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PubMed1978

Pre-lytic release of foot-and-mouth disease virus in cytoplasmic blebs.

The pre-lytic release mechanism of foot-and-mouth disease virus was investigated by immunofluorescence, acridine orange staining, and electron microscopy in infected bovine and porcine kidney coverslip cultures. Cells with cytoplasmic fluorescence and which were positive for single stranded RNA with acridine orange staining were observed at 2 h after infection. Scanning electron microscopy showed cytoplasmic blebs in all cultures examined 2 h after infection. Rounded cells with virus inclusions began to appear 3 h after infection. Rounded cells and cytoplasmic blebs were shown to have single stranded RNA by acridine orange staining. Immunofluorescence and transmission electron microscopy with immunoferritin tagging demonstrated foot-and-mouth disease virus in cytoplasmic blebs. This study presents evidence for a pre-lytic release of foot-and-mouth disease virus through virus-containing cytoplasmic blebs emerging from infected cells.

Aphthovirus↗
PubMed2004

Very fast (and safe) inactivation of foot-and-mouth disease virus and enteroviruses by a combination of binary ethyleneimine and formaldehyde.

For FMD vaccine production, inactivation of the FMD virus is the most critical step. Formerly, from 1940 onwards, the virus was inactivated with formaldehyde. This inactivation was relatively slow, about 0.2 - 0.3 log 10 per hour. Because formaldehyde not only reacts with the virus produced but with many other components in the medium, such as proteins and amino acids, its concentration can become rate-limiting and inactivation plots may show tailing-off, resulting in residual infectivity. Many of the bad stories of post-vaccination outbreaks date back to the use of formaldehyde-inactivated vaccines (e.g. the outbreaks in France in 1981 and in Eastern Germany causing the Danish outbreak in 1982). Much faster and safer inactivation was obtained with aziridines and in the 1980s binary ethyleneimine (BEI) was introduced in practically all vaccine production laboratories. If inactivation plots are made of every production batch, as is now required by the European Pharmacopoeia, and these plots show proper inactivation rates, vaccines can considered to be completely safe. Under optimal conditions, inactivation rates are in the range of 0.5 - 1.0 log 10 per hour. In general, the inactivation takes 40-48 hours,which will guarantee complete inactivation of all virus particles in a batch. Since formaldehyde (FA), the 'classical' inactivating agent, inactivates at a rate of 0.3 logs per hour only, a significant contribution of FA to the inactivation of BEI can hardly be expected. However, here it is shown that FA added during the BEI-inactivation process strongly augments inactivation rates with a hundred to thousand-times (to 2.5-3.5 logs per hour). This will enable inactivation during a working day or just overnight with even higher safety levels of the vaccines. Also, it is known that formaldehyde cross-links viral proteins which will stabilise the antigen. The short inactivation times will limit proteolytic destruction of 146 S antigen and increase antigen yields. It is expected that by the cross-linking activity of FA the stability of the antigen (and of vaccines) and the endurance of the immune response will be favourably influenced.

Animals↗
PubMedDate not supplied

Foot-and-mouth disease virus: a long known virus, but a current threat.

Foot-and-mouth disease virus (FMDV) was the first animal virus identified. Since then, FMDV has become a model system in animal virology and a considerable amount of information on its structure, biology and vaccinology has been obtained. However, the disease that this virus produces (FMD) still constitutes one of the main animal health concerns. In this review, we have attempted to summarise the state of the knowledge in different basic and applied areas of FMDV research, with emphasis on those aspects relevant to the control of the disease.

Animals↗
PubMed2001

A solid-phase competition ELISA for measuring antibody to foot-and-mouth disease virus.

A solid-phase competition ELISA has been developed to measure antibodies to foot-and-mouth disease (FMD) virus and has been validated using an extensive range of sera from cattle. The assay uses polyclonal antisera and inactivated purified 146S antigens of FMD virus and was compared with the liquid-phase blocking ELISA and the virus neutralisation test on a range of serum sets. When examining test sera at a 1:5 dilution with a cut-off point of 30% inhibition of reaction, the solid-phase competition ELISA was as sensitive as the liquid-phase blocking ELISA for sera from infected or vaccinated animals. The limit of detection of the solid-phase ELISA was similar to that of the liquid-phase assay and both tests had lower limit of detection (i.e. were able to detect lower amounts of antibody) than the virus neutralisation test. The specificity of the solid-phase ELISA was considerably higher than that of the liquid-phase blocking ELISA and almost equivalent to that of the virus neutralisation test. The assay thus retains the sensitivity of the liquid-phase blocking ELISA whilst being easier to use, more robust and specific, and therefore offers an improvement for FMD virus antibody detection.

Animals↗
PubMed1992

Genetic relationships between southern African SAT-2 isolates of foot-and-mouth-disease virus.

Sequencing of part of the 1D gene of foot-and-mouth disease virus was used to determine the relationships between SAT-2 viruses isolated from outbreaks which occurred in cattle in Zimbabwe and Namibia and in impala in South Africa between 1979 and 1989. The results demonstrated that the outbreaks in different countries were unrelated. Surprisingly close relationships were shown between all SAT-2 viruses isolated from cattle in Zimbabwe since 1983 but the two major epizootics which occurred in 1989 were caused by viruses which were clearly different. Conversely, two apparently unrelated outbreaks in impala in South Africa were caused by viruses which could not be distinguished.

