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PubMed2003

Clinical characteristics of an outbreak of hand, foot and mouth disease in Singapore.

BACKGROUND: We experienced a hand, foot and mouth disease (HFMD) outbreak in late year 2000 in Singapore. Between 14 September 2000 and 14 November 2000, a total of 3526 cases of HFMD were notified. There were 652 patients clinically suspected to have HFMD, who were seen at the Children's Emergency department of KK Women's and Children's Hospital of Singapore. OBJECTIVE OF THE STUDY: To study the clinical profile and virologic isolates of children admitted with HFMD during the outbreak. STUDY DESIGN: A prospective observational study. METHODS: Analysis of clinical features and virologic studies of 129 selected cases of HFMD and herpangina. RESULTS: The median age was 25 months with a range of between 4 months and 11 years. The majority were less than 5 years old (87%). The male-to-female ratio was 1.3:1. The median numbers of day of illness to presentation to the hospital was 3 days. Poor feeding and loss of appetite accounted for 76.7% of the admissions. Symptoms of vomiting were present in 37.2% of the cases. Oral ulcers were found in 96.1%, rashes over hands in 87.6%, over feet in 86.8% and over buttocks in 54.3%. Only 4.7% exhibited no rashes other than oral ulcers and were labelled as herpangina. The median duration of fever was 3 days, ranging from 2 to 7 days. An intravenous drip was required in 68.2% due to poor feeding. Viral cultures were sent in 89.1% of patients of whom 61.7% of patients were positive for viruses. Of the positive cultures, types of viruses isolated were EV71 (enterovirus 71) in 59/71 (83%), Coxsackievirus (A16, A24, A2 B3, B4) in 6/71 (8.4%), EV Untypable in 4/71 (5.6%) and mixed [EV71, echo25, cytomegalovirus (CMV)] in 2/71 (2.8%). EV71 was isolated mostly from stool samples followed by vesicle fluid culture and throat swabs. Two siblings aged 14 months and 2.5 years died during this period at day 5 of illness, their post-mortem examinations showed interstitial pneumonitis of the lungs. EV71 was isolated from the brain, heart, tonsils, intestines, throat and rectal swabs. A raised total white cell count of 14,000/L versus 12,000/L was significantly associated with complicated HFMD (P = 0.04). There was no difference in clinical characteristics of EV71 versus non-EV71 infections. Other viral illnesses, e.g. measles and CMV, may be mistaken for HFMD in the outbreak setting. CONCLUSIONS: HFMD tends to occur in younger children less than 5 years old due to low herd immunity. Poor feeding due to mouth ulcers accounts for admission to hospital requiring intravenous drip. EV71 accounted for the majority (75%) of the positive isolations, followed by coxsackievirus and untypable EV, mixed infection of echovirus or CMV. The yield of virus isolation was highest from stool, followed by vesicles and throat swabs. There is no difference in clinical characteristics of EV71 and non-EV71 virus infections. Enterovirus can cause mild symptoms to fatal death. Two infants died of interstitial pneumonitis and encephalitis.

Child↗
PubMed2004

Foot-and-mouth disease in tropical wildlife.

This review of foot-and-mouth disease in cloven-hoofed, free-living animals, describes the disease, the wide range of the hosts, the carrier state, and the interrelationship between disease in domestic livestock and wildlife. This information becomes even more crucial to the development of control strategies when linked to the process of pathogenesis and the epidemiology of the disease.

Animals↗
PubMed1980

Sites of release of airborne foot-and-mouth disease virus from infected pigs.

Pigs infected with foot-and-mouth disease virus by different routes of exposure were air-sampled individually, first as 'intact' (I-) pigs and then as 'intubated' (T-) pigs, using an endotracheal tube. Irrespective of the route of infection it was found that during the early stages of disease more virus was recovered from I-pigs than from T-pigs. Most of the virus from I-pigs during incubation and early disease was associated with large and medium sized particles. T-pigs infected by direct or indirect contact excreted a range of particle sizes at this time but T-pigs infected by inoculation only excreted small particles. During advanced disease all sizes of particle were excreted by I- and T-pigs. Greater amount of airborne virus were recovered at this time from I-pigs than T-pigs infected by indirect contact but I-pigs infected by intravenous or intradermal inoculation excreted less infectivity than T-pigs. The results show that the respiratory tract is involved during the early stages of foot-and-mouth disease in pigs infected by either natural or experimental routes of exposure and suggest that upper respiratory infection precedes lower.

