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PubMed2005

Foot-and-mouth disease virus evolution: exploring pathways towards virus extinction.

Foot-and-mouth disease virus (FMDV) is genetically and phenotypically variable. As a typical RNA virus, FMDV follows a quasispecies dynamics, with the many biological implications of such a dynamics. Mutant spectra provide a reservoir of FMDV variants, and minority subpopulations may become dominant in response to environmental demands or as a result of statistical fluctuations in population size. Accumulation of mutations in the FMDV genome occurs upon subjecting viral populations to repeated bottleneck events and upon viral replication in the presence of mutagenic base or nucleoside analogs. During serial bottleneck passages, FMDV survive during extended rounds of replication maintaining low average relative fitness, despite linear accumulation of mutations in the consensus genomic sequence. The critical event is the occurrence of a low frequency of compensatory mutations. In contrast, upon replication in the presence of mutagens, the complexity of mutant spectra increases, apparently no compensatory mutations can express their fitness-enhancing potential, and the virus can cross an error threshold for maintenance of genetic information, resulting in virus extinction. Low relative fitness and low viral load favor FMDV extinction in cell culture. The comparison of the molecular basis of resistance to extinction upon bottleneck passage and extinction by enhanced mutagenesis is providing new insights in the understanding of quasispecies dynamics. Such a comparison is contributing to the development of new antiviral strategies based on the transition of viral replication into error catastrophe.

Biological Evolution↗
PubMed1990

Freeze-drying foot-and-mouth disease virus antigens. I. Infectivity studies.

The ability of foot-and-mouth disease virus strains type O1 BFS 1860 and type A22 IRQ 24/64 to retain infectivity after freeze-drying with or without additives being made to virus suspensions was studied. The infectivity titres of freeze-dried antigens was assessed at intervals over a six month storage period at various temperatures and also after reconstitution to the liquid phase and storage with or without glycerination. Certain additive solutions were necessary to prevent degradation of virus during the freeze-drying procedure which reduced any loss of infectivity caused by storage of products at 4 degrees C and 20 degrees C. Additive solutions composed of 10% sucrose and 5% lactalbumin hydrolysate; 10% skimmed milk; 4% peptone and 1% gelatin; and 5% dextran, 1% sodium glutamate and 5% sucrose all prolonged the keeping qualities of virus at the elevated temperature of 37 degrees C. The results indicate that short-term storage and shipment of freeze-dried foot-and-mouth disease virus antigens is possible without the need for refrigeration, thereby reducing transportation and storage costs. Reconstituted antigens survived better after glycerination and storage at -20 degrees C than did non-glycerinated samples stored at 4 degrees C.

Animals↗
PubMed2004

Emergence of a novel subgroup within the widely circulating lineage of foot-and-mouth disease virus serotype Asia 1 in India.

The complete VP1 encoding (1D) gene of 54 foot-and-mouth disease (FMD) virus serotype Asia1 field isolates, most of which were isolated during 2000 and 2001, was sequenced. The phylogenetic analysis identified a novel subgroup (>10% nucleotide divergence) within the widely circulating lineage of this serotype. The newly emerged viruses were responsible for disease outbreaks in both cattle and buffaloes and were present in six different states in the country. Amino acid sequence comparison of these isolates revealed significant sequence divergence at many of the amino acid positions in comparison to those of lineage VI-A and C. Emergence of such viruses may affect the efficacy of vaccine strain currently used for protection against FMD in India.

Amino Acid Sequence↗
PubMed2003

Detection of carrier cattle and sheep persistently infected with foot-and-mouth disease virus by a rapid real-time RT-PCR assay.

The detection of foot-and-mouth disease virus (FMDV) in persistently infected carriers among exposed ruminants is of great importance in disease control. For this purpose, a real time, fluorogenic reverse transcription polymerase chain reaction (real-time RT-PCR) assay was evaluated for the identification of FMDV carrier animals. The results indicate that this real time RT-PCR assay may be suitable for detection of FMDV carrier animals.

Animals↗
PubMed1995

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

Antigenic variation of type A foot and mouth disease (FMD) virus in Thailand was examined using a total of 82 field viruses isolated between 1986 and 1989. A two-dimensional serum microneutralisation test was used to compare these isolates to a reference strain, A15 Bangkok 1960 (A BKK/60). Viruses regarded as unrelated to A BKK/60 were compared to another reference strain, A22 Nakhon Pathom 1986 (A NPT/86). This approach divided the viruses into two groups. Most of the viruses shared a close antigenic relationship with A BKK/60. Only twelve viruses were regarded as unrelated to A BKK/60, and these were related to A NPT/86. All but one of these twelve isolates were from two provinces in one administrative region of the country. Future type A vaccines in Thailand will need to confer protection against both groups of viruses.