Africa, Southern↗
PubMed1986

Nosocomial outbreak of hand-foot-and-mouth disease among operating suite personnel.

In the fall of 1983 an outbreak of hand-foot-and-mouth disease occurred in a large urban hospital. The outbreak began among surgical nurses confined to one area of the operating suite and appeared to spread by direct contact to personnel working in the other areas. No cases were diagnosed among hospital patients. There was no evidence to support an ongoing community epidemic as only three of 98 physicians surveyed had seen hand-foot-and-mouth disease in their practices, and none occurred among family members of 94 unaffected employees. The outbreak resulted in 82 lost workdays at an estimated cost to the hospital of $5,676. Existing infection control guidelines do not address the issue of transmission of hand-foot-and-mouth disease from hospital personnel to patients; our experience suggests that the risk of transmission, at least in the operating suite environment, may be greater for other personnel than for patients.

Adult↗
PubMed2005

Phylogeny, genome evolution, and antigenic variability among endemic foot-and-mouth disease virus type A isolates from India.

The capsid-coding (P1) and 3A regions of foot-and-mouth disease virus (FMDV) type A field isolates including two vaccine strains collected during 1977-2000 were analyzed. In the phylogenies, the isolates were distributed into two previously identified genotypes VI and VII, with multiple sub-genotypes that are temporally clustered. Comparison of the antigenic relationships of field isolates with the two vaccine strains (IND 17/77 and IND 490/97) and the reference strains of the genotypes VI (IND 233/99) and VII (IND 40/00) indicated two broad antigenic groups that correlate with the phylogenetic groupings (genotypes VI and VII), and are highly divergent from the vaccine strains. The maximum likelihood method of selection analysis identified a number of amino acid sites within the P1 region to be under weak positive selection. Some of the positively selected sites were mapped at/near the antigenically critical amino acid sites of the P1 region, indicating host immune pressure as one of the important driving force behind the observed genetic and antigenic diversity in FMDV. A small number of selected sites are located in the heparan sulphate-binding pocket of the virus, suggesting a fitness advantage for cell entry of the virus. No positive selection was detected in the 3A dataset.

Amino Acid Sequence↗
PubMed1982

[Hand, foot and mouth disease. Report of 10 cases].

Ten children with hand-foot-and-mouth disease are described and their clinical manifestations reported in detail. It is a benign, minor viral disease of childhood, but in our country its real incidence is unknown. Diagnosis in the clinical practice is based on the recognition of typical and atypical localizations of the vesicular eruption, as well as on the identification of extracutaneous and extrabuccal manifestations. The differential diagnosis includes herpangina, aphthous stomatitis, dyshidrosis and erythema multiforme.

Child↗
PubMed2002

Unapparent foot and mouth disease infection (sub-clinical infections and carriers): implications for control.

Unlike animals which are carriers of foot and mouth disease (FMD), sub-clinically infected animals may be highly contagious. The implications of sub-clinical infections for the control of FMD are serious because such animals are likely to disseminate the disease when in contact with susceptible livestock. Recent dissemination of FMD virus (FMDV) in Europe shows that sub-clinically infected animals render trade in animals or animal products a potential risk for importing countries. This clearly demonstrates that the paradigm 'free of FMD without vaccination' is not synonymous with 'risk-free'. The risk of introduction of subclinical FMD into FMD-free countries may increase significantly, with the occurrence of large susceptible animal populations, changed agricultural practices, expansion of trade in live animals and animal movements, increased trade in animal products and greater mobility of people. Such changes in circumstances require that national and international authorities remain continuously vigilant to determine any altered risk for importation of FMD. A few historical reports and some recent observations in southern Africa indicate the possibility of dissemination of FMD by bovine carriers into herds of susceptible cattle. These reports have greatly influenced FMD trade policies and thus, FMD control and eradication strategies. However, other field evidence does not support this claim and several controlled experiments were unable to show that carriers are able to initiate disease. When millions of cattle were systematically vaccinated with good quality vaccines, FMD disappeared in spite of a large sentinel population in the form of calves and unvaccinated sheep and pigs. A low number of carriers most likely persisted, but they did not hamper the eradication of the disease. Vaccination policies and trade regulation must be based on risk assessments taking these factors into consideration.

Animals↗
PubMed1990

Freeze-drying foot-and-mouth disease virus antigens. II. For use in the ELISA.