Aerosols↗
PubMed2003

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↗
PubMed1988

Rapid correlation between field isolates and vaccine strains of foot-and-mouth disease virus.

Antigenic relationships between field isolates of foot-and-mouth disease virus and available vaccine strains can be rapidly determined by ELISA. The most suitable vaccine strain to control an outbreak caused by the field isolate can then be quickly identified. The classical method of subtyping strains of foot-and-mouth disease virus should be replaced with a nomenclature which describes the relationship between a strain and the most antigenically closely related vaccine strain.

Animals↗
PubMed1995

Multiple-infected diagnostic specimens from foot and mouth disease endemic regions.

The current routine diagnostic procedures for foot and mouth disease (FMD) virus antigen detection combine the use of an indirect sandwich enzyme-linked immunosorbent assay (ELISA) with virus isolation and amplification on cell culture. Several field samples recently received by the World Reference Laboratory for Foot and Mouth Disease which were initially diagnosed as containing a single virus type have subsequently been found to contain an additional virus type. Examples are given of the results of ELISAs performed on certain Saudia Arabian samples; these examples illustrate the problem which such multiple-infected samples present for laboratory diagnosis.

Animals↗
PubMed2000

The role of the World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest.

The World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest provide a worldwide diagnostic and surveillance service for these disease for FAO and OIE. Both laboratories are housed within the high security facility of the Institute for Animal Health, Pirbright, UK. Foot-and-mouth disease (FMD) and rinderpest (RP) are OIE List A diseases and historically have caused huge losses to agricultural economies around the world, prompting the establishment of veterinary colleges in Europe and environmentally controversial control programs in Africa. FMD and RP have now been geographically restricted, but the large legal and illegal world trade in live animals and animal products constantly threatens to allow them to spread back into disease-free areas. The Reference Laboratories provide a center of excellence for the development of improved diagnostic techniques and a repository of isolates collected over many years. These libraries provide material for investigations of the molecular epidemiology and evolution of the viruses and a data base against which new isolates can be compared. Thus it is possible to individually characterize new outbreak strains, identify their likely origin and provide the most up-to-date support for their control.

Africa↗
PubMed1997

Structural comparison between retro-inverso and parent peptides: molecular basis for the biological activity of a retro-inverso analogue of the immunodominant fragment of VP1 coat protein from foot-and-mouth disease virus.

Antibodies induced against intact foot-and-mouth disease Virus (FMDV) particles bind to the retro-inverso analogue of fragment 141-159 of the viral coat protein VP1 of FMDV, variant A, equally well as to the parent peptide. A conformational investigation of this retro-inverso peptide was carried out by nmr spectroscopy and restrained molecular modeling in order to identify the structural basis for the antigenic mimicry between these retro-inverso and parent peptides. In 100% trifluoroethanol a well-defined left-handed alpha-helical region exists from residue 150 to residue 159, which is consistently present in all conformational families obtained from restrained modelling. A less-defined left-handed helical region is present in the tract 144-148, which is also consistent for all structures. Conformational flexibility exists about Gly149, which leads to two types of structures, either bent or linear. In the bent structures, a three-residue inverse tight turn is found, which can be classified as an inverse gamma-turn centered at Gly149. The overall structural features of the retro-inverso peptide are shown to be similar to those of the parent L-peptide. The two molecules, however, are roughly mirror images because they share inherently chiral secondary structure elements. By comparing these conformational conclusions with the x-ray structure of the Fab complex of a corresponding VP1 antigenic fragment, a rationale is proposed to account for the topological requirements of specific recognition that are implied by the equivalent antigenic activity of the natural and retro-inverso compounds.

Amino Acid Sequence↗
PubMed1989

Molecular dynamics of the alpha-helical epitope of a novel synthetic lipopeptide foot-and-mouth disease virus vaccine.