Animals↗
PubMed1999

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.

BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Adolescent↗
PubMed1982

Immunosuppression in bovine trypanosomiasis: response of cattle infected with Trypanosoma congolense to foot-and-mouth disease vaccination and subsequent live virus challenge.

The primary and secondary antibody responses to foot-and-mouth disease virus vaccine were examined in cattle infected with Trypanosoma congolense and the response of some of these animals to live foot-and-mouth disease virus challenge was assessed. Infected groups of cattle had rather lower antibody responses than uninfected control cattle after primary vaccination but the antibody titres were not significantly depressed until after secondary vaccination. These levels remained depressed for the duration of the experiment, ie, 183 days. Trypanocidal therapy with diminazene aceturate of infected cattle at the time of vaccination did not significantly improve the antibody response to primary vaccination. Their subsequent response to live virus challenge was somewhat equivocal in that the number of animals protected was not significantly different in comparison to the untreated infected and uninfected controls. It was concluded that trypanosome-infected cattle do not produce optimal responses to foot-and-mouth disease vaccination. Nevertheless, the antibody titres are generally above those considered adequate to confer 95 per cent protection against needle challenge.

Animals↗
PubMed2003

Description of an epidemic simulation model for use in evaluating strategies to control an outbreak of foot-and-mouth disease.

OBJECTIVE: To develop a spatial epidemic model to simulate intraherd and interherd transmission of foot-and-mouth disease (FMD) virus. SAMPLE POPULATION: 2,238 herds, representing beef, dairy, swine, goats, and sheep, and 5 sale yards located in Fresno, Kings, and Tulare counties of California. PROCEDURE: Using Monte-Carlo simulations, a spatial stochastic epidemic simulation model was developed to identify new herds that would acquire FMD following random selection of an index herd and to assess progression of an epidemic after implementation of mandatory control strategies. RESULTS: The model included species-specific transition periods for FMD infection, locations of herds, rates of direct and indirect contacts among herds, and probability distributions derived from expert opinions on probabilities of transmission by direct and indirect contact, as well as reduction in contact following implementation of restrictions on movements in designated infected areas and surveillance zones. Models of supplemental control programs included slaughter of all animals within a specified distance of infected herds, slaughter of only high-risk animals identified by use of a model simulation, and vaccination of all animals within a 5- to 50-km radius of infected herds. CONCLUSIONS AND CLINICAL RELEVANCE: The FMD model represents a tool for use in planning biosecurity and emergency-response programs and in comparing potential benefits of various strategies for control and eradication of FMD appropriate for specific populations.

Animals↗
PubMed2004

Comparison and analysis of the complete nucleotide sequence of foot-and-mouth disease viruses from animals in Korea and other PanAsia strains.

During the last 3 years, foot-and-mouth disease virus serotype O, named PanAsia, caused two outbreaks in the Republic of Korea. To determine if there was an obvious genetic relationship between the virus isolated in 2002 (O/SKR/2002) and the O/SKR/2000, and to further analyze the epidemiological relationships between the PanAsia viruses and the viruses identified in Korea, the complete nucleotide sequence of the O/SKR/2002 and the O/SKR/2000 were determined by automatic cycling sequencing and primer walking. The nucleotides and the deduced amino acid (aa) sequences of the strains identified in Korea were compared with each other and also those enrolled in the GenBank database. In comparison and analysis of the viruses identified in Korea, any deletions or insertions in the specific fragment gene of both the O/SKR/2002 and O/SKR/2000 were not identified. However, comparison of the aa sequence of the identified virus in 2002 from pigs with those of other PanAsia strains revealed significant substitutions of 4 aa in the VPI region and 8 aa in the 3A region. In phylogenetic analysis based on the translated region, the identified virus in 2002 appeared to be the divergence of approximately 1% degree with other PanAsia viruses. Also, animal experiments indicated that O/SKR/2000 is not host-restricted and develop the clinical signs in the main susceptible livestock species (cattle and pigs). However, O/SKR/2002 did not develop the clinical signs in cattle and showed severe clinical signs only in pigs. These analytic data suggest that 2002 outbreaks in Korea is not re-occurred but re-introduced from nowhere.

Amino Acid Sequence↗
PubMed2005

Molecular characterization of foot-and-mouth disease virus type C of Indian origin.

