cells. The complete VP1-encoding region of several identified enterovirus A71 (EV71) and coxsackievirus A16 (CVA16) was subjected to full-length amplification by RT-PCR and then to sequencing and analysis. A total of 52 550 HFMD cases were reported in Gansu from 2008 to 2012, including 205 severe cases and 27 deaths. The incidence rates in the whole province from 2008 to 2012 were 22.42/10(5), 49.29/10(5), 47.20/10(5), 27.27/10(5), and 55.84/10(5), respectively. There were cases in all the 14 cities or prefectures in Gansu, and Lanzhou had the largest number of cases (16 001 cases), accounting for 30.45% of all cases in the province. HFMD cases were mostly reported during May to July, accounting for 51.69% of all cases throughout the year. The male-to-female ratio was 1.69:1. Of all the cases, 87.59% were under the age of five. Of the 5 416 cases for laboratory tests, 3 322 (61.34%) were positive for HEV nucleic acid, including EV71 (46.96%), CVA16 (41.57%), and other HEVs (11.47%). Among the 186 severe cases, 114 (61.29%) were positive for HEV nucleic acid, and 82.46% of the positive cases for EV71. All the 25 dead cases were infected with EV71. A total of 402 strains were isolated from 3 111 specimens collected from hospitals (2 123 throat swab specimens, 705 stool specimens, and 705 herpes specimens), including EV71 (70.15%), CVA16 (27.11), other coxsackievirus A (3.98%), coxsackievirus B (2.49%), echovirus (1

  1. Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination

    PubMed Central

    Takahashi, Saki; Liao, Qiaohong; Van Boeckel, Thomas P.; Xing, Weijia; Sun, Junling; Hsiao, Victor Y.; Metcalf, C. Jessica E.; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Wu, Joseph T.; Cowling, Benjamin J.; Leung, Gabriel M.; Farrar, Jeremy J.; van Doorn, H. Rogier; Grenfell, Bryan T.; Yu, Hongjie

    2016-01-01

    Background Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Methods and Findings Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible–infected–recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces

  2. Novel chimeric foot-and-mouth disease virus-like particles harboring serotype O VP1 protect guinea pigs against challenge.

    PubMed

    Li, Haitao; Li, Zhiyong; Xie, Yinli; Qin, Xiaodong; Qi, Xingcai; Sun, Peng; Bai, Xingwen; Ma, Youji; Zhang, Zhidong

    2016-02-01

    Foot-and-mouth disease is a highly contagious, acute viral disease of cloven-hoofed animal species causing severe economic losses worldwide. Among the seven serotypes of foot-and-mouth disease virus (FMDV), serotype O is predominant, but its viral capsid is more acid sensitive than other serotypes, making it more difficult to produce empty serotype O VLPs in the low pH insect hemolymph. Therefore, a novel chimeric virus-like particle (VLP)-based candidate vaccine for serotype O FMDV was developed and characterized in the present study. The chimeric VLPs were composed of antigenic VP1 from serotype O and segments of viral capsid proteins from serotype Asia1. These VLPs elicited significantly higher FMDV-specific antibody levels in immunized mice than did the inactivated vaccine. Furthermore, the chimeric VLPs protected guinea pigs from FMDV challenge with an efficacy similar to that of the inactivated vaccine. These results suggest that chimeric VLPs have the potential for use in vaccines against serotype O FMDV infection.

  3. Foot-and-mouth disease virus structural protein VP3 degrades Janus kinase 1 to inhibit IFN-γ signal transduction pathways

    PubMed Central

    Li, Dan; Wei, Jin; Yang, Fan; Liu, Hua-Nan; Zhu, Zi-Xiang; Cao, Wei-Jun; Li, Shu; Liu, Xiang-Tao; Zheng, Hai-Xue; Shu, Hong-Bing

    2016-01-01

    ABSTRACT Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV Lpro and 3Cpro on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN-γ-triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways. PMID:26901336

  4. Adjuvant effect of Cliptox on the protective immune response induced by an inactivated vaccine against foot and mouth disease virus in mice.

    PubMed

    Batista, A; Quattrocchi, V; Olivera, V; Langellotti, C; Pappalardo, J S; Di Giacomo, S; Mongini, C; Portuondo, D; Zamorano, P

    2010-08-31

    Foot and Mouth Disease (FMD) is an acute disease caused by Foot and Mouth Disease Virus (FMDV) which causes important economy losses, this is why it is necessary to obtain a vaccine that stimulates a rapid and long-lasting protective immune response. Cliptox is a mineral microparticle that in earlier studies has shown adjuvant activity against different antigens. In this study we have examined the effects of Cliptox on the magnitude and type of immunity elicited in response to inactivated FMDV (iFMDV) vaccine. It was demonstrated that iFMDV-Cliptox stimulates a specific antibody response detected in mucosal and in sera. The different isotype profiles elicited by inoculation with this vaccine indicate a Th1/Th2 response. Also, an increase in dendritic cells and macrophages in the spleen in comparison with the iFMDV vaccine iFMDV-Cliptox was detected. The Cliptox-iFMDV formulation was non toxic by using egg embryos and yielded increased protection against challenge with FMDV in the murine model. Our results show that the incorporation of Cliptox into FMDVi vaccine induces an increase of the specific protective immune response in mice and clearly indicate that Cliptox TM exert an (important) up-regulation on DC and MPhi. Additionally, Cliptox TM adjuvant can be used in vaccines for induction of mucosal immune response.

  5. Destructive tension: mathematics versus experience--the progress and control of the 2001 foot and mouth disease epidemic in Great Britain.

    PubMed

    Mansley, L M; Donaldson, A I; Thrusfield, M V; Honhold, N

    2011-08-01

    The 2001 foot and mouth disease epidemic in Great Britain was characterised by control using both traditional and novel methods, some resulting from conclusions of mathematical models. Seven days before the implementation of the novel controversial automatic pre-emptive culling of all susceptible livestock on premises adjacent to infected premises (the 'contiguous cull'), the spread of infection had already been controlled by a combination of the traditional stamping out policy with a national movement ban on livestock. A second controversial novel policy requiring the slaughter of sheep within 3 km of premises on which disease had been confirmed (the 3-km cull) also commenced after the peak of infection spread, was untargeted and took several weeks to complete; serosurveillance of culled sheep detected infection in only one flock, suggesting that cryptic infection of sheep was not propagating the epidemic. Extensive post-epidemic serological surveillance of sheep found only a small number of seropositive animals in a very few flocks, suggesting that foot and mouth disease may self-limit in extensive sheep populations. The epidemic was finally brought to an end following the introduction of enhanced agricultural movement restrictions and biosecurity measures. A welfare culling scheme of unaffected animals was required to support the prolonged national livestock movement ban. The models that supported the contiguous culling policy were severely flawed, being based on data from dissimilar epidemics; used inaccurate background population data, and contained highly improbable biological assumptions about the temporal and quantitative parameters of infection and virus emission in infected herds and flocks.

  6. Serological evidence indicates that foot-and-mouth disease virus serotype O, C and SAT1 are most dominant in eritrea.

    PubMed

    Tekleghiorghis, T; Moormann, R J M; Weerdmeester, K; Dekker, A

    2014-12-01

    Foot-and-mouth disease (FMD) is endemic in Eritrea and in most parts of Africa. To be able to control FMD using vaccination, information on the occurrence of various foot-and-mouth disease serotypes in Eritrea is needed. In this cross-sectional study, 212 sera samples were collected from FMD infected and recovered animals in Eritrea. These samples were tested for the presence of antibodies against FMD non-structural proteins (NSP) and neutralizing antibodies against six of the seven (all but SAT 3) serotypes of FMD virus (FMDV). Of these, 67.0% tested positive to non-structural protein antibodies in the FMD NS ELISA. By virus neutralization, FMDV serotype O antibodies were shown to be the most dominant (approximately 50%). Virus neutralization test results indicate that infection with serotype C and SAT 1 might have occurred, although there are no reports of isolation of these two serotypes. Because the samples were not randomly selected, further random serological surveillance in all age group animals is necessary both to estimate the prevalence of FMD in the country and to confirm the serological results with serotype C and SAT 1.

  7. The importance of quality assurance/quality control of diagnostics to increase the confidence in global foot-and-mouth disease control.

    PubMed

    De Clercq, K; Goris, N; Barnett, P V; MacKay, D K

    2008-01-01

    The last decade international trade in animals and animal products was liberated and confidence in this global trade can increase only if appropriate control measures are applied. As foot-and-mouth disease (FMD) diagnostics will play an essential role in this respect, the Food and Agriculture Organization European Commission for the Control of Foot-and-Mouth Disease (EUFMD) co-ordinates, in collaboration with the European Commission, several programmes to increase the quality of FMD diagnostics. A quality assurance (QA) system is deemed essential for laboratories involved in certifying absence of FMDV or antibodies against the virus. Therefore, laboratories are encouraged to validate their diagnostic tests fully and to install a continuous quality control (QC) monitoring system. Knowledge of performance characteristics of diagnostics is essential to interpret results correctly and to calculate sample rates in regional surveillance campaigns. Different aspects of QA/QC of classical and new FMD virological and serological diagnostics are discussed in respect to the EU FMD directive (2003/85/EC). We recommended accepting trade certificates only from laboratories participating in international proficiency testing on a regular basis.

  8. Marker vaccine potential of a foot-and-mouth disease virus with a partial VP1 G-H loop deletion.

    PubMed

    Fowler, V L; Knowles, N J; Paton, D J; Barnett, P V

    2010-04-26

    Previous work in cattle and pigs demonstrated that protection against foot-and-mouth disease (FMD) could be achieved following vaccination with chimeric foot-and-mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been substituted with that from another serotype. This indicated that the VP1 G-H loop may not be essential for the protection of natural hosts against FMDV. If this could be substantiated there would be potential to develop FMD marker vaccines, characterised by the absence of this region. Here, we investigate the serological responses to vaccination with a virus with a partial VP1 G-H loop deletion in order to determine the likelihood of achieving protection and the potential of this virus as a marker vaccine. Inactivated, oil adjuvanted, vaccines, consisting of chemically inactivated virus with or without a partially deleted VP1 G-H loop, were used to immunise cattle. Serum was collected on days 0, 7, 14 and 21 and antibody titres calculated using the virus neutralisation test (VNT) to estimate the likelihood of protection. We predict a good likelihood that cattle vaccinated with a vaccine characterised by a partial VP1 G-H loop would be protected against challenge with the same virus containing the VP1 G-H loop. We also present evidence on the potential of such a construct to act as a marker vaccine, when used in conjunction with a novel serological test.

  9. Etiology of Multiple Non-EV71 and Non-CVA16 Enteroviruses Associated with Hand, Foot and Mouth Disease in Jinan, China, 2009-June 2013.

