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Foot- and-mouth disease as zoonosis.

Man's susceptibility to the virus of foot- and-mouth disease (FMD) was debated for many years. Today the virus has been isolated and typed (type O, followed by type C and rarely A) in more than 40 human cases. So no doubt remains that FMD is a zoonosis. Considering the high incidence of the disease (in animals) in the past and in some areas up to date, occurrence in man is quite rare. In the past when FMD was endemic in Central Europe many cases of diseases in man showing vesicles in the mouth or on the hands and feet were called FMD. The first suggestion of a human infection with FMD was reported in 1695 by Valentini in Germany [7]. All reports before 1897, the year of the discovery of the virus of FMD by Loeffler and Frosch [2], were not of course confirmed either by isolation of the virus or by identification of immunoglobulins after infection. Nevertheless the successful self-infection reported by Hertwig in 1834 most likely seems to have been FMD in man: each of three veterinarians drank 250 ml of milk from infected cows on four consecutive days. The three men developed clinical manifestations. The diseases most often confused with FMD are infections with several viruses of the Coxsackie A group (this infection is referred to as "hand and mouth disease"), herpes simplex and sometimes vesicular stomatitis. Beginning in 1921 up to 1969 at least 38 papers were published, which described clinically manifest FMD in man in more than 40 proven cases. One further reported described an asymptomatic infection with FMD in man [10]. Criteria for establishing a diagnosis of FMD in man are the isolation of the virus from the patient and/or identification of specific antibodies after infection. Laboratory tests for diagnosis of human FMD are the same as for animals. Proven cases of FMD in man have occurred in several countries in Europe, Africa and South America. The type of virus most frequently isolated man is type O followed by type C and rarely A. The incubation period in man, although somewhat variable, has not been found to be less than two days and rarely more than six days.

Animals↗

Dose-response relationships for foot and mouth disease in cattle and sheep.

The relationships between the inhaled dose of foot and mouth disease virus and the outcomes of infection and disease were examined by fitting dose-response models to experimental data. The parameters for both the exponential and beta-poisson models were estimated using maximum likelihood and Bayesian methods. The median probability of infection given a single inhaled TCID50 was estimated to be 0.031 with 95% Bayesian credibility intervals (CI) of 0.018-0.052 for cattle, and 0.045 (CI = 0.024-0.080) for sheep. These estimates were used to construct dose-response curves and uncertainty distributions for use in quantitative risk assessments.

Animals↗

Freeze-drying foot-and-mouth disease virus antigens. I. Infectivity studies.

The ability of foot-and-mouth disease virus strains type O1 BFS 1860 and type A22 IRQ 24/64 to retain infectivity after freeze-drying with or without additives being made to virus suspensions was studied. The infectivity titres of freeze-dried antigens was assessed at intervals over a six month storage period at various temperatures and also after reconstitution to the liquid phase and storage with or without glycerination. Certain additive solutions were necessary to prevent degradation of virus during the freeze-drying procedure which reduced any loss of infectivity caused by storage of products at 4 degrees C and 20 degrees C. Additive solutions composed of 10% sucrose and 5% lactalbumin hydrolysate; 10% skimmed milk; 4% peptone and 1% gelatin; and 5% dextran, 1% sodium glutamate and 5% sucrose all prolonged the keeping qualities of virus at the elevated temperature of 37 degrees C. The results indicate that short-term storage and shipment of freeze-dried foot-and-mouth disease virus antigens is possible without the need for refrigeration, thereby reducing transportation and storage costs. Reconstituted antigens survived better after glycerination and storage at -20 degrees C than did non-glycerinated samples stored at 4 degrees C.

Animals↗

Genomic and antigenic characterization of viruses from the 1993 Italian foot-and-mouth disease outbreak.

