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The foot-and-mouth disease outbreak in The Netherlands in 2001 most likely started on a mixed veal-calf/dairy-goat farm. The outbreak among the 74 calves on this farm appeared to be limited to four animals, and no clinical signs of FMD were reported. Also on a second veal-calf farm minor clinical signs and limited virus transmission were observed. Since FMD is known to be a very contagious disease, and can cause severe lesions, these observations were disputed. Therefore, we carried out two experiments to determine whether the Dutch FMD virus isolate from 2001 does spread among individually housed calves with limited contacts, either indirect (experiment 1) or direct (experiment 2). In experiment 1, four pairs of calves were housed in an individual box at 1m distance from each other. In experiment 2, two groups of three calves were housed in individual boxes, directly bordering each other. We infected one animal per pair in experiment 1, and the calf in the middle in experiment 2. We recorded clinical signs, virus shedding in saliva and the development of antibodies. In addition, we determined whether the virus was transmitted from the inoculated calves to the neighbour(s). All inoculated calves showed mild signs of FMD--fever, and some vesicles on hooves and/or in the mouth--but only one calf showed signs that were visible without physical examination. All inoculated calves shed virus in the saliva and developed neutralising antibodies. None of the contact animals seroconverted, indicating that virus transmission did not occur. These experiments showed that no virus transmission among individual housed calves can occur. This finding supports the hypothesis of the route of virus introduction to The Netherlands in 2001 and show that the observations on the two veal-calf farms were not impossible.
Quantified transmission parameters of Foot-and-Mouth Disease Virus (FMDV) are needed for epidemic models used for control and surveillance. In this study, we quantified the within- and between-pen transmission of FMDV in groups of pigs by estimating the daily transmission rate beta, i.e. the number of secondary infections caused by one infectious pig during one day, using an SIR (susceptible-infectious-removed) model. Within-pen transmission was studied in four groups of ten pigs in which 5 infected and 5 susceptible pigs had direct contact; between-pen transmission was studied in one group of ten pigs in which 5 infected and 5 susceptible pigs had indirect contact. Daily results of virus isolation of oropharyngeal fluid were used to quantify the transmission rate beta, using Generalised Linear Modelling (GLM) and a maximum likelihood method. In addition, we estimated the expected time to infection of the first pig within a pen T(w) and in the indirect-contact pen T(b). The between-pen transmission rate beta(b) was estimated to be 0.59 (0.083-4.18) per day, which was significantly lower than the within-pen transmission rate beta(w) of 6.14 (3.75-10.06). T(w) was 1.6 h, and T(b) was 16 h. Our results show that the transmission rate is influenced by contact structure between pigs.
Foot-and-mouth disease virus (FMDV) is the etiologic agent of foot-and-mouth disease (FMD), which is a disease of cattle, swine, and other cloven-footed animals. FMD is characterized by the formation of vesicles on the tongue, nose, muzzle, and coronary bands of infected animals. The virus has several unique characteristics that enable it to cause one of the most economically devastating diseases in today's world. The ease with which it may be transmitted by contact and aerosol, combined with its enhanced ability to initiate infections, virtually ensures that most, if not all, animals in a herd will contract FMD. The long-term survival of FMDV in infected animals' tissues and organs, especially when refrigerated, offers an opportunity for its national and international transmission through the food chain. Multiple serotypes and numerous subtypes reduce the effectiveness and reliability of vaccines. The possible development of carriers in vaccinated animals and those that have recovered from FMD provides additional potential sources of new outbreaks. These features create a disease that can have a major economic impact on farmers and entire nations.
The present investigation was conducted to study the foot and mouth disease virus (FMDV)-specific humoral immune response (HIR) in pigs, following vaccination with oil adjuvanted foot and mouth disease (FMD) vaccine, upto 90 days post vaccination (dpv). For this, 40 Large White Yorkshire (LWY) pigs (20; one-year old female (gilts) and 20; three-month old piglets) were vaccinated @ 2 ml/animal, subcutaneously. Sera samples were collected at fortnight interval from all the animals. The log10 SN50 antibody titres against all the serotypes (Type O, A and Asia-1) were detected in both gilts and piglets from day 7 to 90 dpv indicating the persistence of HIR up to the last day of sampling. The maximum antibody titres were observed on 28 dpv, thereafter, titres started declining, but were present till 90 dpv against all the three FMDV serotypes. HIR was more pronounced in piglets in comparison to gilts, as group mean SN antibody titres against all the three FMDV serotypes were found to be more maintained and significantly higher in piglets.
