Foot‐and‐Mouth Disease Virus Concentrations in Products of Animal Origin

Foot‐and‐mouth disease (FMD) is a highly contagious disease of cloven‐hoofed animals which can have devastating economic consequences. Maintaining an FMD‐free status is a priority for non‐endemic countries, which restrict importation of animals and animal products from countries in which the disease is present or sporadic, thus presenting a considerable barrier to international trade. This review examines the concentration of FMD virus in animal tissues during the viraemic stage of disease and in animal products derived from infected animals.     

Serotype Specificity of Antibodies against Foot‐and‐Mouth Disease Virus in Cattle in Selected Districts in Uganda

Uganda had an unusually large number of foot‐and‐mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot‐and‐mouth disease virus (FMDV) by ELISA for antibodies against non‐structural proteins and structural proteins. Three hundred and forty‐nine cattle sera were collected from seven districts in Uganda, and 65% of these were found positive for antibodies against the non‐structural proteins of FMDV. A subset of these samples were analysed for serotype specificity of the identified antibodies. High prevalences of antibodies against non‐structural proteins and structural proteins of FMDV serotype O were demonstrated in herds with typical visible clinical signs of FMD, while prevalences were low in herds without clinical signs of FMD. Antibody titres were higher against serotype O than against serotypes SAT 1, SAT 2 and SAT 3 in the sera investigated for serotype‐specific antibodies. Only FMDV serotype O virus was isolated from one probang sample. This study shows that the majority of the FMD outbreaks in 2006 in the region studied were caused by FMDV serotype O; however, there was also evidence of antibodies to both SAT 1 and SAT 3 in one outbreak in a herd inside Queen Elizabeth national park area.     

Emergence and Distribution of Foot‐and‐Mouth Disease Virus Serotype A and O in Bangladesh

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

Epidemiological Patterns of Foot‐and‐Mouth Disease Worldwide

Foot‐and‐Mouth Disease (FMD) is a clinical syndrome in animals due to FMD virus that exists in seven serotypes, whereby recovery from one sero‐type does not confer immunity against the other six. So when considering intervention strategies in endemic settings, it is important to take account of the characteristics of the different serotypes in different ecological systems. FMD serotypes are not uniformly distributed in the regions of the world where the disease still occurs. For example, the cumulative incidence of FMD serotypes show that six of the seven serotypes of FMD (O, A, C, SAT‐1, SAT‐2, SAT‐3) have occurred in Africa, while Asia contends with four sero‐types (O, A, C, Asia‐1), and South America with only three (O, A, C). Periodically there have been incursions of Types SAT‐1 and SAT‐2 from Africa into the Middle East. This paper describes the global dynamics for the seven sero‐types and attempts to define FMD epidemiological clusters in the different regions of the world. These have been described on a continent by continent basis. The review has reaffirmed that the movement of infected animals is the most important factor in the spread of FMD within the endemically infected regions. It also shows that the eco‐system based approach for defining the epidemiological patterns of FMD in endemic, which was originally described in South America, can apply readily to other parts of the world. It is proposed that any coordinated regional or global strategy for FMD control should be based on a sound epidemiological assessment of the incidence and distribution of FMD, identifying risk sources as either primary or secondary endemic eco‐systems.     

Foot‐and‐Mouth Disease in Feral Swine: Susceptibility and Transmission

Experimental studies of foot‐and‐mouth disease (FMD) in feral swine are limited, and data for clinical manifestations and disease transmissibility are lacking. In this report, feral and domestic swine were experimentally infected with FMDV (A24‐Cruzeiro), and susceptibility and virus transmission were studied. Feral swine were proved to be highly susceptible to A‐24 Cruzeiro FMD virus by intradermal inoculation and by contact with infected domestic and feral swine. Typical clinical signs in feral swine included transient fever, lameness and vesicular lesions in the coronary bands, heel bulbs, tip of the tongue and snout. Domestic swine exhibited clinical signs of the disease within 24 h after contact with feral swine, whereas feral swine did not show clinical signs of FMD until 48 h after contact with infected domestic and feral swine. Clinical scores of feral and domestic swine were comparable. However, feral swine exhibited a higher tolerance for the disease, and their thicker, darker skin made vesicular lesions difficult to detect. Virus titration of oral swabs showed that both feral and domestic swine shed similar amounts of virus, with levels peaking between 2 to 4 dpi/dpc (days post‐inoculation/days post‐contact). FMDV RNA was intermittently detectable in the oral swabs by real‐time RT‐PCR of both feral and domestic swine between 1 and 8 dpi/dpc and in some instances until 14 dpi/12 dpc. Both feral and domestic swine seroconverted 6–8 dpi/dpc as measured by 3ABC antibody ELISA and VIAA assays. FMDV RNA levels in animal room air filters were similar in feral and domestic swine animal rooms, and were last detected at 22 dpi, while none were detectable at 28 or 35 dpi. The FMDV RNA persisted in domestic and feral swine tonsils up to 33–36 dpi/dpc, whereas virus isolation was negative. Results from this study will help understand the role feral swine may play in sustaining an FMD outbreak, and may be utilized in guiding surveillance, epidemiologic and economic models.     