The origin and evolution of the type O foot-and-mouth disease viruses (FMDV) that caused the outbreak occurrence in Italy in 1993, the first episode of the disease in the EU after adoption of a non-vaccination policy in 1991, have been studied by the analysis of sequences encoding three main antigenic sites on the viral capsid proteins. The phylogenetic tree derived from sequences spanning the carboxyterminal end of VP1 showed that these Italian viruses were grouped in the ME-SA topotype, closely related to viruses that circulated previously in the Middle East. The analysis of the nucleotide sequences in VP1, VP2 and VP3 showed a co-circulation during the epizootic of genetic variants, including viruses with amino acid replacements in VP3. For some of the isolates analyzed, values of fixation of nucleotide substitutions per year were observed in the three regions analyzed, ranging from 1.5 to 5.1 x 10(-2). The use of a panel of new monoclonal antibodies raised against an isolate from this outbreak, as well as monoclonal antibodies to FMDV O1-Switzerland 1965, showed differences in the reactivity pattern among some of the Italian isolates analyzed, which were consistent with the co-circulation of antigenic variants. These results support the potential for FMDV diversification in a limited period of time and under epidemiological conditions in which no vaccination campaigns were being implemented.

Animals↗

The foot-and-mouth disease epidemic in The Netherlands in 2001.

An outbreak of foot-and-mouth disease (FMD) in Great Britain was reported on 21 February 2001, followed by an outbreak of FMD in The Netherlands a month later. This Dutch index outbreak occurred on a mixed, veal-calf/dairy-goat farm in Oene, in the central part of The Netherlands. The most-likely route of infection was the import of Irish veal-calves to this Dutch herd via an FMD-contaminated staging point in France. With hindsight, more herds seemed to be infected by the time the index outbreak was confirmed. The regular EU control measures were implemented, in combination with pre-emptive culling of herds within 1km of each outbreak. Nevertheless, more outbreaks of FMD occurred. Most of the virus infections on those farms were "neighborhood infections". Because the situation seemed out of control locally and the destruction capacity became insufficient, it was decided to implement an emergency vaccination strategy for all biungulates in a large area around Oene to stop further spread of the virus. All susceptible animals on approximately 1800 farms in this area were vaccinated. All farms subsequently were depopulated, starting from 2 weeks after vaccination. In total, 26 outbreaks were detected (the last outbreak on 22 April 2001). In total, approximately 260,000 animals were killed.

Animals↗

Genetic comparison of large fragment of the 5'untranslated region among foot-and-mouth disease viruses with special reference to serotype Asia1.

Foot-and-mouth disease (FMD), the most economically important disease of cloven-hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic grouping of type Asia1 field isolates on the basis of the large fragment of the 5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences of the capsid-coding (VP1) region of the same viruses. The existence of two distinct lineages of type Asia1 suggested by the study on the VP1 region was further supported by the detection of a difference in length and predicted secondary structure of the 5'LF-UTR between the two lineages. Sequence variability between the isolates of the two lineages was also observed within the different domains of the internal ribosome entry site (IRES) around conserved motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF-UTR have been identified. The present study shows that the 5'LF-UTR of FMDV serotype Asia1 field isolates are variable in relation to the length and probable secondary structure of the IRES.

5' Untranslated Regions↗

Serological survey of foot and mouth disease in Saudi Arabia.

An immunodiffusion test using foot and mouth disease (FMD) virus infection-associated (VIA) antigen was used to detect precipitating antibodies in serum samples collected from non-vaccinated indigenous ruminants raised in different regions of Saudi Arabia. Of 5,985 sheep sera, 1,371 goat sera, 1,052 cattle sera and 694 serum samples from unspecified species of ruminants, precipitating activity was detected in 1,209 (20%), 127 (9%), 172 (16%) and 38 (5%) samples, respectively. In addition, 100 sera showing precipitating activity against VIA antigen originating from 13 different regions were tested for the presence of naturally-occurring neutralising antibodies against the four serotypes of FMD virus (O, A, Asia 1, and C) currently prevalent in the region and incorporated in the vaccine being used. All sera tested gave varying titres against serotypes O, A and/or Asia 1. However, none of the sera showed neutralising activities against serotype C. The results obtained are interpreted with regard to the geographical distribution and epizootiology of FMD in Saudi Arabia.