Genome segments of the foot-and-mouth disease virus isolates O1Lombardy and O3 Venezuela that encode, among other products, capsid protein VP1 were amplified using PCR, and the products were cloned and sequenced. The alignment of up to 11 O3-specific sequences revealed six silent nucleotide changes a well as six changes that cause amino acid substitutions in capsid protein VP1 at positions 45, 83, 141, 145, 170 and 178. The heterogeneity of three O1-specific sequences consisted of seven silent exchanges and amino acid changes at positions 85 and 134 on VP1. Amplification, subclonning and sequencing of cloned O3-specific cDNA was performed to examine the nature of the sequence heterogeneity. As no difference was found among five subcloned sequences, we conclude that the Taq polymerase copied the DNA correctly. The sequence heterogeneity observed with both virus isolates is, therefore, consistent with the quasispecies structure of foot-and-mouth disease virus. Furthermore, amino acid changes at a number of sites have been found to be involved in the formation or modulation of neutralizing epitopes. The novel aspect of this study is the ability to estimate, by cloning of PCR products, the number of virus isotypes, possibly varying in antigenicity, that are able to co-propagate. Seven isotypes of O3 Venezuela were identified. Some are of particular interest because they exhibit a change at VP1 codon 145 that causes the replacement of arginine, possibly essential for virus attachment to cells, by isoleucine.
Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.
BACKGROUND: Australian data are currently lacking regarding management guidance, resource usage and outcomes of patients with diabetes requiring hospitalization for management of acute foot complications. AIMS: The aims of the present study were to review hospital admissions for diabetes-related foot complications and current assessment and management of these complications, and to formulate recommendations for future models of care. METHODS: A retrospective review of patient records from 1 July 1999 to 30 June 2000 was carried out. Recorded assessment, investigations, management, amputation rates, referral rates and length of hospital stay were reviewed. RESULTS: There were 69 admission episodes in 12 months (total patients n = 50). The mean age was 64 years, with 44 male patients (64%) and 25 female patients (36%). The mean diabetes duration was 11 years (range <1-47 years). The majority of patients had type 2 diabetes. Assessment for known risk factors for ulceration and amputation was variable with history of previous ulcer/amputation recorded for 24 (35%) admissions, results of neurological assessment recorded for 11 (16%) and assessment of pedal pulses documented for 51 (74%). Glycated haemoglobin was performed during 35 (51%) admissions. Patients were admitted under one of 11 different inpatient units and the average interdepartmental referral rate was one referral per patient per admission. The average length of stay was 17 days, with total bed days occupied 1163 days. Minor amputation was performed in 25 (36%) cases and major amputation in 8 (11%). CONCLUSIONS: Clinical assessment, investigation and management of this population are highly variable. This has a significant impact on the final clinical outcome, and changes to current processes are required to overcome the substantial burden of diabetic foot disease.
A particular genetic lineage of foot-and-mouth disease virus (FMDV) serotype O, which we have named the PanAsia strain, was responsible for an explosive pandemic in Asia and extended to parts of Africa and Europe from 1998 to 2001. In 2000 and 2001, this virus strain caused outbreaks in the Republic of Korea, Japan, Russia, Mongolia, South Africa, the United Kingdom, Republic of Ireland, France, and the Netherlands, countries which last experienced FMD outbreaks decades before (ranging from 1934 for Korea to 1984 for the Netherlands). Although the virus has been controlled in all of these normally FMD-free or sporadically infected countries, it appears to be established throughout much of southern Asia, with geographically separated lineages evolving independently. A pandemic such as this is a rare phenomenon but demonstrates the ability of newly emerging FMDV strains to spread rapidly throughout a wide region and invade countries previously free from the disease.
