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.

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.

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

Predicting infection risk of airborne foot-and-mouth disease.

PubMed

Schley, David; Burgin, Laura; Gloster, John

2009-05-06

Foot-and-mouth disease is a highly contagious disease of cloven-hoofed animals, the control and eradication of which is of significant worldwide socio-economic importance. The virus may spread by direct contact between animals or via fomites as well as through airborne transmission, with the latter being the most difficult to control. Here, we consider the risk of infection to flocks or herds from airborne virus emitted from a known infected premises. We show that airborne infection can be predicted quickly and with a good degree of accuracy, provided that the source of virus emission has been determined and reliable geo-referenced herd data are available. A simple model provides a reliable tool for estimating risk from known sources and for prioritizing surveillance and detection efforts. The issue of data information management systems was highlighted as a lesson to be learned from the official inquiry into the UK 2007 foot-and-mouth outbreak: results here suggest that the efficacy of disease control measures could be markedly improved through an accurate livestock database incorporating flock/herd size and location, which would enable tactical as well as strategic modelling.

The foot-and-mouth disease carrier state divergence in cattle

USDA-ARS?s Scientific Manuscript database

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...

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

Code of Federal Regulations, 2011 CFR

2011-01-01

...-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY...

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

Code of Federal Regulations, 2010 CFR

2010-01-01

...-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY...

Foot-and-mouth disease virus during the incubation period in pigs

USDA-ARS?s Scientific Manuscript database

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...

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 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 FEVER...

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 FEVER...

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

Code of Federal Regulations, 2012 CFR

2012-01-01

... 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 FEVER...

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

Code of Federal Regulations, 2013 CFR

2013-01-01

... 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 FEVER...

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 disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, NEWCASTLE DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER...

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

USDA-ARS?s Scientific Manuscript database

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...

Foot-and-mouth disease virus serotype SAT1 in cattle, Nigeria.

PubMed

Ehizibolo, D O; Haegeman, A; De Vleeschauwer, A R; Umoh, J U; Kazeem, H M; Okolocha, E C; Van Borm, S; De Clercq, K

2017-06-01

The knowledge of foot-and-mouth disease virus (FMDV) dynamics and epidemiology in Nigeria and the West Africa subregion is important to support local and regional control plans and international risk assessment. Foot-and-mouth disease virus serotype South African territories (SAT)1 was isolated, identified and characterized from an FMD outbreak in cattle in Nigeria in 2015, 35 years after the last report of FMDV SAT1 in West Africa. The VP1 coding sequence of the Nigerian 2015 SAT1 isolates diverges from reported SAT1 topotypes resulting in a separate topotype. The reporting of a novel FMDV SAT1 strain in the virus pool 5 (West and Central Africa) highlights the dynamic and complex nature of FMDV in this region of Africa. Sustained surveillance is needed to understand the origin, the extent and distribution of this novel SAT1 topotype in the region as well as to detect and monitor the occurrence of (re-)emerging FMDV strains. © 2017 Blackwell Verlag GmbH.

The pathogenesis of foot-and-mouth disease I; viral pathways in cattle

USDA-ARS?s Scientific Manuscript database

In 1898 foot-and-mouth disease (FMD) earned a place in history as the first disease of animals shown to be caused by a virus. Yet, despite over a century of active investigation and elucidation of many aspects of FMD pathogenesis, critical knowledge about the virus-host interactions is still lacking...

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

USDA-ARS?s Scientific Manuscript database

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 ...

Heterogeneity in the antibody response to foot-and-mouth disease primo-vaccinated calves

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is the most economically important viral disease of wild and domesticated biungulate species and presents a major constraint to international trade of livestock and their associated products. FMD vaccines are routinely used as effective control tools in large regions wor...

Pathogenesis of virulent and attenuated foot and mouth disease virus in cattle

USDA-ARS?s Scientific Manuscript database

The factors defining virulence of foot-and-mouth disease virus (FMDV) in cattle were investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). After simulated-natural, aerosol inoculation, both vi...

Evaluation of Gaussia luciferase and foot-and-mouth disease virus 2A translational interrupter chimeras as polycistronic reporters for transgene expression.

PubMed

Puckette, Michael; Burrage, Thomas; Neilan, John G; Rasmussen, Max

2017-06-12

The Gaussia princeps luciferase is used as a stand-alone reporter of transgene expression for in vitro and in vivo expression systems due to the rapid and easy monitoring of luciferase activity. We sought to simultaneously quantitate production of other recombinant proteins by transcriptionally linking the Gaussia princeps luciferase gene to other genes of interest through the foot-and-mouth disease virus 2A translational interrupter sequence. We produced six plasmids, each encoding a single open reading frame, with the foot-and-mouth disease virus 2A sequence placed either N-terminal or C-terminal to the Gaussia princeps luciferase gene. Two plasmids included novel Gaussia princeps luciferase variants with the position 1 methionine deleted. Placing a foot-and-mouth disease virus 2A translational interrupter sequence on either the N- or C-terminus of the Gaussia princeps luciferase gene did not prevent the secretion or luminescence of resulting chimeric luciferase proteins. We also measured the ability of another polycistronic plasmid vector with a 2A-luciferase sequence placed downstream of the foot-and-mouth disease virus P1 and 3C protease genes to produce of foot-and-mouth disease virus-like particles and luciferase activity from transfected cells. Incorporation of the 2A-luciferase sequence into a transgene encoding foot-and-mouth disease virus structural proteins retained luciferase activity and the ability to form virus-like particles. We demonstrated a mechanism for the near real-time, sequential, non-destructive quantitative monitoring of transcriptionally-linked recombinant proteins and a valuable method for monitoring transgene expression in recombinant vaccine constructs.

Differential replication of foot-and-mouth disease viruses in mice determine lethality

USDA-ARS?s Scientific Manuscript database

Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

[Establishment of chemiluminescent enzyme immunoassay for detecting antibodies against foot-and-mouth disease virus serotype O in swine].

PubMed

Cui, Chen; Huang, Ligang; Li, Jing; Zou, Xingqi; Zhu, Yuanyuan; Xie, Lei; Zhao, Qizu; Yang, Limin; Liu, Wenjun

2016-11-25

Recombinant structural protein VP1 of foot-and-mouth disease virus serotype O was expressed in Escherichia coli and then purified using Nickel affinity chromatography. A chemiluminescent enzyme immunoassay (CLEIA) method was established using the purified recombinant protein as coating antigen to detect antibody of foot-and-mouth disease virus serotype O in swine. The specificity of VP1-CLEIA method is 100%. The coefficients of variation in the plate and between plates are 1.10%-6.70% and 0.66%-4.80%, respectively. Comparing with the commercial indirect ELISA kit or liquid phase block ELISA kit, the calculated coincidence rate is 93.50% or 94.00%. The high specificity and stability suggested this detection method can be used to monitor the antibody level of foot-and-mouth disease virus serotype O in swine.

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

USDA-ARS?s Scientific Manuscript database

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...

[Model of multiple seasonal autoregressive integrated moving average model and its application in prediction of the hand-foot-mouth disease incidence in Changsha].

PubMed

Tan, Ting; Chen, Lizhang; Liu, Fuqiang

2014-11-01

To establish multiple seasonal autoregressive integrated moving average model (ARIMA) according to the hand-foot-mouth disease incidence in Changsha, and to explore the feasibility of the multiple seasonal ARIMA in predicting the hand-foot-mouth disease incidence. EVIEWS 6.0 was used to establish multiple seasonal ARIMA according to the hand-foot- mouth disease incidence from May 2008 to August 2013 in Changsha, and the data of the hand- foot-mouth disease incidence from September 2013 to February 2014 were served as the examined samples of the multiple seasonal ARIMA, then the errors were compared between the forecasted incidence and the real value. Finally, the incidence of hand-foot-mouth disease from March 2014 to August 2014 was predicted by the model. After the data sequence was handled by smooth sequence, model identification and model diagnosis, the multiple seasonal ARIMA (1, 0, 1)×(0, 1, 1)12 was established. The R2 value of the model fitting degree was 0.81, the root mean square prediction error was 8.29 and the mean absolute error was 5.83. The multiple seasonal ARIMA is a good prediction model, and the fitting degree is good. It can provide reference for the prevention and control work in hand-foot-mouth disease.

Attenuation of foot-and-mouth disease virus by engineered viral polymerase fidelity

USDA-ARS?s Scientific Manuscript database

The foot-and-mouth disease virus (FMDV) RNA dependent RNA polymerase (RdRp or 3Dpol) catalyzes viral RNA synthesis. The 3Dpol is a low fidelity enzyme incapable of proofreading which results in a high mutation frequencies that allow the virus to rapidly adapt to different environments. In this study...

Phylodynamics of epidemic and asymptomatic foot-and-mouth disease in Vietnam 2010-2014

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in animal trade within Southeast Asia. The large populations of buffalo, cattle and pigs (all FMDV susceptible species) in Vietnam are important components of food production and of the national livelih...

[Step Fisher discriminant analysis on severe clinical features of hand foot and mouth disease between enterovirus (EV) 71 and other EV].

PubMed

Ruan, Feng; Tan, Ai-jun; Zhang, Xue-bao; Chen, Xue-qin; Xiao, Song-jian; Ye, Zhong-wen; Wang, Song

2011-07-01

To compare the clinical features of severe hand foot and mouth disease between enterovirus (EV) 71 and other EV to find specific diagnosis index of EV71 severe hand foot and mouth disease. Case definition were adopted from national guideline of hand foot and mouth disease diagnose (Version 2010). Clinical data of severe hand foot and mouth disease came from case history and contents of questionnaire would include the ones between the time of onset and diagnoses being made. EV and EV71, Cox A16 nucleic acid tested were by RT-PCR in stool samples. Clinical features of severe hand foot and mouth disease between EV71 and other EV were compare. There appeared statistical differences between neurologic symptoms such as tremor, myoclonic jerk, listlessness, convulsion and white blood cell counts in CSF (P < 0.05). Results from the step Fisher discriminant analysis showed only tremor and white blood cell had an increase in CSF, with statistically significant differences. The discriminant equation of EV71 was Y = 3.059X(1) + 3.83X(5) - 2.742 and the equation of other EV was Y = 1.634X(1) + 1.623X(5) - 1.693. The specificity of EV71 was 91% and the specificity of other EV was 40%. The increase of clinical features of tremor and white blood cell in CSF could be used as diagnosis index of severe EV71.

[Application of R-based multiple seasonal ARIMA model, in predicting the incidence of hand, foot and mouth disease in Shaanxi province].

PubMed

Liu, F; Zhu, N; Qiu, L; Wang, J J; Wang, W H

2016-08-10

To apply the ' auto-regressive integrated moving average product seasonal model' in predicting the number of hand, foot and mouth disease in Shaanxi province. In Shaanxi province, the trend of hand, foot and mouth disease was analyzed and tested, under the use of R software, between January 2009 and June 2015. Multiple seasonal ARIMA model was then fitted under time series to predict the number of hand, foot and mouth disease in 2016 and 2017. Seasonal effect was seen in hand, foot and mouth disease in Shaanxi province. A multiple seasonal ARIMA (2,1,0)×(1,1,0)12 was established, with the equation as (1 -B)(1 -B12)Ln (Xt) =((1-1.000B)/(1-0.532B-0.363B(2))*(1-0.644B12-0.454B12(2)))*Epsilont. The mean of absolute error and the relative error were 531.535 and 0.114, respectively when compared to the simulated number of patients from Jun to Dec in 2015. RESULTS under the prediction of multiple seasonal ARIMA model showed that the numbers of patients in both 2016 and 2017 were similar to that of 2015 in Shaanxi province. Multiple seasonal ARIMA (2,1,0)×(1,1,0)12 model could be used to successfully predict the incidence of hand, foot and mouth disease in Shaanxi province.

The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation

USDA-ARS?s Scientific Manuscript database

The goal of the efforts described in this dissertation was to characterize the early pathogenesis of foot-and-mouth disease (FMD) in cattle after simulated natural infection. More specifically, emphasis was placed upon two critical knowledge gaps: identification of the primary site(s) of infectio...

Foot & Mouth Disease & Ulcerative/Vesicular Rule-outs: Challenges Encountered in Recent Outbreaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hullinger, P

2008-01-28

Foot and mouth disease (FMD) is a highly infectious and contagious viral disease affecting bovidae (cattle, zebus, domestic buffaloes, yaks), sheep, goats, swine, all wild ruminants and suidae. Camelidae (camels, dromedaries, llamas, vicunas) have low susceptibility. Foot and mouth disease is caused by a RNS virus of the family Picornaviridae, genus Aphthovirus. There are seven immunologically distinct serotypes: A, O, C, SAT1, SAT2, SAT3, Asia 1. Foot and mouth disease causes significant economic loss both to countries who manage it as an endemic disease (with or without vaccination), as well as those FMD free countries which may become infected. Themore » mortality rate is low in adult animals, but often higher in young due to myocarditis. Foot and mouth disease is endemic in parts of Asia, Africa, the Middle East and South America (sporadic outbreaks in free areas). The Office of International Epizootics (OIE), also referred to the World Organization for Animal Health maintains an official list of free countries and zones.1 The OIE Terrestrial Code (Chapter 2.2.10) provides detailed information on the categories of freedom that can be allocated to a country as well as guidelines for the surveillance for foot and mouth disease (Appendix 3.8.7). In short, countries may be completely free of FMD, free with vaccination or infected with foot and mouth disease virus (FMDV). Source of FMDV include incubating and clinically affected animals with virus present in breath, saliva, faeces, urine, milk and semen. In experimental settings virus has been detected in milk several days before the onset of clinical signs2. Additional sources of virus are meat and by-products in which pH has remained above 6.0 as well as persistently infected carrier animals. Carrier animals may include cattle and water buffalo; convalescent animals and exposed vaccinates (virus persists in the oropharynx for up to 30 months in cattle or longer in buffalo, 9 months in sheep). Pigs do not become

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

USDA-ARS?s Scientific Manuscript database

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 ...

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.

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. © OIE (World Organisation for Animal Health), 2016.

[The early diagnosis value of EV 71 IgM class antibodies in the hand, foot and mouth disease].

PubMed

Zhao, Jing; Xu, Jun; Chen, Wei-wei; Li, Yong-li; Tang, Yan; Li, Jia; Wang, Hai-bin; Guo, Tong-sheng; Zhao, Min; Li, Bo-an; Mao, Yuan-li

2011-04-01

Assessment of detection of IgM antibodies for human enterovirus 71 (EV 71) in early diagnosis for the hand, foot and mouth disease (HFMD). The sera and throat swabs from 38 patients which were clinical diagnosis as HFMD, were continuous daily collected in our hospital in 2010. These specimens were detected by EV 71 IgM antibodies assay, real time RT-PCR methods for EV 71 and Enterovirus. Among 38 HFMD patients, the cumulative positive rates of EV 71 IgM antibodies were: 60.5% on day 1, 71.1% on day 2, 81.5% in the first 3-4 days, 92.1% on day 5, 92.1% on day 6, and the positive rate of nucleic acid detected by the real time RT-PCR for EV 71 and Enterovirus were 60.5%, 73.6%. The positive rate of EV 71 IgM antibodies in the hand, foot and mouth disease just can occur on day 1, and reach to peak on day 5, which can be used as one of indicators of early diagnosis of hand, foot and mouth disease.

Foot-and-Mouth Disease in a small sample of experimentally infected pronghorn (Antilocapra americana)

USDA-ARS?s Scientific Manuscript database

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 this experimental study, we compared the susceptibility of pronghorn to FMD virus (FMDV) strain O, with that of ...

Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle

USDA-ARS?s Scientific Manuscript database

Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O,A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutral...

Effect of vaccination on cattle herds previously exposed to foot and mouth disease in Cameroon

USDA-ARS?s Scientific Manuscript database

Foot and mouth disease (FMD), caused by FMD virus (FMDV), is one of the most contagious and economically important livestock diseases worldwide. Four serotypes of FMDV are endemic in Cameroon (O, A, SAT1, SAT2), and a trivalent inactivated vaccine against the three most common serotypes (O, A, SAT2)...

Epidemiological analysis, serological prevalence, and genotypic analysis of foot-and-mouth disease in Nigeria 2008-2009

USDA-ARS?s Scientific Manuscript database

The epidemiological situation of foot and mouth disease virus (FMDV) is uncertain in Nigeria, where the disease is endemic, and the majority of outbreaks are unreported. Control measures for FMD in Nigeria are not being implemented due to the absence of locally produced vaccines and an official ban ...

Probability of introducing foot and mouth disease into the United States via live animal importation.

PubMed

Miller, G Y; Ming, J; Williams, I; Gorvett, R

2012-12-01

Foot and mouth disease (FMD) continues to be a disease of major concern for the United States Department of Agriculture (USDA) and livestock industries. Foot and mouth disease virus is a high-consequence pathogen for the United States (USA). Live animal trade is a major risk factor for introduction of FMD into a country. This research estimates the probability of FMD being introduced into the USA via the legal importation of livestock. This probability is calculated by considering the potential introduction of FMD from each country from which the USA imports live animals. The total probability of introduction into the USA of FMD from imported livestock is estimated to be 0.415% per year, which is equivalent to one introduction every 241 years. In addition, to provide a basis for evaluating the significance of risk management techniques and expenditures, the sensitivity of the above result to changes in various risk parameter assumptions is determined.

Growth of Foot-and-Mouth Disease Virus in Dispersed Tissue Cells

PubMed Central

Patty, R. E.; Tozzini, F.; Seibold, H. R.; Callis, J. J.

1962-01-01

Methods are described for rapid and economical production of large quantities of foot-and-mouth disease virus in stationary cultures of trypsin-dispersed bovine kidney cells in a simple medium. Yields of between 107 and 108 plaque-forming units per milliliter were obtained from serum-free cultures containing approximately a million and a half viable trypsin-dispersed cells per milliliter. Some of the advantages and disadvantages of these methods of virus production are discussed. ImagesFig. 1Fig. 2Fig. 3 PMID:17649388

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

USDA-ARS?s Scientific Manuscript database

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 ...

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. © 2015 The Author(s).

Collaborative Response and Recovery from a Foot-and-Mouth Disease Animal Health Emergency: Supporting Decision Making in a Complex Environment with Multiple Stakeholders

DTIC Science & Technology

2013-12-01

RESPONSE AND RECOVERY FROM A FOOT-AND- MOUTH DISEASE ANIMAL HEALTH EMERGENCY: SUPPORTING DECISION MAKING IN A COMPLEX ENVIRONMENT WITH MULTIPLE...Thesis 4. TITLE AND SUBTITLE COLLABORATIVE RESPONSE AND RECOVERY FROM A FOOT-AND- MOUTH DISEASE ANIMAL HEALTH EMERGENCY: SUPPORTING DECISION MAKING...200 words ) This thesis recommends ways to support decision makers who must operate within the multi-stakeholder complex situation of response and

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, S M; Danganan, L; Tammero, L

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 diagnosticmore » 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

Identification of a serotype-independent linear epitope of foot-and-mouth disease virus.

PubMed

Yang, Baolin; Wang, Mingxia; Liu, Wenming; Xu, Zhiqiang; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

2017-12-01

Foot-and-mouth disease (FMD), caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. VP2 is a structural protein of FMDV. In this study, an FMDV serotype-independent monoclonal antibody (MAb), 10B10, against the viral capsid protein VP2 was generated, and a series of GST fusion proteins expressing a truncated peptide of VP2 was subjected to Western blot analysis using MAb 10B10. Their results indicated that the peptide 8 TLLEDRILT 16 of VP2 is the minimal requirement of the epitope recognized by MAb 10B10. Importantly, this linear epitope was highly conserved among all seven serotypes of FMDV in a sequence alignment analysis. Subsequent alanine-scanning mutagenesis analysis revealed that the residues Thr 8 and Asp 12 of the epitope were crucial for MAb-10B10 binding. Furthermore, Western blot analysis also revealed that the MAb 10B10-directed epitope could be recognized by positive sera from FMDV-infected cattle. The discovery that MAb 10B10 recognizes a serotype-independent linear epitope of FMDV suggests potential applications for this MAb in the development of serotype-independent tests for FMDV.

First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam

USDA-ARS?s Scientific Manuscript database

In recent years, foot-and-mouth disease virus (FMDV) serotype O, lineage Ind2001d has spread to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Dak Nong province which borders Cambodia. Three subsequ...

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

USDA-ARS?s Scientific Manuscript database

The goal of the current study was to characterize serological and virological parameters of the foot-and-mouth disease (FMD) carrier state at two farms in Nainital District, Uttarakhand State in northern India. Despite previous vaccination of cattle in these herds, clinical signs of FMD occurred in ...

First detection of foot-and-mouth disease virus O/ME-SA/Ind2001 in China.

