Ulcerative stomatitis associated with yellow bristle grass in New Zealand dairy cows.

CASE HISTORY: A line of 25 cull cows were all found to have ulcerative lesions of the tongue at post-mortem inspection in a New Zealand slaughter plant. A further 9 of 10 cows inspected at the farm of origin had similar oral lesions. There were no other clinical signs or indicators of ill-health observed at ante-mortem inspection in the abattoir or on the farm. The cows had been fed baleage for 3 weeks prior to slaughter, made from pasture in paddocks heavily contaminated with yellow bristle grass (Setaria pumila). CLINICAL FINDINGS: There was extensive and deep transverse linear ulceration in the lingual fossa immediately rostral to the torus linguae. At histological examination, full-thickness ulceration of the stratified squamous epithelium was observed with a bed of disorganised collagenous tissue and extensive mixed inflammatory infiltrate extending into the sub-epithelial connective tissue and skeletal muscle. Barbed plant fragments were embedded in both the superficial and deeper areas of inflammation. Detailed examination of the baleage also found that yellow bristle grass seedheads were present. DIAGNOSIS: Based on the presence of barbed plant material in the tongue and yellow bristle grass seeds in the baleage, a diagnosis of ulcerative stomatitis associated with yellow bristle grass was made. CLINICAL RELEVANCE: Clinicians should be aware of the potential for hay or baleage contaminated with yellow bristle grass to cause oral lesions in cattle.

Erratum: PRAGMATIST: A tool to prioritize foot-and-mouth disease virus antigens held in vaccine banks.

[This corrects the article DOI: 10.3389/fvets.2022.1029075.].

Main factors associated with foot-and-mouth disease virus infection during the 2001 FMD epidemic in Uruguay.

Large epidemics provide the opportunity to understand the epidemiology of diseases under the specific conditions of the affected population. Whilst foot-and-mouth disease (FMD) epidemics have been extensively studied in developed countries, epidemics in developing countries have been sparsely studied. Here we address this limitation by systematically studying the 2001 epidemic in Uruguay where a total of 2,057 farms were affected. The objective of this study was to identify the risk factors (RF) associated with infection and spread of the virus within the country. The epidemic was divided into four periods: (1) the high-risk period (HRP) which was the period between the FMD virus introduction and detection of the index case; (2) the local control measures period (LCM) which encompassed the first control measures implemented before mass vaccination was adopted; (3) the first mass vaccination, and (4) the second mass vaccination round. A stochastic model was developed to estimate the time of initial infection for each of the affected farms. Our analyses indicated that during the HRP around 242 farms were probably already infected. In this period, a higher probability of infection was associated with: (1) animal movements [OR: 1.57 (95% CI: 1.19-2.06)]; (2) farms that combined livestock with crop production [OR: 1.93 (95% CI: 1.43-2.60)]; (3) large and medium farms compared to small farms (this difference was dependent on regional herd density); (4) the geographical location. Keeping cattle only (vs farms that kept also sheep) was a significant RF during the subsequent epidemic period (LCM), and remained as RF, together with large farms, for the entire epidemic. We further explored the RF associated with FMDV infection in farms that raised cattle by fitting another model to a data subset. We found that dairy farms had a higher probability of FMDV infection than beef farms during the HRP [OR: 1.81 (95% CI: 1.12-2.83)], and remained as RF until the end of the first round of vaccination. The delay in the detection of the index case associated with unrestricted animal movements during the HRP may have contributed to this large epidemic. This study contributes to the knowledge of FMD epidemiology in extensive production systems.

An extensive analysis of Codon usage pattern, Evolutionary rate, and Phylogeographic reconstruction in Foot and mouth disease (FMD) serotypes (A, Asia 1, and O) of six major climatic zones of India: A comparative study.