Incursions of Foot‐and‐Mouth Disease Virus into Europe between 1985 and 2006

Foot‐and‐mouth disease (FMD) is one of the biggest threats to animal health in European countries. In the last 22 years (1985–2006), FMD has occurred 37 times in 14 European countries. Serotype O was most frequently involved in these outbreaks followed by A, C and Asia 1. Sometimes, epidemics were very limited and at other times, they were the cause of devastating economic losses. In most cases (22/37), the origin of the outbreaks could not be determined. For some of these outbreaks, however, routes of introduction and spread were identified through epidemiological inquiries. Moreover, in some cases, the origin of the virus was also traced by phylogenetic analysis of the partial or complete sequences of VP1 genes. Lessons learned from the outbreaks are still useful as most of the same risk factors persist. However, efforts made by FMD‐free countries to help those where the disease is endemic are a valuable strategy for the reduction of the global risk. The present and the future potential sources of FMD infection need to be identified to best focus European efforts.     

Epidemiology of the Foot‐and‐Mouth Disease Serotype O Epidemic of November 2010 to April 2011 in the Republic Of Korea

The largest epidemic of foot‐and‐mouth disease (FMD) in Korea since the first record in 1911 occurred between November 2010 and April 2011. The outbreak was confirmed in 153 farms, and more than three million animals were destroyed. This study presents the temporal and spatial distribution patterns, epidemiological investigation and the control measures for the 2010/2011 epidemic in Korea. The index case of this 2010/2011 FMD epidemic was reported in a pig‐farming complex with five piggeries in Andong, GyeongBuk Province, on 28 November 2010, and the outbreak lasted 145 days. The largest number of new detection of the infected farms per day was recorded in mid‐January. Epidemiological investigation revealed that the FMD virus had spread from farm to farm through routine movements associated with animal husbandry operations. In contrast to FMD epidemics in other countries in which movement of the infected animals largely contributed to the spread of the disease, human behaviours were major factors in the spread of the FMD virus in the Korean epidemic. The 2010/2011 epidemic was first confirmed in a local small and medium city where share of smallholder producers is higher than that of other provinces. Although Korea had a well‐developed emergent response system with the experience of controlling infection and re‐obtaining FMD‐free status after the previous epidemics, Korea was prompted to revise their contingency plan by tailoring it to its unique livestock environment. Practical contingency plans tailored to Korea for control of FMD can be fully effective when farmers, livestock‐related agencies, veterinary service providers and the general public work together.     

Molecular Characterisation of Foot‐and‐Mouth Disease Viruses from Pakistan, 2005–2008

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

Review of the Global Distribution of Foot‐and‐Mouth Disease Virus from 2007 to 2014

Foot‐and‐mouth disease (FMD) virus affects livestock worldwide. There are seven different serotypes, each with a diversity of topotypes, genetic lineages and strains. Some lineages have different properties that may contribute to sporadic spread beyond their recognized endemic areas. The objective of this study was to review the most significant FMD epidemiological events that took place worldwide between 2007 and 2014. Severe epidemics were caused by FMD virus (FMDV) lineage O/Asia/Mya‐98 in Japan and South Korea in 2010, both previously free of disease. In India, where FMD is endemic, the most important event was the re‐emergence of lineage O/ME‐SA/Ind‐2001 in 2008. Notably, this lineage, normally restricted to India, Bangladesh, Nepal and Bhutan, was also found in Saudi Arabia and Libya in 2013 and has caused several outbreaks in Tunisia and Algeria in 2014–2015. In January 2011, FMDV‐positive wild boars were found in Bulgaria, where the disease last occurred in 1996, followed by 12 outbreaks in livestock infected with FMDV O/ME‐SA/PanAsia2. In 2012, FMDV SAT2 caused outbreaks in Egypt and the Palestinian Autonomous Territories. Another significant event was the emergence of FMDV Asia1 Sindh‐08 in the Middle East. In South America, one outbreak of FMDV serotype O, topotype Euro‐SA was reported in Paraguay in 2011, which was recognized as FMD‐free with vaccination at the time. Lessons learned from past events, point out the need for an integrated strategy that comprises coordinated global and regional efforts for FMDV control and surveillance. Specific local characteristics related to host, environment and virus that condition FMD occurrence should be carefully considered and incorporated to adapt appropriate strategies into local plans. In this review, we compiled relevant epidemiological FMD events to provide a global overview of the current situation. We further discussed current challenges present in different FMD areas.     

