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PubMed1985

Recombination and oligonucleotide analysis of guanidine-resistant foot-and-mouth disease virus mutants.

Guanidine resistance (gr) mutations of foot-and-mouth disease virus were mapped by recombining pairs of temperature-sensitive mutants belonging to different subtypes. In each cross, one parent possessed a gr mutation. Recombinants were isolated by selection at the nonpermissive temperature and assayed for the ability to grow in the presence of guanidine. From the progeny of three crosses, four different types of recombinant were distinguished on the basis of protein composition and RNA fingerprint. The sequences of the RNase T1-resistant oligonucleotides were determined and located in the full-length sequence of foot-and-mouth disease virus. The resulting maps show that (i) each recombinant was generated by a single genetic crossover, and (ii) both of the gr mutations studied were located within an internal 2.9-kilobase region which spans the P34 gene. This supports our hypothesis that guanidine inhibits the growth of foot-and-mouth disease virus by acting on nonstructural polypeptide P34. Additional evidence was provided by RNA fingerprinting gr mutants. In two of four cases the gr mutation was associated with a change in an oligonucleotide located near the 3' end of the P34 gene; in one of these the nucleotide substitution was identified.

Aphthovirus↗
PubMed2003

Rapid serological profiling by enzyme-linked immunosorbent assay and its use as an epidemiological indicator of foot-and-mouth disease viral activity.

Frequency distribution of reactivity levels of foot-and-mouth disease infection-specific antibodies in livestock populations was analysed. Specific antibody responses against non-capsid polyprotein 3ABC were assessed through a highly sensitive indirect enzyme-linked immonosorbent assay (I-ELISA 3ABC). A graphic display of data was designed based on three negative and three positive categories to illustrate reactivity patterns. The resulting patterns were correlated to the epidemiological status. On this basis, results of over 100,000 sera derived from cattle populations in regions with various well-documented epidemiological situations were compiled and are exemplified in this paper.Distinct distributions of antibody reactivity patterns reflecting the various epidemiological situations were attained. Whereas non-affected areas presented a rather homogenous negative pattern with very limited test-positive reactions, affected regions revealed quite heterogeneous profiles, including positive and negative categories, with distributions that varied according to the region. The use of graphic prints encompassing I-ELISA 3ABC antibody profile responses constituted an adequate epidemiological indicator of the risk of foot-and-mouth disease viral activity, providing immediate visualization for a rapid inference of the epidemiological situation of a region. Moreover, such profiles allowed for convenient follow-up of infection after a focus as a function of time and geographical spread.

Animals↗
PubMed2005

Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice.

Foot-and-mouth disease virus (FMDV) is a picornavirus that causes an acute vesicular disease of cloven-hoofed animals. This virus continues to be threat to livestock worldwide with outbreaks causing severe economic losses. However, very little is known about FMDV pathogenesis, partially due to the inconveniences of working with cattle and swine, the main natural hosts of the virus. Here we demonstrate that C57BL/6 and BALB/C adult mice are highly susceptible to FMDV infection when the virus is administered subcutaneously or intraperitoneally. The first clinical signs are ruffled fur, apathy, humped posture, and wasting, which are followed by neurological signs such as hind-limb paralysis. Within 2-3 days of disease onset, the animals die. Virus is found in all major organs, indicating a systemic infection. Mice developed microvesicles near the basal layer of the epithelium, event that precedes the vesiculation characteristics of FMD. In addition, a lymphoid depletion in spleen and thymus and severe lymphopenia is observed in the infected mice. When these mice were immunized with conventional inactivated FMDV vaccine, they were protected (100% of vaccinated animals) against challenge with a lethal dose of FMDV. The data indicate that this mouse model may facilitate the study of FMDV pathogenesis, and the development of new effective vaccines for FMD.

Acute Disease↗
PubMed2005

Non-capsid proteins to identify foot-and-mouth disease viral circulation in cattle irrespective of vaccination.

The ability of foot-and-mouth disease virus (FMDV) to establish subclinical and even persistent infection, the so called carrier state, imposes the need to reliably demonstrate absence of viral circulation, to monitor the progress of control measures, either during eradication programs or after reintroduction of virus in free areas. This demonstration becomes critical in immunized populations, because of the concern that silent viral circulation could be hidden by immunization. This concern originates from the fact that vaccination against foot-and-mouth disease (FMD) protects against clinical disease, but not necessarily against subclinical infection or establishment of the carrier state in cattle. A novel approach, developed and validated at PANAFTOSA during the 1990s, based on an immunoenzymatic system for detection of antibodies against non-capsid proteins (NCP) has proven valuable for monitoring viral circulation within and between herds, irrespective of the vaccination status. Antibodies against NCP are induced during infection but, in principle, not upon vaccination. The validation of this system led to its international recognition as the OIE index test. The fitness of this serosurvey tool to assess viral circulation in systematically vaccinated populations was demonstrated through its extensive application in most regions in South America. The experience attained in these regions supported the incorporation of the "free of FMD with vaccination" provisions into the OIE code. Likewise, it opened the way to alternatives to the "stamping out" policy. The results gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America, and supported the development of recommendations and guidelines that are being implemented for serosurveys that go with control measures in vaccinated populations.