    PubMed

    Guan, Hengyun; Wang, Ji; Wang, Chunrong; Yang, Mengjie; Liu, Lanzheng; Yang, Guoliang; Ma, Xuejun

    2015-01-01

    Hand, foot, and mouth disease (HFMD) is an infectious disease caused by human enterovirus 71 (EV71), coxsackievirus A16 (CVA16) and other enteroviruses. It is of interest that other enteroviruses associated with HFMD in Jinan have been rarely reported. The aim of the present study is to detect and characterize the circulating serotypes of non-EV71 and non-CVA16 enteroviruses associated with HFMD in Jinan city, Shandong province, China. A total of 400 specimens were collected from clinically diagnosed HFMD cases in Jinan from January 2009 to June 2013. All specimens were infected with non-EV71 and non-CVA16 enteroviruses previously confirmed by RT-PCR or real-time PCR according to the protocols at that time. The GeXP-based multiplex RT-PCR assay (GeXP assay) was performed to investigate the pathogen spectrum of 15 enteroviruses (coxsackieviruses A4, A5, A6, A9, A10, A16; coxsackieviruses B1, B3, B5; Echoviruses 6, 7, 11, 13, 19 and EV71) infections associated with HMFD. For GeXP assay negative samples, reverse transcription nested PCR (nested RT-PCR) based on the 5' -untranslated region (5'- UTR) sequence and phylogenetic analysis were conducted to further explore the etiology of multiple enteroviruses. The results showed that a total of twenty serotypes of enteroviruses (including EV71 and CVA16) were identified by GeXP assay and nested RT-PCR. The most circulating twelve serotypes of enteroviruses with HFMD in Jinan from 2009 to June 2013 were EV71, CVA16, CVA10, CVA6, CVA12, CVA2, Echo3, CVA4, CVA9, CVB1, CVB3 and Echo6. CVA10 and CVA6 were the most prevalent pathogens other than EV71 and CVA16 in Jinan and their most prevalent seasons were spring and summer, and a slight increase was observed in autumn and early winter. It should be noted that mixed-infections were identified by GeXP assay and the phylogenetic tree clearly discriminated the multiple pathogens associated with HFMD. Our results thus demonstrate that there was a clear lack of a reliable testing

  10. Clinical, haematological and biochemical alterations in heat intolerance (panting) syndrome in Egyptian cattle following natural foot-and-mouth disease (FMD).

    PubMed

    Ghanem, Mohamed M; Abdel-Hamid, Omnia M

    2010-08-01

    Clinical signs of heat intolerance (panting) syndrome were observed in Holstein cows in a private farm in Egypt. There were heat intolerance (fever), panting, profuse salivation, hirsutism, lameness and reduced milk production. Blood and serum samples were collected from ten diseased cows and five apparently healthy cows as control. Serological tests confirmed the presence of non-structural protein of foot-and-mouth disease (FMD) infection. There were significant reductions in the total red blood cell count with increased leucocytic and lymphocytic counts in diseased group compared to control. The serum Na, Cl, Ca, Mg, Zn and Fe were significantly reduced but P was increased in diseased animals compared to control. The total protein, albumin, cholesterol and cortisol were significantly reduced but the glucose and malonaldehyde were significantly increased in diseased cows. This was the first report in Egypt to describe the clinical and haemato-biochemical changes in panting syndrome following FMD.

  11. Influence of dipping practices on the seroprevalence of babesiosis and anaplasmosis in the foot-and-mouth disease buffer zone adjoining the Kruger National Park in South Africa.

    PubMed

    Stevens, K B; Spickett, A M; Vosloo, W; Pfeiffer, D U; Dyason, E; Du Plessis, B

    2007-06-01

    A serological survey of bovine babesiosis and anaplasmosis was conducted in the foot-and-mouth disease buffer zone surrounding the Kruger National Park in South Africa between 2001 and 2003 to determine whether the withdrawal of government-subsidized dipping in certain regions had affected the seroprevalence of these tick-borne diseases. Seroprevalence of Anaplasma marginale and Babesia bovis increased during the study period. This increase was greater in Limpopo Province where farmers had to supply their own acaricide than in Mpumalanga Province where dipping materials were provided by the local Veterinary Services. The number of animals testing positive for B. bigemina decreased in both provinces during the study period, which was attributed to possible vector displacement rather than more effective tick control measures. Responses to a questionnaire on ticks and tick-borne diseases revealed local knowledge on the subject to be highly variable and sometimes incorrect.

  12. Experimental infection of cattle and goats with a foot-and-mouth disease virus isolate from the 2010 epidemic in Japan.

    PubMed

    Onozato, Hiroyuki; Fukai, Katsuhiko; Kitano, Rie; Yamazoe, Reiko; Morioka, Kazuki; Yamada, Manabu; Ohashi, Seiichi; Yoshida, Kazuo; Kanno, Toru

    2014-11-01

    In this study, we carried out experimental infections in cattle and goats using a foot-and-mouth disease virus (FMDV) isolate from the 2010 epidemic in Japan to analyze clinical manifestations, virus-shedding patterns and antibody responses in the animals. We found that the FMDV O/JPN/2010 isolate is virulent in cattle and goats, produces clinical signs, is spread efficiently by direct contact within the same species, and is persistently infectious in cattle. Quantitative analysis of levels of viral RNA in the tissues of cattle and goats infected with the isolate showed that the pharyngeal region is an important major target of the FMDV O/JPN/2010. Time course data of viral loads, excretion and transmission of the FMDV O/JPN/2010 in this study are key in providing quantitative data essential for epidemiological investigation and risk analysis in relation to disease controls.

  13. Variation in the VP1 gene of foot-and-mouth disease virus serotype A associated with epidemiological characteristics of outbreaks in the 2001 epizootic in Argentina.

    PubMed

    Perez, Andres M; König, Guido; Späth, Ernesto; Thurmond, Mark C

    2008-07-01

    A mixed binomial Bayesian regression model was used to quantify the relation between nucleotide differences in the VP1 gene of Foot-and-mouth disease virus (FMDV) serotype A, and epidemiologic characteristics of the outbreaks from which the viruses were obtained between January and December 2001 in Argentina. An increase in the probability of different nucleotides between isolates was associated with a longer time between isolation dates, a greater distance between isolation locations, an increase in the difference between attack rates, and an increase in the difference in outbreak durations. The farther apart the outbreak herds were in the southerly and easterly directions, the greater the difference in nucleotide changes. The model accurately predicted genetic distances of isolates obtained in 2001 compared with a 2002 isolate (P < 0.01), which suggested that the predictive modeling approach applied in the present study may be useful in understanding the epidemiology of evolution of FMDV and in forensic analysis of disease epidemics.

  14. Options for managing animal welfare on intensive pig farms confined by movement restrictions during an outbreak of foot and mouth disease.

    PubMed

    East, I J; Roche, S E; Wicks, R M; de Witte, K; Garner, M G

    2014-12-01

    An outbreak of foot and mouth disease in Australia would trigger a major disease control and eradication program that would include restriction of movement of live animals within defined disease control zones. Experiences from outbreaks in other countries show that restrictions that limit the ability to turn off stock can lead to animal welfare compromise on intensively managed farms that are not infected with the disease. Intensive pig farms are considered to be at high risk of developing welfare problems during a control program due to the imposed movement restrictions and limited space available to house growing pigs. This study was designed to investigate strategies that could be used to mitigate animal welfare problems on intensive pig farms during a simulated outbreak of foot and mouth disease in a livestock dense region of Australia. Three strategies for managing farms affected by animal welfare problems were assessed, including on-farm culling of grower and finisher pigs, on-farm culling of finisher pigs only, and permit-based movement of finisher pigs to slaughter at abattoir. Under traditional approaches of giving infected premises (IP) priority over culling of farms with welfare problems (WP), delays of up to 25 days were experienced prior to culling of WPs. Deployment of vaccination did little to reduce the delay to culling of WPs. These delays were sensitive to resources available for control, with reduced resources increasing the time until welfare problems were addressed. Assigning equal priority to all farms requiring culling regardless of status as IP or WP and culling each as they arose reduced the delay to culling of WPs to no more than 4 days without large increases in either the duration or the size of the outbreaks observed.

  15. Intratypic heterologous vaccination of calves can induce an antibody response in presence of maternal antibodies against foot-and-mouth disease virus

    PubMed Central

    2014-01-01

    Background Maternal antibodies can interfere with foot-and-mouth disease vaccination. In this study we determined whether intratypic heterologous vaccination could help to improve herd immunity. Results In unvaccinated calves, a half-life of maternal antibodies of 21 days was determined. At two weeks of age, calves without maternal antibodies showed a good antibody response against both vaccines used in the trial, while in calves with maternal antibodies no antibody response to homologous vaccination (A Turkey 14/98) but a limited antibody response to intratypic heterologous vaccination (A22 Iraq) was observed. Conclusion Two weeks old calves without maternal antibodies respond well to vaccination, but when emergency vaccination is carried out in a region that uses prophylactic vaccination, using an intratypic heterologous vaccine strain may improve the immunity in calves with maternal antibodies. PMID:24906852

  16. Genetic and immunologic relationships between vaccine and field strains for vaccine selection of type A foot-and-mouth disease virus circulating in East Asia.

    PubMed

    Lee, Seo-Yong; Park, Min-Eun; Kim, Rae-Hyung; Ko, Mi-Kyeong; Lee, Kwang-Nyeong; Kim, Su-Mi; Shim, Hang-Sub; Kim, Byounghan; Lee, Jong-Soo; Park, Jong-Hyeon

    2015-01-29

    Of the seven known serotypes of foot-and-mouth disease virus (FMDV), type A has the most diverse variations. Genetic variations also occur frequently at VP1, VP2, VP3, and VP4 because these proteins constitute the viral capsid. The structural proteins of FMDV, which are closely related to immunologic correlations, are the most easily analyzed because they have highly accessible information. In this study we analyzed the type A vaccine viruses by alignment of available sequences in order to find appropriate vaccine strains. The matching rate of ASIA topotype-specific sites (20 amino acids) located on the viral surface, which are mainly VP1 and VP2, was highly related to immunologic reactivity. Among the available vaccines analyzed in this study, we suggest that A Malaysia 97 could be used as a vaccine virus as it has the highest genetic similarity and immunologic aspects to field strains originating in East Asia.

  17. Stable expression of foot-and-mouth disease virus protein VP1 fused with cholera toxin B subunit in the potato (Solanum tuberosum).

    PubMed

    He, Dong-Mei; Qian, Kai-Xian; Shen, Gui-Fang; Li, Yi-Nü; Zhang, Zhi-Fang; Su, Zhong-Liang; Shao, Hong-Bo

    2007-04-01

    The expression vector, pBI121CTBVP1, containing the fusion of the foot and mouth disease virus (FMDV) VP1 gene and the cholera toxin B subunit (CTB) gene was constructed by fused PCR and transferred into potato (Solanum tuberosum L.) by Agrobacterium-mediated transformation. Transformed plants were obtained by selecting on kanamycin-resistant medium strictly and regenerated. The transgenic plantlets were identified by PCR, Southern-blot and the production of fused protein was confirmed and quantified by Western-blot and ELISA assays. The results showed that the fused genes were expressed stablely under the control of specific-tuber patatin promoter. The expressed fused proteins have a certain degree of immunogenicity.

  18. Full genome sequence of a novel coxsackievirus B5 strain isolated from neurological hand, foot, and mouth disease patients in China.

