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Implementation of quality assurance in national foot and mouth disease laboratories, based on the guidelines of the Office International des Epizooties.

The final act of the Uruguay Round of the General Agreement on Tariffs and Trade, 1994, contains the Agreement on the Application of Sanitary and Phytosanitary Measures, which aims to reduce the negative effects of health barriers on international trade to a minimum. Therefore, the Office International des Epizooties (OIE) Regional Commission for Europe proposed that an accreditation system based on the EN 45000 standard should be applied to achieve international recognition of certificates and testing laboratories. To this end, the OIE Standards Commission published a series of guidelines for the evaluation of laboratory quality and proficiency testing. In 1995, the Food and Agriculture Organization European Commission for the Control of Foot and Mouth Disease recommended that the OIE proposal should be applied in all foot and mouth disease (FMD) diagnostic laboratories in Europe. This review summarises the EN 45001 standard and the OIE guidelines, and proposes that these guidelines should be taken as a basis for the implementation of a quality assurance programme in FMD laboratories.

Accreditation↗

FREEZE-DRYING OF FOOT-AND-MOUTH DISEASE VIRUS AND STORAGE STABILITY OF THE INFECTIVITY OF DRIED VIRUS AT 4 C.

Foot-and-mouth disease virus, type A, strain 119, propagated in cultures of calf kidney cells and in the tongue epithelium of cattle was used. The process of freeze-drying was conducted in two cycles on unit volumes of 4 ml in Pyrex ampoules, averaging 150 ampoules per run, and was studied separately from the problems of storage. Ampoules containing freeze-dried virus were flame-sealed for either immediate study or storage at 4 C for later reference. Tissue-culture virus dried with various additives had a mean processing loss of 0.8 log LD(50) per ml for six different preparations. Virus freeze-dried in tissue suspension had a mean loss of 0.8 log LD(50) per ml for three different preparations. A second set of preparations was processed and specifically studied for storage quality at 4 C. The virus in 14 freeze-dried tissue-culture preparations had a mean loss of 0.75 log LD(50) per ml while stored at 4 C for 1 year. Virus in four freeze-dried tissue suspensions had a mean loss of 0.05 log LD(50) per ml held at 4 C for 1 year. None of the specific additives used for conservation of the virus during the freeze-drying process or during storage at 4 C contributed significantly to the stability of the virus preparations over and above that observed with the normal growth medium of the tissue culture or the ordinary diluents used in making suspensions of tissue virus.

Animals↗

Different public health geographies of the 2001 foot and mouth disease epidemic: 'citizen' versus 'professional' epidemiology.

Recently, there have been calls for health geographers to add critical and theoretical debate to 'post-medical' geographies, whilst at the same time informing 'new' public health strategies (Soc. Sci. Med. 50(9)1273; Area 33(4) (2002) 361). In this paper we reflect on how, alongside 'professional epidemiologies', 'citizen epidemiologies' can have credibility in informing public health policy and practice. We do this by drawing on mixed method and participatory research that used a citizens' panel to articulate the health and social outcomes of the 2001 foot and mouth disease disaster. We consider the difficulties of creating dialogue between on the one hand, time-limited, discrete, theoretical, visible and by implication legitimate, 'professional' knowledge and on the other, ongoing, holistic, experiential and often hidden 'citizen' knowledge of the foot and mouth disease epidemic. Despite significant evidence that in disaster and crisis situations, people need to be actively involved in key 'recovery' decisions (see for example At Risk Natural Hazards, People's Vulnerability, and Disasters, Routledge, London; A New Species of Trouble, Norton, New York), lay accounts, which may in themselves provide valuable evidence about the impact of the disaster, are often ignored. If health geographers are to critically inform 'new' public health policy then we need to consider research approaches that give voice to citizens' understanding of health outcomes as well as those of professionals. If 'new' public health is concerned with the material character of health inequalities, with fostering 'healthy' living and working environments, the promotion of community participation and individual empowerment (Area 33(4) (2002) 361), then we argue that situated, negotiated, everyday geographies of lay epidemiologies can and should inform public health policy.

Animal Husbandry↗

The administration of foot and mouth disease vaccine with oil adjuvant and its influence on the diagnosis of bovine tuberculosis.

The possible influence of vaccination with oil adjuvanted foot and mouth disease vaccines on the tuberculin response was investigated in 32 normal guinea pigs and 190 non-tuberculous bovines. Circulating anti-Mycobacterium bovis IgG antibodies were analysed by an enzyme-linked immunosorbent assay (ELISA), in order to determine the effect of the vaccination on the humoral response against mycobacteria in cattle. Control animals were either nonvaccinated or injected with aluminium hydroxide adjuvanted vaccine. Administration of foot and mouth disease vaccine had no apparent influence on the tuberculin responses of either guinea pigs or cattle, nor did it influence the level of anti-M. bovis antibodies in cattle.