Comparison of nucleotide sequences of the partial 1D region of foot-and-mouth disease type C viruses of Indian origin with those of European, South American, and Southeast Asian viruses revealed that the Indian viruses form a distinct genotype. The vaccine strain C IND/51/79 belongs to this genotype and may be a prototype strain of this genotype.

Animals↗
PubMed2002

Carcass disposal: lessons from The Netherlands after the foot and mouth disease outbreak of 2001.

The main logistical problems of the foot and mouth disease (FMD) outbreak that occurred in the Netherlands in 2001 were a lack of culling and rendering capacity. Suppressive vaccination formed the basis for the solution to both problems and was primarily used to halt the possible spread of the virus. This allowed culls to take place on vaccinated farms when sufficient culling capacity eventually became available. In addition, the vaccinated cloven-hoofed animals could be removed alive and then killed in central culling places fourteen or more days after vaccination. Using slaughterhouses as central culling places meant that parts of carcasses could be deep-frozen, which solved the lack of rendering capacity. The deep-frozen carcass parts were destroyed later, when rendering capacity became available. To guarantee that all vaccinated, culled and temporarily deep-frozen cloven-hoofed animals were eventually destroyed, a balanced audit trail, partly based on kilogram records, was vital in this situation.

Abattoirs↗
PubMed2004

The macro-economic impact of a foot-and-mouth disease incursion in New Zealand.

The 2001 outbreak of Foot-and-Mouth Disease (FMD) in the United Kingdom heightened public concern in New Zealand about the economic consequences of an outbreak of FMD, and resulted in the Reserve Bank and Treasury conducting an assessment of the macro-economic impact of a small FMD outbreak in New Zealand. The study was based on a relatively small outbreak in which 50 properties were infected over a period of two months. Cumulative losses calculated over two years from the beginning of the hypothetical outbreak were estimated at around NZ dollars 10 billion, a figure twice as large as the initial Ministry of Agriculture and Forestry estimate. The main reason for this difference is that the Reserve Bank study included the additional macro-economic effects of a slump in domestic demand. The study also demonstrated that in New Zealand under the conditions of the current OIE Terrestrial Animal Health Code for FMD, the economic impact of any programme to control FMD by vaccination in which vaccinated animals are not slaughtered, is significantly worse than rapid eradication by stamping out.

Animals↗
PubMed1990

Foot-and-mouth disease virus in the llama (Lama glama): diagnosis, transmission, and susceptibility.

Foot-and-mouth disease virus (FMDV) was shown to be transmitted from either cattle to llamas, llamas to swine (interspecies), or llamas to llamas (intraspecies). Response to FMDV varied greatly in the 6 llamas studied; 3 llamas developed generalized clinical disease with mild pyrexia, 2 after intradermolingual inoculation, and 1 after exposure to a calf infected with FMDV serotype A24. Another contact llama developed vesicular lesions on all 4 extremities but no oral lesions. Two contact llamas, in separate study groups, did not seroconvert or develop clinical signs of FMDV infection. All 4 llamas showing clinical disease developed virus-neutralizing antibodies against FMDV A24 and antibodies against the virus-infection-associated antigen. Virus-neutralizing antibody titers remained elevated for over 200 days postinoculation or exposure. Antibodies to virus-infection-associated antigen were detected several days after virus-neutralizing antibody appeared and became weaker 100-125 days post-FMDV exposure in 3 of the 4 clinically affected llamas. One inoculated llama was still positive for virus-infection-associated antigen at 360 days after inoculation. Foot-and-mouth disease virus A24 was not detected from esophageal-pharyngeal fluid specimens beyond 8 days postexposure using in vitro techniques.

Animals↗
PubMed2002

Isolation of foot-and-mouth disease virus from Japanese black cattle in Miyazaki Prefecture, Japan, 2000.

Four outbreaks of foot-and-mouth disease (FMD) occurred from March to May 2000 in Miyazaki and Hokkaido Prefectures, Japan. FMD virus isolation was achieved by sampling probang materials from Japanese Black cattle in the third case found in Miyazaki Prefecture. The probang materials were inoculated to bovine kidney (BK) and bovine thyroid cell cultures. CPE was observed in the BK at two days post-inoculation. Specific amplified DNA segments for FMD virus (FMDV) were detected by reverse transcriptase polymerase chain reaction in the culture fluid. The FMDV was identified as type O by enzyme-linked immunosorbent assay (ELISA) for antigen detection and the nucleotide sequence encoding the VPI was determined. This FMDV is a strain that is widespread in Pan-Asia and was designated as O/JPN/2000 by the World Reference Laboratory of the Pirbright Institute, England. This report marks the first isolation of FMDV in Japan.

Animals↗