PubMed

Zhu, Z; Yang, F; He, J; Li, J; Cao, W; Li, J; Xia, Y; Guo, J; Jin, Y; Zhang, K; Zheng, H; Liu, X

2018-05-09

Foot-and-mouth disease (FMD) is endemic in China and is predominantly due to foot-and-mouth disease virus (FMDV) serotype O Mya-98 lineage. In recent years, FMDV O/ME-SA/Ind2001 lineage has spread from the Indian subcontinent to South-East Asia, Middle East and Africa, which may pose potential threats for future trans-regional livestock movements. In this study, we identified the appearance of FMDV O/ME-SA/Ind2001 in China; the first time that this virus lineage has been found there. Sequencing and phylogenetic analysis of VP1 sequences revealed that this newly determined strain belongs to O/ME-SA/Ind2001 sublineage d and is closely related to strains that have caused recent outbreaks of FMD in Nepal, Myanmar, Russia and South Korea. The results suggest extensive movements of the current O/ME-SA/Ind2001 sublineage d viruses and provide essential information for an effective national FMDV control programme in China. © 2018 Blackwell Verlag GmbH.

Foot-and-mouth disease virus transmission dynamics and persistence in a herd of vaccinated dairy cattle in India

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is an important transboundary disease with substantial economic impacts. Although between-herd transmission of the disease has been well studied, studies focusing on within-herd transmission using farm-level outbreak data are rare. The aim of this study was to estimate p...

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

USDA-ARS?s Scientific Manuscript database

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...

An uncommon clinical form of foot-and-mouth disease in beef cattle presented with cornual skin lesions.

PubMed

Mohebbi, M R; Barani, S M; Mahravani, H

2017-01-01

Foot-and-mouth disease (FMD) is a major infectious disease in livestock. The common clinical signs in cattle include epidermal vesicles that are majorly distributed around oronasal cavity, feet and teats. The aim of this report is to document an uncommon clinical form of the disease which comprises the occurrence of classic vesicular lesion in a rarely observed location of the horn vegetative tissue. During Iran's outbreak of FMD in 2013, field investigation, clinical examination and sampling from the affected herds in Qom province were performed. Specimens of mouth epithelium and horn vegetative tissue were collected for virology and histopathologic study. All the samples collected from horns were positive for foot-and-mouth disease virus (FMDV) in both enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) tests, and the strain of the virus was identified as A05. Surprisingly, all the animals with horn lesion came from beef herds, were less than 12 months old and had more severe signs of the systemic disease. Since the same strain of virus did not cause similar lesions in surrounding dairy cows, it was concluded that occurrence of horn lesions may be more associated with host factors rather than virus strain.

Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

PubMed

Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

2017-07-01

Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

Foot-and-mouth disease virus-associated abortion and vertical transmission following acute infection in cattle under natural conditions

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic as well as more than 70 wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. T...

75 FR 54589 - Availability of an Environmental Assessment for Field Testing Foot-and-Mouth Disease Vaccine...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2010-0011] Availability of an Environmental Assessment for Field Testing Foot-and-Mouth Disease Vaccine, Live Adenovirus Vector AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice. SUMMARY: We are advising...

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

Early dissemination of foot-and-mouth disease virus through sheep marketing in February 2001.

PubMed

Mansley, L M; Dunlop, P J; Whiteside, S M; Smith, R G H

2003-07-12

The results of epidemiological investigations suggest that livestock on up to 79 premises, spread widely throughout the British Isles, may have been exposed to infection by foot-and-mouth disease (FMD) virus by the movement of infected sheep before the first case of the disease was confirmed at an abattoir in Essex on February 20, 2001. A further 36 premises may have been infected by this route before the national livestock movement ban was imposed on February 23.

76 FR 44503 - Availability of a Risk Analysis Evaluating the Foot-and-Mouth Disease Status of Japan

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... Foot-and-Mouth Disease Status of Japan AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... disease (FMD) status of Japan and the risk of susceptible animals and animal products from Japan harboring... Health Inspection again recognizes Japan as free of FMD and allows the importation of whole cuts of...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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,...

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…

Optimization of immunohistochemical and fluorescent antibody techniques for localization of foot-and-mouth disease virus in animal tissues

USDA-ARS?s Scientific Manuscript database

Immunohistochemical (IHC) and immunofluorescent (IF) techniques were optimized for the detection of foot-and-mouth disease virus (FMDV) structural and non-structural proteins in frozen and paraformaldehyde-fixed paraffin embedded (PFPE) tissues of bovine and porcine origin. Immunohistochemical local...

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

USDA-ARS?s Scientific Manuscript database

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 ...

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

USDA-ARS?s Scientific Manuscript database

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...

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.

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

USDA-ARS?s Scientific Manuscript database

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 ...

Foot-and-mouth disease in pigs: current epidemiological situation and control methods.

PubMed

León, Emilio A

2012-03-01

Foot-and-mouth disease (FMD) is the paradigm of a transboundary animal disease. Beyond any doubt, it is the most serious challenge for livestock's health. Official Veterinary Services from free countries invest considerable amount of money to prevent its introduction, whereas those from endemic countries invest most of their resources in the control of the disease. A very important volume of scientific production is developed every year in different aspects of FMD, and for that reason, the current knowledge makes the diagnosis of the disease easier to a great extent. However, FMD is still endemic in about two-thirds of the countries, and periodically re-emergent in several countries. This paper is a review of recent publications, focusing mainly on control measures and current world epidemiological situation, emphasizing primarily pigs. © 2012 Blackwell Verlag GmbH.

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

USDA-ARS?s Scientific Manuscript database

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...

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

Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review.

PubMed

Chan, J Hy; Law, C K; Hamblion, E; Fung, H; Rudge, J

2017-04-01

Hand, foot, and mouth disease continues to cause seasonal epidemics in the Asia-Pacific Region. Since the current Enterovirus 71 vaccines do not provide cross-protection for all Enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. This systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness of detection tools and public health preventive measures to interrupt transmission. The findings will be used to recommend policy on the most effective responses and interventions in Hong Kong to effectively minimise and contain the spread of the disease within childcare facilities. We searched the following databases for primary studies written in Chinese or English: MEDLINE, EMBASE, Global Health, WHO Western Pacific Region Index Medicus database, China National Knowledge Infrastructure Databases, and Chinese Scientific Journals Database. Studies conducted during or retrospective to outbreaks of hand, foot, and mouth disease caused by Enterovirus 71 from 1980 to 2012 within childcare facilities and with a study population of 0 to 6 years old were included. Sixteen studies conducted on outbreaks in China showed that hand, foot, and mouth disease spread rapidly within the facility, with an outbreak length of 4 to 46 days, especially in those with delayed notification (after 24 hours) of clustered outbreak (with five or more cases discovered within the facility) to the local Center for Disease Control and Prevention and delayed implementation of a control response. The number of classes affected ranged from 1 to 13, and the attack rate for children ranged from 0.97% to 28.18%. Communication between key stakeholders about outbreak confirmation, risk assessment, and surveillance should be improved. Effective communication facilitates timely notification (within 24 hours) of

Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses

PubMed Central

Lee, Seo-Yong; Lee, Yeo-Joo; Kim, Rae-Hyung; Park, Jeong-Nam; Park, Min-Eun; Ko, Mi-Kyeong; Choi, Joo-Hyung; Chu, Jia-Qi; Lee, Kwang-Nyeong; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jung-Won; Kim, Byounghan; Lee, Myoung-Heon

2017-01-01

ABSTRACT There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV. IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD

Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses.

PubMed

Lee, Seo-Yong; Lee, Yeo-Joo; Kim, Rae-Hyung; Park, Jeong-Nam; Park, Min-Eun; Ko, Mi-Kyeong; Choi, Joo-Hyung; Chu, Jia-Qi; Lee, Kwang-Nyeong; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jung-Won; Kim, Byounghan; Lee, Myoung-Heon; Lee, Jong-Soo; Park, Jong-Hyeon

2017-08-15

There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV. IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD-free countries

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. © 2014 Wiley Periodicals, Inc.

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

Foot-and-mouth disease eradication efforts in the Republic of Korea

PubMed Central

Joo, Yi-Suk; An, Soo-hwan; Kim, Ok-Kyung; Lubroth, Juan; Sur, Jung-Hyang

2002-01-01

On March 20, 2000, a suspected vesicular disease in cattle was reported to the National Veterinary Research and Quarantine Service (NVRQS) of the Republic of Korea. This represented the index case of a foot-and-mouth disease (FMD) outbreak, which spread through several provinces. The Republic of Korea had been free of FMD for 66 years prior to the reintroduction of the virus and had recently suspended imports of pork and pork products from neighboring Japan owing to a reported FMD outbreak in that country. The Korean outbreak was ultimately controlled through the combination of preemptive slaughter, animal movement restrictions, and a strategy of ring vaccination. The purpose of this paper is to review the current FMD situation in Korea in the aftermath of its 2000 epizootic and how it may affect future efforts to eradicate or reduce risk of reintroduction of the disease into Korea. PMID:11989734

Pandemic Strain of Foot-and-Mouth Disease Virus Serotype O

PubMed Central

Samuel, Alan R.; Davies, Paul R.; Midgley, Rebecca J.; Valarcher, Jean-François

2005-01-01

A particular genetic lineage of foot-and-mouth disease virus (FMDV) serotype O, which we have named the PanAsia strain, was responsible for an explosive pandemic in Asia and extended to parts of Africa and Europe from 1998 to 2001. In 2000 and 2001, this virus strain caused outbreaks in the Republic of Korea, Japan, Russia, Mongolia, South Africa, the United Kingdom, Republic of Ireland, France, and the Netherlands, countries which last experienced FMD outbreaks decades before (ranging from 1934 for Korea to 1984 for the Netherlands). Although the virus has been controlled in all of these normally FMD-free or sporadically infected countries, it appears to be established throughout much of southern Asia, with geographically separated lineages evolving independently. A pandemic such as this is a rare phenomenon but demonstrates the ability of newly emerging FMDV strains to spread rapidly throughout a wide region and invade countries previously free from the disease. PMID:16485475

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

USDA-ARS?s Scientific Manuscript database

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...

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

PubMed Central

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

2015-01-01

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. PMID:26296881

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.

Development of single-step multiplex real-time RT-PCR assays for rapid diagnosis of enterovirus 71, coxsackievirus A6, and A16 in patients with hand, foot, and mouth disease.

PubMed

Puenpa, Jiratchaya; Suwannakarn, Kamol; Chansaenroj, Jira; Vongpunsawad, Sompong; Poovorawan, Yong

2017-10-01

Real-time reverse-transcription polymerase chain reaction (rRT-PCR) to detect enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) has facilitated the rapid and accurate identification of the two most common etiological agents underlying hand, foot, and mouth disease (HFMD). However, the worldwide emergence of CV-A6 infection in HFMD necessitates development of an improved multiplex rRT-PCR method. To rapidly determine the etiology of HFMD, two rRT-PCR assays using TaqMan probes were developed to differentiate among three selected common enteroviruses (EV-A71, CV-A16 and CV-A6) and to enable broad detection of enteroviruses (pan-enterovirus assay). No cross-reactions were observed with other RNA viruses examined. The detection limits of both assays were 10 copies per microliter for EV-A71, CV-A6 and CV-A16, and pan-enterovirus. The methods showed high accuracy (EV-A71, 90.6%; CV-A6, 92.0%; CV-A16, 100%), sensitivity (EV-A71, 96.5%; CV-A6, 95.8%; CV-A16, 99.0%), and specificity (EV-A71, 100%; CV-A6, 99.9%; CV-A16, 99.9%) in testing clinical specimens (n=1049) during 2014-2016, superior to those of conventional RT-PCR. Overall, the multiplex rRT-PCR assays enabled highly sensitive detection and rapid simultaneous typing of EV-A71, CV-A6 and CV-A16, and enteroviruses, rendering them feasible and attractive methods for large-scale surveillance of enteroviruses associated with HFMD outbreaks. Copyright © 2017 Elsevier B.V. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

Genome sequence of foot-and-mouth disease virus serotype O lineage ind-2001d collected in Vietnam in 2015

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is endemic in several countries in Asia and Africa and is considered one of the most important livestock diseases worldwide. Three serotypes of FMD virus (A, O and Asia1) contribute to endemicity in mainland Southeast Asia. In 2015, FMDV lineage Ind-2001 was detected for...

Complete Genome Sequence of the Circulatory Foot-and-Mouth Disease Virus Serotype Asia1 in Bangladesh

PubMed Central

Ali, M. Rahmat; Alam, A. S. M. Rubayet Ul; Amin, M. Al; Ullah, Huzzat; Siddique, Mohammad Anwar; Momtaz, Samina; Sultana, Munawar

2017-01-01

ABSTRACT The complete genome sequence of foot-and-mouth disease virus (FMDV) serotype Asia1 isolated from Bangladesh is reported here. Genome analysis revealed amino acid substitutions in the VP1 antigenic region and deletions in both the 5′ and 3′ untranslated regions (UTRs) compared to the genome of the existing vaccine strain (GenBank accession no. AY304994). PMID:29074654

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

USDA-ARS?s Scientific Manuscript database

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...

Evidence of subclinical foot-and-mouth disease virus infection in young calves born from clinically recovered cow under natural condition

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease (FMD) is a highly contagious and economically important, transboundary viral disease of cloven-hoofed animals. It is known that a chronic, asymptomatic FMD syndrome may occur subsequent to acute FMD in adult ruminants. However, neither asymptomatic nor persistent infection has...

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.

Expression of porcine fusion protein IRF7/3(5D) efficiently controls foot-and-mouth disease virus replication

USDA-ARS?s Scientific Manuscript database

Several studies have demonstrated that administration of type I, II, or III interferons (IFN) delivered using a replication defective human adenovirus 5 (Ad5) vector is effective to control Foot-and-Mouth Disease (FMD) in cattle and swine during experimental infections. However, high doses are requi...

Studies on Sam68 a cell factor involved in the life cycle of foot-and-mouth disease virus

USDA-ARS?s Scientific Manuscript database

As with other RNA viruses, Foot-and-Mouth Disease Virus (FMDV) recruits various host cell factors to assist in translation and replication of the virus genome. While FMDV translation has been thoroughly investigated, much remains unknown regarding replication of the positive-sense RNA genome. In th...

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

Virological investigation of hand, foot, and mouth disease in a tertiary care center in South India.

PubMed

Vijayaraghavan, Pavithra M; Chandy, Sara; Selvaraj, Kavitha; Pulimood, Susanne; Abraham, Asha M

2012-07-01

Hand, foot, and mouth disease (HFMD) remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. The aim of this study was to characterize HFMD-related isolates by molecular techniques. Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC), Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot) were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD) cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE) in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR) and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST) algorithm. The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP). Of the 30 suspected HFMD cases, only 17 (57%) were laboratory confirmed and Coxsackievirus A16 (CVA16) was identified as the etiological agent in all these cases. Coxsackievirus A16 (CVA16) was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the epidemiology of HFMD in India.

Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids

USDA-ARS?s Scientific Manuscript database

Analysis of the immune response to infection of livestock by foot-and-mouth disease virus (FMDV) is most often reported as the serum antibody response to the virus. While measurement of neutralizing antibody has been sensitive and specific, measurements of the quality of the antibody response are le...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

Temporal and spatial mapping of hand, foot and mouth disease in Sarawak, Malaysia.

PubMed

Sham, Noraishah M; Krishnarajah, Isthrinayagy; Ibrahim, Noor Akma; Lye, Munn-Sann

2014-05-01

Hand, foot and mouth disease (HFMD) is endemic in Sarawak, Malaysia. In this study, a geographical information system (GIS) was used to investigate the relationship between the reported HFMD cases and the spatial patterns in 11 districts of Sarawak from 2006 to 2012. Within this 7-years period, the highest number of reported HFMD cases occurred in 2006, followed by 2012, 2008, 2009, 2007, 2010 and 2011, in descending order. However, while there was no significant distribution pattern or clustering in the first part of the study period (2006 to 2011) based on Moran's I statistic, spatial autocorrelation (P = 0.068) was observed in 2012.

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

USDA-ARS?s Scientific Manuscript database

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 ...

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

An improved, rapid cELISA using a novel conserved 3B epitope for the serological diagnosis of foot-and-mouth disease

USDA-ARS?s Scientific Manuscript database

The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed livestock and wildlife resulting in heavy economic losses due to loss of trade and recovery from disease. We developed a rapid, sensitive, and specific competitive ELISA to detect serum antibodies to FMDV. This new cELI...

Hand, foot and mouth disease: spatiotemporal transmission and climate.

PubMed

Wang, Jin-feng; Guo, Yan-Sha; Christakos, George; Yang, Wei-Zhong; Liao, Yi-Lan; Li, Zhong-Jie; Li, Xiao-Zhou; Lai, Sheng-Jie; Chen, Hong-Yan

2011-04-05

The Hand-Foot-Mouth Disease (HFMD) is the most common infectious disease in China, its total incidence being around 500,000~1,000,000 cases per year. The composite space-time disease variation is the result of underlining attribute mechanisms that could provide clues about the physiologic and demographic determinants of disease transmission and also guide the appropriate allocation of medical resources to control the disease. HFMD cases were aggregated into 1456 counties and during a period of 11 months. Suspected climate attributes to HFMD were recorded monthly at 674 stations throughout the country and subsequently interpolated within 1456 × 11 cells across space-time (same as the number of HFMD cases) using the Bayesian Maximum Entropy (BME) method while taking into consideration the relevant uncertainty sources. The dimensionalities of the two datasets together with the integrated dataset combining the two previous ones are very high when the topologies of the space-time relationships between cells are taken into account. Using a self-organizing map (SOM) algorithm the dataset dimensionality was effectively reduced into 2 dimensions, while the spatiotemporal attribute structure was maintained. 16 types of spatiotemporal HFMD transmission were identified, and 3-4 high spatial incidence clusters of the HFMD types were found throughout China, which are basically within the scope of the monthly climate (precipitation) types. HFMD propagates in a composite space-time domain rather than showing a purely spatial and purely temporal variation. There is a clear relationship between HFMD occurrence and climate. HFMD cases are geographically clustered and closely linked to the monthly precipitation types of the region. The occurrence of the former depends on the later.

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

2017-06-01

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.

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

USDA-ARS?s Scientific Manuscript database

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 ...

SAT2 Foot-and-Mouth Disease Virus 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

2017-05-15

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

SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability

PubMed Central

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

2017-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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...

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

PubMed

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

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.

Statistical monitoring of the hand, foot and mouth disease in China.

PubMed

Zhang, Jingnan; Kang, Yicheng; Yang, Yang; Qiu, Peihua

2015-09-01

In a period starting around 2007, the Hand, Foot, and Mouth Disease (HFMD) became wide-spreading in China, and the Chinese public health was seriously threatened. To prevent the outbreak of infectious diseases like HFMD, effective disease surveillance systems would be especially helpful to give signals of disease outbreaks as early as possible. Statistical process control (SPC) charts provide a major statistical tool in industrial quality control for detecting product defectives in a timely manner. In recent years, SPC charts have been used for disease surveillance. However, disease surveillance data often have much more complicated structures, compared to the data collected from industrial production lines. Major challenges, including lack of in-control data, complex seasonal effects, and spatio-temporal correlations, make the surveillance data difficult to handle. In this article, we propose a three-step procedure for analyzing disease surveillance data, and our procedure is demonstrated using the HFMD data collected during 2008-2009 in China. Our method uses nonparametric longitudinal data and time series analysis methods to eliminate the possible impact of seasonality and temporal correlation before the disease incidence data are sequentially monitored by a SPC chart. At both national and provincial levels, our proposed method can effectively detect the increasing trend of disease incidence rate before the disease becomes wide-spreading. © 2015, The International Biometric Society.

Construction of stabilized and tagged foot-and-mouth disease virus.

PubMed

Park, Jeong-Nam; Ko, Mi-Kyeong; Kim, Rae-Hyung; Park, Min-Eun; Lee, Seo-Yong; Yoon, Ji-Eun; Choi, Joo-Hyung; You, Su-Hwa; Park, Jung-Won; Lee, Kwang-Nyeong; Chun, Ji-Eun; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Kim, Byounghan; Lee, Myoung-Heon; Park, Jong-Hyeon

2016-11-01

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease that affects cloven-hoofed animals worldwide. Construction and purification of stable antigen for vaccine are necessary but technically difficult and laborious. Here, we have tried to investigate an alternative method by inserting a hexa-histidine tag (6xHIS) in the VP1 C-terminal for easy purification and replacing two amino acids of VP1/VP2 to enhance the stability of the capsid of the FMD virus (FMDV) Asia1/MOG/05. In addition, infectious 6xHIS-tagged stable (S/T) FMDVs were maintained under acidic conditions (pH 6.0) and were readily purified from small-scale cultures using a commercial metal-affinity column. The groups vaccinated with the S/T FMDV antigen showed complete protection comparing to low survival rate in the group vaccinated with non-S/T FMDV against lethal challenge with Asia1 Shamir in mice. Therefore, the present findings indicate that the stabilized and tagged antigen offers an alternative to using the current methods for antigen purification and enhancement of stability and has potential for the development of a new FMD vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial pattern of foot-and-mouth disease virus serotypes in North Central Nigeria

PubMed Central

Wungak, Yiltawe Simwal; Ishola, Olayinka O.; Olugasa, Babasola O.; Lazarus, David D.; Ehizibolo, David O.; Ularamu, Hussaini G.