Foot and mouth disease (FMD) is a major economically important viral disease of cloven-hoofed livestock globally. The FMD virus (FMDV) spreads widely in confined, cool, and humid climatic conditions. Being an RNA virus, FMDV is genetically unstable, and its genome evolution is highly influenced by mutational pressure. The climatic and environmental conditions have a significant impact on mutational pressure. The present study is a primary effort to establish a comprehensive relationship between climatic factors and the molecular evolutionary pattern of serotypes FMDV circulating in India. In this study, isolates of three serotypes (A, Asia 1, and O) were selected from six major climatic zones of India (Montane, Humid subtropical, Tropical wet and dry, Tropical wet, Semi-arid and Arid). Based on the full genome nucleotide sequence data, the codon usage bias, evolutionary and phylogeographic analysis was carried out. The study revealed that the codon use bias indicators in the FMDV serotypes differed significantly depending on the climatic zones. It implies that the selection and mutational pressure influence the codon usage pattern indices, with mutational pressure taking precedence in determining the codon usage bias of the FMDV genome. The tMRCA was estimated to be 1977, 1956, and 1953 for Indian FMD virus serotype-A, Asia 1, and O respectively which is around 32, 60, and 61 years before its actual identification in the field. Based on the evolutionary rates the serotype O is evolving rapidly compare to other serotypes in India. Virus transmission across the region was evident from the phylogeographic analysis. The integrated analysis of codon usage bias, evolutionary rate, and phylogeography analysis signifies the major role of mutational and selection pressure, implying that the FMD virus co-evolution and adaptations are highly influenced by climatic/environmental factors.

PRAGMATIST: A tool to prioritize foot-and-mouth disease virus antigens held in vaccine banks.

Antigen banks have been established to supply foot-and-mouth disease virus (FMDV) vaccines at short notice to respond to incursions or upsurges in cases of FMDV infection. Multiple vaccine strains are needed to protect against specific FMDV lineages that circulate within six viral serotypes that are unevenly distributed across the world. The optimal selection of distinct antigens held in a bank must carefully balance the desire to cover these risks with the costs of purchasing and maintaining vaccine antigens. PRAGMATIST is a semi-quantitative FMD vaccine strain selection tool combining three strands of evidence: (1) estimates of the risk of incursion from specific areas (source area score); (2) estimates of the relative prevalence of FMD viral lineages in each specific area (lineage distribution score); and (3) effectiveness of each vaccine against specific FMDV lineages based on laboratory vaccine matching tests (vaccine coverage score). The output is a vaccine score, which identifies vaccine strains that best address the threats, and consequently which are the highest priority for inclusion in vaccine antigen banks. In this paper, data used to populate PRAGMATIST are described, including the results from expert elicitations regarding FMD risk and viral lineage circulation, while vaccine coverage data is provided from vaccine matching tests performed at the WRLFMD between 2011 and 2021 (n = 2,150). These data were tailored to working examples for three hypothetical vaccine antigen bank perspectives (Europe, North America, and Australia). The results highlight the variation in the vaccine antigens required for storage in these different regions, dependent on risk. While the tool outputs are largely robust to uncertainty in the input parameters, variation in vaccine coverage score had the most noticeable impact on the estimated risk covered by each vaccine, particularly for vaccines that provide substantial risk coverage across several lineages.

Validation of Pretreatment Methods for the In-Process Quantification of Foot-and-Mouth Disease Vaccine Antigens.

Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is controlled by vaccine policy in many countries. For vaccine potency, the content of intact virus particles (146S antigens) is critical, and the sucrose density gradient (SDG) fractionation is the gold standard for the quantification of 146S antigens. However, this method has several drawbacks. Although size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace the classic method, its application is generally confined to purified samples owing to the interfering signals. Therefore, we aimed to develop optimal pretreatment methods for SE-HPLC quantification in less purified samples. Crude virus infection supernatant (CVIS) and semi-purified samples with PEG precipitation (PEG-P) were used. Chloroform pretreatment was essential to remove a high level of non-specific signals in CVIS, whereas it caused loss of 146S antigens without the distinctive removal of non-specific signals in PEG-P. Benzonase pretreatment was required to improve the resolution of the target peak in the chromatogram for both CVIS and PEG-P. Through spiking tests with pure 146S antigens, it was verified that the combined pretreatment with chloroform and benzonase was optimal for the CVIS, while the sole pretreatment of benzonase was beneficial for PEG-P.

Sero-epidemiology of foot-and-mouth disease in Darfur area, Western Sudan.

