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.     

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.     

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.     

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 Tanzania from 2001 to 2006

Foot‐and‐mouth disease (FMD) is endemic in Tanzania, with outbreaks occurring almost each year in different parts of the country. There is now a strong political desire to control animal diseases as part of national poverty alleviation strategies. However, FMD control requires improving the current knowledge on the disease dynamics and factors related to FMD occurrence so control measures can be implemented more efficiently. The objectives of this study were to describe the FMD dynamics in Tanzania from 2001 to 2006 and investigate the spatiotemporal patterns of transmission. Extraction maps, the space‐time K‐function and space‐time permutation models based on scan statistics were calculated for each year to evaluate the spatial distribution, the spatiotemporal interaction and the spatiotemporal clustering of FMD‐affected villages. From 2001 to 2006, 878 FMD outbreaks were reported in 605 different villages of 5815 populated places included in the database. The spatial distribution of FMD outbreaks was concentrated along the Tanzania‐Kenya, Tanzania‐Zambia borders, and the Kagera basin bordering Uganda, Rwanda and Tanzania. The spatiotemporal interaction among FMD‐affected villages was statistically significant (P ≤ 0.01) and 12 local spatiotemporal clusters were detected; however, the extent and intensity varied across the study period. Dividing the country in zones according to their epidemiological status will allow improving the control of FMD and delimiting potential FMD‐free areas.     

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.     

Foot‐and‐Mouth Disease Virus Serotype O Phylodynamics: Genetic Variability Associated with Epidemiological Factors in Pakistan

One of the most challenging aspects of foot‐and‐mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating outbreaks in disease‐free areas. In countries trying to control and eradicate FMD using vaccination strategies, the constantly evolving and wide diversity of field FMDV strains is an obstacle for identifying vaccine strains that are successful in conferring protection against infection with field viruses. Consequently, quantitative knowledge on the factors that are associated with variability of the FMDV is prerequisite for preventing and controlling FMD in the Indian subcontinent. A hierarchical linear model was used to assess the association between time, space, host species and the genetic variability of serotype O FMDV using viruses collected in Pakistan from 2005 to 2011. Significant (P < 0.05) amino acid and nucleotide variations were associated with spatial distance, but not with differences in host species, which is consistent with the frequent multi‐species infection of this serotype O FMDV. Results from this study will contribute to the understanding of FMDV variability and to the design of FMD control strategies in Pakistan. Viruses sequenced here also provide the earliest reported isolate from the Pan Asia II^ANT‐10 sublineage, which has caused several outbreaks in the Middle East and spread into Europe (Bulgaria) and Africa (Libya).     

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.     

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.     

A Review of Network Analysis Terminology and its Application to Foot‐and‐Mouth Disease Modelling and Policy Development

Livestock movements are important in spreading infectious diseases and many countries have developed regulations that require farmers to report livestock movements to authorities. This has led to the availability of large amounts of data for analysis and inclusion in computer simulation models developed to support policy formulation. Social network analysis has become increasingly popular to study and characterize the networks resulting from the movement of livestock from farm‐to‐farm and through other types of livestock operations. Network analysis is a powerful tool that allows one to study the relationships created among these operations, providing information on the role that they play in acquiring and spreading infectious diseases, information that is not readily available from more traditional livestock movement studies. Recent advances in the study of real‐world complex networks are now being applied to veterinary epidemiology and infectious disease modelling and control. A review of the principles of network analysis and of the relevance of various complex network theories to infectious disease modelling and control is presented in this paper.     

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.     

Recent Spread of a New Strain (A‐Iran‐05) of Foot‐and‐Mouth Disease Virus Type A in the Middle East

This report describes the characterization of a new genotype of foot‐and‐mouth disease virus (FMDV) type A responsible for recent FMD outbreaks in the Middle East. Initially identified in samples collected in 2003 from Iran, during 2005 and 2006 this FMDV lineage (proposed to be named A‐Iran‐05) spread into Saudi Arabia and Jordan and then further west into Turkey reaching European Thrace in January 2007. Most recently A‐Iran‐05 has been found in Bahrain. To the east of Iran, it has been recognized in Afghanistan (2004–07) and Pakistan (2006–07). Throughout the region, this lineage is now the predominant genotype of FMDV serotype A sampled, and has appeared to have replaced the A‐Iran‐96 and A‐Iran‐99 strains which were previously encountered. In August 2007, a new A‐Iran‐05 sub‐lineage (which we have called A‐Iran‐05^ARD‐07) was identified in Ardahan, Turkey, close to the border with Georgia. This new sub‐lineage appeared to predominate in Turkey in 2008, but has, so far, not been identified in any other country. Vaccine matching tests revealed that the A‐Iran‐05 viruses are antigenically different to A‐Iran‐96 and more like A₂₂. These findings emphasize the importance of undertaking continued surveillance in the Middle East and Central Asia in order to detect and monitor the emergence and spread of new FMDV strains.     

Investigations into the Cause of Foot‐and‐Mouth Disease Virus Seropositive Small Ruminants in Cyprus During 2007

In 2007, serological evidence for foot‐and‐mouth disease (FMD) infection was found as a result of differential diagnostic testing of Cypriot sheep suspected to be infected with bluetongue or contagious ecthyma. Seropositive sheep and goats were subsequently uncovered on ten geographically clustered flocks, while cattle and pigs in neighbouring herds were all seronegative. These antibodies were specific for serotype‐O FMD virus, reacting with both structural and non‐structural (NS) FMD viral proteins. However, no FMD virus could be recovered from the seropositive flocks. FMD had not been recorded in Cyprus since 1964 and there has been no vaccination programme since 1984. Since all the seropositive animals were at least 3 years old and home‐bred, it was concluded that infection had occurred approximately 3 years previously had passed un‐noticed and died out spontaneously. It therefore appears that antibodies to FMD virus NS proteins can still be detected around 3 years after infection of small ruminants, but that virus carriers cannot be detected at this time. This unusual situation of finding evidence of historical infection in a FMD‐free country caused considerable disruption and alarm and posed questions about the definition of what constitutes a FMD outbreak.     

Review: Evaluation of Foot‐and‐Mouth Disease Control Using Fault Tree Analysis

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.     

Foot‐and‐Mouth Disease Seroprevalence in Cattle in Eritrea

Information about seroprevalence of foot‐and‐mouth disease (FMD) and virus serotypes in Eritrea is unavailable, but is very important as it may guide the choice of intervention measures including vaccination to be implemented. We carried out a cross‐sectional study from February to June 2011 in Eritrea with a two‐stage cluster design, sampling cattle in 155 villages with the objective of determining the seroprevalence of FMD in four administrative regions of the country. We analysed cattle sera (n = 2429) for FMD virus antibodies using the non‐structural ELISA (NS ELISA) and virus neutralization test (VNT). The overall seroprevalence was 26% and 30% for the NS ELISA and VNT, respectively. FMD virus serotypes O (14%) and A (11%) were the most prevalent. Gash Barka showed the highest (39%) seroprevalence both in NS ELISA and VNT compared to the other three administrative regions. Strategic FMD virus vaccination with type O and A (matching circulating strains) in combination of zoo‐sanitary measures would be the best control option for Eritrea which could be started in areas where the disease is less endemic.     

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.