Adjuvants, Immunologic↗

How predictable were the outbreaks of foot and mouth disease in Europe in 2001 and is vaccination the answer?

The author raises three important questions on the outbreaks of foot and mouth disease (FMD) in Europe in 2001: were these linked to stopping preventive vaccination, could these outbreaks have been forecast and were they avoidable, and is vaccination an efficient tool to control outbreaks? The replies to these questions are based on recent history of FMD in Europe. The author demonstrates that the 2001 outbreaks were not linked to ceasing vaccination in Europe in 1991. He also attempts to understand the reasons which encouraged the United Kingdom not to use vaccination to halt the progression of the disease, despite the clear demonstration that vaccination is a useful tool in arresting the spread of an epidemic. In conclusion, the author suggests that substantial changes to European policy for FMD control used for the past ten years are not necessary, but that recourse to emergency vaccination should be considered as an important control option in the future. This option should be optimised by ensuring that differential serological tests are performed in parallel with emergency vaccination, thereby enabling the identification and subsequent elimination of infected herds.

Animals↗

Foot-and-mouth disease virus 3C protease: recent structural and functional insights into an antiviral target.

The 3C protease from foot-and-mouth disease virus (FMDV 3C(pro)) is critical for viral pathogenesis, having vital roles in both the processing of the polyprotein precursor and RNA replication. Although recent structural and functional studies have revealed new insights into the mechanism and function of the enzyme, key questions remain that must be addressed before the potential of FMDV 3C(pro) as an antiviral drug target can be realised.

3C Viral Proteases↗

Electron microscope study of red cell membranes after experimental infection with the virus of foot-and-mouth disease.

Guinea pigs were inoculated with the Vallée O type strain of the virus of foot-and-mouth disease. 42 to 48 hours after inoculation red blood cells washed in saline were found to be infective for normal guinea pigs suggesting that erythrocytes carry virus entities at the height of generalization of the disease. This infection is no longer obtained at 92 hours after inoculation when general symptoms of the disease decline. A replica-transfer technique was developed with which hemolyzed blood smears could be observed under the electron microscope. By direct examination and also shadow-casting with palladium, normal red cell membranes show only a very fine structure on the surface. Rounded masses of high electron density appear in the ghosts between 24 and 72 hours after inoculation with virus. The number and particularly the density of these masses tend to increase from 24 to 42 and 72 hours. In some cases they are disposed preferentially in single lines forming ring figures; in other cases they are distributed at random. At 42 hours after inoculation it was possible to detect dense particles of 20 to 70 mmicro. within the masses. Measurements of 100 masses at 72 hours gave results ranging from 116 to 437 mmicro with a mean diameter of 246 mmicro. Results based on 105 electron micrographs and on thousands of cells demonstrate that practically all red cell membranes contained dense masses 24 to 72 hours after inoculation. 92 hours after inoculation, coinciding with the disappearance of infectivity of the erythrocytes, the masses could no longer be seen and the membranes looked entirely normal. Although the facts reported here may be suggestive of a relationship between the dense masses within the red cell membranes and the presence of virus entities in washed erythrocytes, no definite interpretation of these findings is postulated at present.

Animals↗

Foot-and-Mouth disease 'vaccination-to-live': possibilities and constraints.

Major constraints to the adoption of a 'vaccination to live' policy during an outbreak of foot-and-mouth disease (FMD) in a previously FMD-free country are the dual problems in the development of persistent infection (>28 days) in some vaccinated ruminants exposed to virulent virus and reliably detecting these persistently infected animals. Rapid advances in immunology, virology, molecular biology and information management present significant opportunities for improving the management of FMD outbreaks using a variety of scientifically advanced tools without the need for slaughtering large numbers of animals. A more rapid return to FMD-free status should be capable of being achieved without massive slaughter of animals through: (i) improvements in vaccine efficacy, onset of immunity, and marker specificity; (ii) development of anti-viral compounds as an aid in the control of outbreaks with or without vaccination; (iii) improvement of rapid diagnostic tests to detect early infection and persistent infection accurately and (iv) the capture, validation and management of data on animal identification, vaccination and infection status, and movement. The most effective improvements will occur if all these strategies are used in combination.

Animal Identification Systems↗

Molecular phylogeny of leader proteinase gene of type A of Foot-and-mouth disease virus from India.