A total of 367 bovine sera positive to antibodies against non-structural proteins (NSPs) of foot-and-mouth disease (FMD) virus were screened for serotype O, A and SAT2 antibodies using the virus neutralization test (VNT). Sera had been collected in 2016 from North (228) and South (139) Darfur States in Western Sudan, where high and low circulation of FMD virus, respectively, prevailed. Tested sera represented the positive-NSPs portion in a random sample of 669 sera collected from both States. According to standard statistical methods, calculations for serial testing (NSPs ELISA and VNT) were applied to estimate prevalence rates of serotype-specific antibodies in the two States. In each State, approximately 20% of NSPs positive sera failed typing. Prevalence's detected were 49% ± 5% (O), 27% ± 5% (A) and 14% ± 4% (SAT2) in North Darfur State and 27% ± 5% (O), 17% ± 4% (A) and 8.0% ± 3% (SAT2) in South Darfur State. In both States, prevalence rates were significantly higher for serotype O, followed by A then SAT2; the same order that was known in most parts of Sudan. Consistently, estimated prevalence's were statistically significantly higher (P < 0.05) in North Darfur than in South Darfur State. Apart from serotype SAT2, detected prevalence rates were lower or similar to those inside the country in previous occasions. Frequency and pattern of distribution of serotype O prevalence were consistent with its suggested pattern of circulation from the Nile valley to other parts in Sudan and significant within the country's circulation. Alternatively, serotype SAT2 prevalence and distribution in Darfur area were suggestive of sporadic occurrence. However, slightly higher prevalence rates of SAT2 antibodies in Darfur than in neighbouring Kordofan areas in 2013 reflected the wide dissemination of SAT2 ( http://www.wrlfmd.org ) in Sudan in early 2014. Risk of FMD in Darfur seemed to be associated with the movement of animals to the North in the wet season as part of the pastoral system, and with movement related to trade into urban centers more than with pastoralism across the Western borders. Generally, the result presented little evidence to suggest presence of FMD primary endemic foci in Darfur area.

Molecular Basis of Antigenic Drift in Serotype O Foot-and-Mouth Disease Viruses (2013-2018) from Southeast Asia.

Foot and mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals with serious economic consequences. FMD is endemic in Southeast Asia (SEA) and East Asia (EA) with the circulation of multiple serotypes, posing a threat to Australia and other FMD-free countries. Although vaccination is one of the most important control measures to prevent FMD outbreaks, the available vaccines may not be able to provide enough cross-protection against the FMD viruses (FMDVs) circulating in these countries due to the incursion of new lineages and sub-lineages as experienced in South Korea during 2010, a FMD-free country, when a new lineage of serotype O FMDV (Mya-98) spread to the country, resulting in devastating economic consequences. In this study, a total of 62 serotype O (2013-2018) viruses selected from SEA and EA countries were antigenically characterized by virus neutralization tests using three existing (O/HKN/6/83, O/IND/R2/75 and O/PanAsia-2) and one putative (O/MYA/2009) vaccine strains and full capsid sequencing. The Capsid sequence analysis revealed three topotypes, Cathay, SEA and Middle East-South Asia (ME-SA) of FMDVs circulating in the region. The vaccines used in this study showed a good match with the SEA and ME-SA viruses. However, none of the recently circulating Cathay topotype viruses were protected by any of the vaccine strains, including the existing Cathay topotype vaccine (O/HKN/6/83), indicating an antigenic drift and, also the urgency to monitor this topotype in the region and develop a new vaccine strain if necessary, although currently the presence of this topotype is mainly restricted to China, Hong Kong, Taiwan and Vietnam. Further, the capsid sequences of these viruses were analyzed that identified several capsid amino acid substitutions involving neutralizing antigenic sites 1, 2 and 5, which either individually or together could underpin the observed antigenic drift.

Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock worldwide. Russia is a big agricultural country with a wide geographical area where FMD outbreaks have become an obstacle for the development of the animal and animal products trade. In this study, we aimed to assess the export risk of FMD from Russia. RESULTS: After simulation by Monte Carlo, the results showed that the probability of cattle infected with FMD in the surveillance zone (Surrounding the areas where no epidemic disease has occurred within the prescribed time limit, the construction of buffer areas is called surveillance zone.) of Russia was 1.29 × 10- 6. The probability that at least one FMD positive case was exported from Russia per year in the surveillance zone was 6 %. The predicted number of positive cattle of the 39,530 - 50,576 exported from Russia per year was 0.06. A key node in the impact model was the probability of occurrence of FMD outbreaks in the Russian surveillance zone. By semi-quantitative model calculation, the risk probability of FMD defense system defects was 1.84 × 10- 5, indicating that there was a potential risk in the prevention and control measures of FMD in Russia. The spatial time scan model found that the most likely FMD cluster (P < 0.01) was in the Eastern and Siberian Central regions. CONCLUSIONS: There was a risk of FMDV among cattle exported from Russia, and the infection rate of cattle in the monitored area was the key factor. Understanding the export risk of FMD in Russia and relevant epidemic prevention measures will help policymakers to develop targeted surveillance plans.