Molecular Characterization of Foot‐and‐Mouth Disease Virus: Implications for Disease Control in Bangladesh

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.     

Epidemiology of the 2010 Outbreak of Foot‐and‐Mouth Disease in Mongolia

Foot‐and‐mouth disease (FMD) occurred in five provinces and 24 counties as part of the FMD incursion into Mongolia during 2010. The first detection occurred on 21 April 2010 (confirmed 26 April 2010) with the last detection occurring approximately 8 months later on 13 December 2010. The number of livestock detected in the spring phase of the outbreak was 323 cattle and in the summer phase was 13 485 sheep, 6748 cattle, 5692 goats and 10 camels (total livestock summer phase = 25 935; for spring and summer phases combined = 26 258). Infection of livestock was confirmed by PCR for each affected county but not necessarily for every outbreak cluster involving more than one herder. It is likely that the summer phase of the outbreak was a continuation of the spring event. In the summer phase, the spatio‐temporal pattern of spread suggested an extension of infection from the main cluster in the Sukhbaatar county. There was also a number of long‐distance clusters established. The relative importance of spread by three potential pathways of gazelle, livestock, animal product and fomite movements has not been determined and will require further study. The estimated dissemination ratio (EDR) did not provide evidence of high rate of transmission of infection between herders; however, the data are limited by the quality of surveillance and the method of calculation which used the date of detection rather than the date of infection.     

Temporospatial Clustering of Foot‐and‐Mouth Disease Outbreaks in Israel and Palestine, 2006–2007

Foot‐and‐mouth disease (FMD) is endemic to the Middle East and there is a perception that political instability and limited resources have led to the uncontrolled circulation of FMD virus throughout the region. Certain aspects of FMD epidemiology in the Middle East remain unknown. The goal of this study was to identify the geographical location, temporal extent and direction of spread of clusters of 70 FMD outbreaks reported in Israel and Palestine from February 4, 2006, through July 15, 2007. The space–time permutation model of the scan statistic test detected nine significant (P < 0.1) clusters. Significant (P < 0.05) direction of spread was identified in four of the nine clusters. The Gaza Strip, where no outbreaks were reported, or a nearby location, seemed to be the origin of a cluster of outbreaks located in Hadarom (April 2007); a cluster of outbreaks centered in West Bank (February 2006) may be linked with spread from Northern Israel; a cluster in Hazafon (January 2007) seemed to have originated from nearby the Jordan borders; and a cluster located in Northern Hazafon was likely related to areas next to the Lebanon and Syrian borders. The association between the clusters in West Bank and earlier Israeli samples and between the cluster in Hazafon and Jordan was also supported (P < 0.05) by phylogenetic analysis of samples collected from the outbreaks. These results suggest that the FMD outbreaks reported in Israel and Palestine in 2006 and 2007 were likely a consequence of different epidemics associated with the circulation and spread of FMD virus strains from different regions of the Middle East.     

Genetic Characterization of Serotypes A and Asia‐1 Foot‐and‐mouth Disease Viruses in Balochistan,Pakistan, in 2011