Animals↗

Presence and persistence of foot-and-mouth disease virus in bovine skin.

Gailiunas, Peter (Plum Island Animal Disease Laboratory, Greenport, N. Y.), and George E. Cottral. Presence and persistence of foot-and-mouth disease virus in bovine skin. J. Bacteriol. 91:2333-2338. 1966.-This study established that the seven known antigenic types of foot-and-mouth disease virus (FMDV) have consistent affinity to all areas of bovine skin, even though gross cutaneous lesions usually are found only in the pedal area. Considerable amounts of FMDV were present in skin of 13 different body areas, irrespective of the presence of hair. All skin specimens from the trunk of 50 experimentally infected steers, necropsied from 12 hr to 7 days postinoculation (DPI), contained FMDV in the dermal and epidermal tissues. In skins of some steers, FMDV persisted for as long as 5 days after cessation of viremia. The highest average virus titer, 10(3.6) plaque-forming units (PFU) per g of skin, was found at 2 DPI. Some areas of the trunk and extremities had titers of approximately 10(5.0) PFU per g of skin. Characteristic gross lesions were not observed in sampling areas. The present observations have epizootiological importance for hides offered in international trade, because FMDV localized intracutaneously is more difficult to inactivate than virus adhering to hide surfaces.

Animals↗

Fatal rhabdomyolysis and renal failure associated with hand, foot and mouth disease.

Fatal severe rhabdomyolysis and anuric renal failure developed in a young man who had contracted hand, foot and mouth disease during an epidemic of this disease. Viral studies implicated coxsackievirus A16 as the infecting agent. This appears to be the first reported case of rhabdomyolysis that was associated with hand, foot and mouth disease and infection with coxsackievirus A16.

Adult↗

Vesicular exocytosis of foot- and -mouth disease virus from mammary gland secretory epithelium of infected cows.

Foot-and-mouth disease virus particles were observed by electron microscopy in the cytoplasma of alveolar secretory cells of the bovine mammary gland after contact exposure of uninfected cows to pits with foot-and-mouth disease. Virus, contained in membrane-limited vesicles, was released from the basal and peranuclear portions of the cells into the intracellular and extracellular spaces by an exocytotic mechanism similar to that of the release of th milk-fat globule. Virus was released into the lumen from the apical portion of the cell both by membrane-limited vesicles and by the merocrinal exocytosis of casein-associated virus. The lytic release of virus was observed in 20% of the preparations observed.

Animals↗

Sequencing and analysis for the full-length genome RNA of foot-and-mouth disease virus China/99.

The complete nucleotide sequence of genomic RNA of foot and mouth disease virus (FMDV) strain China/99 from infected bovine tongue epithelium is presented. The nucleotide sequence extending from the 5' end of the genomic RNA to the 5' end of poly (A) tail contains 8173 nucleotides (nt). Its open reading frame, which encodes a single polypeptide of 2332 amino acids, encompasses 6999 nt starting from the initiation codon AUG and terminating at the UAA codon 93 bases upstream from the 5' end of poly (A) tract. The 5' untranslated region (UTR) is composed of 1081 nt. The consensus of the 1d gene of FMDV strain China/99 compared with that of UKG/6/2001, UKG/12/2001, China/99HN4 and China/3/Tibet is over 97%. The result showed the stains belong to the members of the Pan-Asia family. There is a remarkable differentiation in the function-unknown (FUR), p2 and p3 regions between FMDV isolates from infected cattle and swine, especially in 3a gene. No deletion was found in genes I, 1a, 1b, 2a, 2c, 3b, and 3d. These genes might be indispensable to the surviving of FMDV. The secondary structures of small (S) fragments, FUR and an internal ribosome entry site can be classified into three types, and the S fragment and 3' UTR of the positive-sense RNA fold into stem-loop structures similar to the shape of clover.

Animals↗

Epidemiology and control of an outbreak of foot-and-mouth disease in the Republic of Ireland in 2001.