2017-01-01

Aim: This study aimed to determine the foot-and-mouth disease virus (FMDV) serotypes circulating, the prevalence of FMDV serotypes, and the spatial distribution of FMDV among sedentary and pastoral cattle herds in the North-Central Nigeria. Materials and Methods: A cross-sectional study was undertaken, during which a total of 155 sera that tested positive for foot-and-mouth disease (FMD) 3ABC non-structural protein antibodies were selected and screened for FMD structural protein serotypes, A, O, SAT 1, and SAT 2 using a solid-phase competitive enzyme-linked immunosorbent assay (ELISA). Epithelial tissue specimens were collected during outbreak investigations which were tested for FMD using an antigen capture ELISA for serotype A, O, SAT 1, and SAT 2. Results: An overall serotype-specific prevalence of 79.35 (95% confidence interval [CI]: 72.4-85.18) was recorded for serotype O, 65.2% (95% CI: 57.41-72.3) for serotype A, 52.9% (95% CI: 45.03-60.67) for SAT 2, and 33.55% (95% CI: 26.45-41.26) for SAT 1. Evidence of exposure to multiple FMDV serotypes showed that 12.26% of the sera samples had antibodies against four serotypes circulating, 30.97% had antibodies against three serotypes circulating, 22.58% had antibodies against two serotypes, and 17% showed exposure to only one serotype. Clinical specimens (epithelial tissue) collected during outbreak investigations showed that serotype O has the highest proportion of 50% with serotype A - 25%; SAT 2 - 20.8%; and SAT 1 - 4.1%. Conclusion: The study detected diffuse and co-circulation of serotypes A, O, SAT 1, and SAT 2 within the study area, and hence the need for the appropriately matched multivalent vaccine is strongly advocated for FMD control in Nigeria. PMID:28507418

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

USDA-ARS?s Scientific Manuscript database

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...

Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

PubMed

Huang, H; Yang, Z; Xu, Q; Sheng, Z; Xie, Y; Yan, W; You, Y; Sun, L; Zheng, Z

1999-01-01

In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

Foot-and-Mouth Disease in the Middle East Caused by an A/ASIA/G-VII Virus Lineage, 2015-2016.

PubMed

Bachanek-Bankowska, Katarzyna; Di Nardo, Antonello; Wadsworth, Jemma; Henry, Elisabeth K M; Parlak, Ünal; Timina, Anna; Mischenko, Alexey; Qasim, Ibrahim Ahmad; Abdollahi, Darab; Sultana, Munawar; Hossain, M Anwar; King, Donald P; Knowles, Nick J

2018-06-01

Phylogenetic analyses of foot-and-mouth disease type A viruses in the Middle East during 2015-2016 identified viruses belonging to the A/ASIA/G-VII lineage, which originated in the Indian subcontinent. Changes in a critical antigenic site within capsid viral protein 1 suggest possible evolutionary pressure caused by an intensive vaccination program.

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

USDA-ARS?s Scientific Manuscript database

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...

Genetic diversity and comparison of diagnostic tests for characterization of foot-and-mouth disease virus strains from Pakistan 2008-2012

USDA-ARS?s Scientific Manuscript database

We report the laboratory analysis of 125 clinical samples from suspected cases of foot-and-mouth disease (FMD) in cattle and Asian buffalo collected in Pakistan between 2008 and 2012. Of these samples, 89 were found to contain viral RNA by rRT-PCR, of which 88 were also found to contain infectious F...

Evolving perception on the benefits of vaccination as a foot and mouth disease control policy: contributions of South America.

PubMed

Bergmann, Ingrid E; Malirat, Viviana; Falczuk, Abraham J

2005-12-01

Within the past decade, changes in perceptions on the benefits of vaccination as an appropriate tool to achieve complete foot and mouth disease eradication have become evident. The former negative view was derived from misconceptions, resulting mainly from the belief that vaccines are not entirely effective and that vaccination masks asymptomatic viral circulation. The advent in the 1990s of vaccination policies implemented within a strategic eradication plan in South America, and during recurrence of the disease in disease-free regions contributed towards generating more reliable and visible outcomes of vaccination programs, paving the way towards a new perception. Particularly relevant was the development and application of novel serodiagnostic approaches to assess silent viral circulation, irrespective of vaccination. The use in South America of vaccination allied to serosurveys to accompany viral clarification during eradication campaigns and after emergencies clearly established the importance of this control tool to stop the spread of viral infection. This alliance gave input to break many myths associated with the use of vaccines, including the belief that immunized carrier animals pose an epidemiologic risk. This experience launched new concepts that supported the internationally recognized status of foot and mouth disease-free regions with vaccination and the 'vaccination to live' policy as an alternative to 'stamping out'.

Characterization of severe hand, foot, and mouth disease in Shenzhen, China, 2009-2013.

PubMed

Huang, Yun; Zhou, Yuanping; Lu, Hong; Yang, Hong; Feng, Qianjin; Dai, Yingchun; Chen, Long; Yu, Shouyi; Yao, Xiangjie; Zhang, Hailong; Jiang, Ming; Wang, Yujie; Han, Ning; Hu, Guifang; He, Yaqing

2015-09-01

Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with different enteroviruses show varied clinical symptoms. The aim of this study was to determine whether the etiological spectrum of mild and severe HFMD changed, and the association between pathogens and clinical features. From 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. A dynamic view of the etiological spectrum of mild and severe HFMD in Shenzhen city of China was provided. EV71 accounted for the majority proportion of severe HFMD cases and fatalities during 2009-2013. CA16 and EV71 were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent severe symptoms. Nervous system complications, including aseptic encephalitis and aseptic meningitis were observed mainly in patients infected by EV71. Among EV71, CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to develop in patients infected with CA10. Vesicles on the mouth more frequently occurred in the patients with CA6, but less in the patient with EV71. Associations between diverse enterovirus serotypes and various clinical features were discovered in the present study, which may offer further insight into early detection, diagnosis and treatment of HFMD. © 2015 Wiley Periodicals, Inc.

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.

Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, 2011-2013.

PubMed

Fonseca, Magilé C; Sarmiento, Luis; Resik, Sonia; Martínez, Yenisleidys; Hung, Lai Heng; Morier, Luis; Piñón, Alexander; Valdéz, Odalys; Kourí, Vivian; González, Guelsys

2014-09-01

Hand, foot and mouth disease (HFMD) is usually caused by coxsackievirus A16 or enterovirus 71 (EV71). Between 2011 and 2013, HFMD cases were reported from different Cuban provinces. A total of 42 clinical specimens were obtained from 23 patients. Detection, identification and phylogenetic analysis of enterovirus-associated HFMD were carried out by virus isolation, specific enterovirus PCR and partial VP1 sequences. HEV was detected in 11 HFMD cases. Emerging genetic variants of coxsackievirus A6 and EV71 were identified as the causative agents of the Cuban HFMD cases.

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

Multiple origins of foot-and-mouth disease virus serotype Asia 1 outbreaks, 2003-2007.

PubMed

Valarcher, Jean Francois; Knowles, Nick J; Zakharov, Valery; Scherbakov, Alexey; Zhang, Zhidong; Shang, You Jun; Liu, Zai Xin; Liu, Xiang Tao; Sanyal, Aniket; Hemadri, Divakar; Tosh, Chakradhar; Rasool, Thaha J; Pattnaik, Bramhadev; Schumann, Kate R; Beckham, Tammy R; Linchongsubongkoch, Wilai; Ferris, Nigel P; Roeder, Peter L; Paton, David J

2009-07-01

We investigated the molecular epidemiology of foot-and-mouth disease virus (FMDV) serotype Asia 1, which caused outbreaks of disease in Asia during 2003-2007. Since 2004, the region affected by outbreaks of this serotype has increased from disease-endemic countries in southern Asia (Afghanistan, India, Iran, Nepal, Pakistan) northward to encompass Kyrgyzstan, Tajikistan, Uzbekistan, several regions of the People's Republic of China, Mongolia, Eastern Russia, and North Korea. Phylogenetic analysis of complete virus capsid protein 1 (VP1) gene sequences demonstrated that the FMDV isolates responsible for these outbreaks belonged to 6 groups within the Asia 1 serotype. Some contemporary strains were genetically closely related to isolates collected historically from the region as far back as 25 years ago. Our analyses also indicated that some viruses have spread large distances between countries in Asia within a short time.

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

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

USDA-ARS?s Scientific Manuscript database

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...

Bayesian analysis of experimental epidemics of foot-and-mouth disease.

PubMed Central

Streftaris, George; Gibson, Gavin J.

2004-01-01

We investigate the transmission dynamics of a certain type of foot-and-mouth disease (FMD) virus under experimental conditions. Previous analyses of experimental data from FMD outbreaks in non-homogeneously mixing populations of sheep have suggested a decline in viraemic level through serial passage of the virus, but these do not take into account possible variation in the length of the chain of viral transmission for each animal, which is implicit in the non-observed transmission process. We consider a susceptible-exposed-infectious-removed non-Markovian compartmental model for partially observed epidemic processes, and we employ powerful methodology (Markov chain Monte Carlo) for statistical inference, to address epidemiological issues under a Bayesian framework that accounts for all available information and associated uncertainty in a coherent approach. The analysis allows us to investigate the posterior distribution of the hidden transmission history of the epidemic, and thus to determine the effect of the length of the infection chain on the recorded viraemic levels, based on the posterior distribution of a p-value. Parameter estimates of the epidemiological characteristics of the disease are also obtained. The results reveal a possible decline in viraemia in one of the two experimental outbreaks. Our model also suggests that individual infectivity is related to the level of viraemia. PMID:15306359

Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam

PubMed Central

Anh, Nguyen To; Nhu, Le Nguyen Truc; Van, Hoang Minh Tu; Hong, Nguyen Thi Thu; Thanh, Tran Tan; Hang, Vu Thi Ty; Ny, Nguyen Thi Han; Nguyet, Lam Anh; Phuong, Tran Thi Lan; Nhan, Le Nguyen Thanh; Hung, Nguyen Thanh; Khanh, Truong Huu; Tuan, Ha Manh; Viet, Ho Lu; Nam, Nguyen Tran; Viet, Do Chau; Qui, Phan Tu; Wills, Bridget; Sabanathan, Sarawathy; Chau, Nguyen Van Vinh; Thwaites, Louise; Rogier van Doorn, H.; Thwaites, Guy; Rabaa, Maia A.

2018-01-01

Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011–2015. Of these patients, 93 (18%) had severe HFMD. Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare. Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6–associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies. PMID:29553326

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

Modeling the spread and control of foot-and-mouth disease in Pennsylvania following its discovery and options for control

PubMed Central

Tildesley, Michael J.; Smith, Gary; Keeling, Matt J.

2013-01-01

In this paper, we simulate outbreaks of foot-and-mouth disease in the Commonwealth of Pennsylvania, USA – after the introduction of a state-wide movement ban – as they might unfold in the presence of mitigation strategies. We have adapted a model previously used to investigate FMD control policies in the UK to examine the potential for disease spread given an infection seeded in each county in Pennsylvania. The results are highly dependent upon the county of introduction and the spatial scale of transmission. Should the transmission kernel be identical to that for the UK, the epidemic impact is limited to fewer than 20 premises, regardless of the county of introduction. However, for wider kernels where infection can spread further, outbreaks seeded in or near the county with highest density of premises and animals result in large epidemics (>150 premises). Ring culling and vaccination reduce epidemic size, with the optimal radius of the rings being dependent upon the county of introduction. Should the kernel width exceed a given county-dependent threshold, ring culling is unable to control the epidemic. We find that a vaccinate-to-live policy is generally preferred to ring culling (in terms of reducing the overall number of premises culled), indicating that well-targeted control can dramatically reduce the risk of large scale outbreaks of foot-and-mouth disease occurring in Pennsylvania. PMID:22169708

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

USDA-ARS?s Scientific Manuscript database

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 ...

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.

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

An economic assessment of foot and mouth disease in Japan.

PubMed

Hayama, Y; Osada, Y; Oushiki, D; Tsutsui, T

2017-04-01

A large-scale foot and mouth disease (FMD) epidemic in Japan in 2010 caused severe economic losses for livestock and related industries. In this paper, the authors develop a clear and usable framework to estimate the economic impact of this FMD outbreak. An economic analysis is then conducted by combining this framework with an epidemiological model. The framework estimates the direct and indirect costs to livestock and related industries by applying an input-output model, as well as by addressing expenditure on disease control. The direct cost to the livestock industry was estimated at 51.2 billion Japanese yen (JPY), engendering an indirect cost to related industries of JPY 25.5 billion. The expenditure for disease control activities was estimated at JPY 8.2 billion. The total impact of the 2010 FMD epidemic was estimated at almost JPY 85 billion. Within the economic analysis, the authors evaluate several control measure scenarios: a baseline scenario, which assumes that the rapid disease spread observed in the early phase of the 2010 FMD epidemic would continue; prompt culling within 24 hours; early detection of the first case; and emergency vaccination within a radius of 10 km around the affected farms in either seven or 28 days. Prompt culling and early detection were superior from an economic point of view, reducing the total economic impact to 30% and 2% of that in the baseline scenario, respectively. Compared with these scenarios, vaccination was less cost effective. However, vaccination suppressed the speed of disease spread and shortened the duration of the epidemic, suggesting its potential effectiveness in curbing rapid disease spread in a densely populated area.

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

PubMed Central

Ramirez-Carvajal, Lisbeth; Pauszek, Steven J.; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S.; Stockwell, Timothy B.; Rodriguez, Luis L.

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region. PMID:29390015

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

PubMed

Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

2018-01-01

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development.

PubMed

Puckette, Michael; Clark, Benjamin A; Smith, Justin D; Turecek, Traci; Martel, Erica; Gabbert, Lindsay; Pisano, Melia; Hurtle, William; Pacheco, Juan M; Barrera, José; Neilan, John G; Rasmussen, Max

2017-11-15

The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production. Copyright © 2017 Puckette et al.

Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

PubMed

Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

2017-09-01

Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

A traditional evolutionary history of foot-and-mouth disease viruses in Southeast Asia challenged by analyses of non-structural protein coding sequences

USDA-ARS?s Scientific Manuscript database

Molecular epidemiology and evolution of foot-and-mouth disease virus (FMDV) are widely studied using genomic sequences encoding VP1, the capsid protein containing the most relevant antigenic domains. Although sequencing of the full viral genome is not used as a routine diagnostic or surveillance too...

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. Copyright © 2015. Published by Elsevier B.V.

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. © 2010 Blackwell Verlag GmbH.

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007

PubMed Central

Cottam, Eleanor M.; Wadsworth, Jemma; Shaw, Andrew E.; Rowlands, Rebecca J.; Goatley, Lynnette; Maan, Sushila; Maan, Narender S.; Mertens, Peter P. C.; Ebert, Katja; Li, Yanmin; Ryan, Eoin D.; Juleff, Nicholas; Ferris, Nigel P.; Wilesmith, John W.; Haydon, Daniel T.; King, Donald P.; Paton, David J.; Knowles, Nick J.

2008-01-01

Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O1 BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes. PMID:18421380

[Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease : clinical features, MRI findings and follow-up study].

PubMed

Liu, Kun; Ma, Yan-xu; Zhang, Cheng-bing; Chen, Yi-ping; Ye, Xin-jian; Bai, Guang-hui; Yu, Zhi-kang; Yan, Zhi-han

2012-07-03

To explore the clinical and magnetic resonance imaging (MRI) characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. The clinical and MRI manifestations and follow-up outcomes in 35 children, at Second Affiliated Hospital, Wenzhou Medical College from August 2008 to November 2010, hospitalized with neurologic complications of enterovirus 71-infected hand-foot-mouth disease were retrospectively analyzed. Six children with aseptic meningitis presented the clinical symptoms and signs of meningitis. Five of them showed subdural effusion and ventriculomegaly, or both on MRI. At follow-ups, neurologic sequel could not be found. Among 24 cases with brainstem encephalitis, there were myoclonic jerks and tremor, ataxia, or both (grade I disease, n = 12), myoclonus and cranial-nerve involvement (grade II disease, n = 4), and cardiopulmonary failure after brain-stem infection (grade III disease, n = 8). In patients with brainstem encephalitis, lesions were predominantly located at the posterior portions of medulla and pons with hypointensity on T1WI and hyperintensity on T2WI. Cerebellar dentate nucleus, caudate nucleus and lenticular nucleus could also be involved. At follow-ups, the patients with mild symptoms had no neurologic sequel and the lesions within brain stem became small or vanished in most cases. While in the majority of serious patients, neurologic sequel could be found and the lesions located at brain stem became encephalomalacia. Fourteen cases with acute flaccid paralysis presented acute limb myasthenia with tendon reflex and muscular tension decreased. On spinal MRI, the lesions predominantly involved anterior horn regions of spinal cord with hypointensity on T1WI and hyperintensity on T2WI. Most patients improved their muscle strength and most lesions of spinal cord became smaller or vanished during follow-ups. MRI is the most effective modality of diagnosis and follow-up for

Expression of a foot-and-mouth disease virus immunodominant epitope by a filamentous bacteriophage vector.

PubMed

Kim, Y J; Lebreton, F; Kaiser, C; Crucière, C; Rémond, M

2004-02-01

We described the construction of a recombinant filamentous phage displaying on its surface the immunodominant site of VP1 protein of foot-and-mouth disease virus (FMDV). The coding sequence was inserted at the amino-terminus of the major coat protein pVIII via a spacer. The hybrid phage proved to be antigenic as it was recognized by polyclonal and monoclonal anti FMDV sera. In two experiments involving immunisation of guinea-pigs with the recombinant phage, a low antibody response was generated. This suggests a possible role for phage displayed peptides in inducing anti FMDV immunity and the possibility of further development is discussed.

A literature review and case report of hand, foot and mouth disease in an immunocompetent adult.

PubMed

Omaña-Cepeda, Carlos; Martínez-Valverde, Andrea; del Mar Sabater-Recolons, María; Jané-Salas, Enric; Marí-Roig, Antonio; López-López, José

2016-03-15

To report an uncommon case of hand, foot and mouth disease, (HFMD) in an immunocompetent adult; a highly infectious disease, characterized by the appearance of vesicles on the mouth, hands and feet, associated with coxsackieviruses and enteroviruses; including a literature review. A 23 year Caucasian male with no medical or surgical history, no allergies, was not taking any medication and smoked ten cigarettes a day, suffering from discomfort in the oral cavity; itching, burning and pain when swallowing associated with small erythematous lesions located on the hard palate, and small ulcers in tonsillar pillars and right buccal mucosa. Mild fever of 37.8 °C and general malaise. The patient reported he had had contact with a child diagnosed with HFMD. From his background and symptoms, the patient was diagnosed with HFMD. Following symptomatic treatment, the symptoms remitted in 7 days. A literature review in MEDLINE (PubMed). The inclusion criteria were for studies on humans over the last 5 years, using the keywords HFMD. We found 925 articles, which were subsequently reduced to 52 documents after applying the inclusion criteria. Maculopapular lesions were found on hands and feet. Dentists may have a key role diagnosing the disease. A surveillance system to predict future outbreaks, encourage early diagnosis, put appropriate public health measures in place and research vaccine development is vitally important in order to control the disease.

U.K. Foot and Mouth Disease: A Systemic Risk Assessment of Existing Controls.

PubMed

Delgado, João; Pollard, Simon; Pearn, Kerry; Snary, Emma L; Black, Edgar; Prpich, George; Longhurst, Phil

2017-09-01

This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted 'features, events, and processes' (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

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

USDA-ARS?s Scientific Manuscript database

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...

An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help preve...

Monitoring hand, foot and mouth disease by combining search engine query data and meteorological factors.

PubMed

Huang, Da-Cang; Wang, Jin-Feng

2018-01-15

Hand, foot and mouth disease (HFMD) has been recognized as a significant public health threat and poses a tremendous challenge to disease control departments. To date, the relationship between meteorological factors and HFMD has been documented, and public interest of disease has been proven to be trackable from the Internet. However, no study has explored the combination of these two factors in the monitoring of HFMD. Therefore, the main aim of this study was to develop an effective monitoring model of HFMD in Guangzhou, China by utilizing historical HFMD cases, Internet-based search engine query data and meteorological factors. To this end, a case study was conducted in Guangzhou, using a network-based generalized additive model (GAM) including all factors related to HFMD. Three other models were also constructed using some of the variables for comparison. The results suggested that the model showed the best estimating ability when considering all of the related factors. Copyright © 2017 Elsevier B.V. All rights reserved.

