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Hand, foot, and mouth disease.

Hand, foot, and mouth disease, also known as vesicular stomatitis with exanthem, is a vesicular disorder affecting both skin and oral mucosa. The disease is usually caused by Coxsackie virus A-16 and affects mainly children. The oral lesions may require differential diagnosis from other conditions, such as herpetic gingivostomatitis, aphthous stomatitis, and herpangina. Hand, foot, and mouth disease should not be confused with foot-and-mouth disease of cattle, which is rare in human beings and is not caused by Coxsackie virus.

Child, Preschool↗

[Serotype determination of enteroviruses that cause hand-foot-mouth disease; identification of enterovirus 71 and coxsackievirus A16 from clinical specimens by using specific probe].

Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are known to be major causative agents of hand-foot-and-mouth disease prevalent in summer in Japan. Discrimination and identification of these viruses were often hampered by a nonneutralizable or nontypable virus. Therefore, a Southern blot hybridization that utilizes mixed probes specific to serotype was developed. Firstly, an approximately 650 bases spanning 5'-noncoding region to one third of VP2 including entire VP4 was amplified with a set of primers containing enterovirus common sequences and a genomic RNA as template. Secondary, the nucleotide sequences were determined using seven CA16 and eighteen EV71 strains including the standard strains, and the deduced amino acid sequences of VP4 were searched to find residues which are conserved in the same serotypes but diverged among different serotypes. Candidate positions for the mixed probes were defined at the carboxyl terminus of VP4. Thirdly, Southern blot analyses were carried out using thirty-nine enterovirus standard strains, seven CA16 isolates and sixty-six EV71 isolates previously identified by the neutralization test. The results revealed that each mixed probe exclusively bound to the homologous DNAs but not to the heterologous ones. In an attempt to determine serotypes without virus isolation, clinical specimens from hand-foot-and-mouth disease were examined. Of 78 throat swabs and 15 vesicular fluids, 71 (91.0%) and 13 (86.7%) specimens were clearly identified, indicating that the method described here offer advantages over the traditional neutralization assay: It is rapid, specific and less labor-consuming.

Amino Acid Sequence↗

Foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved.

Animals↗

A practitioner's primer on foot-and-mouth disease.

Foot-and-mouth disease (FMD) is caused by an RNA virus of the genus Aphthovirus; 7 immunologically distinct serotypes of the virus have been identified. Susceptible species are mainly domestic and wild even-toed ungulates, such as cattle, sheep, goats, pigs, bison, and deer. All body fluids of infected animals can contain the virus and are considered infective. The primary mode of transmission is animal-to-animal transmission through inhalation or ingestion of aerosols containing the virus. The virus can also be spread mechanically by contaminated organic debris and fomites and can survive for 48 hours on human oral and nasal mucosa and be spread to uninfected animals in this manner. There is a rapid progression of clinical signs after an animal becomes infected, and the virus spreads rapidly throughout a herd. Clinical signs include excessive salivation; fever; vesicles and erosions of the oral and nasal mucosa, coronary band, interdigital area, and teats; lameness; sloughing of claws; reluctance to move; anorexia; mastitis; decreased milk production; and abortion or weak newborns. In mature animals, FMD has high morbidity and low mortality rates. Infected animals can become inapparent carriers of the virus.

Air Microbiology↗

Diagnosis and screening of foot-and-mouth disease.

Foot-and-mouth disease (FMD) diagnostic methods are reviewed. As the presence of clinical signs alone is inconclusive, laboratory diagnosis should always be carried out. The presence of FMD virus can be demonstrated by cell culture isolation, complement fixation test, ELISA or the more recent polymerase chain reaction (PCR) method. Serological diagnosis is also a valuable tool. The virus neutralization test has been replaced by ELISA and the antibody response to some viral non-structural proteins allows to discriminate between vaccinated and infected animals on a herd basis. More rapid and accurate tests as well as an earlier detection system in preclinical state are still needed.

Agglutination Tests↗

Past and present vaccine development strategies for the control of foot-and-mouth disease.

Foot-and-mouth disease (FMD) virus (FMDV) was the first animal virus to be identified. Since then, it has become a model system in animal virology and more information has been obtained about FMDV. The disease causes heavy economic crises in enzootic countries both due to loss of animal health and productivity. The only way of its control in an enzootic area is strict vaccination and restricted animal movement. The first experimental vaccine against FMD was made in 1925 using formaldehyde inactivation of cattle tongue infected with the virus and this approach remained the basic one until late 1940s. Antigenic plurality and continuous co-circulation of different serotypes in a given geographical region and persistence of virus in infected or vaccinated animals make the disease very difficult to control. The latter is solely based upon the application of isolation, slaughter or aphtisation, and vaccination. With the advent of recombinant DNA technology, recombinant protein and/or DNA-based vaccines are being tested in various heterologous systems for development of FMD vaccines. The subunit vaccines, synthetic peptide vaccines, DNA vaccines, cytokine-enhanced DNA vaccines, recombinant empty capsid vaccines, chimeric viral vaccines, genetically engineered attenuated vaccines, recombinant viral vector vaccines, self-replicating genetic vaccines and transgenic plants with expressed FMDV proteins represent the present vaccine development strategies for control of FMD.