    PubMed

    Hu, Y F; Zhao, R; Xue, Y; Yang, Fan; Jin, Q

    2012-10-01

    Coxsackievirus B5 (CVB5) belongs to the human enterovirus B species within the family Picornaviridae. We report the complete genome sequence of a novel CVB5 strain, CVB5/SD/09, that is associated with neurological hand, foot, and mouth disease in China. The complete genome consists of 7,399 nucleotides, excluding the 3' poly(A) tail, and has an open reading frame that maps between nucleotide positions 744 and 7301 and encodes a 2,185-amino-acid polyprotein. Phylogenetic analysis based on different genome region regions reveals that CVB5/SD/09 belongs to a novel CVB5 lineage, and similarity plotting and bootscanning analysis based on the whole genome of CVB5 in the present study and those available in GenBank indicate that the genome of CVB5/SD/09 has a mosaic-like structure, suggesting that recombination between different CVB5 strains may occur.

  19. Enhanced immune responses of foot-and-mouth disease vaccine using new oil/gel adjuvant mixtures in pigs and goats.

    PubMed

    Park, Min-Eun; Lee, Seo-Yong; Kim, Rae-Hyung; Ko, Mi-Kyeong; Lee, Kwang-Nyeong; Kim, Su-Mi; Kim, Byoung-Kwan; Lee, Jong-Soo; Kim, Byounghan; Park, Jong-Hyeon

    2014-09-08

    The immunity and protective capability produced by vaccines can vary remarkably according to the kinds of adjuvants being used. In the case of foot-and-mouth disease (FMD) vaccines in pigs, only oil-adjuvant vaccines have been used, and these tend to show lower immunity in pigs than in cattle. New adjuvants for these vaccines are therefore needed. We made different experimental FMD vaccines using new adjuvants (ISA 201, Carbigen, Emulsigen-D) and well-known adjuvants (ISA 206, aluminum hydroxide gel) and then conducted tests to compare the enhancement in pig immunity. More effective immune responses and protection against challenge were observed with the new adjuvants Emulsigen-D and ISA 201 compared to existing adjuvants. In the case of dairy goats, a mixture of Emulsigen-D and aluminum hydroxide gel produced rapid neutralizing antibody responses that were similar to results from tests conducted with pigs.

  20. Experimental evidence for competitive growth advantage of genotype VII over VI: implications for foot-and-mouth disease virus serotype A genotype turnover in nature.

    PubMed

    Mohapatra, J K; Subramaniam, S; Singh, N K; Sanyal, A; Pattnaik, B

    2012-04-01

    In India, systematic genotype replacement has been observed for serotype A foot-and-mouth disease virus. After a decade of co-circulation of genotypes VI and VII, genotype VII emerged as the single dominant genotype since 2001. To derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. Coinfection of BHK-21 cells demonstrated abrupt loss in the genotype VI viral load with commensurate increase in the load of genotype VII as measured by the genotype differentiating ELISA, RT-PCR and real-time RT-PCR. The superinfection dynamics was shaped by temporal spacing of infection, where the invading genotype VII took more number of passages than coinfection to eventually overtake the resident genotype VI. It was speculated that such superior replicative fitness of genotype VII could have been a possible factor for the ultimate dominance of genotype VII in nature.

  1. Influence of hydrophilic amino acids and GC-content on expression of recombinant proteins used in vaccines against foot-and-mouth disease virus in Escherichia coli.

    PubMed

    Wei, Hongfei; Fang, Mingli; Wan, Min; Wang, Hua; Zhang, Peiyin; Hu, Xiaoping; Wu, Xiuli; Yang, Ming; Zhang, Yongsheng; Zhou, Lei; Jiao, Chengfeng; Hua, Li; Diao, Wenzhen; Xiao, Yue; Yu, Yongli; Wang, Liying

    2014-04-01

    Epitope-based protein expression in Escherichia coli can be improved by adjusting its amino acid composition and encoding genes. To that end, we analyzed 24 recombinant epitope proteins (rEPs) that carry multiple epitopes derived from VP1 protein of foot-and-mouth disease virus. High level expression of the rEPs was attributed to a high content of Arg, Asn, Asp and Thr, a low content of Gln, Pro and Lys, a high content of hydrophilic amino acids and a higher isoelectric point value resulting from abundant Arg. It is also attributed to the appropriate guanine and cytosine content in the encoding genes. The data provide a reference for adjusting the amino acid composition in designing epitope-based proteins used in vaccines and for adjusting the synonymous codons to improve their expressions in E. coli.

  2. L protease from foot and mouth disease virus confers eIF2-independent translation for mRNAs bearing picornavirus IRES.

    PubMed

    Moral-López, Pablo; Alvarez, Enrique; Redondo, Natalia; Skern, Tim; Carrasco, Luis

    2014-11-03

    The leader protease (L(pro)) from foot-and-mouth disease virus (FMDV) has the ability to cleave eIF4G, leading to a blockade of cellular protein synthesis. In contrast to previous reports, our present findings demonstrate that FMDV L(pro) is able to increase translation driven by FMDV IRES. Additionally, inactivation of eIF2 subsequent to phosphorylation induced by arsenite or thapsigargin in BHK cells blocks protein synthesis directed by FMDV IRES, whereas in the presence of L(pro), significant translation is found under these conditions. This phenomenon was also observed in cell-free systems after induction of eIF2 phosphorylation by addition of poly(I:C).

  3. Natural transmission of foot-and-mouth disease virus between African buffalo (Syncerus caffer) and impala (Aepyceros melampus) in the Kruger National Park, South Africa.

    PubMed

    Bastos, A D; Boshoff, C I; Keet, D F; Bengis, R G; Thomson, G R

    2000-06-01

    VP1 gene sequences of SAT-2 type foot-and-mouth disease (FMD) viruses recovered from impala and African buffalo in the Kruger National Park (KNP) were used to determine intra- and interspecies relationships of viruses circulating in these wildlife populations. On this basis five distinct lineages of SAT-2 virus were identified in routine sampling of oesophageopharyngeal epithelium from buffalo between 1988 and 1996. Different lineages were associated with discrete geographic sampling localities. Over the period 1985-95, four unrelated epizootics occurred in impala in defined localities within the KNP. Evidence for natural transmission of FMD between buffalo and impala is presented for the most recent 1995 outbreak, with data linking the 1985 and 1988/9 impala epizootics to viruses associated with specific buffalo herds.

  4. Development of a Feature and Template-Assisted Assembler and Application to the Analysis of a Foot-and-Mouth Disease Virus Genotyping Microarray

    PubMed Central

    Rowland, Jessica M.; Grau, Frederic R.; McIntosh, Michael T.

    2017-01-01

    Several RT-PCR and genome sequencing strategies exist for the resolution of Foot-and-Mouth Disease virus (FMDV). While these approaches are relatively straightforward, they can be vulnerable to failure due to the unpredictable nature of FMDV genome sequence variations. Sequence independent single primer amplification (SISPA) followed by genotyping microarray offers an attractive unbiased approach to FMDV characterization. Here we describe a custom FMDV microarray and a companion feature and template-assisted assembler software (FAT-assembler) capable of resolving virus genome sequence using a moderate number of conserved microarray features. The results demonstrate that this approach may be used to rapidly characterize naturally occurring FMDV as well as an engineered chimeric strain of FMDV. The FAT-assembler, while applied to resolving FMDV genomes, represents a new bioinformatics approach that should be broadly applicable to interpreting microarray genotyping data for other viruses or target organisms. PMID:28045937

  5. Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

    SciTech Connect

    Steinberger, Jutta; Rancan, Chiara; Skern, Tim

    2013-09-01

    The foot-and-mouth disease virus leader proteinase (Lb{sup pro}) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb{sup pro} L200F provide structural evidence for intramolecular self-processing. {sup 15}N-HSQC measurements of Lb{sup pro} L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb{sup pro}, lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb{sup pro}, stably binds its own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb{sup pro} and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb{sup pro}. - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecular complex. • Subdomain orientation explains differences in stability of intramolecular complexes.

  6. Application of non-structural protein antibody tests in substantiating freedom from foot-and-mouth disease virus infection after emergency vaccination of cattle.

    PubMed

    Paton, David J; de Clercq, Kris; Greiner, Matthias; Dekker, Aldo; Brocchi, Emiliana; Bergmann, Ingrid; Sammin, Donal J; Gubbins, Simon; Parida, Satya

    2006-10-30

    There has been much debate about the use of the so-called "vaccinate-to-live" policy for the control of foot-and-mouth disease (FMD) in Europe, according to which, spread of the FMD virus (FMDV) from future outbreaks could be controlled by a short period of "emergency" vaccination of surrounding herds, reducing the need for large-scale preemptive culling of at-risk animals. Since vaccinated animals may become subclinically infected with FMDV following challenge exposure, it is necessary to either remove all vaccinates (vaccinate-to-kill) or to detect and remove vaccinates in which virus is circulating or has established persistent infections (vaccinate-to-live), in order to rapidly regain the most favoured trading status of FMD-free without vaccination. The latter approach can be supported by testing vaccinated animals for the presence of antibodies to certain non-structural proteins (NSP) of FMDV, which are induced by infection with the virus, but not by vaccination with purified FMD vaccines. Using test sensitivity and specificity data established at a recent workshop on NSP assays [Brocchi E, Bergmann I, Dekker A, Paton DJ, Sammin DJ, Greiner M, et al. Comparative performance of six ELISAs for antibodies to the non-structural proteins of foot-and-mouth disease. Vaccine, in press], this paper examines the ways in which serological testing with NSP ELISAs can be used and interpreted and the effect that this will have on the confidence with which freedom from infection can be demonstrated within guidelines specified by the World Animal Health Organisation and the European Commission.

  7. Qualitative assessment of the commodity risk for spread of foot-and-mouth disease associated with international trade in deboned beef.

    PubMed

    Paton, D J; Sinclair, M; Rodríguez, R

    2010-06-01

    The risk of importing foot-and-mouth disease virus (FMDV) restricts trade in livestock and their products from parts of the world where the virus is present. This reduces trade opportunities and investment in the livestock sector of many developing countries and constrains global food supply. This review focuses on the risks associated with trade in deboned beef (DB) from foot-and-mouth disease (FMD)-infected cattle, countries or zones. A definition of DB is provided along with a description of the procedures for its preparation within beef slaughtering operations. Evidence is reviewed for circumstances under which DB can be contaminated with FMDV, and a commodity risk factor approach is used to consider the mitigating efficacy of slaughterhouse procedures. A combination of pre-slaughter and slaughterhouse measures has enabled DB to be safely imported into FMD-free countries from countries that were not nationally or zonally FMD-free. Nevertheless, current evidence does not provide absolute assurance that abattoir procedures for producing DB can result, by themselves, in a commodity with a negligible risk of transmitting FMDV without complementary measures to reduce the likelihood of slaughtering infected cattle. The main areas of uncertainty are the amounts of residual FMDV-harbouring tissues within DB, and our understanding of what constitutes a safe level of contamination. More detailed guidance should be developed to specify the mitigating measures needed in support of the export of DB from regions that are not officially FMD-free. This will help to avoid differences in interpretation of what is needed that give rise to obstacles to trade.