[The etiological and clinical characteristics of hospitalized children with hand, foot and mouth disease in Beijing in 2013].

PubMed

Gu, Hongyan; Liu, Zhida; Zhang, Ling; Chen, Yong; Yang, Siyuan; Zhang, Weiyan; Li, Xingwang

2015-06-01

To investigate the etiology of hand, foot and mouth disease (HFMD) in Beijing during 2013, and study the clinical characteristics of HFMD caused by the main serotypes of enterovirus in the study. Clinical data and 128 stool samples were collected from 128 hospitalized children with HFMD in Beijing Ditan Hospital during 2013. One step RT-PCR method was used for enterovirus genotyping to investigate the etiology of HFMD. Clinical characteristics of HFMD caused by the main serotypes of enterovirus were analyzed. And VP1 segments of the main virus were amplified to construct phylogenetic tree for the phylogenetic analysis. A total of 128 hospitalized children with HFMD were included. HFMD was more likely developed in children under 2 years of age (81.6%, 102/125); 11 different enteroviruses were genotyped, with a total enterovirus positive rate of 76.6% (98/128); the positive rate of coxsackievirus A6 (CA6), 43.0% ( 55/128), was the highest, followed by enterovirus 71 (EV71), accounting for 14.8% (19/128). HFMD caused by CA6 was atypical, the rashes of which involved the perioral, trunk, limbs, face and neck (47%, 26/55), besides the common parts. Of the 55 cases caused by CA6, 6 children had clinical manifestations of nervous system involvement, one of whom even displayed type 2 respiratory failure. Mental status change more likely to occur in EV71-infected children than in CA6-infected ones (42% (8/19) vs. 11% (6/55) (χ(2)=7.041, P=0.008)); 13 children displayed onychomadesis, including 12 CA6 cases (23%, 12/53) and 1 CA10 cases (17%, 1/6), in the convalescence of hand, foot and mouth disease, and the correlation between onychomadesis and CA6 infection was significant (χ(2)=9.297, P=0.002). Phylogenetic analysis of 33 CA6 VP1 showed that the CA6 isolates of this study were highly similar to that of Taiwan and the nucleotide similarity was 95.91%-98.89%. CA6 was the major pathogen of hospitalized children with hand, foot and mouth disease in Beijing during 2013

Detection of genome, antigen, and antibodies in oral fluids from pigs infected with foot-and-mouth disease virus.

PubMed

Senthilkumaran, Chandrika; Yang, Ming; Bittner, Hilary; Ambagala, Aruna; Lung, Oliver; Zimmerman, Jeffrey; Giménez-Lirola, Luis G; Nfon, Charles

2017-04-01

Virus nucleic acids and antibody response to pathogens can be measured using swine oral fluids (OFs). Detection of foot-and-mouth disease virus (FMDV) genome in swine OFs has previously been demonstrated. Virus isolation and viral antigen detection are additional confirmatory assays for diagnosing FMDV, but these methods have not been evaluated using swine OF. The objectives of this study were to further validate the molecular detection of FMDV in oral fluids, evaluate antigen detection and FMDV isolation from swine OFs, and develop an assay for isotypic anti-FMDV antibody detection in OFs. Ribonucleic acid (RNA) from FMDV was detected in OFs from experimentally infected pigs by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) from 1 day post-infection (dpi) to 21 dpi. Foot-and-mouth disease virus (FMDV) was isolated from OFs at 1 to 5 dpi. Additionally, FMDV antigens were detected in OFs from 1 to 6 dpi using a lateral flow immunochromatographic strip test (LFIST), which is a rapid pen-side test, and from 2 to 3 dpi using a double-antibody sandwich enzyme-linked immunosorbent assay (DAS ELISA). Furthermore, FMDV-specific immunoglobulin A (IgA) was detected in OFs using an isotype-specific indirect ELISA starting at dpi 14. These results further demonstrated the potential use of oral fluids for detecting FMDV genome, live virus, and viral antigens, as well as for quantifying mucosal IgA antibody response.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 wasmore » 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.« less

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

USDA-ARS?s Scientific Manuscript database

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 ...

Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging.

PubMed

Logan, Grace; Newman, Joseph; Wright, Caroline F; Lasecka-Dykes, Lidia; Haydon, Daniel T; Cottam, Eleanor M; Tuthill, Tobias J

2017-10-18

Non-enveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals and human. In the picornavirus family of non-enveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. Importance In order to transmit their genetic material to a new host, non-enveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA viruses the requirements for this critical part of the viral life cycle remain poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple and transferable to the

Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

PubMed

Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

2017-08-01

Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D pol ) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D pol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A 24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F HF ) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I LF ) and W237L LF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D pol mutations that affect polymerase

Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity

PubMed Central

Rai, Devendra K.; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A.; Kloc, Anna; de los Santos, Teresa; Peersen, Olve

2017-01-01

ABSTRACT Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3Dpol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3Dpol mutations that affect polymerase fidelity

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. Published by Elsevier Ltd.

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

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

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

PubMed

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; Charleston, Bryan; Juleff, Nicholas

2016-05-15

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. 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 persisted more

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.

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. © 2012 Society for Risk Analysis.

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

USDA-ARS?s Scientific Manuscript database

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...

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

A 12-residue epitope displayed on phage T7 reacts strongly with antibodies against foot-and-mouth disease virus.

PubMed

Wong, Chuan Loo; Yong, Chean Yeah; Muhamad, Azira; Syahir, Amir; Omar, Abdul Rahman; Sieo, Chin Chin; Tan, Wen Siang

2018-05-01

Foot-and-mouth disease (FMD) is a major threat to the livestock industry worldwide. Despite constant surveillance and effective vaccination, the perpetual mutations of the foot-and-mouth disease virus (FMDV) pose a huge challenge to FMD diagnosis. The immunodominant region of the FMDV VP1 protein (residues 131-170) displayed on phage T7 has been used to detect anti-FMDV in bovine sera. In the present study, the functional epitope was further delineated using amino acid sequence alignment, homology modelling and phage display. Two highly conserved regions (VP1 145-152 and VP1 159-170 ) were identified among different FMDV serotypes. The coding regions of these two epitopes were fused separately to the T7 genome and displayed on the phage particles. Interestingly, chimeric phage displaying the VP1 159-170 epitope demonstrated a higher antigenicity than that displaying the VP1 131-170 epitope. By contrast, phage T7 displaying the VP1 145-152 epitope did not react significantly with the anti-FMDV antibodies in vaccinated bovine sera. This study has successfully identified a smaller functional epitope, VP1 159-170 , located at the C-terminal end of the structural VP1 protein. The phage T7 displaying this shorter epitope is a promising diagnostic reagent to detect anti-FMDV antibodies in vaccinated animals.

Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

USDA-ARS?s Scientific Manuscript database

The foot-and-mouth disease virus (FMDV) contains a 5’ untranslated region (5’UTR) with multiple structural domains that regulate viral genome replication, translation, and virus-host interactions. At its 5’terminus, the S fragment of over 360 bp is predicted to form a stable stem-loop that is separ...

Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle

USDA-ARS?s Scientific Manuscript database

Novel vaccination approaches against foot-and-mouth-disease (FMD) include the use of a replication-defective human adenovirus type 5 vector (Ad5) that contains the capsid encoding regions of FMD virus (FMDV). An Ad5.A24 has proven effective as a vaccine against FMD in swine and cattle. However, ther...

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

USDA-ARS?s Scientific Manuscript database

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-...

Some Surface-Active Agents and Their Virucidal Effect on Foot-and-Mouth Disease Virus

PubMed Central

Fellowes, O. N.

1965-01-01

Selected cationic and anionic surface-active compounds were tested to determine their virucidal effect on the foot-and-mouth disease virus, type O, strain M11, propagated in primary calf kidney cells. The chemical inactivation of the virus was tested with 0.5, 1.0, 2.0, and 5.0% concentrations of the selected compounds. Virus controls with pH adjusted to cover the expected range of the mixtures of the chemicals and virus were also tested. The absence of virus from the mixtures of chemical and virus after reaction at 28 C for 2 hr was assayed by inoculating suckling mice with the mixtures. One cationic compound, alkyl methyl isoquinilinium chloride, showed considerable antiviral activity due largely to pH effect. The use of the surface-active agents investigated in this study, in the presence of organic material, would not be recommended as virucides. PMID:4286396

Molecular characterization of foot-and-mouth disease virus: implications for disease control in Bangladesh.

PubMed

Loth, L; Osmani, M G; Kalam, M A; Chakraborty, R K; Wadsworth, J; Knowles, N J; Hammond, J M; Benigno, C

2011-06-01

Foot-and-mouth disease (FMD) is endemic in Bangladesh, and to implement an effective FMD control programme, it is essential to understand the complex epidemiology of the disease. Here, we report on the characterization of FMD virus (FMDV) recovered from FMD outbreaks in Bangladesh in late 2009. All isolated viruses belonged to the FMDV serotype O. The phylogenetic reconstruction showed that all isolates belonged to the Middle East-South Asia (ME-SA) topotype, but fell into two distinct sublineages, one named Ind-2001 (the other has not been named). Within both sublineages, the 2009 Bangladesh isolates were most closely related to viruses from Nepal collected during 2008 and 2009. Additionally, both sublineages contained older viruses from India collected in 2000 and 2001. In South Asia, there is extensive cross-border cattle movement from Nepal and India to Bangladesh. Both these findings have implications for the control of FMD in Bangladesh. Because of the porous borders, a regional FMD control strategy should be developed. Further, animal identification and monitoring animal movements are necessary to identify the cross-border movements and market chain interactions of ruminants, leading to improved border and movement controls. Additionally, a vaccination strategy should be developed with the initial objective of protecting small-scale dairy herds from disease. For any successful FMD control programme, long-term Government commitment and adequate resources are necessary. A sustainable programme will also need farmer education, commitment and financial contributions. © 2011 Blackwell Verlag GmbH.

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.

Dermatological spectrum of hand, foot and mouth disease from classical to generalized exanthema.

PubMed

Hubiche, Thomas; Schuffenecker, Isabelle; Boralevi, Franck; Léauté-Labrèze, Christine; Bornebusch, Laure; Chiaverini, Christine; Phan, Alice; Maruani, Annabel; Miquel, Juliette; Lafon, Marie-Edith; Lina, Bruno; Del Giudice, Pascal

2014-04-01

Hand, foot and mouth disease (HFMD) is classically defined as a childhood fever accompanied by a rash with vesicles or erosions of the oral mucosa, hands, feet and sometimes the buttocks. Severe neurological complications are associated with enterovirus 71 outbreaks in Asia. Recently, it has been suggested that HFMD is related to coxsackie virus A6 (CV-A6) when there is an atypical rash. The objective of the study is to determine the dermatological pattern of HFMD and to identify the virus serotypes associated with a specific dermatological pattern. A prospective, cross-sectional study was conducted in 7 pediatric dermatology units in France from March 2010 to February 2012. All children with clinically suspected diagnosis of HFMD were included. Clinical data were collected and swabs from the nasopharynx and vesicles were taken for reverse transcription polymerase chain reaction and genotyping. Only children with confirmed HFMD--defined by clinical diagnosis of HFMD and positive enterovirus polymerase chain reaction results--were included for analysis. One hundred and four children consulted for suspected HFMD, including 89 (mean age: 25.7 months; sex ratio M/F 1.54) with confirmed HFMD. Seventy-eight (87.6%) had skin lesions on sites other than hand, feet and mouth. Thirty-seven (41.5%) had 5 or more anatomical sites involved (hand, feet and mouth, buttocks, legs, arms and trunk) considered as widespread exanthema. Widespread vesicular exanthema was observed with both CV-A6 and CV-A16. Peri-oral rash was associated with CV-A6 (P < 0.001). HFMD has a clinical spectrum ranging from classical to generalized vesicular exanthema. Generalized and atypical exanthema were observed with both CV-A6 and CV-A16 infections. CV-A6 is associated with peri-oral rash.

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PubMed

Lian, Zhou-Yang; Li, He-Hong; Zhang, Bin; Dong, Yu-Hao; Deng, Wu-Xu; Liu, Jing; Luo, Xiao-Ning; Huang, Biao; Liang, Chang-Hong; Zhang, Shui-Xing

The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Foot and mouth disease vaccine strain selection: Current approaches and future perspectives.

PubMed

Mahapatra, Mana; Parida, Satya

2018-06-27

Lack of cross protection between foot and mouth disease (FMD) virus (FMDV) serotypes as well as incomplete protection between some subtypes of FMDV affect the application of vaccine in the field. Further, the emergence of new variant FMD viruses periodically makes the existing vaccine inefficient. Consequently, periodical vaccine strain selection either by in vivo methods or in vitro methods become an essential requirement to enable utilisation of appropriate and efficient vaccines. Areas covered: Here we describe the cross reactivity of the existing vaccines with the global pool of circulating viruses and the putative selected vaccine strains for targeting protection against the two major circulating serotype O and A FMD viruses for East Africa, the Middle East, South Asia and South East Asia. Expert Commentary: Although in vivo cross protection studies are more appropriate methods for vaccine matching and selection than in vitro neutralisation test or ELISA, in the face of an outbreak both in vivo and in vitro methods of vaccine matching are not easy, and time consuming. The FMDV capsid contains all the immunogenic epitopes, and therefore vaccine strain prediction models using both capsid sequence and serology data will likely replace existing tools in the future.

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.

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

USDA-ARS?s Scientific Manuscript database

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...

Structure-based energetics of protein interfaces guide Foot-and-Mouth Disease virus vaccine design

PubMed Central

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.

2018-01-01

Summary Virus capsids are primed for disassembly yet capsid integrity is key to generating a protective immune response. Here we devise a computational method to assess relative stability of protein-protein interfaces and use it to design improved candidate vaccines for two of the least stable, but globally important, serotypes of Foot-and-Mouth Disease virus (FMDV), O and SAT2. FMDV capsids comprise identical pentameric protein subunits held together by tenuous non-covalent 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. We use a novel restrained molecular dynamics strategy, to rank mutations predicted to strengthen the pentamer interfaces to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralising antibody responses to stabilised particles over parental viruses and wild-type capsids. PMID:26389739

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

USDA-ARS?s Scientific Manuscript database

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 ...

Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

PubMed Central

Cox, Jonathan A.; Hiscox, Julian A.; Solomon, Tom; Ooi, Mong-How; Ng, Lisa F. P.

2017-01-01

Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host–viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions. PMID:29238324

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

PubMed

Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

2016-08-01

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. 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 occurs within

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

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

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

PubMed

Rodríguez Pulido, Miguel; Sáiz, Margarita

2017-01-01

Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

A partial deletion within foot-and-mouth disease virus non-structural protein 3A causes clinical attenuation in cattle but does not prevent subclinical infection

USDA-ARS?s Scientific Manuscript database

Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are associated with decreased virulence in cattle; however, the mechanisms are unknown. We compared experimental infection of cattle with virulent FMDV O1Campos (O1Ca) and a mutant derivative (O1Ca-delta3A) lacking residues...

Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand.

PubMed

Hayman, Rebecca; Shepherd, Michael; Tarring, Claire; Best, Emma

2014-10-01

Hand-foot-and-mouth disease is a common, usually mild childhood illness caused by enteroviruses. Over the last five years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia and America. It has an atypical presentation compared with other enteroviruses, with more widespread rash, larger blisters and subsequent skin peeling and/or nail shedding. We give the first description of an outbreak of coxsackievirus A6 in New Zealand and how health-care communication networks enabled detection of and dissemination of information about this emergent strain. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems

USDA-ARS?s Scientific Manuscript database

Infection dynamics of a recent field isolate of foot-and-mouth disease virus (FMDV), serotype O, topotype South East Asia, lineage Myamar ’98 were evaluated in sheep using four different systems for virus exposure. Two novel, simulated natural, inoculation systems consisting of intra-nasopharyngeal ...

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.

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.

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

PubMed Central

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. PMID:26755102

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

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.

Development of a multiplex Luminex assay for detecting swine antibodies to structural and nonstructural proteins of foot-and-mouth disease virus in Taiwan.

PubMed

Chen, Tsu-Han; Lee, Fan; Lin, Yeou-Liang; Pan, Chu-Hsiang; Shih, Chia-Ni; Tseng, Chun-Hsien; Tsai, Hsiang-Jung

2016-04-01

Foot-and-mouth disease (FMD) and swine vesicular disease (SVD) are serious vesicular diseases that have devastated swine populations throughout the world. The aim of this study was to develop a multianalyte profiling (xMAP) Luminex assay for the differential detection of antibodies to the FMD virus of structural proteins (SP) and nonstructural proteins (NSP). After the xMAP was optimized, it detected antibodies to SP-VP1 and NSP-3ABC of the FMD virus in a single serum sample. These tests were also compared with 3ABC polypeptide blocking enzyme-linked immunosorbent assay (ELISA) and virus neutralization test (VNT) methods for the differential diagnosis and assessment of immune status, respectively. To detect SP antibodies in 661 sera from infected naïve pigs and vaccinated pigs, the diagnostic sensitivity (DSn) and diagnostic specificity (DSp) of the xMAP were 90.0-98.7% and 93.0-96.5%, respectively. To detect NSP antibodies, the DSn was 90% and the DSp ranged from 93.3% to 99.1%. The xMAP can detect the immune response to SP and NSP as early as 4 days postinfection and 8 days postinfection, respectively. Furthermore, the SP and NSP antibodies in all 15 vaccinated but unprotected pigs were detected by xMAP. A comparison of SP and NSP antibodies detected in the sera of the infected samples indicated that the results from the xMAP had a high positive correlation with results from the VNT and a 3ABC polypeptide blocking ELISA assay. However, simultaneous quantitation detected that xMAP had no relationship with the VNT. Furthermore, the specificity was 93.3-94.9% with 3ABC polypeptide blocking ELISA for the FMDV-NSP antibody. The results indicated that xMAP has the potential to detect antibodies to FMDV-SP-VP1 and NSP-3ABC and to distinguish FMDV-infected pigs from pigs infected with the swine vesicular disease virus. Copyright © 2014. Published by Elsevier B.V.

Unilateral acute maculopathy associated with adult onset hand, foot and mouth disease: case report and review of literature.

PubMed

Agrawal, Rupesh; Bhan, Kanchan; Balaggan, Kam; Lee, Richard Wj; Pavesio, Carlos E; Addison, Peter Kf

2015-01-01

Acute maculopathy is a rare condition of unknown aetiology and Coxsackie virus is known to be associated with this macular chorioretinitis. We report a case of acute unilateral maculopathy in a 35-year-old woman with concurrent hand foot and mouth disease. Furthermore, we display multimodal imaging (colour fundus photographs, autofluorescence, spectral domain ocular coherence tomography, fluorescein angiography and indocyanine green angiography) charting the course of the disease. The source of the virus was thought to be the patient's child. Empirical treatment with oral corticosteroids was commenced and the inflammation resolved, leaving a residual macular scar. We present this case combined with the review of literature of adult onset Coxsackie-virus-associated retinitis. This case reiterates the fact that Coxsackie virus is an uncommon but important consideration in the differential diagnosis of chorioretinitis and posterior uveitis with atypical retinopathy.

Multiplexing Short Primers for Viral Family PCR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S N; Hiddessen, A L; Hara, C A

We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets for large, diverse, and unalignable sets of target sequences. The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment. We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers ({approx}3700 18-mers or {approx}2000 10-mers) to generate amplicons from all sequenced viruses. We then designed primer sets separately for each viral family, and formore » several diverse species such as foot-and-mouth disease virus, hemagglutinin and neuraminidase segments of influenza A virus, Norwalk virus, and HIV-1.« less

Identification of a conformational neutralizing epitope on the VP1 protein of type A foot-and-mouth disease virus.