Animals↗

Passive immunization of guinea pigs with llama single-domain antibody fragments against foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious disease that occasionally causes outbreaks in Europe. There is a need for therapies that provide rapid protection against FMD in outbreak situations. We aim to provide such rapid protection by passive immunization with llama single-domain antibody fragments (VHHs). Twenty-four VHHs binding serotype O FMDV in vitro were isolated from immunized llamas by phage display and expressed in bakers yeast for further characterization. They recognized four functionally independent antigenic sites. Six strongly FMDV neutralizing VHHs bound to a peptide representing the GH-loop of viral protein 1 known to be involved in binding to the cellular receptor of FMDV. Clone M8, recognizing this antigenic site, and clone M23, recognizing another antigenic site, showed synergistic in vitro virus neutralization. Three FMDV specific VHHs were PEGylated in order to decrease their rapid blood clearance and thus enable in vivo guinea pig protection experiments. Passive immunization with individual VHHs showed no protection, but a mixture of M8 and M23 showed partial transient protection. The protection afforded by these VHHs was however low as compared to the complete protection afforded by convalescent guinea pig serum. In contrast, these VHHs showed far more efficient in vitro FMDV neutralization than convalescent guinea pig serum. This lack of correlation between in vitro neutralization and in vivo protection lends further credence to the notion that opsonophagocytosis of FMDV is important for protection in vivo.

Amino Acid Sequence↗

Developments in diagnostic techniques for differentiating infection from vaccination in foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious and economically significant disease of cattle, pigs, sheep, goats and wild ruminant species. The FMD virus genome encodes a unique polyprotein from which the different viral polypeptides are cleaved by viral proteases, including eight different non-structural proteins (NSPs). Both structural and non-structural antigens induce the production of antibodies in infected animals. In contrast, vaccinated animals which have not been exposed to replicating virus will develop antibodies only to the viral antigens in the inactivated material. Vaccination against FMD is a key element in the control of the disease in addition to slaughter and movement restrictions. However, countries that vaccinate in the event of an outbreak will have to re-establish their FMD free status to the satisfaction of their trading partners. Because currently available vaccines stimulate the production of antibodies indistinguishable from those produced by infected animals in response to live virus and because vaccinated animals can be infected and become carriers of FMD virus, efforts have been made to develop diagnostic test that can differentiate vaccinated animals from those that are convalescent and from those that have been vaccinated and become carriers following subsequent contact with live virus. Currently the detection of antibodies to non-structural protein's (NSPs) is the preferred diagnostic method to distinguish virus infected, carrier, animals from vaccinated animals. However this is currently only possible at the herd level because of the great variability in the initiation, specificity and duration of the immune response in individual animals to the NSPs shown in many studies. Considerable effort and attention is now being directed toward the development of new methods and techniques for the rapid and accurate detection of anti-NSP antibodies, harmonization and standardization of current diagnostic techniques, as well as the production of defined reagents.

Animals↗

The interference by maternally-derived antibody with active immunization of farm animals against foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious disease affecting ruminants and pigs. In countries in which control of FMD relies predominantly on vaccination, young stock ingest specific anti-FMD virus antibodies in the colostrum. This maternally-derived antibody (MDA) provides immediate protection against infection with FMD virus, but also interferes with the development of active immunity following vaccination. However, susceptibility to infection precedes the ability to respond to vaccination in the presence of MDA. Currently available vaccines cannot overcome this inhibitory effect of MDA, and protection of young stock can only be provided by their isolation from FMD virus.

Animals↗

Echovirus 4 associated to hand, foot and mouth disease.

Hand, foot and mouth disease (HFMD) is a contagious enteroviral infection occurring primarily in children and characterized by vesicular palmoplantar eruptions and erosive stomatitis. Echovirus 4 (EV-4) has been commonly associated with aseptic meningitis. The association of HFMD with EV-4 has not been reported previously. Two samples of a 14-month child who presented mild fever, sores in the mouth, rash with blisters on the palm of hands and soles of feet were sent to Enteric Viruses Laboratory of Adolfo Lutz Institute. Clinical samples were inoculated in three different cell lines, and those which presented cytopathic effect (CPE), were submitted to Indirect Immunofluorescence Assay (IFA) and "one step" RT-PCR. Agarose gel electrophoresis from RT-PCR product, showed a product with 437 bp, which is characteristic of Enterovirus group. Echovirus 4 was identified by IFA. Although HFMD is a viral infection associated mainly with Enterovirus 71 (HEV-71) and Coxsackievirus A16 (CV-A16), our results demonstrate a diversity of serotype related to HFMD and stress the importance of epidemiological surveillance to this disease and its complications.

Electrophoresis, Agar Gel↗