File Name: foot and mouth disease in cattle .zip
Foot and mouth disease is a viral disease of cloven hoofed anials including pigs, cattle, water fuffalo, sheep, goats and deer.
- Foot-and-mouth disease: past, present and future
- Foot-and-mouth disease
- Petition To Manufacture Foot-and-Mouth Disease Vaccine in the United States
Metrics details. Foot-and-mouth disease FMD is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus FMDV , a picornavirus.
Foot-and-mouth disease: past, present and future
The greatest proportion of foot-and-mouth disease FMD clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies specific to pigs. However, accumulated evidence from FMD outbreaks and experimental investigations suggest that critical components of FMD pathogenesis, immunology, and vaccinology cannot be extrapolated from investigations performed in cattle to explain or to predict outcomes of infection or vaccination in pigs.
Furthermore, it has been shown that failure to account for these differences may have substantial consequences when FMD outbreaks occur in areas with dense pig populations.
Recent experimental studies have confirmed some aspects of conventional wisdom by demonstrating that pigs are more susceptible to FMD virus FMDV infection via exposure of the upper gastrointestinal tract oropharynx than through inhalation of virus.
The infection spreads rapidly within groups of pigs that are housed together, although efficiency of transmission may vary depending on virus strain and exposure intensity. Multiple investigations have demonstrated that physical separation of pigs is sufficient to prevent virus transmission under experimental conditions.
Detailed pathogenesis studies have recently demonstrated that specialized epithelium within porcine oropharyngeal tonsils constitute the primary infection sites following simulated natural virus exposure. Furthermore, epithelium of the tonsil of the soft palate supports substantial virus replication during the clinical phase of infection, thus providing large amounts of virus that can be shed into the environment.
Due to massive amplification and shedding of virus, acutely infected pigs constitute a considerable source of contagion. FMDV infection results in modulation of several components of the host immune response.
The infection is ultimately cleared in association with a strong humoral response and, in contrast to ruminants, there is no subclinical persistence of FMDV in pigs. The aim of this review is to provide an overview of knowledge gained from experimental investigations of FMD pathogenesis, transmission, and host response in pigs. Details of the temporo-anatomic progression of infection are discussed in relation to specific pathogenesis events and the likelihood of transmission.
Additionally, relevant aspects of the host immune response are discussed within contexts of conventional and novel intervention strategies of vaccination and immunomodulation.
Foot-and-mouth disease FMD is recognized as one of the most contagious and economically important diseases of domestic livestock. The etiological agent, FMD virus FMDV , an aphthovirus of the Picornaviridae family, is capable of infecting a multitude of cloven-hoofed animal species including both ruminants and suids 1 , 2. Although domestic cattle are often prioritized with regards to FMD prevention and strategic countermeasures, it is important to recognize that pigs constitute a substantial proportion of agricultural production in large areas of the world.
Even though cattle and pigs may be similarly susceptible to FMDV infection under most circumstances, there are critical differences in FMD pathogenesis and infection dynamics that emphasize the importance of species-specific experimental investigations and adaptation of countermeasure policies. Important distinctions between cattle and pigs in FMD pathogenesis events include variations in permissiveness to infection by different routes of virus exposure and thereby differences in the most likely mechanisms of virus transmission between animals.
Furthermore, variations in the quantities of virus shed by aerogenous routes, as well as the capability of long-term persistence of infectious virus in tissues of ruminants, but not pigs, indicate important differences pertaining to risk assessments and practical management of infected or convalescent animals.
It is well known that the clinical severity of FMD may vary greatly depending both on the virus strain and the affected host species 1 , 2. Acute clinical FMD has been reported to be more severe in pigs compared to ruminant species 1. It has also been widely accepted that while pigs are capable of generating large amounts of aerosolized virus, they are less susceptible to airborne infection compared to ruminants 4 , 5.
Demonstrated variability in host range of certain FMDV strains that are significantly attenuated in cattle, yet virulent in pigs provides additional evidence of the existence of host-specific differences in the molecular pathways of FMDV infection 6 — 9. Specifically, it was confirmed that a mutation within the FMDV 3A coding region was the determinant for the strictly porcinophilic phenotype of the serotype O FMDV that caused an outbreak in Taiwan in 8 , A large proportion of experimental studies investigating FMDV pathogenesis and vaccinology have been performed in cattle.