Animals↗
PubMed2004

Control of a foot-and-mouth disease epidemic in Argentina.

A major epidemic of foot-and-mouth disease affected Argentina during 2001. The epidemic was controlled by mass-vaccination of the national herd and movement restrictions. The median herd disease reproduction ratio (RH) decreased significantly from 2.4 (before the epidemic was officially recognized) to 1.2 during the mass-vaccination campaign and < 1 following the mass-vaccination campaign. The largest distance between two outbreaks was similar during (1905 km) and after (1890 km) the mass-vaccination. However, after mass-vaccination was completed, the proportion of herd outbreaks clustered decreased from 70.4% to 66.8%, respectively. Although a combination of vaccination and livestock-movement restrictions was effective in controlling the epidemic, 112 herd outbreaks occurred up to 6 months after the end of the mass-vaccination campaign. Mass-vaccination and movement restrictions might be an effective strategy to control FMD; however, the time taken to end large, national epidemics might be > 1 year.

Animal Husbandry↗
PubMed2000

Genetic determinants of altered virulence of Taiwanese foot-and-mouth disease virus.

In 1997, a devastating outbreak of foot-and-mouth disease (FMD) in Taiwan was caused by a serotype O virus (referred to here as OTai) with atypical virulence. It produced high morbidity and mortality in swine but did not affect cattle. We have defined the genetic basis of the species specificity of OTai by evaluating the properties of genetically engineered chimeric viruses created from OTai and a bovine-virulent FMD virus. These studies have shown that an altered nonstructural protein, 3A, is a primary determinant of restricted growth on bovine cells in vitro and significantly contributes to bovine attenuation of OTai in vivo.

Amino Acid Sequence↗
PubMed2002

A farming perspective on the 2001 foot and mouth disease epidemic in the United Kingdom.

The outbreak of foot and mouth disease (FMD) that occurred in the United Kingdom (UK) in 2001 was the single largest epidemic of FMD the world had ever experienced. This outbreak raises important issues about future FMD control strategies, including the use of vaccination. The outbreak has also stimulated a wider debate in the UK on the role and direction of agriculture. The author presents the views of the National Farmers' Union of England and Wales on the handling of the outbreak by the UK Government and summarises some of the key lessons to be learned from a farming perspective.

Agriculture↗
PubMed1976

Experimental placental transfer of foot-and-mouth disease virus in mice.

An attenuated type O foot-and-mouth disease (FMD) virus which was virulent for infant, but not for pregnant, mice proved to be superior to a virulent type C FMD virus in the development of a model system for the study of placental transfer of FMD in mice. When mice were inoculated at day 8 or 12 of gestation with type O FMD virus, the virus was detectable in the maternal pancreas for 3 days and in the placenta for 6 days. Viral levels in the fetus and the amniotic fluid were inconsistent and were apparently due to a spillover from the placental infection. The elimination of the virus from the placenta coincided with the expected production of maternal 7S antibody. Mice inoculated from days 0 to 12 of gestation did not have a significant increase in dead young by day 18 (the day of necropsy). Similarly inoculated mice, when permitted to go to term, produced and raised normal-size litters. Inoculation on day 15 of gestation resulted in an increased number of deaths due to morbidity of the dams. It was concluded that the placenta serves as an active site of infection for FMD virus in pregnant mice, but the fetus is relatively resistant to infection.

Animals↗
PubMedDate not supplied

Chemical basis of antigenic variation in foot-and-mouth disease virus.

One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.

Amino Acid Sequence↗
PubMed1984

Preventing diabetic foot problems.

Complications of diabetic foot disease may be prevented through regular office followup that includes inspection of the feet and patient education. Peripheral vascular disease and neuropathy are the pathophysiological factors underlying the development of ulcers and gangrene. Evaluation should include careful assessment of the neurological and vascular integrity of the legs and feet, risk factors for underlying disease and self-care abilities. When ulceration occurs, management includes bed rest, appropriate antibiotic therapy, topical care and treatment of any underlying large vessel disease. Worthwhile goals in caring for the diabetic individual's feet include: appropriate choice of shoes; good nail and skin care; excellent blood sugar control; smoking cessation; regular exercise; and maintaining normal blood pressure, cholesterol and triglyceride levels; and infection-free feet. Involving the family, the visiting nurse and/or the podiatrist may be helpful in achieving these goals.

Adult↗
PubMed2005

Genomic and antigenic characterization of viruses from the 1993 Italian foot-and-mouth disease outbreak.