Live and inactivated preparations of foot-and-mouth disease virus strains 01 BFS 1860 and A22 IRQ 24/64 were freeze-dried in the presence or absence of additive solutions and assessed for their reactivity by ELISA at intervals over a six month storage period at various temperatures and also after reconstitution and subsequent storage with or without glycerination. The type specificity of all antigen preparations was maintained throughout the study period and the potency of antigens, judged by titration in ELISA, remained constant during the freeze-drying procedure and throughout subsequent storage at -20 degrees C and 4 degrees C with or without additives having been made to virus suspensions prior to freeze-drying. This was also the case with antigens reconstituted and stored at either -20 degrees C with glycerol or at 4 degrees C without glycerol. Certain additive solutions were necessary, however, to preserve the activity of antigens stored at the elevated temperature of 37 degrees C. The reactivity of all freeze-dried antigens was not unduly affected in the liquid-phase blocking ELISA using bovine convalescent antisera of each of the seven serotypes of foot-and-mouth disease virus and known negative, non-immune bovine sera. The results suggest that shipment and long-term storage of freeze-dried foot-and-mouth disease virus antigens is possible for use in the ELISA in the absence of refrigeration. This has attractive advantages for reducing both shipment and storage costs of antigens and for the development of ELISA kits for the diagnosis of foot-and-mouth disease virus.

Animals↗
PubMed1995

Serological comparison of type Asia 1 foot and mouth disease virus isolates from Thailand.

Antigenic variation of type Asia 1 foot and mouth disease (FMD) virus in Thailand was examined using a total of 50 field viruses isolated between 1986 and 1992. A two-dimensional serum neutralisation test was used to calculate r values for comparison of these isolates with a reference vaccine strain, Asia 1 Bangkok 1960 (BKK/60). Viruses were also compared to two field isolates, Asia 1 36-2/88 and Asia 1 45/88, and some were compared to another vaccine strain, Asia 1 Nakhon Pathom 1984 (NPT/84). In 80% of cases, field isolates were deemed to be significantly different from the vaccine virus Asia 1 BKK/60, and the distribution of r values indicated that there would be some advantage in selecting a new vaccine strain more closely related to contemporary field strains.

Animals↗
PubMed2003

Foot and mouth disease and cryptosporidiosis: possible interaction between two emerging infectious diseases.

During 2001, a large outbreak of foot and mouth disease occurred in the United Kingdom, during which approximately 2,030 confirmed cases of the disease were reported, >6 million animals were slaughtered, and strict restrictions on access to the countryside were imposed. We report a dramatic decline in the reported incidence of human cryptosporidiosis in northwest England during weeks 13-38 in 2001, compared with the previous 11 years. This decline coincided with the period of foot and mouth restrictions. No similar reduction occurred in the other 26 weeks of the year. We also noted a substantial decline in the proportion of human infections caused by the bovine strain (genotype 2) of Cryptosporidium parvum during weeks 13-38 in that year but not during the other weeks.

Animals↗
PubMedDate not supplied

[Effect of hormones on the susceptibility of the swine cell line IB-RS-2 to foot-and-mouth disease virus].

The actions of hydrocortisone and insulin on the multiplication of foot-and-mouth disease virus were studied. The data obtained showed that the infectivity and the synthesis of the virus nucleic acid as evaluated through the plaque assay method and the kinetics of Uridine-3H incorporation were increased or decreased by hydrocortisone (2 x 10(-6) M). The induction of both effects seems to be related to the carbohydrate metabolism: when the maintenance medium contained glucose or glucose plus calf serum there was an inhibition on virus multiplication and no effect was observed in the absence of both serum and glucose. This was found both when the hormone was added to the cell culture 24 hours before infection as well as when it was added immediately or thirty minutes after virus adsorption. The possibility that these effects could be related to the synthesis of viral RNA-polimerase is discussed. Insulin (50 ng/ml) did not induce any effect on foot-and-mouth disease virus multiplication. However this hormone antagonized the action of hydrocortisone on the infectivity and on the synthesis of foot-and-mouth disease virus nucleic acid.

Animals↗
PubMed2002

History of the control of foot and mouth disease.

From the many existing documents on the history of foot and mouth disease, it is possible to describe the practical measures adopted for disease surveillance and control from ancient times until the 20th century. Surveillance was based on diagnosis or post-mortem examination, and also on knowledge of the conditions under which infection occurred: aetiology, pathogenesis, mode of infection, susceptible species, virulent material, etc. The historical facts are assembled and compared, with comments on each of these points. Control was based upon the application of isolation, then slaughter or aphtisation, then vaccination. A study of these various procedures makes it possible to compare their efficacy.

Animals↗
PubMed2005

A review of foot-and-mouth disease with special consideration for the clinical and epidemiological factors relevant to predictive modelling of the disease.

Modelling the epidemiology of foot-and-mouth disease (FMD) has been undertaken since the early 1970s. We review here clinical factors and modelling procedures that have been used in the past, differentiating between those that have proved to be more relevant in controlling FMD epidemics, and those that have showed less significance. During the 2001 UK FMD epidemic, many previously developed FMD models were available for consideration and use. Accurate epidemiological models can become useful tools for determining relevant control policies for different scenarios and, conversely, inaccurate models may become an abuse for disease control. Inaccuracy presents two opposing difficulties. Firstly, too much control (in terms of animal slaughter for 2001) would negatively impact the farming community for many subsequent years, whilst too little control would permit an epidemic to persist. Accuracy however, presents the optimal permutation of control measures that could be implemented for a given set of conditions, and is a prerequisite to boosting public confidence in the use of epidemiological models for future epidemics.

Animals↗