PubMed

Liu, Wenming; Yang, Baolin; Wang, Mingxia; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

2017-12-01

Foot-and-mouth disease (FMD) caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. In recent years, outbreaks of serotype A FMD have occurred in many countries. High-affinity neutralizing antibodies against a conserved epitope could provide protective immunity against diverse subtypes of FMDV serotype A and protect against future pandemics. In this study, we generated a serotype A FMDV-specific potent neutralizing monoclonal antibody (MAb), 6C9, which recognizes a conformation-dependent epitope. MAb 6C9 potently neutralized FMDV A/XJBC/CHA/2010 with a 50% neutralization titer (NT 50 ) of 4096. Screening of a phage-displayed random 12-mer peptide library revealed that MAb 6C9 bound to phages displaying the consensus motif YxxPxGDLG, which is highly homologous to the 135 YxxPxxxxxGDLG 147 motif found in the serotype A FMDV virus-encoded structural protein VP1. To further verify the authentic epitope recognized by MAb 6C9, two FMDV A/XJBC/CHA/2010 mutant viruses, P138A and G144A, were generated using a reverse genetic system. Subsequent micro-neutralization assays and double-antibody sandwich (DAS) ELISA analyses revealed that the Pro 138 and Gly 144 residues of the conformational epitope that are recognized by 6C9 are important for MAb 6C9 binding. Importantly, the epitope 135 YxxPxxxxxGDLG 147 was highly conserved among different topotypes of serotype A FMDV strains in a sequence alignment analysis. Thus, the results of this study could have potential applications in the development of novel epitope-based vaccines and suitable a MAb-based diagnostic method for the detection of serotype A FMDV and the quantitation of antibodies against this serotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of accelerated hydrogen peroxide® disinfectant on foot-and-mouth disease virus, swine vesicular disease virus and Senecavirus A.

PubMed

Hole, K; Ahmadpour, F; Krishnan, J; Stansfield, C; Copps, J; Nfon, C

2017-03-01

In a laboratory, disinfectants used to inactivate pathogens on contaminated surfaces and to prevent spread of diseases often have adverse side effects on personnel and the environment. It is, therefore, essential to find safer, fast-acting and yet effective disinfectants. The objective of this study was to evaluate an accelerated hydrogen peroxide ® (AHP ® )-based disinfectant against high consequence foreign animal disease pathogens such as foot-and-mouth disease virus (FMDV) and swine vesicular disease virus (SVDV), as well as Senecavirus A (SVA), which causes similar lesions as FMDV and SVDV. We tested varying dilutions and contact times of AHP against FMDV, SVDV and SVA by the standard US EPA and modified methods. AHP was effective against all three viruses, albeit at a higher concentration and double the manufacturer recommended contact time when testing wet films of SVDV. AHP is an effective disinfectant against FMDV, SVDV and SVA. AHP-based disinfectant can, therefore, be used in high containment laboratories working with FMDV, SVDV and related pathogens. © 2016 The Canadian Food Inspection Agency. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

PubMed

Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

2016-03-31

Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy.

PubMed

Aswathyraj, S; Arunkumar, G; Alidjinou, E K; Hober, D

2016-10-01

Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV-A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin-inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy.

Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus.

PubMed

Xin, Xiu; Wang, Hailong; Han, Lingling; Wang, Mingzhen; Fang, Hui; Hao, Yao; Li, Jiadai; Zhang, Hu; Zheng, Congyi; Shen, Chao

2018-05-01

Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G 2 /M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell. IMPORTANCE It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells. Copyright © 2018 American Society for Microbiology.

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.

Foot-and-mouth disease virus (FMDV) with a stable FLAG epitope in the VP1 G-H loop as a new tool for studying FMDV pathogenesis

USDA-ARS?s Scientific Manuscript database

In this study, we generated a recombinant foot-and-mouth disease virus (FMDV) particle derived from A24 Cruzeiro with a FLAG tag (DYKDDDDK) substitution in the hypervariable antigenic site of the G-H loop of the VP1 capsid protein in an effort to expand the immunogenicity of the virus particle and t...

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.

Field-Deployable Reverse Transcription-Insulated Isothermal PCR (RT-iiPCR) Assay for Rapid and Sensitive Detection of Foot-and-Mouth Disease Virus.

PubMed

Ambagala, A; Fisher, M; Goolia, M; Nfon, C; Furukawa-Stoffer, T; Ortega Polo, R; Lung, O

2017-10-01

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which can decimate the livestock industry and economy of countries previously free of this disease. Rapid detection of foot-and-mouth disease virus (FMDV) is critical to containing an FMD outbreak. Availability of a rapid, highly sensitive and specific, yet simple and field-deployable assay would support local decision-making during an FMDV outbreak. Here we report validation of a novel reverse transcription-insulated isothermal PCR (RT-iiPCR) assay that can be performed on a commercially available, compact and portable POCKIT ™ analyser that automatically analyses data and displays '+' or '-' results. The FMDV RT-iiPCR assay targets the 3D region of the FMDV genome and was capable of detecting 9 copies of in vitro-transcribed RNA standard with 95% confidence. It accurately identified 63 FMDV strains belonging to all seven serotypes and showed no cross-reactivity with viruses causing similar clinical diseases in cloven-hoofed animals. The assay was able to identify FMDV RNA in multiple sample types including oral, nasal and lesion swabs, epithelial tissue suspensions, vesicular and oral fluid samples, even before the appearance of clinical signs. Clinical sensitivity of the assay was comparable or slightly higher than the laboratory-based real-time RT-PCR assay in use. The assay was able to detect FMDV RNA in vesicular fluid samples without nucleic acid extraction. For RNA extraction from more complex sample types, a commercially available taco ™ mini transportable magnetic bead-based, automated extraction system was used. This assay provides a potentially useful field-deployable diagnostic tool for rapid detection of FMDV in an outbreak in FMD-free countries or for routine diagnostics in endemic countries with less structured laboratory systems. © 2016 Her Majesty the Queen in Right of Canada.

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

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

PubMed

Zhao, Jijun; 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.

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

Production of foot-and-mouth disease virus capsid proteins by the TEV protease.

PubMed

Puckette, Michael; Smith, Justin D; Gabbert, Lindsay; Schutta, Christopher; Barrera, José; Clark, Benjamin A; Neilan, John G; Rasmussen, Max

2018-06-10

Protective immunity to viral pathogens often includes production of neutralizing antibodies to virus capsid proteins. Many viruses produce capsid proteins by expressing a precursor polyprotein and related protease from a single open reading frame. The foot-and-mouth disease virus (FMDV) expresses a 3C protease (3Cpro) that cleaves a P1 polyprotein intermediate into individual capsid proteins, but the FMDV 3Cpro also degrades many host cell proteins and reduces the viability of host cells, including subunit vaccine production cells. To overcome the limitations of using the a wild-type 3Cpro in FMDV subunit vaccine expression systems, we altered the protease restriction sequences within a FMDV P1 polyprotein to enable production of FMDV capsid proteins by the Tobacco Etch Virus NIa protease (TEVpro). Separate TEVpro and modified FMDV P1 proteins were produced from a single open reading frame by an intervening FMDV 2A sequence. The modified FMDV P1 polyprotein was successfully processed by the TEVpro in both mammalian and bacterial cells. More broadly, this method of polyprotein production and processing may be adapted to other recombinant expression systems, especially plant-based expression. Published by Elsevier B.V.

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.

Construction and characterization of a full-length infectious cDNA clone of foot-and-mouth disease virus strain O/JPN/2010 isolated in Japan in 2010.

PubMed

Nishi, Tatsuya; Onozato, Hiroyuki; Ohashi, Seiichi; Fukai, Katsuhiko; Yamada, Manabu; Morioka, Kazuki; Kanno, Toru

2016-06-01

A full-length infectious cDNA clone of the genome of a foot-and-mouth disease virus isolated from the 2010 epidemic in Japan was constructed and designated pSVL-f02. Transfection of Cos-7 or IBRS-2 cells with this clone allowed the recovery of infectious virus. The recovered virus had the same in vitro characterization as the parental virus with regard to antigenicity in neutralization and indirect immunofluorescence tests, plaque size and one-step growth. Pigs were experimentally infected with the parental virus or the recombinant virus recovered from pSVL-f02 transfected cells. There were no significant differences in clinical signs or antibody responses between the two groups, and virus isolation and viral RNA detection from clinical samples were similar. Virus recovered from transfected cells therefore retained the in vitro characteristics and the in vivo pathogenicity of their parental strain. This cDNA clone should be a valuable tool to analyze determinants of pathogenicity and mechanisms of virus replication, and to develop genetically engineered vaccines against foot-and-mouth disease virus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.

PubMed

Bian, Lianlian; Wang, Yiping; Yao, Xin; Mao, Qunying; Xu, Miao; Liang, Zhenglun

2015-01-01

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (HFMD) worldwide. Other human enterovirus A (HEV-A) serotypes tend to cause only sporadic HFMD cases. However, since a HFMD caused by coxsackievirus A6 broke out in Finland in 2008, CA6 has been identified as the responsible pathogen for a series of HFMD outbreaks in Europe, North America and Asia. Because of the severity of the clinical manifestations and the underestimated public health burden, the epidemic of CA6-associated HFMD presents a new challenge to the control of HFMD. This article reviewed the epidemic characteristics, molecular epidemiology, clinical features and laboratory diagnosis of CA6 infection. The genetic evolution of CA6 strains associated with HFMD was also analyzed. It indicated that the development of a multivalent vaccine combining EV71, CA16 and CA6 is an urgent necessity to control HFMD.

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

The macro-economic impact of a foot-and-mouth disease incursion in New Zealand.

PubMed

Belton, D J

2004-01-01

The 2001 outbreak of Foot-and-Mouth Disease (FMD) in the United Kingdom heightened public concern in New Zealand about the economic consequences of an outbreak of FMD, and resulted in the Reserve Bank and Treasury conducting an assessment of the macro-economic impact of a small FMD outbreak in New Zealand. The study was based on a relatively small outbreak in which 50 properties were infected over a period of two months. Cumulative losses calculated over two years from the beginning of the hypothetical outbreak were estimated at around NZ dollars 10 billion, a figure twice as large as the initial Ministry of Agriculture and Forestry estimate. The main reason for this difference is that the Reserve Bank study included the additional macro-economic effects of a slump in domestic demand. The study also demonstrated that in New Zealand under the conditions of the current OIE Terrestrial Animal Health Code for FMD, the economic impact of any programme to control FMD by vaccination in which vaccinated animals are not slaughtered, is significantly worse than rapid eradication by stamping out.

Immune Response and Viral Persistence in Indian Buffaloes (Bubalus bubalis) Infected with Foot-and-Mouth Disease Virus Serotype Asia 1 ▿

PubMed Central

Maddur, Mohan S.; Kishore, Subodh; Gopalakrishna, S.; Singh, Nem; Suryanarayana, V. V.; Gajendragad, Mukund R.

2009-01-01

Despite their potential role in the spread of foot-and-mouth disease (FMD), the immune response and viral persistence in FMD virus (FMDV)-infected Indian buffaloes (Bubalus bubalis) have been unexplored. We found similar kinetics of neutralizing antibody responses in the sera and secretory fluids of buffaloes following experimental FMDV Asia 1 infection, but the lymphocyte-proliferative response in infected buffaloes was of low magnitude. Despite inducing a significant systemic and secretory immune response, viral persistence seems to be a common outcome in buffaloes following FMDV Asia 1 infection, which is associated with a weak cellular immune response. PMID:19828770

Single-Tube Multiplexed Molecular Detection of Endemic Porcine Viruses in Combination with Background Screening for Transboundary Diseases

PubMed Central

Wernike, Kerstin; Hoffmann, Bernd

2013-01-01

Detection of several pathogens with multiplexed real-time quantitative PCR (qPCR) assays in a one-step setup allows the simultaneous detection of two endemic porcine and four different selected transboundary viruses. Reverse transcription (RT)-qPCR systems for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2), two of the most economically important pathogens of swine worldwide, were combined with a screening system for diseases notifiable to the World Organization of Animal Health, namely, classical and African swine fever, foot-and-mouth disease, and Aujeszky's disease. Background screening was implemented using the identical fluorophore for all four different RT-qPCR assays. The novel multiplex RT-qPCR system was validated with a large panel of different body fluids and tissues from pigs and other animal species. Both reference samples and clinical specimens were used for a complete evaluation. It could be demonstrated that a highly sensitive and specific parallel detection of the different viruses was possible. The assays for the notifiable diseases were even not affected by the simultaneous amplification of very high loads of PRRSV- and PCV2-specific sequences. The novel broad-spectrum multiplex assay allows in a unique form the routine investigation for endemic porcine pathogens with exclusion diagnostics of the most important transboundary diseases in samples from pigs with unspecific clinical signs, such as fever or hemorrhages. The new system could significantly improve early detection of the most important notifiable diseases of swine and could lead to a new approach in syndromic surveillance. PMID:23303496

Overview of foot-and-mouth disease awareness among farmers and veterinarians in France.

PubMed

Raut, Noémie; Rivière, Julie; Hosteing, Soline; Collin, Eric; Philizot, Stéphanie; Debaere, Olivier; Zanella, Gina

2018-06-15

Foot-and-mouth disease (FMD) is of major concern in most countries including Europe, where no outbreaks have occurred since a decade. Indeed, the risk of FMD introduction from infected countries is not negligible and the awareness of field stakeholders (farmers, veterinarians) is essential to ensure an effective detection of the viral circulation. The French veterinary services launched in 2015 a survey to estimate the awareness of farmers and veterinarians and their knowledge about epidemiological and regulatory aspects of FMD. Official health visits were used to collect information from cattle farmers and veterinarians through two separate questionnaires. The results show that not all cattle farmers were aware of the risk of FMD reintroduction in France and of its routes of infection and speed of dissemination. As for the veterinarians, their promptness to report a suspicion was dependent on the occurrence of FMD cases in European countries. These results highlight key aspectsregarding FMD epidemiology which should be regularly reminded to the field stakeholders in FMD-free countries to increase their awareness and thus ensure an effective early detection in case of FMD introduction. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluating the efficacy of hydrogen peroxide vapour against foot-and-mouth disease virus within a BSL4 biosafety facility.

PubMed

Petit, B M; Almeida, F C; Uchiyama, T R; Lopes, F O C; Tino, K H; Chewins, J

2017-10-01

An evaluation was made of the efficacy of 35% hydrogen peroxide vapour (HPV) against foot-and-mouth disease virus (FMDV) in a biosafety facility. Biological indicators (BIs) were produced using three serotypes of FMDV, all with a titre of ≥10 6 TCID 50 per ml. Fifteen BIs of each serotype were distributed across five locations, throughout a 30-m 3 airlock chamber, producing a total of 45 BIs. Thirty-five percent HPV was generated and applied using a Bioquell vaporization module located in the centre of the chamber. After a dwell period of 40 min, the HPV was removed via the enclosures air handling system and the BIs were collected. The surfaces of the BIs were recovered into Glasgow's modified Eagle's medium (GMEM), cultivated in BHK21 Cl13 cell culture and analysed for evidence of cytopathic effect (CPE). No CPE was detected in any BI sample. Positive controls showed CPE. The experimentation shows that FMDV is susceptible to HPV decontamination and presents a potential alternative to formaldehyde. Foot-and-mouth disease virus (FMDV) is an important pathogen in terms of biosafety due to its infectious nature and wide range of host animals, such as cattle, sheep, goats and pigs. Outbreaks of FMDV can have a severe impact on livestock production, causing morbidity, mortality, reduced yields and trade embargoes. Laboratories studying FMDV must possess BSL4 robust bio-decontamination methods to prevent inadvertent release. Formaldehyde has been the primary agent for environmental decontamination, but its designation as a human carcinogen has led to a search for alternatives. This study shows 35% hydrogen peroxide vapour has the potential to be a rapid, effective, residue-free alternative. © 2017 The Society for Applied Microbiology.

[Construction and characterization of an epitope-mutated Asia 1 type foot-and-mouth disease virus].

PubMed

Zhang, Yan; Hu, Yonghao; Yang, Fan; Yang, Bo; Wang, Songhao; Zhu, Zixiang; Zheng, Haixue

2015-01-01

To generate an epitope-mutated foot-and-mouth disease virus (FMDV) as a marker vaccine, the infectious clone pAsia 1-FMDV containing the complete genomic cDNA of Asia 1 type FMDV was used as backbone, the residues at positions 27 and 31 in the 3D gene were mutated (H27Y and N31R). The resulting plasmid pAsia 1-FMDV-3DM encoding a mutated epitope was transfected into BHK-21 cells and the recombinant virus rAsia 1-3DM was rescued. The recombinant virus showed similar biological characteristics comparable with the parental virus. In serological neutralization test the antisera against recombine virus have a good reactivity with parental virus. The antisera against the mutant virus were shown to be reactive with the mutated epitope but not the wild-type one. The results indicated that the two virus strains could be distinguished by western blotting using synthetic peptides. This epitope-mutated FMDV strain will be evaluated as a potential marker vaccine against FMDV infections.

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.

Highly sensitive fetal goat tongue cell line for detection and isolation of foot-and-mouth disease virus.

PubMed

Brehm, K E; Ferris, N P; Lenk, M; Riebe, R; Haas, B

2009-10-01

A fetal goat cell line (ZZ-R 127) supplied by the Collection of Cell Lines in Veterinary Medicine of the Friedrich Loeffler Institute was examined for susceptibility to infection by foot-and-mouth disease (FMD) virus (FMDV) and by two other viruses causing clinically indistinguishable vesicular conditions, namely, the viruses of swine vesicular disease and vesicular stomatitis. Primary bovine thyroid (BTY) cells are generally the most sensitive cell culture system for FMDV detection but are problematic to produce, particularly for laboratories that infrequently perform FMD diagnostic tests and for those in countries where FMD is endemic that face problems in sourcing thyroid glands from FMD-negative calves. Strains representing all seven serotypes of FMDV could be isolated in ZZ-R 127 cells with a sensitivity that was considerably higher than that of established cell lines and within 0.5 log of that for BTY cells. The ZZ-R 127 cell line was found to be a sensitive, rapid, and convenient tool for the isolation of FMDV and a useful alternative to BTY cells for FMD diagnosis.

Degradation of foot-and-mouth disease virus during composting of infected pig carcasses

PubMed Central

Guan, J.; Chan, M.; Grenier, C.; Brooks, B.W.; Spencer, J.L.; Kranendonk, C.; Copps, J.; Clavijo, A.

2010-01-01

The objective of this study was to investigate the inactivation and degradation of foot-and-mouth disease (FMD) virus during composting of infected pig carcasses as measured by virus isolation in tissue culture and by real-time reverse transcriptase polymerase chain reaction (RRT-PCR). Three FMD-infected pig carcasses were composted in a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. Compost temperatures had reached 50°C and 70°C by days 10 and 19, respectively. Under these conditions, FMD virus was inactivated in specimens in compost by day 10 and the viral RNA was degraded in skin and internal organ tissues by day 21. In comparison, at ambient temperatures close to 20°C, FMD virus survived to day 10 in the skin tissue specimen from the pig that had the highest initial level of viral RNA in its tissues and the viral RNA persisted to day 21. Similarly, beta-actin mRNA, tested as a PCR control, persisted to day 21 in specimens held at ambient temperatures, but it was degraded in the remnants of tissues recovered from compost on day 21. Results from this study provide evidence that composting could be used for safe disposal of pig carcasses infected with FMD virus. PMID:20357957

Economic aspects of foot and mouth disease: perspectives of a free country, Australia.

PubMed

Garner, M G; Fisher, B S; Murray, J G

2002-12-01

Australia is a significant livestock producer and a major exporter of livestock, livestock products and livestock genetic material. An outbreak of foot and mouth disease (FMD) would have severe economic consequences on the economy. A recent study found that in an outbreak lasting six months, real gross domestic product in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by 0.8%, and a depreciation of 3% would be recorded in the exchange rate in the first year. Much of this impact would be due to the loss of export markets. Given the significant consequences of an outbreak of FMD, Australia invests considerable resources in prevention and planning. These measures can be viewed at three levels, namely: pre-border, border and post-border. Australia recently further enhanced quarantine at the border to minimise the risk of entry of FMD. However, no matter how much is invested, there is no guarantee that FMD will not enter the country. Accordingly, it is important to ensure that comprehensive contingency plans are also in place. Recent outbreaks in previously free countries have shown that a large outbreak of FMD poses major problems for the animal health services of a country and a combined government and industry response is required.

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

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

USDA-ARS?s Scientific Manuscript database

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 ...

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. © 2013 Blackwell Verlag GmbH.

Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

PubMed

Jones, Eben; Pillay, Timesh D; Liu, Fengfeng; Luo, Li; Bazo-Alvarez, Juan Carlos; Yuan, Chen; Zhao, Shanlu; Chen, Qi; Li, Yu; Liao, Qiaohong; Yu, Hongjie; Rogier van Doorn, H; Sabanathan, Saraswathy

2018-04-20

Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. There was no specific funding for this study. See below for researcher funding. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Multiplex primer prediction software for divergent targets

PubMed Central

Gardner, Shea N.; Hiddessen, Amy L.; Williams, Peter L.; Hara, Christine; Wagner, Mark C.; Colston, Bill W.