In many regions, it is common practice to vaccinate only cattle, but not pigs, based on the assumption that this practice may be sufficient to prevent dissemination of a potential outbreak. This premise may be misguided if extrapolated to regions with intensive pig production or substantial quantities of wild suids. Several experimental studies have demonstrated difficulty in achieving sufficient protection against clinical FMD in pigs by vaccination, especially when the virus challenge consisted of direct exposure to clinically infected pigs 12 — Additionally, recent experiences from South Korea have shown that high quality FMDV vaccines with confirmed efficacy in cattle may fail to elicit sufficient levels of immunity based on serum neutralization testing when administered to pigs in commercial production settings These distinct, porcinocentric scenarios may be explained by species-specific differences in susceptibility to the virus or by differences in the host response to vaccination.
Regardless of the causality, the documented variations between cattle and pigs in outcomes of both vaccination and infection suggest that FMD control policies may, justifiably, be based on species-specific data and should be adapted to account for the composition of the animal population in any given region. Such differences are also highly relevant for disease modeling, wherein it is critical to account for species-specific aspects of FMDV infection dynamics and transmission in order to precisely model distinct scenarios.
Early experimental studies performed by Terpstra 17 concluded that pigs were highly susceptible to FMDV via artificial aerosol exposure, while a fold higher inoculation dose was required to achieve successful infection by virus instillation in the oral cavity. This was subsequently contradicted in works by Alexandersen and Donaldson which demonstrated that pigs were largely resistant to FMDV infection by inhalation of naturally produced aerosols 4 , 5.
Additionally, more recent investigations have confirmed that the porcine upper respiratory tract nasopharynx is less permissive to inoculation by direct deposition of virus when compared to the upper gastrointestinal tract oropharynx 18 , Infection via the oral route is likely mediated by virus entry through the mucosal surfaces of the oropharyngeal tonsils rather than trough the lower gastrointestinal tract.
This is supported by demonstrated tropism of tonsillar epithelium to primary FMDV infection 20 as well as the instability of FMDV at low pH 21 , 22 , which likely leads to dissociation of virus particles that reach the stomach.
The predilection for virus entry via the porcine upper gastrointestinal tract is in direct contrast to primary FMDV infection of cattle, which has been demonstrated to occur in the upper respiratory tract 23 — However, despite this apparent discrepancy in anatomic location, there are striking similarities in microanatomic characteristics of the epithelium that supports primary FMDV replication in both cattle and pigs 19 , 23 , Specifically, in both species, primary infection occurs at distinct regions of epithelium overlaying mucosa-associated lymphoid tissue MALT.
In these regions so-called reticular- or follicle-associated epithelium , the epithelium is intimately associated with the subjacent lymphoid follicles, the basement membrane is discontinuous, and there are abundant intraepithelial transmigrating and resident leukocytes. The relative resistance of pigs to aerogenous FMDV infection has been further corroborated by several experimental studies, which have shown that physical separation of pigs is sufficient to prevent transmission of virus under experimental conditions 27 — Contrastingly, direct contact exposure leads to rapid transmission of infection within groups of pigs that are housed together.
Furthermore, it has been demonstrated that this system of virus exposure is often sufficient to overcome vaccine protection 15 even though vaccination may reduce shedding of virus and thereby lower the transmission rate 12 , Additionally, external factors, such as housing density, the intensity of interactions between animals, and the duration of exposure, will directly influence the outcome of experimental transmission studies 30 , 32 , Even though these findings strongly suggest that direct physical contact between pigs facilitates FMDV transmission, the specific route of virus entry during contact exposure has not been completely identified.
The susceptibility of the porcine oropharyngeal mucosa to FMDV infection would support virus transmission via the oral route, e. However, direct entry of virus through skin abrasions and punctures derived from biting or oral entry mediated through direct contact to exposed vesicular lesions on donor animals may also constitute likely transmission routes.
There are many options for challenge systems for FMD experimentation in pigs, which reflect the differences described above. FMDV infection in pigs is often achieved by intraepithelial injection of the heel bulb 27 , 34 — This technique is convenient for vaccine studies, as the pedal epithelium is highly permissive to FMDV infection, leading to substantial amplification of the injected virus at the inoculation site and consistently rapid progression of generalized FMD in susceptible animals.
Despite the convenience and consistency of injection-based inoculation techniques, these systems are less appropriate for studies of disease pathogenesis as they are based on an artificial route of virus entry that bypasses the natural barrier of the mucosal immune system. As mentioned above, direct contact exposure to infected animals is highly efficient in generating infection in susceptible animals.