  8. Expanding specificity of class 1 restricted CD8+ T cells for viral epitopes following multiple inoculations of swine with a human adenivorus vectored foot-and-mouth disease virus (FMDV) vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune response to the highly acute foot-and-mouth disease virus (FMDV) is routinely reported as a measure of serum antibody. However, a critical effector function of immune responses combating viral infection of mammals is the cytotoxic T lymphocyte (CTL) response, mediated by virus specific ...

  9. Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic immune response to vaccination and challenge was studied in 47 Holstein steers. Eighteen steers which had received one dose of recombinant FMDV A vaccine t...

  10. Disease dynamics over very different time-scales: foot-and-mouth disease and scrapie on the network of livestock movements in the UK.

    PubMed

    Kao, Rowland R; Green, Darren M; Johnson, Jethro; Kiss, Istvan Z

    2007-10-22

    We analyse the relationship between the network of livestock movements in the UK and the dynamics of two diseases: foot-and-mouth disease (FMD), which has an incubation period of days, and scrapie, which incubates over years. For FMD, the time-scale of expected epidemics is similar to the time-scale of the evolution of the network. We argue that, under appropriate conditions, a static network analysis can be an appropriate tool for gaining insights into disease dynamics even when the relevant time-scales are similar, as with FMD. We show that a subclass of 'linkage moves' maintains the network structure, and so removing these links has a dramatic effect on the number of potentially infected farms, an effect corroborated by simulations. In contrast, because scrapie has a low probability of transmission per contact and a long incubation period, a static network representation is probably appropriate; however, the signature of the network in the pattern of transmission is likely to be faint. Scrapie-notifying farms were more likely to be associated with each other via trading at markets than were control farms; however, network community structure proves to be less representative of prevalence patterns than geographical region. These contradictory indicators emphasize that appropriate observation time frames and good discrimination among types of potentially infectious contacts are vital in order for network analysis to be a valuable epidemiological tool.

  11. Subcellular distribution of swine vesicular disease virus proteins and alterations induced in infected cells: A comparative study with foot-and-mouth disease virus and vesicular stomatitis virus

    SciTech Connect

    Martin-Acebes, Miguel A.; Gonzalez-Magaldi, Monica; Rosas, Maria F.; Borrego, Belen; Brocchi, Emiliana; Armas-Portela, Rosario; Sobrino, Francisco

    2008-05-10

    The intracellular distribution of swine vesicular disease virus (SVDV) proteins and the induced reorganization of endomembranes in IBRS-2 cells were analyzed. Fluorescence to new SVDV capsids appeared first upon infection, concentrated in perinuclear circular structures and colocalized to dsRNA. As in foot-and-mouth disease virus (FMDV)-infected cells, a vesicular pattern was predominantly found in later stages of SVDV capsid morphogenesis that colocalized with those of non-structural proteins 2C, 2BC and 3A. These results suggest that assembly of capsid proteins is associated to the replication complex. Confocal microscopy showed a decreased fluorescence to ER markers (calreticulin and protein disulfide isomerase), and disorganization of cis-Golgi gp74 and trans-Golgi caveolin-1 markers in SVDV- and FMDV-, but not in vesicular stomatitis virus (VSV)-infected cells. Electron microscopy of SVDV-infected cells at an early stage of infection revealed fragmented ER cisternae with expanded lumen and accumulation of large Golgi vesicles, suggesting alterations of vesicle traffic through Golgi compartments. At this early stage, FMDV induced different patterns of ER fragmentation and Golgi alterations. At later stages of SVDV cytopathology, cells showed a completely vacuolated cytoplasm containing vesicles of different sizes. Cell treatment with brefeldin A, which disrupts the Golgi complex, reduced SVDV ({approx} 5 log) and VSV ({approx} 4 log) titers, but did not affect FMDV growth. Thus, three viruses, which share target tissues and clinical signs in natural hosts, induce different intracellular effects in cultured cells.

  12. Cattle, sheep and pigs vaccinated against foot and mouth disease: does trade in these animals and their products present a risk of transmitting the disease?

    PubMed

    Garland, A J M; de Clercq, K

    2011-04-01

    The foot and mouth disease (FMD) status of a country or region has a profound bearing on access to export markets for live animals and animal products. In countries without FMD-free status, and in accordance with the international standards of the World Organisation for Animal Health (OIE), restrictions may be applied to trade in both vaccinated and unvaccinated animals and their products. Available information suggests that, provided there is compliance with essential criteria concerning vaccines, vaccination and other zoosanitary measures (especially quarantine and ante- and post-mortem inspection), the risk of spreading FMD through the importation of vaccinated cattle, sheep and pigs is extremely small. The risk from products derived from vaccinated animals is even smaller, provided that appropriate risk mitigation measures are applied. Knowledge of the zoosanitary status of the exporting country is critical for risk assessment, but can be difficult to verify. Although empirical evidence and practical experience strongly indicate low risk, it is not possible to assert that the risk is zero for vaccinated animals or their products. In the absence of key factual data, risk analysis is only practicable on a qualitative or semi-quantitative basis. However, a very low level of risk is both unavoidable and acceptable if such trade is to be conducted.

  13. The foot-and-mouth disease epidemic of 2001 in the UK: implications for the USA and the "war on terror".

    PubMed

    Gibbs, Paul

    2003-01-01

    While there is no evidence to suggest that the recent epidemic of foot-and-mouth disease (Fmd) in the Uk and its subsequent spread to continental Europe were caused by bioterrorism, the extent of the epidemic shows that Fmd could be a very powerful weapon for a bioterrorist wishing to cause widespread disease in livestock and economic disruption for the targeted country. This paper describes the epidemic. It then examines the contentious issues that arose through the use of extensive slaughter to control the epidemic and explores how, in turn, the concerns of society are being translated into a radical change in policy within the European Union with respect to the control of Fmd and other foreign animal diseases. The crisis generated by the Fmd epidemic in Europe in 2001 provides many lessons to be learned for the US and highlights the need for creative thinking in research and teaching within colleges of veterinary medicine to more effectively address the threat of epidemic diseases under the "new world order." There is general agreement that the veterinary profession in the US plays a unique role in protecting the nation against epidemic livestock diseases, whether caused naturally or through bioterrorism. The profession also has a significant role in protecting the public's health, since several epidemic diseases of animals, such as rift valley fever, are zoonotic. However, improved financial support at the federal and state levels is urgently needed to support epidemic-diseases research and teaching in colleges of veterinary medicine.

  14. Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

    PubMed Central

    Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

    2016-01-01

    ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome

  15. Orally delivered foot-and-mouth disease virus capsid protomer vaccine displayed on T4 bacteriophage surface: 100% protection from potency challenge in mice.

    PubMed

    Ren, Z J; Tian, C J; Zhu, Q S; Zhao, M Y; Xin, A G; Nie, W X; Ling, S R; Zhu, M W; Wu, J Y; Lan, H Y; Cao, Y C; Bi, Y Z

    2008-03-10

    An orally delivered foot-and-mouth disease (FMD) vaccine has not previously been reported. By using a T4 bacteriophage nanoparticle surface gene-protein display system (T4-S-GPDS), we created a foot-and-mouth disease virus (FMDV) entire capsid protein vaccine candidate. On the T4 phage surface SOC site, a full length FMDV capsid precursor polyprotein (P1, 755 aa) and proteinase 3C (213 aa) derived from an infected pig of serotype O strain GD-10 (1999), were separately displayed on different T4 phage particle surfaces through inserting their coding region DNAs into the T4 phage genome, yielding phage strains T4-P1 and T4-3C. We also constructed a series of FMDV sub-full length capsid structural protein (subunit) containing T4 phage recombinant vaccines. Both sucking and young BALB/c mice were used as two kinds of FMDV vaccine potency evaluation models. Many groups of both model mice were vaccinated orally or by subcutaneous injection with varying FMDV-T4 phage recombinant vaccines, with and without addition of adjuvant, then challenged with a lethal dose of cattle source virulent FMDV. In the case of immunization with a mixture of phage T4-P1 and phage T4-3C particles without any adjuvant added, all mice were 100% protected following either oral or injection immunization, whereas 100% of the control, non-immunized mice and mice immunized with only T4 phage vector Z1/Zh(-) or wild-type T4(+)D phage died; in contrast, with FMDV subunit vaccine, less than 75% protection followed the same potency challenge in both mice model groups. In addition, two pigs immunized with a phage T4-P1 and phage T4-3C mix were protected upon housing together with infected pigs. This study represents a clear example of how FMD and other pathogenic disease vaccines can be prepared by a simple and efficient bacteriophage route.

  16. Evaluation of a 3A-truncated foot-and-mouth disease virus in pigs for its potential as a marker vaccine.

    PubMed

    Li, Pinghua; Lu, Zengjun; Bai, Xingwen; Li, Dong; Sun, Pu; Bao, Huifang; Fu, Yuanfang; Cao, Yimei; Chen, Yingli; Xie, Baoxia; Yin, Hong; Liu, Zaixin

    2014-05-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals in the world. The disease can be effectively controlled by vaccination of susceptible animals with the conventional inactivated vaccine. However, one major concern of the inactivated FMD virus (FMDV) vaccine is that it does not allow serological discrimination between infected and vaccinated animals, and therefore interferes with serologic surveillance and the epidemiology of disease. A marker vaccine has proven to be of great value in disease eradication and control programs. In this study, we constructed a marker FMDV containing a deletion of residues 93 to 143 in the nonstructural protein 3A using a recently developed FMDV infectious cDNA clone. The marker virus, r-HN/3A93-143, had similar growth kinetics as the wild type virus in culture cell and caused a symptomatic infection in pigs. Pigs immunized with chemically inactivated marker vaccine were fully protected from the wild type virus challenge, and the potency of this marker vaccine was 10 PD50 (50% pig protective dose) per dose, indicating it could be an efficacious vaccine against FMDV. In addition, we developed a blocking ELISA targeted to the deleted epitope that could clearly differentiate animals infected with the marker virus from those infected with the wild type virus. These results indicate that a marker FMDV vaccine can be potentially developed by deleting an immunodominant epitope in NSP 3A.

  17. Insights into cleavage specificity from the crystal structure of foot-and-mouth disease virus 3C protease complexed with a peptide substrate.