Development of a Potent Stabilizer for Long-Term Storage of Foot-and-Mouth Disease Vaccine Antigens.

A local virus isolate, O/SKR/JC/2014 (O JC), has been considered as a candidate vaccine strain in the development of a domestic foot-and-mouth disease (FMD) vaccine in Korea. However, producing and preserving a sufficient quantity of intact vaccine antigens from the O JC strain was difficult owing to its distinctive structural instability compared to other candidate vaccine strains. Based on this feature, the O JC strain was adopted as a model virus for the stabilization study to determine the optimal stabilizer composition, which enables long-term storage of the FMD vaccine antigen in both aqueous and frozen phases. In contrast to O JC vaccine antigens stored in routinely used Tris-buffered or phosphate-buffered saline, those stored in Tris-KCl buffer showed extended shelf-life at both 4 °C and -70 °C. Additionally, the combined application of 10% sucrose and 5% lactalbumin hydrolysate could protect O JC 146S particles from massive structural breakdown in an aqueous state for up to one year. The stabilizer composition was also effective for other FMDV strains, including serotypes A and Asia 1. With this stabilizer composition, FMD vaccine antigens could be flexibly preserved during the general production process, pending status under refrigeration and banking under ultrafreezing.

Genetic Basis of Antigenic Variation of SAT3 Foot-And-Mouth Disease Viruses in Southern Africa.

Foot-and-mouth disease (FMD) continues to be a major burden for livestock owners in endemic countries and a continuous threat to FMD-free countries. The epidemiology and control of FMD in Africa is complicated by the presence of five clinically indistinguishable serotypes. Of these the Southern African Territories (SAT) type 3 has received limited attention, likely due to its restricted distribution and it being less frequently detected. We investigated the intratypic genetic variation of the complete P1 capsid-coding region of 22 SAT3 viruses and confirmed the geographical distribution of five of the six SAT3 topotypes. The antigenic cross-reactivity of 12 SAT3 viruses against reference antisera was assessed by performing virus neutralization assays and calculating the r1-values, which is a ratio of the heterologous neutralizing titer to the homologous neutralizing titer. Interestingly, cross-reactivity between the SAT3 reference antisera and many SAT3 viruses was notably high (r1-values >0.3). Moreover, some of the SAT3 viruses reacted more strongly to the reference sera compared to the homologous virus (r1-values >1). An increase in the avidity of the reference antisera to the heterologous viruses could explain some of the higher neutralization titers observed. Subsequently, we used the antigenic variability data and corresponding genetic and structural data to predict naturally occurring amino acid positions that correlate with antigenic changes. We identified four unique residues within the VP1, VP2, and VP3 proteins, associated with a change in cross-reactivity, with two sites that change simultaneously. The analysis of antigenic variation in the context of sequence differences is critical for both surveillance-informed selection of effective vaccines and the rational design of vaccine antigens tailored for specific geographic localities, using reverse genetics.

Complex Circulation of Foot-and-Mouth Disease Virus in Cattle in Nigeria.

Nigeria is a large densely populated country in West Africa. Most of its livestock is raised in a pastoralist production system with typical long distance migration in search of water and feed. As the demand for animal products largely exceeds the domestic production, large numbers of livestock are imported from neighboring countries without sanitary restrictions. In Nigeria, foot-and-mouth disease virus (FMDV) serotypes O, A, and Southern African Territories (SAT)2 are endemic for a long time. Clinical outbreaks of FMD due to serotype SAT1 are described again since 2015, after an absence of more than 30 years. Historically, outbreaks of FMD due to serotypes O, A, SAT1, and SAT2 were each time associated with trade of cattle entering Nigeria from neighboring countries. In the present study, tissue samples from 27 outbreaks of FMD were collected in Nigerian cattle from 2012 until 2017 in six different States and in the Federal Capital Territory. FMDV was isolated and serotyped and further characterized by VP1 sequencing and phylogenetic analysis to gain more knowledge on FMDV circulation in Nigeria. Half of the outbreaks were characterized as FMDV topotype O/EA-3, while outbreaks with other serotypes and topotypes were-in descending order-less prevalent: A/Africa/G-IV, SAT1/X, SAT2/VII, and O/WA. The high dynamics and omnipresence of FMD in Nigeria were illustrated in Plateau State where FMDV serotypes O, SAT1, and SAT2 were isolated during the course of the study, while at some point in the study, outbreaks due to FMDV serotype A were observed in three remote States. The genetic and phylogenetic analysis suggests a mixed origin of FMD outbreaks. Some outbreaks seem to be caused by sustained local transmission of FMDV strains present in Nigeria since a number of years, while other outbreaks seem to be related to recent incursions with new FMDV strains. The role of African buffaloes in the etiology of FMD in Nigeria is unclear, and sampling of wildlife is needed. The results of the present study suggest that systematic sample collection is essential to understand the complex concomitance of FMDV strains in Nigeria and essential to support the implementation of a vaccination-based control plan.

