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Predicting the spread of foot and mouth disease by airborne virus.

Foot and mouth disease (FMD) can spread by a variety of mechanisms which, under certain climatic and epidemiological conditions, includes the windborne spread of disease. Recent advances in knowledge of the aerobiological features of FMD are described. The strain of virus and species of infected animal are major determinants of airborne virus emission. Pigs emit most virus, cattle and sheep lesser but similar amounts to each other. Peak excretion of airborne virus by sheep occurs before the clinical phase of disease, whereas with cattle and pigs, it coincides with the development of early clinical disease. The probability of aerogenous infection differs greatly between livestock species. Cattle are the most susceptible, followed by sheep, whereas pigs are very resistant. Computer-based simulation models have been developed to analyse and predict the risk of airborne spread of FMD and have been used successfully during outbreaks to support decision-making. Further research is required to refine and extend the models for operational use.

Aerosols↗

Models of foot-and-mouth disease.

During the 2001 foot-and-mouth disease outbreak in the UK, three very different models were used in an attempt to predict the disease dynamics and inform control measures. This was one of the first times that models had been used during an epidemic to support the decision-making process. It is probable that models will play a pivotal role in any future livestock epidemics, and it is therefore important that decision makers, veterinarians and farmers understand the uses and limitations of models. This review describes the utility of models in general before focusing on the three foot-and-mouth disease models used in 2001. Finally, the future of modelling is discussed, analysing the advances needed if models are to be successfully applied during any subsequent epidemics.

Animals↗

Multiple proteases in foot-and-mouth disease virus replication.

Translation of foot-and-mouth disease virus RNA in a rabbit reticulocyte lysate for short time intervals resulted in the production of the peptides P20a , P16, and P88 (Lab, Lb, and P1) (R. R. Rueckert , Recommendations of the 3rd European Study Group on Molecular Biology of Picornavirus, Urbino , Italy, 1983). If further translation was prevented, the structural protein precursor P88 was not cleaved, even after prolonged incubation. This result indicates that the mechanism of the cleavage between P20a -P16 and P88 and of that between P88 and P52 (P2) differs from the mechanism of the secondary cleavages which produce the structural proteins. Furthermore, treatment of foot-and-mouth disease virus-infected cells with the protease inhibitor D-valyl phenylalanyl lysyl chloromethyl ketone prevented the in vivo cleavage between P20a -P16 and P88 but had no effect on any of the other cleavage events. These results suggest that the cleavage of the foot-and-mouth disease virus polyprotein utilizes two different host proteases.

Animals↗

[Isolation of foot-and mouth disease virus in swine with other diseases].

The authors took a survey of foot-and-mouth disease samples of myocardium and tonsil from swine which was died without clinicals signs of foot-and-mouth disease, with isolation of virus, type O, A and C. It was observed and accentuated relation between the incidence of hog cholera, pneumonia and atipic foot-and-mouth disease, especially from suckling pigs.

Animals↗

Novel viral disease control strategy: adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease.

We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-alpha/beta). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-alpha or IFN-beta (Ad5-pIFNalpha or Ad5-pIFNbeta). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10(9) PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10(9) PFU of Ad5-pIFNalpha were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.

Adenoviridae↗

Hand, foot, and mouth disease: a case report.

Hand, foot, and mouth disease is a viral infection related to coxsackieviruses A5, A6, A9, and A10, coxsackieviruses B2 and B5, and echovirus 11. It generally affects children, but this article presents a clinical case of a young woman with hand, foot, and mouth disease. Patients with this disease have oral and skin lesions that may be confused with other diseases. The differential diagnosis is very important because both dental and medical professionals may misdiagnose the disease and sometimes prescribe an inappropriate medication.

Adult↗

Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production.

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.

Animals↗

International approach to eradication and surveillance for foot-and-mouth disease in the Americas.