We previously demonstrated the presence of three genotypes (IV, VI and VII) of type A (subtype A22) of Foot-and-mouth disease virus (FMDV) in India based on 1D gene sequence analysis. In the present study, the leader proteinase (L(pro)) gene sequences of 35 type A FMDV field isolates sampled over a period of 24 years (1977-2000) have been analyzed. Maximum-likelihood (ML) phylogenetic analysis revealed four distinct genetic lineages (A-D), indicating high divergence in L gene of type A FMDV. Lineages A and D correspond to the earlier genotypes IV, and VII, respectively. The genotype VI isolates were divided into two separate lineages (B and C) in the tree with high confidence values (96-99%). One isolate (IND 21/90) showed incongruous grouping between the (1D and L) gene-based analyses, which could be due to intergenotypic recombination. The ML molecular clock hypothesis was easily rejected on the data set studied indicating the absence of clock-like evolution in the L gene. ML codon-substitution models identified positive selection in the amino acid site 194 of C-terminal extension of the Lb(pro) with high posterior probability (>99%). The catalytic triad of the L(pro) at C-51, H-148 and D-163 were conserved across all the Indian isolates studied. Finally, amino acid differences between the lineages have been discussed briefly.

Amino Acid Sequence↗

Morphogenesis of vesiculation in foot-and-mouth disease.

The morphogenesis of vesiculation in cattle inoculated (aerosol expsoure) with foot-and-mouth disease virus was investigated by examining alternate, frozen sections of selected tissues stained by fluorescent antibody technique and with hematoxylin and eosin. Viremia preceded the development of lesions, and virus appeared to be transported to the epithelium via papillae. Lesions were initiated usually by the infection of single cells in the stratum spinosum adjacent to the papillae. Three types of lesions were observed. A vesicle developed mainly from the lysis of swollen, spherical cells and the release of intracellular fluid. The 2nd type of lesion was formed mainly by the accumulation of intercellular edema. The 3rd type was characterized by the absence of a vesicle due to seepage and loss of edema fluid and desiccation of the lesion.

Animals↗

Detection of carriers of foot-and-mouth disease virus among vaccinated cattle.

To investigate and optimise detection of carriers, we vaccinated 15 calves with an inactivated vaccine based on foot-and-mouth disease virus (FMDV) A Turkey strain and challenged them and two further non-vaccinated calves with the homologous virus four weeks later. To determine transmission to a sensitive animal, we put a sentinel calf among the infected cattle from 60 days post-infection until the end of the experiment at 609 days post-infection. Samples were tested for the presence of FMDV, viral genome, specific IgA antibodies, antibodies against FMDV non-structural (NS) proteins or neutralising antibodies. Virus and viral genome was intermittently isolated from probang samples and the number of isolations decreased over time. During the first 100 days significantly more samples were positive by RT-PCR than by virus isolation (VI), whereas, late after infection more samples were positive by virus isolation. All the inoculated cattle developed high titres of neutralising antibodies that remained high during the entire experiment. An IgA antibody response was intermittently detected in the oropharyngeal fluid of 14 of the 17 calves, while all of them developed detectable levels of antibodies to NS proteins of FMDV in serum, which declined slowly beyond 34 days post-infection. Nevertheless, at 609 days after inoculation, 10 cattle (60%) were still positive by NS ELISA. Of the 17 cattle in our experiment, 16 became carriers. Despite frequent reallocation between a different pair of infected cattle no transmission to the sentinel calf occurred. It remained negative in all assays during the entire experiment. The results of this experiment show that the NS ELISA is currently the most sensitive method to detect carriers in a vaccinated cattle population.

Animals↗

Ring vaccination against foot-and-mouth disease.

The study of the available information, notably after the epizootic of foot-and-mouth disease (FMD) which raged in Western Europe in 2001, shows that, in the current conditions of the international sanitary rules relative to this disease, in a FMD-free country of Western Europe accidentally infected, ring vaccination is a solution which, with regard to preventive slaughter, contains more inconveniences (notably economic) than advantages. The appeal to ring vaccination would be interesting only as far as the international sanitary rules would be modified by taking into account the results expected from the coordinated use of highly purified vaccines and differential research kits (vaccine-linked versus infection-linked antibodies). Propositions are this way made.

Animals↗

Simulated economic consequences of foot-and-mouth disease epidemics and their public control in France.

The efficient management of foot-and-mouth disease (FMD) epidemics in France was examined through a simulation model which combines epidemiological and economic modules. From the reactions of the importing countries in terms of the products subject to import bans and the regionalization commitments, the economic module assesses the financial consequences of FMD outbreaks borne not only by the breeding sector but also by the other economic sectors on regional and national levels. Among the control options for FMD, the strategy of stamping out infected herds and dangerous in-contact herds most often contributes to reducing the economic consequences of FMD epidemics. Implementing a campaign of emergency vaccination is socially optimal if the additional export losses associated with the delay of slaughtering the vaccinated animals are offset by the gains of reducing the duration of the FMD epidemic. The importance of reducing as much as possible the total duration of the import bans is stressed by the estimated cost of an extra week of import bans. The optimal control strategy was unaffected by the introduction of stochastic parameters.