    PubMed

    Zunszain, Patricia A; Knox, Stephen R; Sweeney, Trevor R; Yang, Jingjie; Roqué-Rosell, Núria; Belsham, Graham J; Leatherbarrow, Robin J; Curry, Stephen

    2010-01-15

    Picornavirus replication is critically dependent on the correct processing of a polyprotein precursor by 3C protease(s) (3C(pro)) at multiple specific sites with related but non-identical sequences. To investigate the structural basis of its cleavage specificity, we performed the first crystallographic structural analysis of non-covalent complexes of a picornavirus 3C(pro) with peptide substrates. The X-ray crystal structure of the foot-and-mouth disease virus 3C(pro), mutated to replace the catalytic Cys by Ala and bound to a peptide (APAKQ|LLNFD) corresponding to the P5-P5' region of the VP1-2A cleavage junction in the viral polyprotein, was determined up to 2.5 A resolution. Comparison with free enzyme reveals significant conformational changes in 3C(pro) on substrate binding that lead to the formation of an extended interface of contact primarily involving the P4-P2' positions of the peptide. Strikingly, the deep S1' specificity pocket needed to accommodate P1'-Leu only forms when the peptide binds. Substrate specificity was investigated using peptide cleavage assays to show the impact of amino acid substitutions within the P5-P4' region of synthetic substrates. The structure of the enzyme-peptide complex explains the marked substrate preferences for particular P4, P2 and P1 residue types, as well as the relative promiscuity at P3 and on the P' side of the scissile bond. Furthermore, crystallographic analysis of the complex with a modified VP1-2A peptide (APAKE|LLNFD) containing a Gln-to-Glu substitution reveals an identical mode of peptide binding and explains the ability of foot-and-mouth disease virus 3C(pro) to cleave sequences containing either P1-Gln or P1-Glu. Structure-based mutagenesis was used to probe interactions within the S1' specificity pocket and to provide direct evidence of the important contribution made by Asp84 of the Cys-His-Asp catalytic triad to proteolytic activity. Our results provide a new level of detail in our understanding of the

  18. Challenges and Economic Implications in the Control of Foot and Mouth Disease in Sub-Saharan Africa: Lessons from the Zambian Experience

    PubMed Central

    Sinkala, Y.; Simuunza, M.; Pfeiffer, D. U.; Munang'andu, H. M.; Mulumba, M.; Kasanga, C. J.; Muma, J. B.; Mweene, A. S.

    2014-01-01

    Foot and mouth disease is one of the world's most important livestock diseases for trade. FMD infections are complex in nature and there are many epidemiological factors needing clarification. Key questions relate to the control challenges and economic impact of the disease for resource-poor FMD endemic countries like Zambia. A review of the control challenges and economic impact of FMD outbreaks in Zambia was made. Information was collected from peer-reviewed journals articles, conference proceedings, unpublished scientific reports, and personal communication with scientists and personal field experiences. The challenges of controlling FMD using mainly vaccination and movement control are discussed. Impacts include losses in income of over US$ 1.6 billion from exports of beef and sable antelopes and an annual cost of over US$ 2.7 million on preventive measures. Further impacts included unquantified losses in production and low investment in agriculture resulting in slow economic growth. FMD persistence may be a result of inadequate epidemiological understanding of the disease and ineffectiveness of the control measures that are being applied. The identified gaps may be considered in the annual appraisal of the FMD national control strategy in order to advance on the progressive control pathway. PMID:25276472

  19. The tale of a modern animal plague: tracing the evolutionary history and determining the time-scale for foot and mouth disease virus.

    PubMed

    Tully, Damien C; Fares, Mario A

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  20. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  1. Distribution of cow-calf producers' beliefs regarding gathering and holding their cattle and observing animal movement restrictions during an outbreak of foot-and-mouth disease.

    PubMed

    Delgado, Amy H; Norby, Bo; Scott, H Morgan; Dean, Wesley; McIntosh, W Alex; Bush, Eric

    2014-12-01

    The voluntary cooperation of producers with disease control measures such as movement restrictions and gathering cattle for testing, vaccination, or depopulation is critical to the success of many disease control programs. A cross-sectional survey was conducted in Texas in order to determine the distribution of key beliefs about obeying movement restrictions and gathering and holding cattle for disease control purposes. Two questionnaires were developed and distributed to separate representative samples of Texas cow-calf producers, respectively. The context for each behavior was provided through the use of scenarios in the questionnaire. Belief strength was measured using a 7-point Likert-like scale. Producers surveyed were unsure about the possible negative consequences of gathering and holding their cattle when requested by authorities, suggesting a key need for communication in this area during an outbreak. Respondents identified a lack of manpower and/or financial resources to gather and hold cattle as barriers to their cooperation with orders to gather and hold cattle. Producers also expressed uncertainty about the efficacy of movement restrictions to prevent the spread of foot-and-mouth disease and concern about possible feed shortages or animal suffering. However, there are emotional benefits to complying with movement restrictions and strong social expectations of cooperation with any movement bans put in place.

  2. Development of a Lightcycler-based reverse transcription polymerase chain reaction for the detection of foot-and-mouth disease virus.

    PubMed

    Oem, Jae Ku; Kye, Soo Jeong; Lee, Kwang Nyeong; Kim, Yong Joo; Park, Jee Yong; Park, Jong Hyeon; Joo, Yi Seok; Song, Hee Jong

    2005-09-01

    One step TaqMan real-time reverse transcription polymerase chain reaction (R/T RT-PCR) using a set of primers/probes was developed for the detection of foot-and-mouth disease (FMD) virus. The gene-specific probes labeled fluorogen for the internal ribosomal entry site, Leader sequence and 2B regions were used to detect FMD virus (FMDV). This assay specifically detected FMDV both in cell culture preparations and clinical samples, and was capable of distinguishing FMD from other viral diseases similar to clinical signs (swine vesicular disease, vesicular stomatitis and bovine viral diarrhea). This assay was shown to be 1000-fold more sensitive than the conventional RT-PCR method. The detection limits of this assay was 1 TCID(50)/ml of the FMDV RNA concentration. Quantification was obtained by a standard curves plotting threshold cycle values versus known infectivity titer. The assay was sensitive, specific and rapid enough to detect FMDV RNA genome in probang samples. As such, the described method is reliable and provides faster disease diagnostics than the conventional RT-PCR procedure to detect FMDV.

  3. Collection of Oral Fluids Using Cotton Ropes as a Sampling Method to Detect Foot-and-Mouth Disease Virus Infection in Pigs.

    PubMed

    Vosloo, W; Morris, J; Davis, A; Giles, M; Wang, J; Nguyen, H T T; Kim, P V; Quach, N V; Le, P T T; Nguyen, P H N; Dang, H; Tran, H X; Vu, P P; Hung, V V; Le, Q T; Tran, T M; Mai, T M T; Le, Q T V; Singanallur, N B

    2015-10-01

    In high-density farming practices, it is important to constantly monitor for infectious diseases, especially diseases that have the potential to spread rapidly between holdings. Pigs are known to amplify foot-and-mouth disease (FMD) by excreting large amounts of virus, and it is therefore important to detect the virus quickly and accurately to minimize the spread of disease. Ropes were used to collect oral fluid samples from pigs, and each sample was compared to saliva samples collected from individual animals by detecting FMD virus RNA using real-time PCR. Two different experiments are described where groups of pigs were infected with different serotypes of FMD virus, either with or without vaccination, and unvaccinated pigs were kept in aerosol contact. The sensitivity of the rope sampling varied between 0.67 and 0.92, and the statistical agreement between this method and individual sampling ranged from substantial to moderate for the two different serotypes. The ease of collecting oral fluids using ropes together with the high sensitivity of subsequent FMD detection through PCR indicates that this could be a useful method to monitor pig populations for FMD virus infection. With further validation of the sensitivity of detection of FMD virus RNA, this can be a cost-effective, non-invasive diagnostic tool.

  4. A web-based system for near real-time surveillance and space-time cluster analysis of foot-and-mouth disease and other animal diseases.

    PubMed

    Perez, Andres M; Zeng, Daniel; Tseng, Chun-ju; Chen, Hsinchun; Whedbee, Zachary; Paton, David; Thurmond, Mark C

    2009-09-01

    Considerable attention has been given lately to the need for global systems for animal disease surveillance that support real-time assessment of changing temporal-spatial risks. Until recently, however, prospects for development of such systems have been limited by the lack of informatics tools and an overarching collaboration framework to enable real-time data capturing, sharing, analysis, and related decision-making. In this paper, we present some of the tools of the FMD BioPortal System (www.fmd.ucdavis.edu/bioportal), which is a web-based system that facilitates near real-time information sharing, visualization, and advanced space-time cluster analysis for foot-and-mouth disease (FMD). Using this system, FMD information that is collected and maintained at various data acquisition and management sites around the world can be submitted to a data repository using various mutually agreed upon Extensible Markup Language (XML) formats, including Health Level Seven (HL7). FMD BioPortal makes available a set of advanced space-time cluster analysis techniques, including scan statistic-based methods and machine learning-based clustering methods. These techniques are aimed at identifying local clusters of disease cases in relation to the background risk. Data and analysis results can be displayed using a novel visualization environment, which supports multiple views including GIS, timeline, and periodical patterns. All FMD BioPortal functionalities are accessible through the Web and data confidentiality can be secured through user access control and computer network security techniques such as Secure Sockets Layer (SSL). FMD BioPortal is currently operational with limited data routinely collected by the Office International des Epizooties, the GenBank, the FMD World Reference Laboratory in Pirbright, and by the FMD Laboratory at the University of California in Davis. Here we describe technical attributes and capabilities of FMD BioPortal and illustrate its functionality

  5. Association of the time that elapsed from last vaccination with protective effectiveness against foot-and-mouth disease in small ruminants.

    PubMed

    Elnekave, Ehud; Even-Tov, Boris; Gelman, Boris; Sharir, Beni; Klement, Eyal

    2015-01-01

    Routine and emergency vaccination of small ruminants against foot-and-mouth disease (FMD) is mandatory in many endemic countries, yet data on the field effectiveness of the vaccines used is scarce. We conducted an investigation of a serotype O FMD outbreak that took place in a sheep and goat pen, and estimated the effectiveness of various routine vaccination statuses. We also evaluated the protection provided by colostrum administration and emergency vaccination. Animals which were routinely vaccinated twice were not clinically affected while disease incidence was observed among animals routinely vaccinated only once (p = 0.004 according to a two-sided Fisher's exact test). In groups vaccinated only once, there was a significant association between the average time that elapsed since last vaccination and the disease incidence (n = 5; Spearman correlation coefficient: rs = 1.0, p < 0.01). In addition, non-vaccinated lambs fed colostrum from dams vaccinated more than 2 months before parturition had a mortality rate of 33%. Administration of emergency vaccination 2 days after the occurrence of the index case was the probable reason for the rapid blocking of the FMD spread within 6 days from its onset in the pen.

  6. Analysis of factors associated with hesitation to restart farming after depopulation of animals due to 2010 foot-and-mouth disease epidemic in Japan

    PubMed Central

    KADOWAKI, Hazumu; KAYANO, Taishi; TOBINAGA, Takaharu; TSUTSUMI, Atsuro; WATARI, Michiko; MAKITA, Kohei

    2016-01-01

    An outbreak of foot-and-mouth disease (FMD) occurred in Miyazaki Prefecture, Japan, in 2010. This epidemic was controlled with culling and vaccination, and resulted in the death of nearly 290,000 animals. This paper describes the factors associated with hesitation to restart farming after the epidemic. A questionnaire survey was conducted to assess the mental health of farmers one year after the end of the FMD epidemic in affected areas, and univariate and multivariable analyses were performed. Of 773 farms which had answered the question about restart farming, 55.4% (428/773) had resumed or were planning to resume operation. The farms hesitated restarting were characterized by small scale (P=0.06) and having multiple sources of income (P<0.01). Personal attributes associated with hesitation to restart were advanced age of the owner (P<0.01), with someone with bad physical conditions (P=0.04) and small family size (P<0.01). Factors related to disease control during the epidemic that were associated with hesitation to restart were vaccination of animals (P<0.01), not assisting with culling on other farms (P<0.01), and higher satisfaction with information provided by the government (P=0.02). We found that farmers hesitated to resume farming because they had a limited labor force, had an alternative business or were mentally distressed during disease control. PMID:27149890

  7. Association of the time that elapsed from last vaccination with protective effectiveness against foot-and-mouth disease in small ruminants

    PubMed Central

    Even-Tov, Boris; Gelman, Boris; Sharir, Beni; Klement, Eyal

    2015-01-01

    Routine and emergency vaccination of small ruminants against foot-and-mouth disease (FMD) is mandatory in many endemic countries, yet data on the field effectiveness of the vaccines used is scarce. We conducted an investigation of a serotype O FMD outbreak that took place in a sheep and goat pen, and estimated the effectiveness of various routine vaccination statuses. We also evaluated the protection provided by colostrum administration and emergency vaccination. Animals which were routinely vaccinated twice were not clinically affected while disease incidence was observed among animals routinely vaccinated only once (p = 0.004 according to a two-sided Fisher's exact test). In groups vaccinated only once, there was a significant association between the average time that elapsed since last vaccination and the disease incidence (n = 5; Spearman correlation coefficient: rs = 1.0, p < 0.01). In addition, non-vaccinated lambs fed colostrum from dams vaccinated more than 2 months before parturition had a mortality rate of 33%. Administration of emergency vaccination 2 days after the occurrence of the index case was the probable reason for the rapid blocking of the FMD spread within 6 days from its onset in the pen. PMID:25293489

  8. Epidemiological study on foot-and-mouth disease in cattle: seroprevalence and risk factor assessment in South Omo zone, south-western Ethiopia.