However, critical factors, such as the dose and timing of virus challenge, are difficult to control in contact-based systems, which may lead to inconsistencies across studies or misinterpretations of experimental outcomes. Recent studies have demonstrated that controlled exposure of the porcine upper gastrointestinal tract by deposition of virus inoculum in the oropharynx of sedated pigs is highly efficient in generating consistent and synchronous clinical FMD and may thus be considered a valid alternative to the more traditional injection-based challenge systems 18 — Relatively few experimental studies have been dedicated to investigation of the progression of FMDV infection in porcine tissues following natural or simulated natural virus exposure 17 , 20 , 34 , 36 , There is general agreement across these investigations that epithelial tissues of the oropharynx constitute the main sites of virus replication during early infection, whereas abundant amplification of virus occurs in vesicular lesions at secondary peripheral replication sites Figure 1.
However, there are slight variations among published works regarding the interpretation of the precise events that constitute the initial phase of FMDV infection in pigs.
Figure 1. Schematic illustration of virus distribution in tissues during distinct phases of FMD in pigs. A During the pre-viremic phase of infection, primary virus replication is localized to epithelium of oropharyngeal tonsils.
B During the clinical phase of infection, FMDV can be recovered from essentially every tissue or organ sampled due to high titers of virus in blood. Virus replication in oropharyngeal tonsil epithelium continues, while substantial amplification of FMDV occurs in vesicular lesions on the feet, snout, and in the oral cavity.
C After resolution of viremia and clinical disease, FMDV genome and antigen can be recovered from lymph nodes that drain lesion sites for up to 2 months. However, there is no persistence of infectious virus.
A recent investigation demonstrated specific predilection of primary FMDV infection to porcine paraepiglottic tonsils Figure 2 A. Additionally, FMDV structural and non-structural viral proteins were localized to crypt epithelium of this specific tonsil by immunomicroscopy at 6—24 h post intraoropharyngeal inoculation Early detection of FMDV RNA and infectious virus was more variable in the tonsil of the soft palate, lingual tonsil, and the dorsal soft palate, suggesting that these sites may also be potential sites of primary infection.
A similar investigation performed by Murphy et al. However, the earliest time point for tissue collection in this study was 24 h post contact exposure, which may account for the somewhat wider distribution of viral genome. Additionally, in this study, localization of viral replication was not confirmed by VI or microscopy.
Similarly, an earlier investigation by Alexandersen et al. However, there are multiple distinct tonsils in the porcine oropharynx, including the tonsil of the soft palate, lingual tonsil, and paraepiglottic tonsils Figure 2. Development of microvesicles within oropharyngeal tonsil epithelium during early infection. A Earliest detection of infection occurs within paraepiglottic tonsil at 24 h post intraoropharyngeal inoculation.
FMDV antigen red in clusters of infected cytokeratin-positive green epithelial cells in superficial layers of crypt epithelium. B At 48 h post intraoropharyngeal inoculation, a single microvesicle is present within the tonsil of the soft palate. Focus of FMDV-infected red epithelial cells expanding through deeper layers of epithelium green.
C At 78 h post intraoropharyngeal inoculation, three distinct microvesicles are present within crypt epithelium of the tonsil of the soft palate. An earlier study by Brown et al. This study described widespread dissemination of FMDV genome in the epidermis from 24 to 96 hours post infection hpi , at sites with or without visible FMDV-associated lesions The study does not include determination of the onset of viremia and systemic dissemination of virus in relation to the time points for tissue collection.
However, it is mentioned that pigs euthanized at 24 hpi, corresponding to the earliest time point investigated, were clinically depressed with marked vesicles at the epithelial inoculation sites on the snout and lips. The somewhat different findings between these published studies highlights the differences in experimental outcomes pertaining to experimental design, e. Combining multiple techniques incurs additional cost and time investment, but ultimately provides a more detailed and substantiated experimental output.
In all in vivo studies, the onset of viremia is a critical milestone in FMD pathogenesis, as it accompanies a surge in contagion and predicts the impending clinical syndrome. In pigs, viremia may be detected as early as 24 h after natural or artificial virus exposure, and it is associated with a substantial increase in shedding of infectious virus via the oropharyngeal route 3 , 20 , 30 , The onset of clinical FMD, which usually occurs approximately 24 h after detection of viremia, is characterized by fever, loss of appetite, and the appearance of vesicular lesions on feet, snout, and within the oral cavity 20 , 30 , The initial phase of infection, consisting of the progression from primary, pre-viremic, infection to viremia and clinical disease may be prolonged following exposure to an FMDV strain of reduced virulence, or if exposure conditions are less stringent e.