The origin and evolution of the type O foot-and-mouth disease viruses (FMDV) that caused the outbreak occurrence in Italy in 1993, the first episode of the disease in the EU after adoption of a non-vaccination policy in 1991, have been studied by the analysis of sequences encoding three main antigenic sites on the viral capsid proteins. The phylogenetic tree derived from sequences spanning the carboxyterminal end of VP1 showed that these Italian viruses were grouped in the ME-SA topotype, closely related to viruses that circulated previously in the Middle East. The analysis of the nucleotide sequences in VP1, VP2 and VP3 showed a co-circulation during the epizootic of genetic variants, including viruses with amino acid replacements in VP3. For some of the isolates analyzed, values of fixation of nucleotide substitutions per year were observed in the three regions analyzed, ranging from 1.5 to 5.1 x 10(-2). The use of a panel of new monoclonal antibodies raised against an isolate from this outbreak, as well as monoclonal antibodies to FMDV O1-Switzerland 1965, showed differences in the reactivity pattern among some of the Italian isolates analyzed, which were consistent with the co-circulation of antigenic variants. These results support the potential for FMDV diversification in a limited period of time and under epidemiological conditions in which no vaccination campaigns were being implemented.

Animals↗
PubMed2003

The foot-and-mouth disease epidemic in The Netherlands in 2001.

An outbreak of foot-and-mouth disease (FMD) in Great Britain was reported on 21 February 2001, followed by an outbreak of FMD in The Netherlands a month later. This Dutch index outbreak occurred on a mixed, veal-calf/dairy-goat farm in Oene, in the central part of The Netherlands. The most-likely route of infection was the import of Irish veal-calves to this Dutch herd via an FMD-contaminated staging point in France. With hindsight, more herds seemed to be infected by the time the index outbreak was confirmed. The regular EU control measures were implemented, in combination with pre-emptive culling of herds within 1km of each outbreak. Nevertheless, more outbreaks of FMD occurred. Most of the virus infections on those farms were "neighborhood infections". Because the situation seemed out of control locally and the destruction capacity became insufficient, it was decided to implement an emergency vaccination strategy for all biungulates in a large area around Oene to stop further spread of the virus. All susceptible animals on approximately 1800 farms in this area were vaccinated. All farms subsequently were depopulated, starting from 2 weeks after vaccination. In total, 26 outbreaks were detected (the last outbreak on 22 April 2001). In total, approximately 260,000 animals were killed.

Animals↗
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↗
PubMed2002

Review of the status and control of foot and mouth disease in sub-Saharan Africa.

Six of the seven serotypes of foot and mouth disease (FMD) virus (i.e. all but Asia 1) are prevalent in Africa although there are marked regional differences in distribution. Three of these serotypes are unique to Africa, namely the three South African Territories (SAT) serotypes. Serotype C may also now be confined to Africa because it has not been reported elsewhere recently. In southern Africa at least, the SAT serotypes have an intimate and probably ancient association with African buffalo (Syncerus caffer) that is instrumental in their maintenance. Within each of the six prevalent serotypes, with the possible exception of C, there are a number of different lineages with more or less defined distributions (i.e. topotypes) that in some cases are sufficiently immunologically different from one another to require specific vaccines to ensure efficient control. This immunological diversity in prevalent serotypes and topotypes, in addition to uncontrolled animal movement in most parts of the continent, render FMD difficult to control in present circumstances. This fact, together with poorly developed intercontinental trade in animals and animal products has resulted in the control of FMD being afforded a low priority in most parts of the continent, although the northern and southern regions of the continent are an exception. As a consequence, eradication of FMD from Africa as a whole is not a prospect within the foreseeable future. In southern Africa, the use of fencing and other means to strictly control the movement of wildlife and livestock as well as judicious application of vaccine has resulted in countries of the region being able to access beef and other livestock markets in Europe and elsewhere in the developed world. Significant marketing of livestock and livestock products from Africa outside the continent is unlikely to be achieved unless similar approaches can be developed for other regions of Africa. This will result in continuing under-exploitation of a valuable resource in the arid and semi-arid regions of Africa, with increasing marginalisation of human populations living there.

Africa South of the Sahara↗
PubMed1986

Management of the diabetic foot.

Foot disease in diabetics is caused by peripheral neuropathy and peripheral vascular disease. Initial evaluation involves repeated physical examinations, including careful inspection for infection, and Doppler analysis of perfusion. A tracing of the ulceration should be obtained so that healing can be monitored. Properly fitting shoes are imperative for prophylactic care. Shoe modification is possible using moldable plastics and metatarsal bars. Patient and family education are also important elements of management.

Anti-Bacterial Agents↗
PubMed2005

Genetic comparison of large fragment of the 5'untranslated region among foot-and-mouth disease viruses with special reference to serotype Asia1.

Foot-and-mouth disease (FMD), the most economically important disease of cloven-hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic grouping of type Asia1 field isolates on the basis of the large fragment of the 5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences of the capsid-coding (VP1) region of the same viruses. The existence of two distinct lineages of type Asia1 suggested by the study on the VP1 region was further supported by the detection of a difference in length and predicted secondary structure of the 5'LF-UTR between the two lineages. Sequence variability between the isolates of the two lineages was also observed within the different domains of the internal ribosome entry site (IRES) around conserved motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF-UTR have been identified. The present study shows that the 5'LF-UTR of FMDV serotype Asia1 field isolates are variable in relation to the length and probable secondary structure of the IRES.

5' Untranslated Regions↗