Foot-and-mouth disease (FMD) was introduced into the Americas in 1870. At that time the disease was described simultaneously in the North coast of the United States of North America, the Province of Buenos Aires in Argentina, the central region of Chile, Uruguay, and South Brazil. At the beginning of the twentieth century the disease spread to the rest of Brazil, Bolivia, Paraguay, and Perú. In 1950 the disease was introduced into Venezuela, and in the same year to Colombia, and from there to Ecuador. The United States of America eradicated an outbreak of FMD in 1929. Outbreaks of FMD were also eradicated from Mexico in 1947 and from Canada in 1952. The last outbreak that occurred in Mexico in 1954 was also eradicated. In 1951 the Americas Animal Health Authorities decided to establish a Pan-American Foot-and-Mouth Disease Center (PANAFTOSA), initially as a special program within the American States Organization (OAS). The center was later transferred to the Pan-American Health Organization (PAHO). In the early 1970s PANAFTOSA developed a proposal for a continental surveillance system for vesicular diseases, which was approved by Agriculture Ministers at an International Meeting for FMD and Zoonoses (RICAZ). Since then, PANAFTOSA dedicated all efforts to collaborate with each country in the implementation of the system and to receive, analyze, and distribute a weekly report of vesicular diseases. The model was elaborated using coordinate grid maps, one for the South American Continent, others for each country in the region. The reports from each country consist of the grid location for any suspicious outbreak of vesicular disease. Using the information gathered during visits to the countries, as well as weekly reports, and by studying the most frequent animal movements within the region, PANAFTOSA developed a proposal for FMD eradication. This plan was approved by the Government of South America and implemented in cooperation with PANAFTOSA. The hemispheric plan for FMD eradication (PHEFA), has been implemented and today Chile and Uruguay are FMD free without vaccination; Argentina, Paraguay, and the states of Rio Grande do Sul and Santa Catarina in Brazil are also recognized by the OIE to be FMD Free, with vaccination. The use of the continental surveillance system is the main strategy for achieving the eradication of FMD in South America. At this time PANAFTOSA is working to improve the system, and to add other diseases indicated by the governments of the Americas.

Animals↗

Recombinant human enterovirus 71 in hand, foot and mouth disease patients.

Hand, foot and mouth disease (HFMD) is a common illness of infants and young children <10 years of age. It is characterized by fever, ulcers in the oral cavity, and rashes with blisters that appear on the palm and sole. The most common causal agents of HFMD are coxsackievirus A16 (CV-A16) and human enterovirus 71 (HEV71), but other enteroviruses, including CV-A5 and CV-A10, can also cause it. When caused by CV-A16 infection, it is usually a mild disease, and patients normally recover without requiring any special medical attention.

Disease Outbreaks↗

Immune enhancing effects of recombinant bovine IL-18 on foot-and-mouth disease vaccination in mice model.

Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals and can cause a considerable socio-economic loss for affected countries. Interleukin-18 (IL-18) is a pleiotropic cytokine and plays important role in both the development of a functional immune system as well as the response of the organism to infection. In the present study, bovine IL-18 (BoIL-18), Foot-and-mouth disease virus VP1 and VP1/BoIL-18 fusion genes were cloned and expressed in pichia pastoris (P. pastoris) and subsequently immune effects were evaluated to study the immune enhancing effects of recombinant BoIL-18 (rBoIL-18) on FMD vaccination. The results showed that the genes encoding for BoIL-18, VP1 and VP1/BoIL-18 are successfully expressed in P. pastoris and the expressed recombinant VP1 (rVP1) proteins could induce both humoral and marginal cell-mediated immune responses in mice, while the co-inoculation with rBoIL-18 could markedly enhance both of immune responses, and the inoculation of the fusion product rVP1/BoIL-18 showed even more dramatic immune responses, suggesting rBoIL-18 has a potential to enhance the efficacy of vaccination against FMDV infection.

Adjuvants, Immunologic↗

Hand-foot-and-mouth disease.

Hand-foot-and-mouth disease is a highly contagious disease most often seen in children during the summer. It is caused most commonly by the virus coxsackie A16, but other enteroviruses have been implicated. It presents with low grade fever, and a vesicular eruption on the hands, feet, and mouth. More serious manifestations are seen less commonly. Diagnosis is most often clinical and treatment is symptomatic in nature. The infection in a male adult is presented.

Child, Preschool↗

Hand, foot, and mouth disease: a viral disease of importance to dentists.

Hand, foot, and mouth disease is a disease of viral origin that produces characteristic lesions in the mouth and on the hands and feet. Knowledge of the disease is important to dentists since the oral vesicular and ulcerative lesions are usually the first clinical signs of the disease, and the epidemiclike patterns of the disease make it likely that the dentist will contract the disease himself or possibly become a carrier of the virus. The lesions of hand, foot, and mouth disease usually regress in two to three weeks, and complications are rare. Treatment is basically palliative to reduce the pain and irritation. Differential diagnosis of the disease must include consideration of herpes simplex, herpangina, recurrent aphthae, erythema multiforme, and animal foot and mouth disease. A case involving a dentist and his family is reported.

Adult↗

Defined medium for growth of foot-and-mouth disease virus.

Pledger, Richard A. (Plum Island Animal Disease Laboratory, Greenport, N. Y.) and Jerome Polatnick. Defined medium for growth of foot-and-mouth disease virus. J. Bacteriol. 83:579-583. 1962.-Foot-and-mouth disease virus, grown in primary bovine calf-kidney cell layers with a defined medium containing glucose as the only organic substrate, produced virus titers equivalent to those obtained with complex media containing serum and lactalbumin hydrolyzate. Mannose was the only other substrate examined that could replace glucose. Krebscycle intermediates did not or only partially supported viral replication. Phosphate was also found essential for reproduction of foot-and-mouth disease virus. The rate of heat inactivation of foot-and-mouth disease virus in defined medium was more than twice that in complex medium. This, however, did not interfere with the usefulness of the defined medium for short-term biochemical investigations.