During clinical FMD, the highest quantities of infectious virus are found in vesicular lesions in cornified epithelium of the feet heel bulbs and coronary bands , on the snout and on the dorsal surface of the tongue 20 , 34 , 36 , It has recently been demonstrated that during clinical disease abundant virus replication occurs in epithelial crypts of the tonsil of the soft palate, and that microscopic vesicular lesions containing large quantities of viral protein can be detected at this site Figures 2 B,C It is well established that clinically infected pigs release infectious FMDV in exhaled air at quantities substantially greater than cattle 43 — However, the anatomic source of exhaled virus remains incompletely elucidated.
Donaldson and Ferris 47 used an approach of direct air sampling from intact or intubated pigs to evaluate the sources of exhaled virus during different phases of FMD.
This demonstrated that infectious FMDV was primarily recovered from the upper respiratory tract during early infection, but that both upper and lower segments of the respiratory tract contributed to exhaled virus during the clinical phase of FMD Unfortunately, there was no collection or analysis of tissue samples in this study, and more detailed conclusions regarding the anatomic sites of released virus are therefore lacking.
With the exception of Terpstra 17 , tissue-based pathogenesis studies have failed to demonstrate substantial amplification of FMDV in porcine lungs 20 , 34 ,
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Neeta Longjam, Rajib Deb, A. Sarmah, Tilling Tayo, V. Awachat, V. Foot-and-mouth disease FMD is one of the highly contagious diseases of domestic animals. Effective control of this disease needs sensitive, specific, and quick diagnostic tools at each tier of control strategy. In this paper we have outlined various diagnostic approaches from old to new generation in a nutshell.
Foot-and-mouth disease FMD is a highly contagious viral disease of cloven footed animals artiodactyls , characterised by fever, vesicles on the buccal mucosa and feet and sudden death in the young of susceptible species. FMD is caused by an a FMD is caused by an aphthovirus, an RNA virus with a positive-sense single-stranded genome, in the family Picornaviridae. Domestic cattle, pigs, sheep, goats, buffalo and all species of wild ruminant and pig are susceptible. In endemic situations, local breeds frequently show a degree of resistance to clinical disease, although there is no evidence that they have increased resistance to infection. Infected zebu cattle in Africa rarely show many disease signs.
We would like to thank the DHS. Animal Resources Branch at PIADC for caring for these animals during this project. Cover photos courtesy of luciegaillard.org 2.
Petition To Manufacture Foot-and-Mouth Disease Vaccine in the United States
Foot-and-mouth disease FMD or hoof-and-mouth disease HMD is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals , including domestic and wild bovids. FMD has very severe implications for animal farming , since it is highly infectious and can be spread by infected animals comparatively easily through contact with contaminated farming equipment, vehicles, clothing, and feed, and by domestic and wild predators. Susceptible animals include cattle , water buffalo , sheep , goats , pigs ,   antelope , deer , and bison. It has also been known to infect hedgehogs and elephants ;   llamas and alpacas may develop mild symptoms, but are resistant to the disease and do not pass it on to others of the same species. Humans are only extremely rarely infected by foot-and-mouth disease virus.
Момент истины настал в одно ненастное октябрьское утро. Провели первый реальный тест. Несмотря на сомнения относительно быстродействия машины, в одном инженеры проявили единодушие: если все процессоры станут действовать параллельно, ТРАНСТЕКСТ будет очень мощным. Вопрос был лишь в том, насколько мощным.
Ну и порядки. Звук мотора, похожий на визг циркулярной пилы, заставил его повернуться. Парень крупного сложения и прильнувшая к нему сзади девушка въехали на стоянку на стареньком мотоцикле Веспа-250.
Там его дожидается лирджет. Прогремел выстрел. Пуля ударила в асфальт в нескольких метрах позади. Беккер оглянулся. Убийца целился, высунувшись из окна. Беккер вильнул в сторону, и тут же боковое зеркало превратилось в осколки. Он почувствовал, как этот удар передался на руль, и плотнее прижался к мотоциклу.
Сделайте это, - приказал. - И тут же доложите. ГЛАВА 34 Сьюзан сидела одна в помещении Третьего узла, ожидая возвращения Следопыта.
Никто не сомневался, что АНБ проиграло сражение. Цель была достигнута. Все глобальное электронное сообщество было обведено вокруг пальца… или так только. ГЛАВА 5 Куда все подевались? - думала Сьюзан, идя по пустому помещению шифровалки. - Ничего себе чрезвычайная ситуация.