    PubMed

    Molla, B; Ayelet, G; Asfaw, Y; Jibril, Y; Ganga, G; Gelaye, E

    2010-10-01

    A cross-sectional sero-epidemiological study was conducted in seven districts of the South Omo zone, south-western Ethiopia, between October 2008 and May 2009 with the objective of determining the seroprevalence of foot-and-mouth disease (FMD) in cattle and identifying the potential risk factors associated with the disease. In total, 770 cattle sera samples were collected and submitted to the National Veterinary Institute (NVI), Debre Zeit, Ethiopia, for screening using the 3ABC-ELISA. The overall seroprevalence of 8.18% (n=63) was recorded in the study. The highest district-level prevalence was observed in Bennatsemay district (30.2%), and the lowest prevalence was in Malle and Debub Aari districts, each with prevalence of 6.3%. The difference in seropositivity of FMD in the studied districts was found to be statistically significant. From the various risk factors analysed, age of animal, contact history with wild animals, distance of the herd from parks and wild animals' sanctuary and movement pattern of herds in search of pasture and water from area to area were found to be significantly associated (P<0.05) with the seroprevalence of FMD. The results of this study showed that FMD is an important cattle disease in the study areas. Thus, an appropriate control strategy has to be designed and applied, which could involve regulation of transboundary cattle movement, prevention of contact with wildlife and vaccination against the circulating virus strain.

  9. Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide.

    PubMed

    Cubillos, Carolina; de la Torre, Beatriz G; Jakab, Annamaria; Clementi, Giorgia; Borrás, Eva; Bárcena, Juan; Andreu, David; Sobrino, Francisco; Blanco, Esther

    2008-07-01

    The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

  10. Early protection in sheep against intratypic heterologous challenge with serotype O foot-and-mouth disease virus using high-potency, emergency vaccine.

    PubMed

    Horsington, Jacquelyn; Zhang, Zhidong; Bittner, Hilary; Hole, Kate; Singanallur, Nagendrakumar B; Alexandersen, Soren; Vosloo, Wilna

    2015-01-09

    In 2009-2011, spread of a serotype O foot-and-mouth disease virus (FMDV) belonging to the South East Asia topotype led to the culling of over 3.5 million cattle and pigs in Japan and Korea. The O1 Manisa vaccine (belonging to the Middle East-South Asian topotype) was used at high potency in Korea to limit the expansion of the outbreak. However, no data are available on the spread of this virus or the efficacy of the O1 Manisa vaccine against this virus in sheep. In this study, the early protection afforded with a high potency (>6 PD50) FMD O1 Manisa vaccine against challenge with the O/SKR/2010 virus was tested in sheep. Sheep (n=8) were vaccinated 4 days prior to continuous direct-contact challenge with donor sheep. Donor sheep were infected with FMDV O/SKR/2010 by coronary band inoculation 24h prior to contact with the vaccinated animals, or unvaccinated controls (n=4). Three of the four control sheep became infected, two clinically. All eight O1 Manisa vaccinated sheep were protected from clinical disease. None had detectable antibodies to FMDV non-structural proteins (3ABC), no virus was isolated from nasal swabs, saliva or oro-pharyngeal fluid and none became carriers. Using this model of challenge, sheep were protected against infection as early as 4 days post vaccination.

  11. A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.

    PubMed

    Lefebvre, David J; De Vleeschauwer, Annebel R; Goris, Nesya; Van Borm, Steven; Chimirri, Alba; Monforte, Anna Maria; Valdazo-Gonzalez, Begona; King, Donald P; Neyts, Johan; De Clercq, Kris

    2014-12-12

    The stamping-out policy for the control of foot-and-mouth disease virus (FMDV) in countries that are free from FMD without vaccination has a dramatic socio-economic impact, huge animal welfare issues and may result in the loss of farm animal genetic resources. As an alternative to pre-emptive culling or emergency vaccination we further explore the possibility to use antiviral drugs in the event of an FMD outbreak. In the present study, we tested the in vitro cytotoxicity and anti-FMDV activity of 1,2,4,5-tetrahydro-[1,4]thiazepino[4,5-a]benzimidazole. The molecule was shown to inhibit the replication of reference strains of the Eurasian FMDV serotypes O, A, C and Asia but not the FMDV serotypes from the South African Territories (SAT) neither a related picornavirus, i.e. swine vesicular disease virus. The molecule can be added until 2h post inoculation in a 'single replication cycle experiment' without losing its antiviral activity. The genetic characterization of progressively selected resistant FMD viruses shows that the molecule presumably interacts with the non-structural 2C protein of FMDV. Further studies are required on the use of this molecule in vivo.

  12. Engagement of soluble resistance-related calcium binding protein (sorcin) with foot-and-mouth disease virus (FMDV) VP1 inhibits type I interferon response in cells.

    PubMed

    Li, Xiaying; Wang, Jianchang; Liu, Jue; Li, Zhonghua; Wang, Yongqiang; Xue, Yanfei; Li, Xiaoqi; Cao, Hong; Zheng, Shijun J

    2013-09-27

    Foot-and-mouth disease (FMD) is an acute, highly contagious animal disease caused by FMD virus (FMDV). Although FMDV-induced immunosuppression in host has been well established, the exact molecular mechanism for such induction is not very clear. We report here the identification of FMDV VP1 as an interferon-suppressor by interacting with soluble resistance-related calcium binding protein (sorcin). We found that VP1 suppressed tumor necrosis factor (TNF)-α or Sendai virus (SeV)-induced type I interferon response in HEK293T cells, and that this suppression could be completely abolished by knockdown of sorcin by shRNA. Furthermore, overexpression of sorcin inhibited type I interferon response. Conversely, TNF- or SeV-induced type I interferon response increased when sorcin knocked down, leading to inhibition of vesicular stomatitis virus (VSV) replication. Thus, VP1-induced suppression of type I interferon is mediated by interacting with sorcin, a protein that appears to regulate cell response to viral infections.

  13. The Association between Ambient Temperature and Childhood Hand, Foot, and Mouth Disease in Chengdu, China: A Distributed Lag Non-linear Analysis

    PubMed Central

    Yin, Fei; Zhang, Tao; Liu, Lei; Lv, Qiang; Li, Xiaosong

    2016-01-01

    Hand, foot and mouth disease (HFMD) has recently been recognized as a critical challenge to disease control and public health response in China. This study aimed to quantify the association between temperature and HFMD in Chengdu. Daily HFMD cases and meteorological variables in Chengdu between January 2010 and December 2013 were obtained to construct the time series. A distributed lag non-linear model was performed to investigate the temporal lagged association of daily temperature with age- and gender-specific HFMD. A total of 76,403 HFMD cases aged 0–14 years were reported in Chengdu during the study period, and a bimodal seasonal pattern was observed. The temperature-HFMD relationships were non-linear in all age and gender groups, with the first peak at 14.0–14.1 °C and the second peak at 23.1–23.2 °C. The high temperatures had acute and short-term effects and declined quickly over time, while the effects in low temperature ranges were persistent over longer lag periods. Males and children aged <1 year were more vulnerable to temperature variations. Temperature played an important role in HFMD incidence with non-linear and delayed effects. The success of HFMD intervention strategies could benefit from giving more consideration to local climatic conditions. PMID:27248051

  14. Survey for foot-and-mouth disease in the endangered marsh deer (Blastocerus dichotomus) from marshlands of the Parana River Basin, Brazil.

    PubMed

    Araújo, João Pessoa; Nogueira, Márcia F; Duarte, José M B

    2010-07-01

    Habitat fragmentation and diseases have resulted in a decline of the marsh deer (Blastocerus dichotomus) throughout its South American range. Our objectives were to determine whether marsh deer intended for translocation from a region of the Rio Paraná Basin had been infected previously by foot-and-mouth disease virus (FMDV) and whether they were carrying virus. We captured marsh deer from June to October 1998 and collected blood from 108 animals and esophageal-pharyngeal fluid from 53. Serum was tested for antibodies against three FMDV serotypes (O, A, and C) by liquid-phase-blocking sandwich enzyme-linked immunosorbent assay (ELISA). Esophageal-pharyngeal fluid was tested for FMDV RNA by reverse transcription polymerase chain reaction (RT-PCR) and inoculation into three successive baby hamster kidney (BHK-21) cell subcultures, followed by RT-PCR of cultures. We detected low log(10) titers (range 1.0-1.5) to FMDV subtype A(24) Cruzeiro in 19 of 108 sampled marsh deer, but failed to isolate FMDV or detect FMDV RNA in any samples. We conclude that marsh deer from our study site were unlikely to carry FMDV; however, as a preventive measure, the 19 animals with titers for FMDV were not sent to FMDV-free Brazilian states.

  15. A DNA vaccine encoding foot-and-mouth disease virus B and T-cell epitopes targeted to class II swine leukocyte antigens protects pigs against viral challenge.

    PubMed

    Borrego, Belén; Argilaguet, Jordi M; Pérez-Martín, Eva; Dominguez, Javier; Pérez-Filgueira, Mariano; Escribano, José M; Sobrino, Francisco; Rodriguez, Fernando

    2011-11-01

    Development of efficient and safer vaccines against foot-and-mouth disease virus (FMDV) is a must. Previous results obtained in our laboratory have demonstrated that DNA vaccines encoding B and T cell epitopes from type C FMDV, efficiently controlled virus replication in mice, while they did not protect against FMDV challenge in pigs, one of the FMDV natural hosts. The main finding of this work is the ability to improve the protection afforded in swine using a new DNA-vaccine prototype (pCMV-APCH1BTT), encoding FMDV B and T-cell epitopes fused to the single-chain variable fragment of the 1F12 mouse monoclonal antibody that recognizes Class-II Swine Leukocyte antigens. Half of the DNA-immunized pigs were fully protected upon viral challenge, while the remaining animals were partially protected, showing a delayed, shorter and milder disease than control pigs. Full protection in a given vaccinated-pig correlated with the induction of specific IFNγ-secreting T-cells, detectable prior to FMDV-challenge, together with a rapid development of neutralizing antibodies after viral challenge, pointing towards the relevance that both arms of the immune response can play in protection. Our results open new avenues for developing future FMDV subunit vaccines.