Animals↗

Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus.

We provide evidence that the quasispecies nature (extreme genetic heterogeneity) of foot-and-mouth disease virus is relevant to the virus evading an immune response. A monoclonal antibody neutralizing the viral infectivity (clone SD6) recognizes an epitope located around a highly conserved sequence (amino acid sequence Arg-Gly-Asp-Leu-Ala at positions 141-145) in the capsid protein VP1 of foot-and-mouth disease virus of serotype C1. The amino acid substitutions Ala-138----Thr and Leu-147----Ile (or ----Val) reduced 100-fold the binding titer of monoclonal antibody SD6 to virions or to VP1. The effect of those substitutions was quantitatively reproduced with synthetic peptides representing the relevant sequences. This provides evidence that the two chemically conservative amino acids replacements--and not other substitutions present in the virus quasispecies--are responsible for the modified interaction with neutralizing monoclonal antibody SD6. The three substitutions were fixed in the viral capsid during one occurrence of foot-and-mouth disease and, furthermore, they are of a type found frequently among independent foot-and-mouth disease virus isolates. The results implicate the extreme heterogeneity of foot-and-mouth disease virus as an important element of viral pathogenesis.

Amino Acid Sequence↗

Prospects for improved foot and mouth disease vaccines.

Improved foot and mouth disease (FMD) vaccines which have increased efficiency and stability are highly desirable. Work which aims to increase the stability of FMD virus particles for vaccine use is described and the use of these particles and of antigenic fragments of the virus for controlled release vaccine products is considered.

Animals↗

Development and comparison of genome detection assays for the diagnosis of foot-and-mouth disease suspected clinical samples.

Detection of foot-and-mouth disease virus (FMDV) from clinical specimens by conventional sandwich enzyme-linked immunosorbent assay (ELISA) and virus isolation in cell culture is often compromised owing to limited sensitivity and inactivation during transit, respectively. A RT-PCR (oligoprobing) ELISA in both solid and aqueous phase hybridization formats targeting an across serotype conserved site at 3C-3D region was developed and its effectiveness was compared with that of the known targets at the IRES region. A non-isotopic RNA dot hybridization assay with colorimetric detection targeting both the IRES and the 3D region were also validated, which is capable of handling high throughput samples with ease. RT-PCR (oligoprobing) ELISA and dot hybridization assay showed 1000- and 10-fold greater sensitivity than the sandwich ELISA, respectively. Robustness of these diagnostic methods was explored by examining on sandwich ELISA-negative clinical samples. Both the assays developed in the present study were able to detect viral genomes in samples undetectable by conventional ELISA, thereby demonstrating 'proof of sensitivity'. Although the potential of these assays for providing definitive diagnosis in carrier hosts and in species where clinical disease is inapparent remains to be examined, nevertheless these assays can be adapted for comprehensive surveillance of foot-and-mouth disease in India.

3C Viral Proteases↗

Selection and characterization of RNA aptamers to the RNA-dependent RNA polymerase from foot-and-mouth disease virus.

Foot-and-mouth disease virus causes a highly contagious disease of agricultural livestock and is of enormous economic importance. Replication of the RNA genome of the virus, via negative strand intermediates, involves an RNA-dependent RNA polymerase (3Dpol). RNA aptamers specific to this enzyme have been selected and characterized. Some of these molecules inhibit enzymatic activity in vitro, with IC50 values of <20 nM and Ki values of 18-75 nM. Two of these show similarity, both with each other and with regions of the viral genome. Furthermore, truncated versions of one of the aptamers have been used to define the parts of the molecule responsible for its inhibitory activity.

Aptamers, Nucleotide↗

Foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) is an aphthovirus of the family Picornaviridae and the etiological agent of the economically most important animal disease. As a typical picornavirus, FMD virions are nonenveloped particles of icosahedral symmetry and its genome is a single stranded RNA of about 8500 nucleotides and of positive polarity. FMDV RNA is infectious and it replicates via a complementary, minus strand RNA. FMDV RNA replication is error-prone so that viral populations consist of mutant spectra (quasispecies) rather than a defined genomic sequence. Therefore FMDV in nature is genetically and antigenically diverse. This poses important challenges for the diagnosis, prevention and control of FMD. A deeper understanding of FMDV population complexity and evolution has suggested requirements for a new generation of anti-FMD vaccines. This is relevant to the current debate on the adequacy of non-vaccination versus vaccination policies for the control of FMD.

Animals↗