Animals↗

Prevention measures against foot-and-mouth disease in Europe in recent years.

The paper describes the situation of foot-and-mouth disease in Europe over the past 2 years and analyses the origin of the disease during the last decades. Preventive vaccination has been banned in Europe in the early nineties. Since then, despite several incursion of the virus, the disease has always been rapidly contained and eradicated. Therefore the ban on vaccination did not result in an increase of FMD outbreaks. Based on the recent source of introduction of the virus, the author reviews the lines of defence which should be reinforced to reduce the risk of further introduction of the disease.

Animals↗

Long distance transport of foot-and-mouth disease virus over the sea.

The conditions required for the transport of foot-and-mouth disease (FMD) virus in the atmosphere over long distances and in sufficient concentrations to cause infection in exposed animals are described. Using these factors a series of 23 outbreaks of FMD in Europe, where the original outbreaks were separated from later outbreaks by sea passage, have been investigated. The findings obtained support the hypothesis that under certain conditions the airborne transmission of FMD over a long sea passage is possible.

Air Microbiology↗

A comparison of methods for measuring the antibody response in mice and cattle following vaccination against foot and mouth disease.

We present a comparison of methods for evaluating the potency of foot and mouth disease vaccine in the laboratory. The anti-FMDV antibodies (Ab) in vaccinated mice were tested by liquid phase (lp) ELISA, solid phase (sp) ELISA and virus neutralization (VN), and were compared with the Ab titres detected by lpELISA, which is the official test in Argentina for testing the potency of FMD vaccines and protection against a virulent challenge in cattle. The results demonstrated that it is possible to relate the Ab levels induced in vaccinated mice with both the Ab and protective responses elicited in cattle. Furthermore, it was found that the anti-FMDV Ab titres in mice detected by lpELISA 14 days after vaccination should be an accurate parameter for predicting the results of the challenge test in cattle. Thus, this test in mice appears to be an inexpensive and rapid alternative for testing FMD vaccines in cattle.

Animals↗

Modelling the initial spread of foot-and-mouth disease through animal movements.

Livestock movements in Great Britain (GB) are well recorded and are a unique record of the network of connections among livestock-holding locations. These connections can be critical for disease spread, as in the 2001 epidemic of foot-and-mouth disease (FMD) in the UK. Here, the movement data are used to construct an individual-farm-based model of the initial spread of FMD in GB and determine the susceptibility of the GB livestock industry to future outbreaks under the current legislative requirements. Transmission through movements is modelled, with additional local spread unrelated to the known movements. Simulations show that movements can result in a large nationwide epidemic, but only if cattle are heavily involved, or the epidemic occurs in late summer or early autumn. Inclusion of random local spread can considerably increase epidemic size, but has only a small impact on the spatial extent of the disease. There is a geographical bias in the epidemic size reached, with larger epidemics originating in Scotland and the north of England than elsewhere.

Animals↗

Molecular epidemiology of serotype O foot-and-mouth disease virus isolated from cattle in Ethiopia between 1979-2001.

Partial 1D gene characterization was used to study phylogenetic relationships between 17 serotype O foot-and-mouth disease (FMD) viruses in Ethiopia as well as with other O-type isolates from Eritrea, Kenya, South and West Africa, the Middle East, Asia and South America. A homologous region of 495 bp corresponding to the C-terminus end of the 1D gene was used for phylogenetic analysis. This study described three lineages, viz. African/Middle East-Asia, Cathay and South American. Within lineage I, three topotypes were defined, viz. East and West Africa and the Middle East-Asia together with the South African isolate. The Ethiopian isolates clustered as part of topotype I, the East African topotype. Two clades (based on < 12 % nucleotide difference) A and B were identified within the East African isolates, with clade A being further classified into three significant branches, A1 (80% bootstrap support), A2 (89% bootstrap support) and A3 (94% bootstrap support). Clade B consisted of two Kenyan isolates. Within topotype I, the 17 Ethiopian isolates showed genetic heterogeneity between themselves with sequence differences ranging from 4.6-14 %. Lineage 2 and 3 could be equated to two significant topotypes, viz. Cathay and South America. Comparison of amino acid variability at the immunodominant sites between the vaccine strain (ETH/19/77) and other Ethiopian outbreak isolates revealed variations within these sites. These results encourage further work towards the reassessment of the type O vaccine strain currently being used in Ethiopia to provide protection against field variants of the virus.

Amino Acid Sequence↗