2009-01-01

We describe a Multiplex Primer Prediction (MPP) algorithm to build multiplex compatible primer sets to amplify all members of large, diverse and unalignable sets of target sequences. The MPP algorithm is scalable to larger target sets than other available software, and it does not require a multiple sequence alignment. We applied it to questions in viral detection, and demonstrated that there are no universally conserved priming sequences among viruses and that it could require an unfeasibly large number of primers (∼3700 18-mers or ∼2000 10-mers) to generate amplicons from all sequenced viruses. We then designed primer sets separately for each viral family, and for several diverse species such as foot-and-mouth disease virus (FMDV), hemagglutinin (HA) and neuraminidase (NA) segments of influenza A virus, Norwalk virus, and HIV-1. We empirically demonstrated the application of the software with a multiplex set of 16 short (10 nt) primers designed to amplify the Poxviridae family to produce a specific amplicon from vaccinia virus. PMID:19759213

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.

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

PubMed

Gloster, John; Ebert, Katja; Gubbins, Simon; Bashiruddin, John; Paton, David J

2011-11-21

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. 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. 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.

Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability.

PubMed

Caridi, Flavia; Vázquez-Calvo, Ángela; Borrego, Belén; McCullough, Kenneth; Summerfield, Artur; Sobrino, Francisco; Martín-Acebes, Miguel A

2017-05-01

Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. Vaccines based on inactivated FMDV virions provide a useful tool for the control of this pathogen. However, long term storage at 4°C (the temperature for vaccine storage) or ruptures of the cold chain, provoke the dissociation of virions, reducing the immunogenicity of the vaccine. An FMDV mutant carrying amino acid replacements VP1 N17D and VP2 H145Y isolated previously rendered virions with increased resistance to dissociation at 4°C. We have evaluated the immunogenicity in swine (a natural FMDV host) of a chemically inactivated vaccine based on this mutant. The presence of these amino acid substitutions did not compromise the immunological potential, including its ability to elicit neutralizing antibodies. These results support the feasibility of this kind of mutants with increased capsid stability as suitable viruses for producing improved FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Foot-and-Mouth Disease Impact on Smallholders - What Do We Know, What Don't We Know and How Can We Find Out More?

PubMed

Knight-Jones, T J D; McLaws, M; Rushton, J

2017-08-01

Foot-and-mouth disease (FMD) endemic regions contain three-quarters of the world's FMD susceptible livestock and most of the world's poor livestock keepers. Yet FMD impact on smallholders in these regions is poorly understood. Diseases of low mortality can exert a large impact if incidence is high. Modelling and field studies commonly find high FMD incidence in endemic countries. Sero-surveys typically find a third of young cattle are sero-positive, however, the proportion of sero-positive animals that developed disease, and resulting impact, are unknown. The few smallholder FMD impact studies that have been performed assessed different aspects of impact, using different approaches. They find that FMD impact can be high (>10% of annual household income). However, impact is highly variable, being a function of FMD incidence and dependency on activities affected by FMD. FMD restricts investment in productive but less FMD-resilient farming methods, however, other barriers to efficient production may exist, reducing the benefits of FMD control. Applying control measures is costly and can have wide-reaching negative impacts; veterinary-cordon-fences may damage wildlife populations, and livestock movement restrictions and trade bans damage farmer profits and the wider economy. When control measures are ineffective, farmers, society and wildlife may experience the burden of control without reducing disease burden. Foot-and-mouth disease control has benefitted smallholders in South America and elsewhere. Success takes decades of regional cooperation with effective veterinary services and widespread farmer participation. However, both the likelihood of success and the full cost of control measures must be considered. Controlling FMD in smallholder systems is challenging, particularly when movement restrictions are hard to enforce. In parts of Africa this is compounded by endemically infected wildlife and limited vaccine performance. This paper reviews FMD impact on

Inactivation of Foot-and-Mouth Disease Virus by Citric Acid and Sodium Carbonate with Deicers

PubMed Central

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

2015-01-01

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. PMID:26319879

Foot-and-mouth Disease Transmission in Africa: Implications for Control, a Review.

PubMed

Tekleghiorghis, T; Moormann, R J M; Weerdmeester, K; Dekker, A

2016-04-01

In Africa, for the control of foot-and-mouth disease (FMD), more information is needed on the spread of the disease at local, regional and inter-regional level. The aim of this review is to identify the role that animal husbandry, trade and wildlife have on the transmission of FMD and to provide a scientific basis for different FMD control measures in Africa. Review of literature, published reports and databases shows that there is more long distance spread of FMD virus serotypes within North, West, Central and East Africa than in southern Africa. In North, West, Central and East Africa migratory animal husbandry systems often related with search for grazing and water as well as trade are practiced to a greater extent than in southern Africa. In southern Africa, the role of African buffalo (Syncerus caffer) is more extensively studied than in the other parts of Africa, but based on the densities of African buffalo in Central and East Africa, one would assume that buffalo should also play a role in the epidemiology of FMD in this part of Africa. More sampling of buffalo is necessary in West, Central and East Africa. The genetic analysis of virus strains has proven to be valuable to increase our understanding in the spread of FMD in Africa. This review shows that there is a difference in FMD occurrence between southern Africa and the rest of the continent; this distinction is most likely based on differences in animal husbandry and trade systems. Insufficient data on FMD in wildlife outside southern Africa is limiting our understanding on the role wildlife plays in the transmission of FMD in the other buffalo inhabited areas of Africa. © 2014 Blackwell Verlag GmbH.

A comparison between two simulation models for spread of foot-and-mouth disease.

PubMed

Halasa, Tariq; Boklund, Anette; Stockmarr, Anders; Enøe, Claes; Christiansen, Lasse E

2014-01-01

Two widely used simulation models of foot-and-mouth disease (FMD) were used in order to compare the models' predictions in term of disease spread, consequence, and the ranking of the applied control strategies, and to discuss the effect of the way disease spread is modeled on the predicted outcomes of each model. The DTU-DADS (version 0.100), and ISP (version 2.001.11) were used to simulate a hypothetical spread of FMD in Denmark. Actual herd type, movements, and location data in the period 1st October 2006 and 30th September 2007 was used. The models simulated the spread of FMD using 3 different control scenarios: 1) A basic scenario representing EU and Danish control strategies, 2) pre-emptive depopulation of susceptible herds within a 500 meters radius around the detected herds, and 3) suppressive vaccination of susceptible herds within a 1,000 meters radius around the detected herds. Depopulation and vaccination started 14 days following the detection of the first infected herd. Five thousand index herds were selected randomly, of which there were 1,000 cattle herds located in high density cattle areas and 1,000 in low density cattle areas, 1,000 swine herds located in high density swine areas and 1,000 in low density swine areas, and 1,000 sheep herds. Generally, DTU-DADS predicted larger, longer duration and costlier epidemics than ISP, except when epidemics started in cattle herds located in high density cattle areas. ISP supported suppressive vaccination rather than pre-emptive depopulation, while DTU-DADS was indifferent to the alternative control strategies. Nonetheless, the absolute differences between control strategies were small making the choice of control strategy during an outbreak to be most likely based on practical reasons.

A Comparison between Two Simulation Models for Spread of Foot-and-Mouth Disease

PubMed Central

Halasa, Tariq; Boklund, Anette; Stockmarr, Anders; Enøe, Claes; Christiansen, Lasse E.

2014-01-01

Two widely used simulation models of foot-and-mouth disease (FMD) were used in order to compare the models’ predictions in term of disease spread, consequence, and the ranking of the applied control strategies, and to discuss the effect of the way disease spread is modeled on the predicted outcomes of each model. The DTU-DADS (version 0.100), and ISP (version 2.001.11) were used to simulate a hypothetical spread of FMD in Denmark. Actual herd type, movements, and location data in the period 1st October 2006 and 30th September 2007 was used. The models simulated the spread of FMD using 3 different control scenarios: 1) A basic scenario representing EU and Danish control strategies, 2) pre-emptive depopulation of susceptible herds within a 500 meters radius around the detected herds, and 3) suppressive vaccination of susceptible herds within a 1,000 meters radius around the detected herds. Depopulation and vaccination started 14 days following the detection of the first infected herd. Five thousand index herds were selected randomly, of which there were 1,000 cattle herds located in high density cattle areas and 1,000 in low density cattle areas, 1,000 swine herds located in high density swine areas and 1,000 in low density swine areas, and 1,000 sheep herds. Generally, DTU-DADS predicted larger, longer duration and costlier epidemics than ISP, except when epidemics started in cattle herds located in high density cattle areas. ISP supported suppressive vaccination rather than pre-emptive depopulation, while DTU-DADS was indifferent to the alternative control strategies. Nonetheless, the absolute differences between control strategies were small making the choice of control strategy during an outbreak to be most likely based on practical reasons. PMID:24667525

Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberger, Jutta; Kontaxis, Georg; Rancan, Chiara

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 itsmore » 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.« less

Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

PubMed Central

Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng

2013-01-01

Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840

Identification of foot and mouth disease risk areas using a multi-criteria analysis approach

PubMed Central

Silva, Gustavo Sousa e; Weber, Eliseu José; Hasenack, Heinrich; Groff, Fernando Henrique Sautter; Todeschini, Bernardo; Borba, Mauro Riegert; Medeiros, Antonio Augusto Rosa; Leotti, Vanessa Bielefeldt; Canal, Cláudio Wageck; Corbellini, Luis Gustavo

2017-01-01

Foot and mouth disease (FMD) is a highly infectious disease that affects cloven-hoofed livestock and wildlife. FMD has been a problem for decades, which has led to various measures to control, eradicate and prevent FMD by National Veterinary Services worldwide. Currently, the identification of areas that are at risk of FMD virus incursion and spread is a priority for FMD target surveillance after FMD is eradicated from a given country or region. In our study, a knowledge-driven spatial model was built to identify risk areas for FMD occurrence and to evaluate FMD surveillance performance in Rio Grande do Sul state, Brazil. For this purpose, multi-criteria decision analysis was used as a tool to seek multiple and conflicting criteria to determine a preferred course of action. Thirteen South American experts analyzed 18 variables associated with FMD introduction and dissemination pathways in Rio Grande do Sul. As a result, FMD higher risk areas were identified at international borders and in the central region of the state. The final model was expressed as a raster surface. The predictive ability of the model assessed by comparing, for each cell of the raster surface, the computed model risk scores with a binary variable representing the presence or absence of an FMD outbreak in that cell during the period 1985 to 2015. Current FMD surveillance performance was assessed, and recommendations were made to improve surveillance activities in critical areas. PMID:28552973

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. © 2014 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Innate immune responses against foot-and-mouth disease virus: current understanding and future directions.

PubMed

Summerfield, Artur; Guzylack-Piriou, Laurence; Harwood, Lisa; McCullough, Kenneth C

2009-03-15

Foot-and-mouth disease (FMD) represents one of the most economically important diseases of farm animals. The basis for the threat caused by this virus is the high speed of replication, short incubation time, high contagiousness, and high mutation rate resulting in constant antigenic changes. Thus, although protective immune responses against FMD virus (FMDV) can be efficacious, the rapidity of virus replication and spread can outpace immune defence development and overrun the immune system. FMDV can also evade innate immune responses through its ability to shut down cellular protein synthesis, including IFN type I, in susceptible epithelial cells. This is important for virus evolution, as FMDV is quite sensitive to the action of IFN. Despite this, innate immune responses are probably induced in vivo, although detailed studies on this subject are lacking. Accordingly, this interaction of FMDV with cells of the innate immune system is of particular interest. Dendritic cells (DC) can be infected by FMDV and support viral RNA replication, and viral protein synthesis but the latter is inefficient or abortive, leading most often to incomplete replication and progeny virus release. As a result DC can be activated, and particularly in the case of plasmacytoid DC (pDC), this is manifest in terms of IFN-alpha release. Our current state of knowledge on innate immune responses induced by FMDV is still only at a relatively early stage of understanding. As we progress, the investigations in this area will help to improve the design of current vaccines and the development of novel control strategies against FMD.

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

PubMed

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

2017-04-02

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. Copyright © 2017 Elsevier B.V. All rights reserved.

CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle.

PubMed

Carr, B Veronica; Lefevre, Eric A; Windsor, Miriam A; Inghese, Cristina; Gubbins, Simon; Prentice, Helen; Juleff, Nicholas D; Charleston, Bryan

2013-01-01

We have performed a series of studies to investigate the role of CD4(+) T-cells in the immune response to foot-and-mouth disease virus (FMDV) post-vaccination. Virus neutralizing antibody titres (VNT) in cattle vaccinated with killed FMD commercial vaccine were significantly reduced and class switching delayed as a consequence of rigorous in vivo CD4(+) T-cell depletion. Further studies were performed to examine whether the magnitude of T-cell proliferative responses correlated with the antibody responses. FMD vaccination was found to induce T-cell proliferative responses, with CD4(+) T-cells responding specifically to the FMDV antigen. In addition, gamma interferon (IFN-γ) was detected in the supernatant of FMDV antigen-stimulated PBMC and purified CD4(+) T-cells from vaccinated cattle. Similarly, intracellular IFN-γ could be detected specifically in purified CD4(+) T-cells after restimulation. It was not possible to correlate in vitro proliferative responses or IFN-γ production of PBMC with VNT, probably as a consequence of the induction of T-independent and T-dependent antibody responses and antigen non-specific T-cell responses. However, our studies demonstrate the importance of stimulating CD4(+) T-cell responses for the induction of optimum antibody responses to FMD-killed vaccines.

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.

Thermal Inactivation of Foot-and-Mouth Disease Viruses in Suspension▿

PubMed Central

Kamolsiripichaiporn, Somjai; Subharat, Supatsak; Udon, Romphruke; Thongtha, Panithan; Nuanualsuwan, Suphachai

2007-01-01

The heat resistance of foot-and-mouth disease virus (FMDV) strains isolated from outbreaks in Thailand was investigated in phosphate-buffered saline (PBS) at 50, 60, 70, 80, 90, and 100°C. The first-order kinetic model fitted most of the observed linear inactivation curves. The ranges of decimal-reduction time (D value) of FMDV strains at 50, 60, 70, 80, 90, and 100°C were 732 to 1,275 s, 16.37 to 42.00 s, 6.06 to 10.87 s, 2.84 to 5.99 s, 1.65 to 3.18 s, and 1.90 to 2.94 s, respectively. The heat resistances of FMDV strains at lower temperature (50°C) were not serotype specific. The effective inactivating temperature is approximately 60°C. Heat resistances of FMDV strains at 90 and 100°C were not statistically different (P > 0.05), while the FMDV serotype O (OPN) appeared to be the most heat resistant at 60 to 80°C. The other observed inactivation curves were linear with shoulder or tailing (biphasic curves). The shoulder effect was mostly observed at 90 and 100°C, while the tailing effect was mostly observed at 50 to 80°C. The adjusted D values in the case of shoulder and tailing effects did not affect the overall estimated heat resistance of these FMDV strains, so even unadjusted D values of deviant inactivation curves were legitimate. The z values of FMDV serotypes O, A, and Asia 1 were 21.78 to 23.26, 20.75 to 22.79, and 19.87°C, respectively. The z values of FMDV strains studied were not statistically significantly different (P > 0.05). The results of this study indicated that the heat resistance in PBS of FMDV strains from Thailand was much less than had been reported for foreign epidemic FMDV strains. PMID:17660312

Estimating the incubation period of hand, foot and mouth disease for children in different age groups.

PubMed

Yang, Zhongzhou; Zhang, Qiqi; Cowling, Benjamin J; Lau, Eric H Y

2017-11-28

Hand, foot and mouth disease (HFMD) is a childhood disease causing large outbreaks frequently in Asia and occasionally in Europe and the US. The incubation period of HFMD was typically described as about 3-7 days but empirical evidence is lacking. In this study, we estimated the incubation period of HFMD from school outbreaks in Hong Kong, utilizing information on symptom onset and sick absence dates of students diagnosed with HFMD. A total of 99 HFMD cases from 12 schools were selected for analysis. We fitted parametric models accounting for interval censoring. Based on the best-fitted distributions, the estimated median incubation periods were 4.4 (95% CI 3.8-5.1) days, 4.7 (95% CI 4.5-5.1) days and 5.7 (95% CI 4.6-7.0) days for children in kindergartens, primary schools and secondary schools respectively. From the fitted distribution, the estimated incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD cases in kindergarten and secondary schools respectively. Our results show that the incubation period of HFMD for secondary schools students can be longer than the ranges commonly described. An extended period of enhanced personal hygiene practice and disinfection of the environment may be needed to control outbreaks.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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. © 2014 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle.

PubMed

Arzt, Jonathan; Pacheco, Juan M; Stenfeldt, Carolina; Rodriguez, Luis L

2017-05-02

Understanding the mechanisms of attenuation and virulence of foot-and-mouth disease virus (FMDV) in the natural host species is critical for development of next-generation countermeasures such as live-attenuated vaccines. Functional genomics analyses of FMDV have identified few virulence factors of which the leader proteinase (L pro ) is the most thoroughly investigated. Previous work from our laboratory has characterized host factors in cattle inoculated with virulent FMDV and attenuated mutant strains with transposon insertions within L pro . In the current study, the characteristics defining virulence of FMDV in cattle were further investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). The only difference between the two viruses was an insertion mutation in the inter-AUG region of the leader proteinase of FMDV-Mut. All cattle were infected by simulated-natural, aerosol inoculation. Both viruses were demonstrated to establish primary infection in the nasopharyngeal mucosa with subsequent dissemination to the lungs. Immunomicroscopic localization of FMDV antigens indicated that both viruses infected superficial epithelial cells of the nasopharynx and lungs. The critical differences between the two viruses were a more rapid establishment of infection by FMDV-WT and quantitatively greater virus loads in secretions and infected tissues compared to FMDV-Mut. The slower replicating FMDV-Mut established a subclinical infection that was limited to respiratory epithelial sites, whereas the faster replication of FMDV-WT facilitated establishment of viremia, systemic dissemination of infection, and clinical disease. The mutant FMDV was capable of achieving all the same early pathogenesis landmarks as FMDV-WT, but was unable to establish systemic infection. The precise mechanism of attenuation remains undetermined; but current data suggests that the impaired replication

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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves

PubMed Central

Feng, Xia; Ma, Jun-Wu; Sun, Shi-Qi; Guo, Hui-Chen; Yang, Ya-Min; Jin, Ye; Zhou, Guang-Qing; He, Ji-Jun; Guo, Jian-Hong; Qi, Shu-yun; Lin, Mi; Cai, Hu; Liu, Xiang-Tao

2016-01-01

The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 μg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings. PMID:26930597

Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves.

PubMed

Feng, Xia; Ma, Jun-Wu; Sun, Shi-Qi; Guo, Hui-Chen; Yang, Ya-Min; Jin, Ye; Zhou, Guang-Qing; He, Ji-Jun; Guo, Jian-Hong; Qi, Shu-yun; Lin, Mi; Cai, Hu; Liu, Xiang-Tao

2016-01-01

The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 μg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings.

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.

Foot-and-mouth disease control and eradication in the Bicol Surveillance Buffer Zone of the Philippines.

PubMed

Windsor, P A; Freeman, P G; Abila, R; Benigno, C; Verin, B; Nim, V; Cameron, A

2011-10-01

Following the onset of an epidemic of foot and mouth disease (FMD) commencing in 1994 and affecting mainly pigs in the Philippines, a National Plan for the Control and Eradication of the disease was initiated. A disease surveillance buffer zone in the southern Luzon region of Bicol was established to protect the Visayas and Mindanao from infection and enable eventual elimination of the disease in Luzon. With achievement of Office International Epizooties (OIE)-certified FMD freedom with vaccination in the Philippines now imminent, the four components of the disease control strategy are reviewed, including quarantine and animal movement controls, strategic vaccination, surveillance and disease investigation, and enhanced public awareness with school on the air radio programmes. Although numbers of outbreaks declined following widespread vaccination, evaluation of serological responses in vaccinates suggested low levels of immune protection. The cessation of outbreaks was considered more likely a result of animal movement controls, improved surveillance and emergency response capability, and reduction in FMD-risk behaviours by livestock owners, particularly through efforts to enhance public awareness of biosecurity measures by the training of traders, livestock industry personnel and both commercial and smallholder farmers. A two-stage random sampling serosurveillance strategy enabled identification of residual infection that was not detected through opportunistic sampling and negative incident reporting. Intensive investigations of FMD outbreaks, particularly in Albay province in 1999, enabled improved understanding of the risk factors involved in disease transmission and implementation of appropriate interventions. The findings from this review are offered to assist development of FMD control and eradication programmes in other countries in south-east Asia that are now being encouraged to support the OIE goal of FMD freedom with vaccination by 2020. © 2011

PREVALENCE OF HUMAN ENTEROVIRUS AMONG PATIENTS WITH HAND, FOOT, AND MOUTH DISEASE AND HERPANGINA IN THAILAND, 2013.