Multi-criteria decision analysis to evaluate foot and mouth disease control strategies with the perspectives of Chief Veterinary Officers in the Asia-Oceania region.

The objective of this study was to evaluate the effectiveness of foot and mouth disease (FMD) control strategies using multi-criteria decision analysis (MCDA). The FMD control strategies were evaluated for epidemiological, economic and social-environmental criteria, accounting for the preferences of Chief Veterinary Officers (CVOs) from the Asia-Oceania region, with the preferences quantified using a questionnaire study. Previously reported simulation results of an FMD epidemic were used to measure the epidemiological effectiveness of FMD control strategies. The simulated FMD epidemic results, such as the number of infected farms, the duration of the epidemic and the outbreak area, were compared for a number of FMD control strategies. Based on previous simulation and economic modelling results and incorporating a literature search to quantify the social and environmental outcomes of an FMD outbreak, MCDA analysis was conducted to evaluate control strategies. According to the overall score in the MCDA results, an FMD control strategy which consisted of a 3-km radius of pre-emptive slaughter, 100 days of movement restriction and vaccinating all FMD-susceptible animals (baseline strategy) was the preferred strategy, with the highest overall score of 62.99. In contrast, the same duration of movement restriction and vaccination strategy with a 0.5-km radius of pre-emptive slaughter was least preferred, with the lowest overall score of 37.05. The evaluation of the FMD control strategies presented here using MCDA has provided scientific evidence for selecting an appropriate baseline FMD control strategy, based on the preferences of CVOs.

Les auteurs présentent les résultats d'une étude qui visait à évaluer l'efficacité d'un certain nombre de stratégies de lutte contre la fièvre aphteuse en recourant à une analyse décisionnelle multicritères (ADMC). Diverses stratégies de lutte contre la fièvre aphteuse ont été évaluées au regard de critères épidémiologiques, économiques et socio-environnementaux, en prenant en compte les préférences exprimées par les chefs des Services vétérinaires de la région Asie-Océanie, recueillies et quantifiées lors d'une étude par questionnaire. L'efficacité des stratégies de lutte contre la fièvre aphteuse au plan épidémiologique a été évaluée à partir des résultats d'une simulation d'épidémie de fièvre aphteuse effectuée au préalable. Les résultats de la simulation, notamment le nombre d'exploitations infectées, la durée de l'épidémie et l'extension de la zone focale, ont été comparés au regard de chacune des stratégies de lutte pouvant être appliquées contre la fièvre aphteuse. Une ADMC a été réalisée pour évaluer les stratégies de lutte en s'appuyant sur les résultats de simulations antérieures et de modélisations économiques, ainsi que sur les données réunies lors d'une recherche documentaire visant à quantifier les répercussions sociales et environnementales d'un foyer de fièvre aphteuse. Il ressort du classement des notes globales attribuées par l'ADMC que la stratégie préférée de lutte contre la fièvre aphteuse (note globale de 62,99) était celle associant l'abattage préventif dans un rayon de 3 km à une restriction des déplacements d'animaux pendant une période de 100 jours et à la vaccination de toutes les espèces sensibles au virus de fièvre aphteuse (stratégie de référence). En revanche, la stratégie associant une restriction des déplacements d'animaux de même durée, la vaccination et l'abattage préventif dans un rayon de 0,5 km recueillait le score le plus bas dans l'ordre de préférence (note globale de 37,05). Les évaluations des stratégies de lutte contre la fièvre aphteuse présentées par les auteurs à partir des résultats de l'ADMC fournissent des éléments scientifiques probants pour choisir une stratégie de référence appropriée afin de lutter contre la fièvre aphteuse, fondée sur les préférences des chefs des Services vétérinaires.