  16. Re-emergence of circulatory foot-and-mouth disease virus serotypes Asia1 in Bangladesh and VP1 protein heterogeneity with vaccine strain IND 63/72.

    PubMed

    Ullah, H; Siddique, M A; Al Amin, Md; Das, B C; Sultana, M; Hossain, M A

    2015-02-01

    Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for significant number of disease outbreaks in Bangladesh; however serotype Asia1 has not been reported in circulation since 1996. The present investigation reports the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks. The farms were located in Jessore and Gazipur districts, and one of these farms was under vaccine control programme. Phylogenetic analysis of the complete VP1 gene revealed that FMDV Asia1 is under genetic lineage C having close similarity to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed VP1 protein sequence heterogeneity of eight amino acid substitutions within the G-H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination programme. ELISA assay revealed that, of seven, only one local field serum sample (cattle vaccinated 38 days earlier) was positive at a titre level of >2.4 (log10) but failed to protect the cattle from infection occurred by the virus. This investigation focused that the eight amino acid substitution in VP1 protein at G-H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for current vaccination failure.

  17. Early protection against foot-and-mouth disease virus in cattle using an inactivated vaccine formulated with Montanide ESSAI IMS D 12802 VG PR adjuvant.

    PubMed

    Quattrocchi, V; Pappalardo, J S; Langellotti, C; Smitsaart, E; Fondevila, N; Zamorano, P

    2014-04-17

    Foot and mouth disease is an acute disease of cattle with a broad distribution around the world. Due to the fast spread of FMDV infections, control measures must be applied immediately after an outbreak, such as the use of vaccines that induce fast protection. Previously, it was shown that mice vaccinated with FMD inactivated virus (iFMDV) formulated with Montanide™ ESSAI IMS D 12802 VG PR adjuvant (802-iFMDV) were protected when they were challenged 4 and 7 days post-vaccination (dpv) with homologous virus. In this work, we describe the successful use of this formulation in cattle. In addition, adjuvant Montanide™ IMS 1313 VG NPR was also tested. 802-iFMDV vaccine was able to confer 100% protection against viral challenge at 4 and 7 dpv, while eliciting low antibody levels, at 7 dpv. 1313-iFMDV vaccine induced protection in 60% of cattle. At 4 dpv, 1313-iFMDV vaccinated animals presented increased levels of IFNγ but not of macrophages. At 4 and 7 dpv, macrophages, IFNγ, nasal IgA and IgG1 antibodies against FMDV, and opsonophagocytosis were increased in animals vaccinated with 802-iFMDV indicating that these phenomena could be involved in protection.It is the first time that total protection against FMDV at early stages post-vaccination is reported using a single dose of the formulation iFMDV plus Montanide™ ESSAI D IMS 12802 VG PR adjuvant.

  18. Correlation analysis of EV71 detection and case severity in hand, foot, and mouth disease in the Hunan Province of China.

    PubMed

    Gao, Li-Dong; Hu, Shi-Xiong; Zhang, Hong; Luo, Kai-Wei; Liu, Yun-Zhi; Xu, Qiao-Hua; Huang, Wei; Deng, Zhi-Hong; Zhou, Shuai-Feng; Liu, Fu-Qiang; Zhang, Fan; Chen, Yu

    2014-01-01

    An increase in the incidence of hand, foot and mouth disease (HFMD) cases has been observed in the Hunan province of mainland China since 2009 with a particularly higher level of severe cases in 2010-2012. Intestinal viruses of the picornaviridae family are responsible for the human syndrome associated with HFMD with enterovirus 71 (EV71) and Coxsackievirus A16 (Cox A16) being the most common causative strains. HFMD cases associated with EV71 are generally more severe with an increased association of morbidity and mortality. In this study, the etiology surveillance data of HFMD cases in Hunan province from March 2010 to October 2012 were analyzed to determine if there is a statistically relevant linear correlation exists between the detection rate of EV71 in mild cases and the proportion of severe cases among all HFMD patients. As the cases progressed from mild to severe to fatal, the likelihood of EV71 detection increased (25.78%, 52.20% and 84.18%, respectively). For all cases in the timeframe evaluated in this study, the presence of virus was detected in 63.21% of cases; among cases showing positivity for virus, EV71 infection accounted for 50.14%. These results provide evidence to support the observed higher morbidity and mortality associated with this outbreak and emphasizes the importance of early detection in order to implement necessary prevention measures to mitigate disease progression.

  19. Rapid detection of foot-and-mouth disease virus, influenza A virus and classical swine fever virus by high-speed real-time RT-PCR.

    PubMed

    Wernike, Kerstin; Beer, Martin; Hoffmann, Bernd

    2013-10-01

    High sensitivity, minor risk of cross-contamination and in particular the rapid reaction time make quantitative real-time polymerase chain reaction (qPCR) assays well suited for outbreak investigations as well as for monitoring epidemics of pathogens. In this study qPCR assays for three highly contagious animal diseases, namely foot-and-mouth-disease (FMD), influenza A (IA) and classical swine fever (CSF) have been developed. Furthermore, an amplification control targeting 18S ribosomal RNA was included. Each assay was validated with samples from infected animals using three different standard qPCR-machines in two thermal profiles: one standard and one high-speed approach, respectively. The high-speed PCR assays allowed the reliable diagnosis of FMD, influenza A and CSF in less than 28 min with an analytical sensitivity of at least 200 genome copies/μl in every case, with slight differences regarding reaction time and sensitivity for the individual PCR-cycler instruments. Therefore, the newly established rapid RT-PCR systems will be a valuable method for the monitoring and control of these three important viruses and will be a robust option for the development of novel molecular pen-side tests.

  20. Disinfection of foot-and-mouth disease and African swine fever viruses with citric acid and sodium hypochlorite on birch wood carriers.

    PubMed

    Krug, Peter W; Larson, Christopher R; Eslami, Angelique C; Rodriguez, Luis L

    2012-04-23

    Transboundary animal disease viruses such as foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV) are highly contagious and cause severe morbidity and mortality in livestock. Proper disinfection during an outbreak can help prevent virus spread and will shorten the time for contaminated agriculture facilities to return to food production. Wood surfaces are prevalent at these locations, but there is no standardized method for porous surface disinfection; commercial disinfectants are only certified for use on hard, nonporous surfaces. To model porous surface disinfection in the laboratory, FMDV and ASFV stocks were dried on wood coupons and exposed to citric acid or sodium hypochlorite. We found that 2% citric acid was effective at inactivating both viruses dried on a wood surface by 30 min at 22°C. While 2000 ppm sodium hypochlorite was capable of inactivating ASFV on wood under these conditions, this chemical did not meet the 4-log disinfection threshold for FMDV. Taken together, our data supports the use of chemical disinfectants containing at least 2% citric acid for porous surface disinfection of FMDV and ASFV.

  1. Transient Gene Expression in Serum-Free Suspension-Growing Mammalian Cells for the Production of Foot-and-Mouth Disease Virus Empty Capsids

    PubMed Central

    Mignaqui, Ana Clara; Ruiz, Vanesa; Perret, Sylvie; St-Laurent, Gilles; Singh Chahal, Parminder; Transfiguracion, Julia; Sammarruco, Ayelén; Gnazzo, Victoria; Durocher, Yves; Wigdorovitz, Andrés

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. It produces severe economic losses in the livestock industry. Currently available vaccines are based on inactivated FMD virus (FMDV). The use of empty capsids as a subunit vaccine has been reported to be a promising candidate because it avoids the use of virus in the vaccine production and conserves the conformational epitopes of the virus. In this report, we explored transient gene expression (TGE) in serum-free suspension-growing mammalian cells for the production of FMDV recombinant empty capsids as a subunit vaccine. The recombinant proteins produced, assembled into empty capsids and induced protective immune response against viral challenge in mice. Furthermore, they were recognized by anti-FMDV bovine sera. By using this technology, we were able to achieve expression levels that are compatible with the development of a vaccine. Thus, TGE of mammalian cells is an easy to perform, scalable and cost-effective technology for the production of a recombinant subunit vaccine against FMDV. PMID:23977353

  2. Short-term effect of El Niño-Southern Oscillation on pediatric hand, foot and mouth disease in Shenzhen, China.

    PubMed

    Lin, Hualiang; Zou, Hong; Wang, Qinzhou; Liu, Chunxiao; Lang, Lingling; Hou, Xuexin; Li, Zhenjun

    2013-01-01

    Hand, foot and mouth disease (HFMD) was an emerging viral infectious disease in recent years in Shenzhen. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effect of El Niño-Southern Oscillation on pediatric HFMD in Shenzhen, China. Daily count of HFMD among children aged below 15 years old, Southern Oscillation Index (SOI), and weather variables were collected to construct the time series. A distributed lag non-linear model was applied to investigate the effect of daily SOI on pediatric HFMD occurrence during 2008-2010. We observed an acute effect of SOI variation on HFMD occurrence. The extremely high SOI (SOI = 45, with 0 as reference) was associated with increased HFMD, with the relative risk (RR) being 1.66 (95% Confidence Interval [CI]: 1.34-2.04). Further analyses of the association between HFMD and daily mean temperature and relative humidity supported the correlation between pediatric HFMD and SOI. Meteorological factors might be important predictors of pediatric HFMD occurrence in Shenzhen.

  3. Antioxidant activity and phytochemical constituent of two plants used to manage foot and mouth disease in the Far North Region of Cameroon

    PubMed Central

    Vougat, Ronald Romuald Bebey Ngom; Foyet, Harquin Simplice; Ziebe, Roland; Garabed, Rebecca B.

    2015-01-01

    Aim: Plants used in the Far North Region of Cameroon by livestock farmers to manage foot and mouth disease (FMD) in cattle and the phytochemical composition and antioxidant potentials of two of them (Boscia senegalensis [BS] and Tapinanthus dodoneifolius [TD]) were investigated in this study. Materials and Methods: Ethno veterinary data were collected from 325 livestock farmers using semi-structured interviews from September 2011 to April 2012. The 2,2-diphenyl-picrylhydrazyl radical scavenging activity and total phenolic content (TPC) were first performed with five different solvents to choose the best extract of each plant based on these two factors. To achieve our aim, the ferric iron reducing activity, hydroxyl radical scavenging activity (HRSA), free radical scavenging activity (FRSA), vitamin E and iron content were analyzed on extracts selected using current techniques. Results: The results showed that 12 plants of 8 different families are regularly used by farmers to manage FMD. It also demonstrated that acetone extract of TD and methanolic extract of BS are the extracts which showed the best total antioxidant activity (AA) and the best TPC. In general, TD show the best AA during the HRSA and FRSA analysis compared with BS. Similarly, TD content more phenolic compounds and tannins than BS. Both plants contain proteins, saponins, tannins, phenols, alkaloid, and polyphenols which are known to have many biological activities. Conclusion: These results support the AA of both plants and can justify their use by herders to treat FMD which is often followed by many secondary diseases. PMID:26401383

  4. Temporal and spatial analysis of hand, foot, and mouth disease in relation to climate factors: A study in the Mekong Delta region, Vietnam.