A novel synthetic foot-and-mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B-cell and macrophage activator covalently linked to an amphiphilic alpha-helical T-cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-serine (P3CSS) as built-in adjuvant. The vaccine, tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl-FMDV-VP1 (VP1 = serotype O1K 135-154) induces protection against homologous challenge and serotype-specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV-VP1 segment 135-154 of strain O Wuppertal produced only poor cross-protection against challenge with O1K virus. The antigenic determinant VP1(135-154) is an amphiphilic alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-helical conformation during binding to its T-cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex.

Amino Acid Sequence↗
PubMed1983

Synthetic peptides mimic subtype specificity of foot-and-mouth disease virus.

The major immunogen of foot-and-mouth disease virus (FMDV) is located between amino acids 141-160 of the capsid protein VP1. Synthetic peptides corresponding to the major immunogenic region give good neutralising antibody responses and protection in guinea pigs. To define more precisely the immunogenic site of the virus, we have examined serological differences between subtypes of the A serotype using synthetic peptides covering the 141-160 region. We show that these synthetic peptides carry determinants which mimic the subtype specificity of the virus. The correlation between these results and predictive structural models, based on the amino acid sequence, is discussed.

Amino Acid Sequence↗
PubMed1993

Use of substituted and tandem-repeated peptides to probe the relevance of the highly conserved RGD tripeptide in the immune response against foot-and-mouth disease virus.

Antigenic site A of foot-and-mouth disease virus (FMDV) is an exposed, mobile loop which includes a central, highly conserved Arg-Gly-Asp tripeptide (RGD, VP1 residues 141-143 in serotype C) thought to be part of the cell attachment site. We have analyzed the contribution of RGD to the interaction of site A with antibodies by incorporating selected amino acid replacements at RGD into synthetic peptides representing site A, and analyzing the reactivity of substituted peptides with site A-specific monoclonal antibodies (MAbs). Replacement of Arg-141, Gly-142 or Asp-143 by alanine resulted in the loss of one, three and five epitopes, respectively, out of seven epitopes probed. Other replacements resulted in the loss of even larger numbers of epitopes, suggesting that the amino acids of the RGD region are either directly involved in interaction with antibodies or that they exert an important influence on the interaction of surrounding residues with antibodies. Thus, we explored the ability of tandem repeats of the RGDL sequence (corresponding to FMDV C-S8c1) to evoke neutralizing antibodies in rabbits and guinea pigs. Neutralizing activity was generally low but with a broad specificity for different FMDV serotypes and variants. Significant decreases in neutralizing titers were observed with boosting, suggesting a possible suppression of those anti-peptide antibodies which may also be directed to cellular RGD sequences. The results point to an involvement of RGD in the antigenic structure of site A, and open the possibility that broadly neutralizing antibodies might be induced by tandem repeats of the critical, conserved domain.

Amino Acid Sequence↗
PubMed1983

An investigation into causes of resistance of a cloned line of BHK cells to a strain of foot-and-mouth disease virus.

The reduced ability of foot-and-mouth disease virus (FMDV) strain Asia 1 Iran 1/73 to replicate in the cloned BHK cell line AA7 was not due to lack of virus attachment at the cell surface. Instead, the main restriction in the viral growth cycle occurred during synthesis and processing of viral macromolecules, and/or during the earliest stages of their assembly. Reduced efficiency of penetration and uncoating of virus attached to the cells may also have contributed to inhibition of virus replication. Viral components or subviral particles did not accumulate and defective interfering particles were not detected. The reduced number of infective virions produced was released from infected cells at the normal rate. No interferon production could be demonstrated.

Animals↗
PubMed2001

Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C1-Barcelona.

Foot-and-mouth disease virus (FMDV) isolate C(1)-Barcelona (or C-S30) includes four replacements within its immunodominant site (GH loop, residues 136-150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C-S8c1 (YTASARGDLAHLTTT). Although one of the mutations in C-S30 (147Leu-->Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised against FMDV C1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8c1 or C1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation that 15-residue peptides reproducing the C-S30 and C-S8c1 GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Nevertheless, surface plasmon resonance (SPR) kinetic analyses of the interactions between these peptides and three anti-GH loop mAbs have now revealed that the linear C-S30 peptides were less antigenic in solution than their C-S8c1 and C1-Brescia counterparts. We have, therefore, tried to modulate peptide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-1H NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation seems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved.

Amino Acid Sequence↗