An outbreak of foot-and-mouth disease was confirmed in a flock of sheep on a farm in the Cooley peninsula, County Louth, on March 22, 2001. The virus was similar to other viruses of the serotype O PanAsian strain and virtually indistinguishable from other isolates from Northern Ireland and Great Britain. The epidemiological evidence suggested that infected sheep brought from Great Britain on February 19, 2001, were the source of the infection. The disease was eradicated by epidemiological investigation, serological testing and extensive culling.

Animals↗

Review of the status and control of foot and mouth disease in sub-Saharan Africa.

Six of the seven serotypes of foot and mouth disease (FMD) virus (i.e. all but Asia 1) are prevalent in Africa although there are marked regional differences in distribution. Three of these serotypes are unique to Africa, namely the three South African Territories (SAT) serotypes. Serotype C may also now be confined to Africa because it has not been reported elsewhere recently. In southern Africa at least, the SAT serotypes have an intimate and probably ancient association with African buffalo (Syncerus caffer) that is instrumental in their maintenance. Within each of the six prevalent serotypes, with the possible exception of C, there are a number of different lineages with more or less defined distributions (i.e. topotypes) that in some cases are sufficiently immunologically different from one another to require specific vaccines to ensure efficient control. This immunological diversity in prevalent serotypes and topotypes, in addition to uncontrolled animal movement in most parts of the continent, render FMD difficult to control in present circumstances. This fact, together with poorly developed intercontinental trade in animals and animal products has resulted in the control of FMD being afforded a low priority in most parts of the continent, although the northern and southern regions of the continent are an exception. As a consequence, eradication of FMD from Africa as a whole is not a prospect within the foreseeable future. In southern Africa, the use of fencing and other means to strictly control the movement of wildlife and livestock as well as judicious application of vaccine has resulted in countries of the region being able to access beef and other livestock markets in Europe and elsewhere in the developed world. Significant marketing of livestock and livestock products from Africa outside the continent is unlikely to be achieved unless similar approaches can be developed for other regions of Africa. This will result in continuing under-exploitation of a valuable resource in the arid and semi-arid regions of Africa, with increasing marginalisation of human populations living there.

Africa South of the Sahara↗

The application of new techniques to the improved detection of persistently infected cattle after vaccination and contact exposure to foot-and-mouth disease.

Detection of antibodies to the non-structural proteins (NSP) of foot-and-mouth disease virus (FMDV) was compared with conventional serological and virological methods and with RT-PCR for the identification of FMDV carrier animals obtained after experimental contact challenge of vaccinated cattle. Transmission from carriers to sentinels was also monitored. Twenty FMDV vaccinated and five unvaccinated cattle were challenged by direct contact with five donor cattle excreting FMDV and monitored until 28 days post challenge-exposure . Twelve vaccinated and three unvaccinated animals were retained up to 24 weeks post exposure to FMDV in order to monitor viral persistence, transmission and antibody responses. In nine vaccinated animals, infection persisted beyond 28 days post exposure, virus being detected more frequently and for longer in oesophagopharyngeal samples from these animals when examined by RT-PCR rather than by virus isolation. Although recovery of FMDV RNA became increasingly sporadic over time, the number of RNA copies detected in positive samples declined only slowly. Two naïve sentinel cattle housed with the persistently infected animals between 93 and 168 days after the latter had been challenge-exposed to FMDV did not become infected. There were differences in the ability of commercially available serological tests to detect antibodies to FMDV non-structural proteins (NSP) in vaccinated and subsequently challenged cattle. Although no single test could identify all of the vaccinated cattle that became persistently infected, the most poorly recognised animals were those with the least evidence of virus replication based on other tests. The potential of the detection of antibodies to the 2B NSP of FMDV for diagnosing persistent FMDV infection was demonstrated.

Animals↗

A note on outbreaks caused by mixed foot-and-mouth disease virus infections.

Two outbreaks of foot-and-mouth disease (FMD) in vaccinated cattle were investigated wherein a mixed infection due to FMD virus (FMDV) types O and Asia 1 was detected by sandwich enzyme-linked immunosorbent assay (ELISA) and confirmed by antigen capture polymerase chain reaction (PCR). The clinical picture and the epidemiological data on these outbreaks are presented. The isolated virus strains were compared to the respective vaccine strains by means of monoclonal antibody (MAb) profiling and nucleotide sequence analysis. The probable cause of the mixed FMDV infection and its significance in disease control are discussed.