Los autores describen un estudio encaminado a evaluar la eficacia de distintas estrategias de control de la fiebre aftosa, para lo cual se siguió un proceso de análisis de decisiones con empleo de múltiples criterios de tipo epidemiológico, económico y socioambiental que recogían las preferencias de los jefes de los Servicios Veterinarios de la región Asia-Oceanía (preferencias cuantificadas con empleo de un cuestionario). Para medir la eficacia epidemiológica de las estrategias de lucha se utilizaron los resultados previamente descritos de simulaciones de una epidemia de fiebre aftosa. Después se compararon entre sí los resultados (por ejemplo, número de explotaciones infectadas, duración de la epidemia o territorio afectado por el brote) que deparaban distintas estrategias de lucha en una epidemia simulada de fiebre aftosa. A partir de los resultados de simulaciones y modelizaciones económicas anteriores e incorporando una búsqueda bibliográfica para cuantificar los efectos sociales y ambientales de un brote de fiebre aftosa, se procedió a evaluar las estrategias de lucha empleando el análisis de decisiones por criterios múltiples. A tenor de la puntuación global que arrojaban los resultados de este análisis, se determinó que la estrategia preferible de lucha contra la fiebre aftosa era la consistente en sacrificios sanitarios preventivos en un radio de 3 kilómetros, restricciones de desplazamientos durante 100 días y vacunación de todos los animales sensibles a la enfermedad (estrategia básica), pues era la que deparaba la puntuación global más elevada (62,99). La menos eficaz, es decir, la que deparaba la puntuación global más baja (37,05), preveía la aplicación de restricciones de desplazamientos durante el mismo período e idéntica estrategia de vacunación, pero con sacrificios sanitarios preventivos en un radio de solo 0,5 kilómetros. La evaluación de estrategias de lucha mediante un análisis de decisiones por criterios múltiples que aquí se presenta ha aportado sólidos datos científicos con los que seleccionar, partiendo de las preferencias de los jefes de los Servicios Veterinarios, una estrategia básica adecuada para combatir la fiebre aftosa.

Potential role of wildlife in the USA in the event of a foot-and-mouth disease virus incursion.

Foot-and-mouth disease (FMD) is caused by foot-and-mouth disease virus (FMDV) which affects domestic and wild cloven-hoofed species. The FMD-free status of the USA and the tremendous economic impact of a virus incursion motivated the development of this evaluation of the potential role of wildlife in the event of a virus introduction. Additionally, this manuscript contains a summary of US vulnerabilities for viral incursion and persistence which focuses specifically on the possible role of wildlife. The legal movement of susceptible live animals, animal products, by-products and animal feed containing animal products pose a risk of virus introduction and spread. Additionally, the illegal movement of FMD-susceptible animals and their products and an act of bioterrorism present additional routes where FMDV could be introduced to the USA. Therefore, robust surveillance and rapid diagnostics in the face of a possible introduction are essential for detecting and controlling FMD as quickly as possible. Wildlife species and feral pigs present an added complexity in the case of FMDV introduction as they are typically not closely monitored or managed and there are significant logistical concerns pertaining to disease surveillance and control in these populations. Recommendations highlight the need to address existing knowledge gaps relative to the potential role of wildlife in FMDV introduction events.

Deciphering foot-and-mouth disease (FMD) virus-host tropism.

The pattern of interactions between foot and mouth disease (FMD) viral protein 1 (VP1) with susceptible and resistant host integrins were deciphered. The putative effect of site-directed mutation on alteration of interaction is illustrated using predicted and validated 3D structures of VP1, mutated VP1 and integrins of Bos taurus, Gallus and Canis. Strong interactions were observed between FMDV-VP1 protein motifs at conserved tripeptide, Arg-Gly-Asp 143RGD145 and at domain 676SIPLQ680 in alpha-integrin of B. taurus. Notably, in-silico site-directed mutation in FMDV-VP1 protein led to complete loss of interaction between FMD-VP1 protein and B. taurus integrin, which confirmed the active role of arginine-glycine-aspartic acid (RGD) domain. Interestingly, in-vitro analysis demonstrates the persistence of the putative tropism site 'SIPLQ' in different cattle breeds undertaken. Thus, the attempt to decipher the tropism of FMDV at host receptor level interaction might be useful for future FMD control strategies through development of mimetic marker vaccines and/or host receptor manipulations. Communicated by Ramaswamy H. Sarma.