This study reports characterization of foot‐and‐mouth disease virus (FMDV) in samples collected from Balochistan, Pakistan. FMDV was detected by pan‐FMDV real‐time RT‐PCR in 31 samples (epithelial and oral swabs) collected in 2011 from clinical suspect cases. Of these, 29 samples were serotyped by serotype‐specific real‐time RT‐PCR assays and were confirmed by sequencing the VP1 coding region. Sixteen samples were found positive for serotype A and eight for serotype Asia‐1, whereas five samples were found positive for both serotypes A and Asia‐1. Two serotype A positive samples were found positive for two different strains of serotype A FMDV each. Phylogenetic analyses of serotype A FMDVs showed circulation of at least three different sublineages within the A‐Iran05 lineage. These included two earlier reported sublineages, A‐Iran05^HER−10 and A‐Iran05^FAR−11, and a new sublineage, designated here as A‐Iran05^BAL−11. This shows that viruses belonging to the A‐Iran05 lineage are continuously evolving in the region. Viruses belonging to the A‐Iran05^FAR−11 sublineage showed close identity with the viruses circulating in 2009 in Pakistan and Afghanistan. However, viruses belonging to the A‐Iran05^HER−10 detected in Balochistan, Pakistan, showed close identity with the viruses circulating in Kyrgyzstan, Iran and Kazakhstan in 2011 and 2012, showing that viruses responsible for outbreak in these countries have a common origin. Serotype Asia‐1 FMDVs reported in this study all belonged to the earlier reported Group‐VII (Sindh‐08), which is currently a dominant strain in the West Eurasian region. Detection of two different serotypes of FMDV or/and two different strains of the same serotype in one animal/sample shows complexity in occurrence of FMD in the region.     

The Epidemiological Characteristics of the 2007 Foot‐and‐Mouth Disease Epidemic in Sarpang and Zhemgang Districts of Bhutan

This study was undertaken to compare the epidemiological characteristics of the 2007 foot‐and‐mouth disease outbreak in two districts of Sarpang and Zhemgang in Bhutan. Zhemgang district recorded a significantly higher cumulative incidence in all species (26.9%) as well as for cattle (29.3%) compared to Sarpang (6.5% and 7.4%, respectively). The case fatality for cattle in Zhemgang (14.1%) was significantly higher than in Sarpang (3.3%). A total of 404 cattle and 73 pigs died of FMD in Zhemgang, whereas only 21 cattle died in Sarpang. Although all four species were affected in Sarpang, no sheep or goats were affected in Zhemgang. Spatiotemporal analyses showed the existence of four significant clusters, a primary one in Sarpang and three secondary clusters in Zhemgang. The virus belonged to the PanAsia strain of the Middle‐East South‐Asia topotype (O serotype), and the strain was closely related to the PanAsia strain that circulated in Bhutan during the 2003/2004 outbreaks. The severity of FMD infection in Zhemgang district could be attributed to low vaccination coverage (36.5% in 2006 when compared to 87.6% in Sarpang), inadequate biosecurity, poor nursing care of the sick animals and delayed reporting to the livestock centre. This study highlights the ability of the PanAsia strain of the O serotype to cause unprecedented morbidity and mortality, especially in a naïve population. The study also highlights the benefits of maintaining good herd immunity in the susceptible population, through adequate vaccination coverage, to minimize the severity of infection and limit the spread of disease from infected to non‐infected herds.     

Heterogeneity in the Antibody Response to Foot‐and‐Mouth Disease Primo‐vaccinated Calves

Foot‐and‐mouth disease (FMD) vaccines are routinely used as effective control tools in large regions worldwide and to limit outbreaks during epidemics. Vaccine‐induced protection in cattle has been largely correlated with the FMD virus (FMDV)‐specific antibodies. Genetic control of cattle immune adaptive responses has been demonstrated only for peptide antigens derived from FMDV structural proteins. Here, we quantify the heterogeneity in the antibody response of cattle primo‐vaccinated against FMD and study its association with the genetic background in Holstein and Jersey sires. A total of 377 FMDV‐seronegative calves (122 and 255 calves from 16 and 15 Holstein and Jersey sires, respectively) were included in the study. Samples were taken the day prior to primo‐vaccination and 45 days post‐vaccination (dpv). Animals received commercial tetravalent FMD single emulsion oil vaccines formulated with inactivated FMDV. Total FMDV‐specific antibody responses were studied against three viral strains included in the vaccine, and antibody titres were determined by liquid‐phase blocking ELISA. Three linear hierarchical mixed regression models, one for each strain, were formulated to assess the heterogeneity in the immune responses to vaccination. The dependent variables were the antibody titres induced against each FMDV strain at 45 dpv, whereas sire's ‘breed’ was included as a fixed effect, ‘sire’ was included as a random effect, and ‘farm’ was considered as a hierarchical factor to account for lack of independence of within herd measurements. A significant association was found between anti‐FMDV antibody responses and sire's breed, with lower immune responses found in the Jersey sires’ offspring compared with those from Holstein sires. No significant intrabreed variation was detected. In addition, farm management practices were similar in this study, and results of the serological assays were shown to be repeatable. It therefore seems plausible that differences in the immune response may be expected in the event of a mass vaccination campaigns.