    PubMed

    Nguyen, Huong Xuan; Chu, Cordia; Nguyen, Huong Lien Thi; Nguyen, Ha Thanh; Do, Cuong Manh; Rutherford, Shannon; Phung, Dung

    2017-03-01

    This study examined the temporal and spatial patterns of hand, foot, and mouth disease (HFMD) in the Mekong Delta region in Vietnam. A time-series analysis was used to examine the temporal patterns of HFMD in relation to climate factors while a retrospective space-time scan was used to detect the high-risk space-time clusters of this disease. A 1°C increase in average temperature was associated with 5.6% increase in HFMD rate at lag 5days (95% CI 0.3-10.9). A 1% increase in humidity had equal influence of 1.7% increases on HFMD rate at both lag 3days and 6days (95% CI 0.7-2.7 and 95% CI 0.8-2.6, respectively). An increase in 1 unit of rainfall was associated with a 0.5% increase of HFMD rate on the lag 1 and 6days (95% CI 0.2-0.9 and 95% CI 0.1-0.8, respectively). The predictive model indicated that the peak of HFMD was from October to December - the rainy season in the Mekong Delta region. Most high-risk clusters were located in areas with high population density and close to transport routes. The findings suggest that HFMD is influenced by climate factors and is likely to increase in the future due to climate change related weather events.

  5. Enhanced immunogenicity of multiple-epitopes of foot-and-mouth disease virus fused with porcine interferon alpha in mice and protective efficacy in guinea pigs and swine.

    PubMed

    Du, Yijun; Li, Yufeng; He, Hairong; Qi, Jing; Jiang, Wenming; Wang, Xinglong; Tang, Bo; Cao, Jun; Wang, Xianwei; Jiang, Ping

    2008-04-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In this study, three amino acid residues 21-60, 141-160 and 200-213 from VP1 protein of FMDV were selected as multiple-epitopes (VPe), and a recombinant adenovirus expressing the multiple-epitopes fused with porcine interferon alpha (rAd-pIFN alpha-VPe) was constructed. Six groups of female BALB/c mice (18 mice per group) were inoculated subcutaneously (s.c.) twice at 2-week intervals with the recombinant adenoviruses and the immune responses were examined. Following this the protective efficacy of rAd-pIFN alpha-VPe was examined in guinea pigs and swine. The results showed that both FMDV-specific humoral and cell-mediated immune responses could be induced by rAd-VPe and increased when rAd-pIFN alpha is included in this regime in mice model. Moreover, the levels of the immune responses in the group inoculated with rAd-pIFN alpha-VPe were significantly higher than the group inoculated with rAd-VPe plus rAd-pIFN alpha. All guinea pigs and swine vaccinated with rAd-pIFN alpha-VPe were completely protected from viral challenge. It demonstrated that recombinant adenovirus rAd-pIFN alpha-VPe might be an attractive candidate vaccine for preventing FMDV infection.

  6. Environmental impacts of the foot and mouth disease outbreak in Great Britain in 2001: the use of risk analysis to manage the risks in the countryside.

    PubMed

    Taylor, K C

    2002-12-01

    Restrictions imposed for more than ten months throughout Great Britain in 2001 to control and eradicate foot and mouth disease (FMD) had a damaging effect on tourism and rural businesses. Risk assessment can play a valuable role in ensuring that the action taken is proportionate to the risk, and that countryside activities are allowed to resume when this can be done without compromising the objective of controlling and eradicating the disease. A risk assessment unit was established at the commencement of the epidemic to consider the risks posed by particular activities, to identify ways of managing those risks, and to make recommendations which could be used by policy makers when deciding what action to take. The assessments produced by the unit were published and the scientific rationale which supported policy and procedural changes was thereby exposed to public scrutiny and criticism. The author lists the activities subjected to veterinary risk assessments and describes how the process was used to consider public access to the countryside, leading to policy changes which within nine months resulted in the reopening of more than 96% of footpaths and bridleways without causing new outbreaks of FMD. A completed risk assessment is also included.

  7. Socio-ecological factors and hand, foot and mouth disease in dry climate regions: a Bayesian spatial approach in Gansu, China.

    PubMed

    Gou, Faxiang; Liu, Xinfeng; Ren, Xiaowei; Liu, Dongpeng; Liu, Haixia; Wei, Kongfu; Yang, Xiaoting; Cheng, Yao; Zheng, Yunhe; Jiang, Xiaojuan; Li, Juansheng; Meng, Lei; Hu, Wenbiao

    2017-01-01

    The influence of socio-ecological factors on hand, foot and mouth disease (HFMD) were explored in this study using Bayesian spatial modeling and spatial patterns identified in dry regions of Gansu, China. Notified HFMD cases and socio-ecological data were obtained from the China Information System for Disease Control and Prevention, Gansu Yearbook and Gansu Meteorological Bureau. A Bayesian spatial conditional autoregressive model was used to quantify the effects of socio-ecological factors on the HFMD and explore spatial patterns, with the consideration of its socio-ecological effects. Our non-spatial model suggests temperature (relative risk (RR) 1.15, 95 % CI 1.01-1.31), GDP per capita (RR 1.19, 95 % CI 1.01-1.39) and population density (RR 1.98, 95 % CI 1.19-3.17) to have a significant effect on HFMD transmission. However, after controlling for spatial random effects, only temperature (RR 1.25, 95 % CI 1.04-1.53) showed significant association with HFMD. The spatial model demonstrates temperature to play a major role in the transmission of HFMD in dry regions. Estimated residual variation after taking into account the socio-ecological variables indicated that high incidences of HFMD were mainly clustered in the northwest of Gansu. And, spatial structure showed a unique distribution after taking account of socio-ecological effects.

  8. Socio-ecological factors and hand, foot and mouth disease in dry climate regions: a Bayesian spatial approach in Gansu, China

    NASA Astrophysics Data System (ADS)

    Gou, Faxiang; Liu, Xinfeng; Ren, Xiaowei; Liu, Dongpeng; Liu, Haixia; Wei, Kongfu; Yang, Xiaoting; Cheng, Yao; Zheng, Yunhe; Jiang, Xiaojuan; Li, Juansheng; Meng, Lei; Hu, Wenbiao

    2017-01-01

    The influence of socio-ecological factors on hand, foot and mouth disease (HFMD) were explored in this study using Bayesian spatial modeling and spatial patterns identified in dry regions of Gansu, China. Notified HFMD cases and socio-ecological data were obtained from the China Information System for Disease Control and Prevention, Gansu Yearbook and Gansu Meteorological Bureau. A Bayesian spatial conditional autoregressive model was used to quantify the effects of socio-ecological factors on the HFMD and explore spatial patterns, with the consideration of its socio-ecological effects. Our non-spatial model suggests temperature (relative risk (RR) 1.15, 95 % CI 1.01-1.31), GDP per capita (RR 1.19, 95 % CI 1.01-1.39) and population density (RR 1.98, 95 % CI 1.19-3.17) to have a significant effect on HFMD transmission. However, after controlling for spatial random effects, only temperature (RR 1.25, 95 % CI 1.04-1.53) showed significant association with HFMD. The spatial model demonstrates temperature to play a major role in the transmission of HFMD in dry regions. Estimated residual variation after taking into account the socio-ecological variables indicated that high incidences of HFMD were mainly clustered in the northwest of Gansu. And, spatial structure showed a unique distribution after taking account of socio-ecological effects.

  9. Characterisation of a SAT-1 outbreak of foot-and-mouth disease in captive African buffalo (Syncerus caffer): clinical symptoms, genetic characterisation and phylogenetic comparison of outbreak isolates.

    PubMed

    Vosloo, W; de Klerk, L-M; Boshoff, C I; Botha, B; Dwarka, R M; Keet, D; Haydon, D T

    2007-03-10

    African buffalo (Syncerus caffer) play an important role in the maintenance of the SAT types of foot-and-mouth disease (FMD) in southern Africa. These long-term carriers mostly become sub-clinically infected, maintaining the disease and posing a threat to other susceptible wildlife and domestic species. During an unrelated bovine tuberculosis experiment using captive buffalo in the Kruger National Park (KNP), an outbreak of SAT-1 occurred and was further investigated. The clinical signs were recorded and all animals demonstrated significant weight loss and lymphopenia that lasted 100 days. In addition, the mean cell volume and mean cell haemoglobin values were significantly higher than before the outbreak started. Virus was isolated from several buffalo over a period of 167 days post infection and the molecular clock estimated to be 3 x 10(-5) nucleotide substitutions per site per day. Seven amino acid changes occurred of which four occurred in hypervariable regions previously described for SAT-1. The genetic relationship of the outbreak virus was compared to buffalo viruses previously obtained from the KNP but the phylogeny was largely unresolved, therefore the relationship of this outbreak strain to others isolated from the KNP remains unclear.

  10. Effect of Meteorological and Geographical Factors on the Epidemics of Hand, Foot, and Mouth Disease in Island-Type Territory, East Asia

    PubMed Central

    Lee, Chang-Chun David; Tang, Jia-Hong; Hwang, Jing-Shiang; Shigematsu, Mika; Chan, Ta-Chien

    2015-01-01

    Hand, foot, and mouth disease (HFMD) has threatened East Asia for more than three decades and has become an important public health issue owing to its severe sequelae and mortality among children. The lack of effective treatment and vaccine for HFMD highlights the urgent need for efficiently integrated early warning surveillance systems in the region. In this study, we try to integrate the available surveillance and weather data in East Asia to elucidate possible spatiotemporal correlations and weather conditions among different areas from low to high latitude. The general additive model (GAM) was applied to understand the association between HFMD and latitude, as well as meteorological factors for islands in East Asia, namely, Japan, Taiwan, Hong Kong, and Singapore, from 2012 to 2014. The results revealed that latitude was the most important explanatory factor associated with the timing and amplitude of HFMD epidemics (P < 0.0001). Meteorological factors including higher dew point, lower visibility, and lower wind speed were significantly associated with the rise of epidemics (P < 0.01). In summary, weather conditions and geographic location could play some role in affecting HFMD epidemics. Regional integrated surveillance of HFMD in East Asia is needed for mitigating the disease risk. PMID:26290875

  11. Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014–2015

    PubMed Central

    le Sage, François Vié; Pereira, Bruno; Cohen, Robert; Levy, Corinne; Archimbaud, Christine; Peigue-Lafeuille, Hélène; Bailly, Jean-Luc; Henquell, Cécile

    2016-01-01

    The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated. To investigate the prevalence of enterovirus serotypes and the clinical presentations associated with HFMD in France, we conducted prospective ambulatory clinic–based surveillance of children during April 2014–March 2015. Throat or buccal swabs were collected from children with HFMD and tested for the enterovirus genome. Physical examinations were recorded on a standardized form. An enterovirus infection was detected in 523 (79.3%) of 659 children tested. Two epidemic waves occurred, dominated by coxsackievirus (CV) A6, which was detected in 53.9% of enterovirus-infect