The virus of foot and mouth disease causes severe epizootics in animals and infrequently evokes painful, but transient, clinical signs in man. Adults in certain occupational groups and young children are particularly exposed to risk. Infected persons may disseminate virus for up to about 14 days. The virus can be transmitted from animals to animals, from animals to man, from man to animals and, probably, from man to man. Evidence for transfer of the disease between human and animal populations is reviewed in detail and modern methods of diagnosis are described. Predisposing factors play an important role in the development of overt foot and mouth disease in man. Subclinical infection occurs. The possibility of aerial transfer of the virus between man and domestic livestock constitutes a hazard, especially to the latter. Attention is directed to the need for sophisticated diagnostic techniques, to requirements for adequate precautions in the handling and disposal of affected animals, and to hygienic measures for disease control.
Foot-and-mouth disease (FMD) virus is poorly immunogenic. There is need to improve the quality of the vaccine by incorporating enhanced quantity of purified virus antigen to prevent sporadic breakdown of immunity in regularly vaccinated organized herds. A technique has been standardized for virus purification and concentration by polyethylene glycol (PEG) treatment for large scale production of concentrated FMD vaccine. The vaccine prepared with tenfold concentrated antigen was given field trial in an organised farm with a reduced dose as compared to the conventional vaccine. High level serum neutralizing antibody in cattle was observed throughout the entire period of study. The concentrated vaccine controlled the spread of the disease when used in face of outbreak in villages adjacent to the organized farm.
Foot-and-mouth disease virus (FMDV) type O outbreaks have been reported frequently in vaccinated cattle in India. Twenty-five field isolates, recovered from outbreaks in vaccinated and unvaccinated cattle between 1987 and 1991, were analyzed in relation to the vaccine strain (R2/75) by complement fixation, serum neutralization and partial nucleotide sequencing of the VP1 gene. These sequences were compared with the viral sequences in GenEMBL database. Although the Indian type O viruses were close to the European type O1 viruses, they constituted a separate group of type O FMDVs. One of the field viruses, isolated from an outbreak in vaccinated cattle and designated as BAK/90, showed significant serological and nucleotide sequence variations from the vaccine strain. Phylogenetic analysis showed that the BAK/90 and R2/75 viruses belong to separate subgroups. The other isolates were found to be serologically related to both the BAK/90 and the vaccine strain. The BAK/90 strain gave broader antigenic coverage, showed better immunogenicity, and yielded larger amounts of 146S particles in suspension cultures as compared with R2/75. Taken together, these results favour inclusion of the BAK/90 strain in the vaccine to provide adequate protection against the field variants of type O FMDV currently circulating in India.
The dynamics of foot-and-mouth disease epidemics in France was examined through simulations based on an extended state-transition model. Contagion modelling depended on specific parameters: the so-called dissemination rates. Estimation of these parameters relied on a specific discrete-event simulation model. We were able to address the problem of the hidden spread of the epidemic, before the first outbreak is diagnosed. Furthermore, we took into account the silent development of the disease in affected herds before the diagnosis. The effect of control measures such as the active search for secondary outbreaks could thus be studied. We used the model to compare the development of FMD epidemics in two very different French regions and for different control strategies implemented by the animal-health authorities. These strategies gave similar results in a low herd density area, whereas in a high herd density area, the slaughter of contact herds greatly improved the stamping-out strategy. Finally, key parameters of the model were detected through a sensitivity analysis.
Foot-and-mouth disease is a serious world-wide economic disease of livestock and diverse animal species. The closing of borders to infected countries is a frequent aftermath of disease outbreaks. Historically, animals and animal products have been implicated as vehicles for transmission of the disease. Control programs encompass stringent importation policies, vaccination, quarantine, and slaughter. Joint efforts have been instituted successfully in previous control campaigns and would be the logical approach to large-scale eradication schemas.
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.
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.
Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain.
The foot-and-mouth disease virus (FMDV) genome contains a 5' untranslated region (S fragment) capable of forming a stem-loop structure of over 350 bases, which is separated from the remainder of the genome by a homopolymeric cytidylic acid tract (poly(C)) of variable length. The sequence of the S fragment of serotype A12 appears more similar to those of type O1 or type C3 than to subtype A10. The relatively large difference between the S fragment sequences of two type A viruses suggests that the sequences per se of this region of the genome are not critical for the maintenance of function, and suggests the possibility of a relatively recent recombination event within the poly(C) region of the A12 genome.