Amino Acid Sequence↗

Experimental foot-and-mouth disease in fattening pigs, sows and piglets in relation to outbreaks in the field.

The progression of foot-and-mouth disease in sows and their litters of piglets following exposure to O1 Lausanne virus has been investigated. The majority of piglets died with acute myocarditis but without developing vesicles. Deaths occurred before and also when sows began showing early evidence of vesicle formation. This clinical picture parallels that seen at the beginning of both the Normandy 1979 and Britanny 1981 epidemics in France and points to the necessity of including foot-and-mouth disease in the differential diagnosis of acute death among cloven-hoofed livestock and furthermore the importance of extending clinical inspections to adult animals on premises when such events take place. In investigations in which the susceptibility of fattening pigs to infection with O1 Lausanne virus given by the intramuscular route was examined it was found that the 50 per cent infective dose was log (10)4.8 TCID50. This finding suggests that large amounts of virus are required for successful initiation of disease. This is more likely to come from animals already infected than by inoculation with contaminated material.

Acute Disease↗

Psychosocial effects of the 2001 UK foot and mouth disease epidemic in a rural population: qualitative diary based study.

OBJECTIVES: To understand the health and social consequences of the 2001 foot and mouth disease epidemic for a rural population. DESIGN: Longitudinal qualitative analysis. SETTING: North Cumbria, the worst affected area in Britain. SAMPLE: Purposive sample of 54 respondents divided in six demographically balanced rural occupational and population groups. MAIN OUTCOME MEASURES: 3071 weekly diaries contributed over 18 months; 72 semistructured interviews (with the 54 diarists and 18 others); 12 group discussions with diarists RESULTS: The disease epidemic was a human tragedy, not just an animal one. Respondents' reports showed that life after the foot and mouth disease epidemic was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Distress was experienced across diverse groups well beyond the farming community. Many of these effects continued to feature in the diaries throughout the 18 month period. CONCLUSIONS: The use of a rural citizens' panel allowed data capture from a wide spectrum of the rural population and showed that a greater number of workers and residents had traumatic experiences than has previously been reported. Recommendations for future disaster management include joint service reviews of what counts as a disaster, regular NHS and voluntary sector sharing of intelligence, debriefing and peer support for front line workers, increased community involvement in disposal site or disaster management, and wider, more flexible access to regeneration funding and rural health outreach work.

Agricultural Workers' Diseases↗

Identification of geographic factors associated with early spread of foot-and-mouth disease.

OBJECTIVE: To explore whether early analysis of spatial data may result in identification of variables associated with epidemic spread of foot and mouth disease. SAMPLE POPULATION: 37 farms with infected cattle (ie, case farms) reported within the first 6 days of the 2001 Uruguayan foot-and-mouth disease epidemic. PROCEDURE: A georeferenced database was created and retrospective analysis was performed on case farm location in relation to farm density, cattle density, farm type (ie, beef vs dairy cattle production), road density, case farm distance to the nearest road, farm size, farm ownership, and day of infection. Mean or median results of 1 to 3 day versus 4 to 6 day spatial data were compared. Spatial-temporal associations were investigated by correlation analysis. RESULTS: Comparison of mean or median values between the first 3 days and days 4 to 6 of the epidemic and results of correlation analysis indicated a significant increase in road density, cattle density, and dairy cattle production and a significant decrease in farm size and case farm distance to the nearest road that developed over time. A route that linked most case farms by the shortest possible distance and also considered significantly associated variables was created. It included 86.1% of all case farms reported by 60 days into the epidemic. CONCLUSIONS AND CLINICAL RELEVANCE: Epidemic direction can be assessed on the basis of road density and other spatial variables as early as 6 days into an epidemic. Epidemic control areas may be more effectively identified if local and regional georeferenced data are considered.

Agriculture↗