PubMed

Mauleekoonphairoj, John; Puenpa, Jiratchaya; Korkong, Sumeth; Vongpunsawad, Sompong; Poovorawan, Yong

2015-11-01

Human enterovirus (EV) infection causes hand, foot, and mouth disease (HFMD) and herpangina (HA). We studied the prevalence of enterovirus (EV) among patients with HFMD and HA in Thailand during 2013. We conducted a study in archived specimens of patients sent for screening for enterovirus. A total of 203 clinical specimens from 184 individuals with painful blister in the oropharynx and on the palms, soles, knees, elbows or buttock were examined by semi-nested polymerase chain reaction (PCR) for the 5'UTR and VP1 genes of EV. Eighty-six samples were positive: EV71 was detected in 14 (30%), CV-A8 in 12 (26%) and CV-A16 in 10 (21%). Classification of EV species detected revealed that 46 specimens were EV-A, 14 specimens were EV-B, 1 specimen was EV-D, and 16 specimens were positive for unclassified enterovirus. The majority of individuals with EV infection were aged 2-6 years. Multiple EV-A serotypes were detected among HFMD and HA patients in our study.

Is high relative humidity associated with childhood hand, foot, and mouth disease in rural and urban areas?

PubMed

Yang, H; Wu, J; Cheng, J; Wang, X; Wen, L; Li, K; Su, H

2017-01-01

To examine the relationship between relative humidity and childhood hand, foot and mouth disease (HFMD) in Hefei, China, and to explore whether the effect is different between urban and rural areas. Retrospective ecological study. A Poisson generalized linear model combined with a distributed lag non-linear model was used to examine the relationship between relative humidity and childhood HFMD in a temperate Chinese city during 2010-2012. The effect of relative humidity on childhood HFMD increased above a humidity of 84%, with a 0.34% (95% CI: 0.23%-0.45%) increase of childhood HFMD per 1% increment of relative humidity. Notably, urban children, male children, and children aged 0-4 years appeared to be more vulnerable to the effect of relative humidity on HFMD. This article study indicates that high relative humidity may trigger childhood HFMD in a temperate area, Hefei, particularly for those who are young and from urban areas. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The influence of temperature and humidity on the incidence of hand, foot, and mouth disease in Japan.

PubMed

Onozuka, Daisuke; Hashizume, Masahiro

2011-12-01

The increasing evidence for rapid global climate change has highlighted the need for investigations examining the relationship between weather variability and infectious diseases. However, the impact of weather fluctuations on hand, foot, and mouth disease (HFMD), which primarily affects children, is not well understood. We acquired data related to cases of HFMD and weather parameters of temperature and humidity in Fukuoka, Japan between 2000 and 2010, and used time-series analyses to assess the possible relationship of weather variability with pediatric HFMD cases, adjusting for seasonal and interannual variations. Our analysis revealed that the weekly number of HFMD cases increased by 11.2% (95% CI: 3.2-19.8) for every 1°C increase in average temperature and by 4.7% (95% CI: 2.4-7.2) for every 1% increase in relative humidity. Notably, the effects of temperature and humidity on HFMD infection were most significant in children under the age of 10 years. Our study provides quantitative evidence that the number of HFMD cases increased significantly with increasing average temperature and relative humidity, and suggests that preventive measures for limiting the spread of HFMD, particularly in younger children, should be considered during extended periods of high temperature and humidity. Copyright © 2011 Elsevier B.V. All rights reserved.

Expression and Stability of Foreign Epitopes Introduced into 3A Nonstructural Protein of Foot-and-Mouth Disease Virus

PubMed Central

Li, Pinghua; Bai, Xingwen; Cao, Yimei; Han, Chenghao; Lu, Zengjun; Sun, Pu; Yin, Hong; Liu, Zaixin

2012-01-01

Foot-and-mouth disease virus (FMDV) is an aphthovirus that belongs to the Picornaviridae family and causes one of the most important animal diseases worldwide. The capacity of other picornaviruses to express foreign antigens has been extensively reported, however, little is known about FMDV. To explore the potential of FMDV as a viral vector, an 11-amino-acid (aa) HSV epitope and an 8 aa FLAG epitope were introduced into the C-terminal different regions of 3A protein of FMDV full-length infectious cDNA clone. Recombinant viruses expressing the HSV or FLAG epitope were successfully rescued after transfection of both modified constructs. Immunofluorescence assay, Western blot and sequence analysis showed that the recombinant viruses stably maintained the foreign epitopes even after 11 serial passages in BHK-21 cells. The 3A-tagged viruses shared similar plaque phenotypes and replication kinetics to those of the parental virus. In addition, mice experimentally infected with the epitope-tagged viruses could induce tag-specific antibodies. Our results demonstrate that FMDV can be used effectively as a viral vector for the delivery of foreign tags. PMID:22848509

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

Detection and characterization of viruses causing hand, foot and mouth disease from children in Seri Kembangan, Malaysia.

PubMed

Ling, Beh Poay; Jalilian, Farid Azizi; Harmal, Nabil Saad; Yubbu, Putri; Sekawi, Zamberi

2014-12-01

Hand, foot and mouth disease (HFMD) is a common viral infection among infants and children. The major causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were reported in neighboring countries. Infected infants and children may present with fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71 infections might cause fatal neurological complications. Since 1997, EV71 caused fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to identify and classify the viruses which detected from the patients who presenting clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December 2012 until July 2013, a total of 28 specimens were collected from patients with clinical case definitions of HFMD. The HFMD viruses were detected by using semi-nested reverse transcription polymerase chain reaction (snRT-PCR). The positive snRT-PCR products were sequenced and phylogenetic analyses of the viruses were performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6 (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis studies, EV71 strains were identified as sub-genotype B5; CVA16 strains classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by different types of Enterovirus, which were EV71, CVA6 and CVA16.

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

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

PubMed

Baluka, Sylvia Angubua

2016-06-01

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. 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. 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. 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.

Foot-and-mouth disease in the Americas: epidemiology and ecologic changes affecting distribution.

PubMed

Saraiva, Victor

2004-10-01

Foot-and-mouth disease(FMD) was first recorded in South America (SA) circa 1870, in Buenos Aires, Argentina, in Uruguay, and in southern Brazil as a result of the introduction of cattle from Europe during the early days of colonization. Livestock production to trade with neighboring countries was established in the La Plata Region, and the trade of livestock and products with Chile, northeastern and central western states of Brazil, to Peru, Bolivia, and Paraguay spread FMD, which reached Venezuela and Colombia in the 1950s and finally Ecuador in 1961. The traditional forms of livestock husbandry influence the diffusion and maintenance of the FMD virus (FMDV) in different areas. Cattle production in SA depends mainly on a strong relation between cattle-calf operations and fattening operations in a complementary cycle, revealing the vulnerability and susceptibility of these areas to FMDV. Understanding the relationship between time-space behavior of the disease and the forms of production defines the FMD ecosystems, a key concept to elaborating the control/eradication strategies of national FMD eradication programs, which must be modified when trade opportunities between zones of differing sanitary status change. The role of other susceptible species besides bovines, including wildlife, in maintaining and spreading FMDV has been the subject of several studies, but in SA, bovines are so far considered to determine disease presentation. Buffalo (Bubalus bubalis) have been implicated in the spread of the disease between farms in at least one case in Brazil. Sheep are almost on a par with bovine in terms of number, especially in the Southern Cone, but their role in the maintenance of infection is not considered important, possibly owing to rearing practices. Camelid populations in the Andean region do not play an important role in the maintenance of FMD, because of short persistence of infection and low population densities in these species. The importance of wildlife

Decisions on control of foot-and-mouth disease informed using model predictions.

PubMed

Halasa, T; Willeberg, P; Christiansen, L E; Boklund, A; Alkhamis, M; Perez, A; Enøe, C

2013-11-01

The decision on whether or not to change the control strategy, such as introducing emergency vaccination, is perhaps one of the most difficult decisions faced by the veterinary authorities during a foot-and-mouth disease (FMD) epidemic. A simple tool that may predict the epidemic outcome and consequences would be useful to assist the veterinary authorities in the decision-making process. A previously proposed simple quantitative tool based on the first 14 days outbreaks (FFO) of FMD was used with results from an FMD simulation exercise. Epidemic outcomes included the number of affected herds, epidemic duration, geographical size and costs. The first 14 days spatial spread (FFS) was also included to further support the prediction. The epidemic data was obtained from a Danish version (DTU-DADS) of a pre-existing FMD simulation model (Davis Animal Disease Spread - DADS) adapted to model the spread of FMD in Denmark. The European Union (EU) and Danish regulations for FMD control were used in the simulation. The correlations between FFO and FFS and the additional number of affected herds after day 14 following detection of the first infected herd were 0.66 and 0.82, respectively. The variation explained by the FFO at day 14 following detection was high (P-value<0.001). This indicates that the FFO may take a part in the decision of whether or not to intensify FMD control, for instance by introducing emergency vaccination and/or pre-emptive depopulation, which might prevent a "catastrophic situation". A significant part of the variation was explained by supplementing the model with the FFS (P-value<0.001). Furthermore, the type of the index-herd was also a significant predictor of the epidemic outcomes (P-value<0.05). The results of the current study suggest that national veterinary authorities should consider to model their national situation and to use FFO and FFS to help planning and updating their contingency plans and FMD emergency control strategies. Copyright �

First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam.

PubMed

Vu, Le T; Long, Ngo T; Brito, Barbara; Stenfeldt, Carolina; Phuong, Nguyen T; Hoang, Bui H; Pauszek, Steven J; Hartwig, Ethan J; Smoliga, George R; Vu, Pham P; Quang, Le T V; Hung, Vo V; Tho, Nguyen D; Dong, Pham V; Minh, Phan Q; Bertram, Miranda; Fish, Ian H; Rodriguez, Luis L; Dung, Do H; Arzt, Jonathan

2017-01-01

In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Đắk Nông province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Đắk Nông province, pigs in Đắk Lắk province and Đắk Nông province, and cattle in Ninh Thuận province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia.

A Portable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of Foot-and-Mouth Disease Virus

PubMed Central

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. PMID:23977101

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.

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 5 - Biotherapeutics and Disinfectants.

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 knowledge gaps in foot-and-mouth disease (FMD) research. Findings are reported in a series of papers, and in this article, we consider biotherapeutics and disinfectants. 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. While vaccines will remain the key immunological intervention used against FMD virus (FMDV) for the foreseeable future, it takes a few days for the immune system to respond to vaccination. In an outbreak situation, protection could potentially be provided during this period by the application of rapid, short-acting biotherapeutics, aiming either to stimulate a non-specific antiviral state in the animal or to specifically inhibit a part of the viral life cycle. Certain antiviral cytokines have been shown to promote rapid protection against FMD; however, the effects of different immune-modulators appear to vary across species in ways and for reasons that are not yet understood. Major barriers to the effective incorporation of biotherapeutics into control strategies are cost, limited understanding of their effect on subsequent immune responses to vaccines and uncertainty about their potential impact if used for disease containment. Recent research has highlighted the importance of environmental contamination in FMDV transmission. Effective disinfectants for FMDV have long been available, but research is being conducted to further develop methods for quantitatively evaluating their performance under field, or near-field, conditions. During outbreaks in South Korea in 2010 there was public concern about potential environmental contamination after the mass use of disinfectant and mass burial of culled stock; this should be considered during outbreak contingency planning. © 2016 Blackwell Verlag GmbH.

The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 eventsmore » 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.« less

Foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells.

PubMed

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

2010-09-01

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 alphav beta6, 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-beta) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-beta mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-alpha 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.

The characteristics of autonomic nervous system disorders in burning mouth syndrome and Parkinson disease.

PubMed

Koszewicz, Magdalena; Mendak, Magdalena; Konopka, Tomasz; Koziorowska-Gawron, Ewa; Budrewicz, Sławomir

2012-01-01

To conduct a clinical electrophysiologic evaluation of autonomic nervous system functions in patients with burning mouth syndrome and Parkinson disease and estimate the type and intensity of the autonomic dysfunction. The study involved 83 subjects-33 with burning mouth syndrome, 20 with Parkinson disease, and 30 controls. The BMS group included 27 women and 6 men (median age, 60.0 years), and the Parkinson disease group included 15 women and 5 men (median age, 66.5 years). In the control group, there were 20 women and 10 men (median age, 59.0 years). All patients were subjected to autonomic nervous system testing. In addition to the Low autonomic disorder questionnaire, heart rate variability (HRV), deep breathing (exhalation/inspiration [E/I] ratio), and sympathetic skin response (SSR) tests were performed in all cases. Parametric and nonparametric tests (ANOVA, Kruskal-Wallis, and Scheffe tests) were used in the statistical analysis. The mean values for HRV and E/I ratios were significantly lower in the burning mouth syndrome and Parkinson disease groups. Significant prolongation of SSR latency in the foot was revealed in both burning mouth syndrome and Parkinson disease patients, and lowering of the SSR amplitude occurred in only the Parkinson disease group. The autonomic questionnaire score was significantly higher in burning mouth syndrome and Parkinson disease patients than in the control subjects, with the Parkinson disease group having the highest scores. In patients with burning mouth syndrome, a significant impairment of both the sympathetic and parasympathetic nervous systems was found but sympathetic/parasympathetic balance was preserved. The incidence and intensity of autonomic nervous system dysfunction was similar in patients with burning mouth syndrome and Parkinson disease, which may suggest some similarity in their pathogeneses.

Evolutionary Analysis of Structural Protein Gene VP1 of Foot-and-Mouth Disease Virus Serotype Asia 1

PubMed Central

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. PMID:25793223

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.

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

Challenges and economic implications in the control of foot and mouth disease in sub-saharan Africa: lessons from the zambian experience.

PubMed

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.

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.

Hydrolytic properties and substrate specificity of the foot-and-mouth disease leader protease.

PubMed

Santos, Jorge A N; Gouvea, Iuri E; Júdice, Wagner A S; Izidoro, Mario A; Alves, Fabiana M; Melo, Robson L; Juliano, Maria A; Skern, Tim; Juliano, Luiz

2009-08-25

Foot-and-mouth disease virus, a global animal pathogen, possesses a single-stranded RNA genome that, on release into the infected cell, is immediately translated into a single polyprotein. This polyprotein product is cleaved during synthesis by proteinases contained within it into the mature viral proteins. The first cleavage is performed by the leader protease (Lb(pro)) between its own C-terminus and the N-terminus of VP4. Lb(pro) also specifically cleaves the two homologues of cellular eukaryotic initiation factor (eIF) 4G, preventing translation of capped mRNA. Viral protein synthesis is initiated internally and is thus unaffected. We used a panel of specifically designed FRET peptides to examine the effects of pH and ionic strength on Lb(pro) activity and investigate the size of the substrate binding site and substrate specificity. Compared to the class prototypes, papain and the cathepsins, Lb(pro) possesses several unusual characteristics, including a high sensitivity to salt and a very specific substrate binding site extending up to P(7). Indeed, almost all substitutions investigated were detrimental to Lb(pro) activity. Analysis of structural data showed that Lb(pro) binds residues P(1)-P(3) in an extended conformation, whereas residues P(4)-P(7) are bound in a short 3(10) helix. The specificity of Lb(pro) as revealed by the substituted peptides could be explained for all positions except P(5). Strikingly, Lb(pro) residues L178 and L143 contribute to the architecture of more than one substrate binding pocket. The diverse functions of these two Lb(pro) residues explain why Lb(pro) is one of the smallest, but simultaneously most specific, papain-like enzymes.

Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle.

PubMed

Sreenivasa, B P; Mohapatra, J K; Pauszek, S J; Koster, M; Dhanya, V C; Tamil Selvan, R P; Hosamani, M; Saravanan, P; Basagoudanavar, Suresh H; de Los Santos, T; Venkataramanan, R; Rodriguez, L L; Grubman, M J

2017-05-01

Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O, A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutralizing antibody response in indigenous cattle (Bos indicus). Purified Ad5-FMD viruses were inoculated in cattle as monovalent (5×10 9 pfu/animal) or trivalent (5×10 9 pfu/animal per serotype) vaccines. Animals vaccinated with monovalent Ad5-FMD vaccines were boosted 63days later with the same dose. After primary immunization, virus neutralization tests (VNT) showed seroconversion in 83, 67 and 33% of animals vaccinated with Ad5-FMD O, A and Asia 1, respectively. Booster immunization elicited seroconversion in all of the animals (100%) in the monovalent groups. When used in a trivalent form, the Ad5-FMD vaccine induced neutralizing antibodies in only 33, 50 and 16% of animals against serotypes O, A and Asia 1, respectively on primo-vaccination, and titers were significantly lower than when the same vectors were used in monovalent form. Neutralizing antibody titers differed by serotype for both Ad5-FMD monovalent and trivalent vaccines, with Asia 1 serotype inducing the lowest titers. Antibody response to Ad5 vector in immunized cattle was also assessed by VNT. It appeared that the vector immunity did not impact the recall responses to expressed FMDV antigens on booster immunization. In summary, the study suggested that the recombinant Ad5-FMD vaccine has a potential use in monovalent form, while its application in multivalent form is not currently encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

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

The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis.

PubMed

Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y; Tan, Chong Yew; Chen, Mark Ic; Horby, Peter; Cook, Alex R

2016-10-01

Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). This study reports a systematic review of the epidemiology of HFMD in Asia. PubMed, Web of Science and Google Scholar were searched up to December 2014. Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. 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. Diversity of study designs complicates attempts to identify features of HFMD epidemiology. 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.

Feasibility of depopulation of a large feedlot during a foot-and-mouth disease outbreak.

PubMed

McReynolds, Sara W; Sanderson, Michael W

2014-02-01

To examine the feasibility of depopulation of a large feedlot during a foot-and-mouth disease (FMD) outbreak in the United States. Delphi survey followed by facilitated discussion. 27 experts, including veterinary toxicologists and pharmacologists, animal welfare experts, feedlot managers, and consulting veterinarians. 4 veterinary pharmacologists, 5 veterinary toxicologists, 4 animal welfare experts, 26 consulting veterinarians, and 8 feedlot managers were invited to participate in a Delphi survey to identify methods for depopulation of a large feedlot during an FMD outbreak. A facilitated discussion that included 1 pharmacologist, 1 toxicologist, 1 animal welfare expert, 2 consulting veterinarians, and 2 feedlot managers was held to review the survey results. 27 of 47 invited experts participated in the Delphi survey. Survey consensus was that, although several toxic agents would effectively cause acute death in a large number of animals, all of them had substantial animal welfare concerns. Pentobarbital sodium administered IV was considered the most effective pharmacological agent for euthanasia, and xylazine was considered the most effective sedative. Animal welfare concerns following administration of a euthanasia solution IV or a penetrating captive bolt were minimal; however, both veterinarians and feedlot managers felt that use of a captive bolt would be inefficient for depopulation. Veterinarians were extremely concerned about public perception, human safety, and timely depopulation of a large feedlot during an FMD outbreak. Depopulation of a large feedlot during an FMD outbreak would be difficult to complete in a humane and timely fashion.

Impact of temperature variability on childhood hand, foot and mouth disease in Huainan, China.

PubMed

Xu, J; Zhao, D; Su, H; Xie, M; Cheng, J; Wang, X; Li, K; Yang, H; Wen, L; Wang, B

2016-05-01

The short-term temperature variation has been shown to be significantly associated with human health. However, little is known about whether temperature change between neighbouring days (TCN) and diurnal temperature range (DTR) have any effect on childhood hand, foot and mouth disease (HFMD). This study aims to explore whether temperature variability has any effect on childhood HFMD. Ecological study. The association between meteorological variables and HFMD cases in Huainan, China, from January 1st 2012 to December 31st 2014 was analysed using Poisson generalized linear regression combined with distributed lag non-linear model (DLNM) after controlling for long-term trend and seasonality, mean temperature and relative humidity. An adverse effect of TCN on childhood HFMD was observed, and the impact of TCN was the greatest at five days lag, with a 10% (95% CI: 4%-15%) increase of daily number of HFMD cases per 3 °C (10th percentile) decrease of TCN. Male children, children aged 0-5 years, scattered children and children in high-risk areas appeared to be more vulnerable to the TCN effect than others. However, there was no significant association between DTR and childhood HFMD. Our findings indicate that TCN drops may increase the incidence of childhood HFMD in Huainan, highlighting the importance of protecting children from forthcoming TCN drops, particularly for those who are male, young, scattered and from high-risk areas. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Purification of foot-and-mouth disease virus by heparin as ligand for certain strains.