Retrospect and Risk Analysis of Foot-and-Mouth Disease in China Based on Integrated Surveillance and Spatial Analysis Tools.

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock and seriously affects the development of animal husbandry. It is necessary to defend the spread of FMD. To explore the distribution characteristics and transmission of FMD between 2010 and 2017 in China, Global Moran's I test and Getis-Ord Gi index were used to analyze the spatial cluster. A space-time permutation scan statistic was applied to analyze the spatio-temporal pattern. GIS-based method was employed to create a map representing the distribution pattern, directional trend, and hotspots for each outbreak. The number of cases was defined as the number of animals with FMD for the above analysis. We also constructed a phylogenetic tree to compare the homology and variation of FMD virus (FMDV) to provide a clue for the potential development of an effective vaccine. The results indicated that the FMD outbreaks in China had obvious time patterns and clusters in space and space-time, with the outbreaks concentrated in the first half of each year. The outbreaks of FMD decreased each year from 2010 with an obvious downward trend of hotspots. Spatial analysis revealed that the distribution of FMD outbreaks in 2010, 2015, and 2017 exhibited a clustered pattern. Space-time scanning revealed that the spatio-temporal clusters were centered in Guangdong, Tibet and the junction of Wuhan, Jiangxi, Anhui. Comparison of the spatial analysis and space-time analysis of FMD outbreaks revealed that Guangdong was the same cluster of the two in 2010. In addition, the directional trend analysis indicated that the FMD transmission was oriented northwest-southeast. The findings demonstrated that FMDV in China can be divided into three pedigrees and the homology of these strains is very high while comparing the first FMDV strain with the others. The data provide a basis for the effective monitoring and prevention of FMD, and for the development of an FMD vaccine in China.

Macroeconomic impact of foot-and-mouth disease vaccination strategies for an outbreak in the Midwestern United States: A computable general equilibrium.

The impacts of alternative responses to a hypothetical foot-and-mouth disease (FMD) outbreak occurring in the Midwestern United States are estimated using the Regional Economic Modelling Incorporated Policy Insight + (REMI) computable general equilibrium model, with particular attention paid to the employment impact estimates. The impact on employment and GDP is estimated using forecasts of a 10-year period with disease outbreak duration up to 2 years. Fifteen different vaccination protocols are compared to a disease control protocol that relies on animal depopulation with no vaccination. Results show that over the 10-year study period, the strictly depopulation strategy that made no use of vaccination results in approximately 677,000 jobs lost with $47 billion GDP loss. Based on the analysis conducted, losses can be reduced through protocols that utilize vaccination strategies. Through a vaccinate-to-live strategy with the highest vaccination capacity and largest vaccination zone, savings can be as many as 509,000 jobs in comparison to the strategy that relies strictly on slaughter with no use of vaccination. By including detailed job losses by occupation, this study highlights the downstream employment effects and shows that job losses resulting from an FMD outbreak can go far beyond the farm sector impacts that have been reported in earlier studies. Understanding the impacts on employment by sector provides more actionable information than producer and consumer surplus estimates frequently reported in economic impact studies.

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

INTRODUCTION: 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 utilization 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 neutralization 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.

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

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.

Full Genome Sequencing Reveals New Southern African Territories Genotypes Bringing Us Closer to Understanding True Variability of Foot-and-Mouth Disease Virus in Africa.

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that poses a constant burden on farmers in endemic regions and threatens the livestock industries in disease-free countries. Despite the increased number of publicly available whole genome sequences, FMDV data are biased by the opportunistic nature of sampling. Since whole genomic sequences of Southern African Territories (SAT) are particularly underrepresented, this study sequenced 34 isolates from eastern and southern Africa. Phylogenetic analyses revealed two novel genotypes (that comprised 8/34 of these SAT isolates) which contained unusual 5′ untranslated and non-structural encoding regions. While recombination has occurred between these sequences, phylogeny violation analyses indicated that the high degree of sequence diversity for the novel SAT genotypes has not solely arisen from recombination events. Based on estimates of the timing of ancestral divergence, these data are interpreted as being representative of un-sampled FMDV isolates that have been subjected to geographical isolation within Africa by the effects of the Great African Rinderpest Pandemic (1887–1897), which caused a mass die-out of FMDV-susceptible hosts. These findings demonstrate that further sequencing of African FMDV isolates is likely to reveal more unusual genotypes and will allow for better understanding of natural variability and evolution of FMDV.