PubMed

Du, Ping; Sun, Shiqi; Dong, Jinjie; Zhi, Xiaoying; Chang, Yanyan; Teng, Zhidong; Guo, Huichen; Liu, Zaixin

2017-04-01

The goal of this project was to develop an easily operable and scalable process for the recovery and purification of foot-and-mouth disease virus (FMDV) from cell culture. Heparin resins HipTrap Heparin HP and AF-Heparin HC-650 were utilized to purify FMDV O/HN/CHA/93. Results showed that the purity of AF-Heparin HC-650 was ideal. Then, the O/HN/CHA/93, O/Tibet/CHA/99, Asia I/HN/06, and A/CHA/HB/2009 strains were purified by AF-Heparin HC-650. Their affinity/virus recoveries were approximately 51.2%/45.8%, 71.5%/70.9%, 96.4%/73.5, and 59.5%/42.1%, respectively. During a stepwise elution strategy, the viral particles were mainly eluted at 300mM ionic strength peaks. The heparin affinity chromatography process removed more than 94% of cellular and medium proteins. Anion exchange resin Capto Q captured four FMD virus particles; 40% of binding proteins and 80%-90% of viral particles were eluted at 450mM NaCl. Moreover, ionic strength varied from 30 to 450mM had no effect on the immunity to FMDV. The results revealed that heparin sulfate may be the main receptor for CHA/99 strain attachment-susceptible cells. Heparin affinity chromatography can reach perfect results, especially when used as a ligand of the virus. Anion exchange is useful only as previous step for further purification. Copyright © 2016. Published by Elsevier B.V.

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.

2017-08-01

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.

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

PubMed Central

Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

2015-01-01

ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against

Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China.

PubMed

Long, Lu; Gao, Li-Dong; Hu, Shi-Xiong; Luo, Kai-Wei; Chen, Zhen-Hua; Ronsmans, Carine; Zhou, Ding-Lun; Lan, Ya-Jia

2016-10-01

In recent years, outbreaks of hand, foot, and mouth disease (HFMD) have increased throughout East and Southeast Asia, especially in mainland China. The disease now presents as an increasingly serious public health threat in China. A case-control study was designed to examine risk factors associated with death from severe HFMD. A total of 553 severe HFMD cases were collected from the National Surveillance System. Multifactorial logistic regression was used to analyse independent associations between potential influence factors and death from severe HFMD. We found that the migrants were more likely to die from severe HFMD than the resident population (OR = 3.07, 95%CI: 1.39-8.32). Additionally, the children whose first visit was to a village-level clinic had a high risk of death from severe HFMD. Patients with EV71 infection or symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting had an increased risk of death from severe HFMD. While breastfeeding children, having a confirmed diagnosis at the first visit to the hospital and with symptom of hyperarousal were identified as protective factors for death from severe HFMD. To reduce the mortality from severe HFMD, doctors and health care providers need to pay attention to the patients with EV71 infection or with symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting. Health administration departments should pay more attention to the rational allocation of health resources. Furthermore, they should increase financial support and manpower in village-level health institutions.

Phylodynamic reconstruction of O CATHAY topotype foot-and-mouth disease virus epidemics in the Philippines.

PubMed

Di Nardo, Antonello; Knowles, Nick J; Wadsworth, Jemma; Haydon, Daniel T; King, Donald P

2014-08-24

Reconstructing the evolutionary history, demographic signal and dispersal processes from viral genome sequences contributes to our understanding of the epidemiological dynamics underlying epizootic events. In this study, a Bayesian phylogenetic framework was used to explore the phylodynamics and spatio-temporal dispersion of the O CATHAY topotype of foot-and-mouth disease virus (FMDV) that caused epidemics in the Philippines between 1994 and 2005. Sequences of the FMDV genome encoding the VP1 showed that the O CATHAY FMD epizootic in the Philippines resulted from a single introduction and was characterised by three main transmission hubs in Rizal, Bulacan and Manila Provinces. From a wider regional perspective, phylogenetic reconstruction of all available O CATHAY VP1 nucleotide sequences identified three distinct sub-lineages associated with country-based clusters originating in Hong Kong Special Administrative Region (SAR), the Philippines and Taiwan. The root of this phylogenetic tree was located in Hong Kong SAR, representing the most likely source for the introduction of this lineage into the Philippines and Taiwan. The reconstructed O CATHAY phylodynamics revealed three chronologically distinct evolutionary phases, culminating in a reduction in viral diversity over the final 10 years. The analysis suggests that viruses from the O CATHAY topotype have been continually maintained within swine industries close to Hong Kong SAR, following the extinction of virus lineages from the Philippines and the reduced number of FMD cases in Taiwan.

Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

PubMed

Zhao, Fu-Rong; Xie, Yin-Li; Liu, Ze-Zhong; Shao, Jun-Jun; Li, Shi-Fang; Zhang, Yong-Guang; Chang, Hui-Yun

2017-11-01

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID 50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo. © 2017 Wiley Periodicals, Inc.

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.

Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase

PubMed Central

Han, Shi-Chong; Guo, Hui-Chen; Sun, Shi-Qi; Jin, Ye; Wei, Yan-Quan; Feng, Xia; Yao, Xue-Ping; Cao, Sui-Zhong; Xiang Liu, Ding; Liu, Xiang-Tao

2016-01-01

Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na+/H+ exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses. PMID:26757826

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

Farmers’ Intentions to Implement Foot and Mouth Disease Control Measures in Ethiopia

PubMed Central

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

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

Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain

PubMed Central

Chis Ster, Irina; Ferguson, Neil M.

2007-01-01

Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models. PMID:17551582

Development of a Blocking ELISA Using a Monoclonal Antibody to a Dominant Epitope in Non-Structural Protein 3A of Foot-and-Mouth Disease Virus, as a Matching Test for a Negative-Marker Vaccine.

PubMed

Fu, Yuanfang; Li, Pinghua; Cao, Yimei; Wang, Na; Sun, Pu; Shi, Qian; Ji, Xincheng; Bao, Huifang; Li, Dong; Chen, Yingli; Bai, Xingwen; Ma, Xueqing; Zhang, Jing; Lu, Zengjun; Liu, Zaixin

2017-01-01

Foot-and-mouth disease (FMD) is a devastating animal disease. Strategies for differentiation of infected from vaccinated animals (DIVA) remain very important for controlling disease. Development of an epitope-deleted marker vaccine and accompanying diagnostic method will improve the efficiency of DIVA. Here, a monoclonal antibody (Mab) was found to recognize a conserved "AEKNPLE" epitope spanning amino acids 109-115 of non-structural protein (NSP) 3A of foot-and-mouth disease virus (FMDV; O/Tibet/CHA/99 strain), which could be deleted by a reverse-genetic procedure. In addition, a blocking ELISA was developed based on this Mab against NSP 3A, which could serve as a matching test for a negative-marker vaccine. The criterion of this blocking ELISA was determined by detecting panels of sera from different origins. The serum samples with a percentage inhibition (PI) equal or greater than 50% were considered to be from infected animals, and those with <50% PI were considered to be from non-infected animals. This test showed similar performance when compared with other 2 blocking ELISAs based on an anti-NSP 3B Mab. This is the first report of the DIVA test for an NSP antibody based on an Mab against the conserved and predominant "AEKNPLE" epitope in NSP 3A of FMDV.

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. © 2016 Blackwell Verlag GmbH.

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.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Market Impact of Foot-and-Mouth Disease Control Strategies: A UK Case Study

PubMed Central

Feng, Siyi; Patton, Myles; Davis, John

2017-01-01

Foot-and-mouth disease (FMD) poses a serious threat to the agricultural sector due to its highly contagious nature. Outbreaks of FMD can lead to substantial disruptions to livestock markets due to loss of production and access to international markets. In a previously FMD-free country, the use of vaccination to augment control of an FMD outbreak is increasingly being recognized as an alternative control strategy to direct slaughtering [stamping-out (SO)]. The choice of control strategy has implications on production, trade, and hence prices of the sector. Specific choice of eradication strategies depends on their costs and benefits. Economic impact assessments are often based on benefit–cost framework, which provide detailed information on the changes in profit for a farm or budget implications for a government (1). However, this framework cannot capture price effects caused by changes in production due to culling of animals; access to international markets; and consumers’ reaction. These three impacts combine to affect equilibrium within commodity markets (2). This paper provides assessment of sectoral level impacts of the eradication choices of FMD outbreaks, which are typically not available from benefit–cost framework, in the context of the UK. The FAPRI-UK model, a partial equilibrium model of the agricultural sector, is utilized to investigate market outcomes of different control strategies (namely SO and vaccinate-to-die) in the case of FMD outbreaks. The outputs from the simulations of the EXODIS epidemiological model (number of animals culled/vaccinated and duration of outbreak) are used as inputs within the economic model to capture the overall price impact of the animal destruction, export ban, and consumers’ response. PMID:28920059

Quantifying the influence of temperature on hand, foot and mouth disease incidence in Wuhan, Central China.

PubMed

Huang, Jiao; Chen, Shi; Wu, Yang; Tong, Yeqing; Wang, Lei; Zhu, Min; Hu, Shuhua; Guan, Xuhua; Wei, Sheng

2018-01-31

Hand, foot and mouth disease (HFMD) is a substantial burden throughout Asia, but the effects of temperature pattern on HFMD risk are inconsistent. To quantify the effect of temperature on HFMD incidence, Wuhan was chosen as the study site because of its high temperature variability and high HFMD incidence. Daily series of HFMD counts and meteorological variables during 2010-2015 were obtained. Distributed lag non-linear models were applied to characterize the temperature-HFMD relationship and to assess its variability across different ages, genders, and types of child care. Totally, 80,219 patients of 0-5 years experienced HFMD in 2010-2015 in Wuhan. The cumulative relative risk of HFMD increased linearly with temperature over 7 days (lag0-7), while it presented as an approximately inverted V-shape over 14 days (lag0-14). The cumulative relative risk at lag0-14 peaked at 26.4 °C with value of 2.78 (95%CI: 2.08-3.72) compared with the 5 th percentile temperature (1.7 °C). Subgroup analyses revealed that children attended daycare were more vulnerable to temperature variation than those cared for at home. This study suggests that public health actions should take into consideration local weather conditions and demographic characteristics.

The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage

PubMed Central

Abeyratne, S. A. E.; Amarasekera, S. S. C.; Knowles, N. J.; Wadsworth, J.; Puvanendiran, S.; Kothalawala, H.; Jayathilake, B. K.; Wijithasiri, H. A.; Chandrasena, M. M. P. S. K.

2018-01-01

Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many times in the past. Despite its seriousness, limited attempts have been made to understand the disease to ameliorate its effects–current recommendation for vaccines being based solely on immunological assessments rather than on molecular identification. The general belief is that the cattle population in Sri Lanka acquired the FMD virus (FMDV) strains via introductions from India. However, there could be endemic FMDV lineages circulating in Sri Lanka. To infer the phylogenetic relationships of the FMDV strains in the island, we sequenced the VP1 genomic region of the virus isolates collected during the 2014 outbreak together with a few reported cases in 2012 and 1997 and compared them to VP1 sequences from South Asia. The FMDV strains collected in the 2014 outbreak belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected in 2012 and 1997 belonged to another lineage called 'unnamed' by the World Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively, suggesting that Srl-97 evolves slowly. PMID:29570746

The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage.

PubMed

Abeyratne, S A E; Amarasekera, S S C; Ranaweera, L T; Salpadoru, T B; Thilakarathne, S M N K; Knowles, N J; Wadsworth, J; Puvanendiran, S; Kothalawala, H; Jayathilake, B K; Wijithasiri, H A; Chandrasena, M M P S K; Sooriyapathirana, S D S S

2018-01-01

Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many times in the past. Despite its seriousness, limited attempts have been made to understand the disease to ameliorate its effects-current recommendation for vaccines being based solely on immunological assessments rather than on molecular identification. The general belief is that the cattle population in Sri Lanka acquired the FMD virus (FMDV) strains via introductions from India. However, there could be endemic FMDV lineages circulating in Sri Lanka. To infer the phylogenetic relationships of the FMDV strains in the island, we sequenced the VP1 genomic region of the virus isolates collected during the 2014 outbreak together with a few reported cases in 2012 and 1997 and compared them to VP1 sequences from South Asia. The FMDV strains collected in the 2014 outbreak belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected in 2012 and 1997 belonged to another lineage called 'unnamed' by the World Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively, suggesting that Srl-97 evolves slowly.

Evolutionary phylodynamics of foot-and-mouth disease virus serotypes O and A circulating in Vietnam.

PubMed

Le, Van Phan; Vu, Thi Thu Hang; Duong, Hong-Quan; Than, Van Thai; Song, Daesub

2016-11-29

Foot-and-mouth disease virus (FMDV) is one of the highest risk factors that affects the animal industry of the country. The virus causes production loss and high ratio mortality in young cloven-hoofed animals in Vietnam. The VP1 coding gene of 80 FMDV samples (66 samples of the serotype O and 14 samples of the serotype A) collected from endemic outbreaks during 2006-2014 were analyzed to investigate their phylogeny and genetic relationship with other available FMDVs globally. Phylogenetic analysis indicated that the serotype O strains were clustered into two distinct viral topotypes (the SEA and ME-SA), while the serotype A strains were all clustered into the genotype IX. Among the study strains, the amino acid sequence identities were shared at a level of 90.1-100, 92.9-100, and 92.8-100% for the topotypes SEA, ME-SA, and genotype IX, respectively. Substitutions leading to changes in the amino acid sequence, which are critical for the VP1 antigenic sites were also identified. Our results showed that the studied strains are most closely related to the recent FMDV isolates from Southeast Asian countries (Myanmar, Thailand, Cambodia, Malaysia, and Laos), but are distinct from the earlier FMDV isolates within the genotypes. This study provides important evidence of recent movement of FMDVs serotype O and A into Vietnam within the last decade and their genetic accumulation to be closely related to strains causing FMD in surrounding countries.

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

2017-08-01

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 log 10 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 log 10 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. © 2016 Blackwell Verlag GmbH.

Molecular characterization of serotype Asia-1 foot-and-mouth disease viruses in Pakistan and Afghanistan; emergence of a new genetic Group and evidence for a novel recombinant virus.

PubMed

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

2011-12-01

Foot-and-mouth disease (FMD) is endemic in Pakistan and Afghanistan. The FMD virus serotypes O, A and Asia-1 are responsible for the outbreaks in these countries. Diverse strains of FMDV, even within the same serotype, co-circulate. Characterization of the viruses in circulation can facilitate appropriate vaccine selection and tracing of outbreaks. The present study characterized foot-and-mouth disease serotype Asia-1 viruses circulating in Pakistan and Afghanistan during the period 1998-2009. Phylogenetic analysis of FMDV type Asia-1 revealed that three different genetic Groups of serotype Asia-1 have circulated in Pakistan during this time. These are Group-II, -VI and, recently, a novel Group (designated here as Group-VII). This new Group has not been detected in neighbouring Afghanistan during the study period but viruses from Groups I and -II are in circulation there. Using near complete genome sequences, from FMD viruses of serotypes Asia-1 and A that are currently circulating in Pakistan, we have identified an interserotypic recombinant virus, which has the VP2-VP3-VP1-2A coding sequences derived from a Group-VII Asia-1 virus and the remainder of the genome from a serotype A virus of the A-Iran05(AFG-07) sub-lineage. The Asia-1 FMDVs currently circulating in Pakistan and Afghanistan are not efficiently neutralized by antisera raised against the Asia-1/Shamir vaccine strain. Thus, new Asia-1 vaccine strains may be required to block the spread of the current Asia-1 viruses. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge.

PubMed

Barrionuevo, Florencia; Di Giacomo, Sebastián; Bucafusco, Danilo; Ayude, Andrea; Schammas, Juan; Miraglia, M Cruz; Capozzo, Alejandra; Borca, Manuel V; Perez-Filgueira, Mariano

2018-05-01

The role of passively transferred sera in the protection against aerogenous foot-and-mouth disease (FMD) virus infection in cattle was evaluated using vaccine-induced immune serum preparations obtained at 7 and 26 days post-vaccination (dpv). We showed that circulating antibodies were sufficient to prevent disease generalization after oronasal infection in animals passively transferred with 26-dpv serum but not with the 7-dpv serum. Conversely, conventional FMD vaccination provided clinical protection at 7 dpv, promoting fast and robust antibody responses upon challenge and even though antibody titers were similar to those found in animals passively immunized with 7-dpv serum. These results demonstrate that presence of antigen-specific antibodies is critical to prevent the dissemination of the virus within the animal. Conventional FMD vaccination additionally promoted the deployment of rapid, high titer and isotype-switched antibody responses at systemic and mucosal levels after infection, thus conferring protection even in the presence of low pre-challenge antibody titers. Copyright © 2018 Elsevier Inc. All rights reserved.

Epidemiological analysis, serological prevalence and genotypic analysis of foot-and-mouth disease in Nigeria 2008-2009.

PubMed

Ehizibolo, D O; Perez, A M; Carrillo, C; Pauszek, S; AlKhamis, M; Ajogi, I; Umoh, J U; Kazeem, H M; Ehizibolo, P O; Fabian, A; Berninger, M; Moran, K; Rodriguez, L L; Metwally, S A

2014-12-01

The epidemiological situation of foot-and-mouth disease virus (FMDV) is uncertain in Nigeria, where the disease is endemic, and the majority of outbreaks are unreported. Control measures for FMD in Nigeria are not being implemented due to the absence of locally produced vaccines and an official ban on vaccine importation. This study summarizes the findings of a 3-year study aimed at quantifying the seroprevalence of FMD, its distribution in susceptible species and the genetic diversity of FMDV isolated from the Plateau State of Nigeria. A 29% FMD prevalence was estimated using 3ABC enzyme-linked immunosorbent assay (3ABC ELISA). Farms with suspected FMD nearby, with contact with wildlife, that used drugs or FMD vaccines or with >100 animals, and animals of large ruminant species and in pastures other than nomadic grazing were significantly (P < 0.05) associated with FMD. Antibodies against five FMDV serotypes, (A, O, SAT1, SAT2 and SAT3) were detected by the virus neutralization test (VNT) at various titres (<100->800) from all tested sera from most parts of the region. This is probably the first report of the presence of FMDV SAT3 in Nigeria. Further studies to investigate the potential probable presence and prevalence of SAT 3 virus in Nigeria are required. Tissue samples collected from clinical animals were positive for FMDV. Virus isolates were sequenced and confirmed as serotype A. All of the isolates showed marked genetic homogeneity with >99% genetic identity in the VP1 region and were most closely related to a previously described virus collected from Cameroon in 2000. This study provides knowledge on the epidemiological situation of FMD in Plateau State, Nigeria, and will probably help to develop effective control and preventive strategies for the disease in Nigeria and other countries in the West African subregion. © 2013 Blackwell Verlag GmbH.

Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle.

PubMed

Zhang, Zhidong; Doel, Claudia; Bashiruddin, John B

2015-11-19

The factors leading to persistent infection of foot-and-mouth disease (FMD) virus in ruminants are not well defined. This paper provides evidence of the presence of interleukin-10 (IL-10) early in the course of infection (1-4 days) as a factor in the development of persistence of FMD virus in cattle. Results showed that serum IL-10 in carrier cattle infected with FMD virus type O (n = 4) was detected and peaked at 1 or 2 days post infection and rapidly declined thereafter. In contract, serum IL-10 levels in non-carrier cattle (n = 21) were very low or undetectable during the same period.

Ambient temperature, humidity and hand, foot, and mouth disease: A systematic review and meta-analysis.

PubMed

Cheng, Qiang; Bai, Lijun; Zhang, Yanwu; Zhang, Heng; Wang, Shusi; Xie, Mingyu; Zhao, Desheng; Su, Hong

2018-06-01

The relationship between ambient temperature, humidity and hand, foot, and mouth disease (HFMD) has been highlighted in East and Southeast Asia, which showed multiple different results. Therefore, our goal is to conduct a meta-analysis to further clarify this relationship and to quantify the size of these effects as well as the susceptible populations. PubMed, Web of science, and Cochrane library were searched up to November 22, 2017 for articles analyzing the relationships between ambient temperature, humidity and incidence of HFMD. We assessed sources of heterogeneity by study design (temperature measure and exposed time resolution), population vulnerability (national income level and regional climate) and evaluated pooled effect estimates for the subgroups identified in the heterogeneity analysis. We identified 11 studies with 19 estimates of the relationship between ambient temperature, humidity and incidence of HFMD. It was found that per 1°C increase in the temperature and per 1% increase in the relative humidity were both significantly associated with increased incidence of HFMD (temperature: IRR, 1.05; 95% CI, 1.02-1.08; relative humidity: IRR, 1.01; 95% CI, 1.00-1.02). Subgroup analysis showed that people living in subtropical and middle income areas had a higher risk of incidence of HFMD. Ambient temperature and humidity may increase the incidence of HFMD in Asia-Pacific regions. Further studies are needed to clarify the relationship between ambient temperature, humidity and incidence of HFMD in various settings with distinct climate, socioeconomic, and demographic features. Copyright © 2018. Published by Elsevier B.V.