Foot and Mouth Disease - available
Control ToolsDiagnostics availabilityDiagnostics for FMD are only available from a small number of commercial suppliers. The main reagents used, can only be obtained from IAH-Pirbright or produced in National Laboratories. The main commercial reagents include serology kits for NSP testing while commercial kits for structural antibodies are highly limited and often focused on rather old methods, such as the liquid phase blocking ELISA. Commercial reagents for serotype specific solid-phase ELISAs and for broad reacting structural antibodies are needed. Several diagnostic kits need to be checked for performance in a number of hosts, in particular in wildlife. GAP: commercially available stable ELISA/LFD for typing of FMD. See above. Ref Labs: Virus isolation, antigen-ELISA, antibody-ELISAs, virus neutralization test, RT-PCR, sequencing. GAP: sufficient panels for test validation across all serotypes and species are lacking. Virus isolation, antigen-ELISA, antibody-ELISAs, virus neutralization test, RT-PCR, sequencing. GAP: sufficient panels for test validation across all serotypes and species are lacking. Low. NSP tests are available but more validations are needed. (Intended for eradication of disease or economic control of disease/ need and nature of the desired DIVA test). Serological tests can be used to help detect vaccinated and infected animals that show minimal disease. These tests rely on the fact that replicating virus, but not immunisation with purified vaccines, elicits an antibody response to the viral NSPs. An advantage of NSP serology tests is that they are not serotype specific and a single test can detect antibodies induced by all serotypes of FMDV. GAPS:
More effective and specific differential tests , faster diagnostics and field pen side tests. Vaccines availabilityInactivated, semi-purified FMD virus vaccines with either aluminium hydroxide and saponin adjuvants (aqueous vaccine) or as an oil vaccine (usually double oil emulsion (DOE)). Vaccines are usually inactivated by binary ethylenimine. Aqueous vaccines are generally applied subcutaneously while oil adjuvant vaccines are applied intramuscularly. Merial (UK marketing authorisation) and Intervet produce vaccines with market authorisation in EU Member States.Inactivated vaccine. EU and some Member States maintain reserves of deep frozen vaccine antigens that can be formulated into many doses of vaccine within a few days. GAPS:
Inactivated, whole virion FMD vaccines can be considered used as “a marker vaccine” provided that the purification process has removed most contaminating proteins, including viral non-structural proteins, from the vaccine. Sufficiently purified vaccines will only raise a host reaction against the structural proteins while a reaction towards the non-structural proteins, e.g. 3-ABC, can be used as a marker indicating infection rather than vaccination. See above. Current vaccines are rather efficient provided that they are applied before exposure to live virus (at least 1 week before exposure) and provided that the vaccine strain has been carefully selected to match the outbreak strain and provided that the sufficient amount of intact antigen is included in the vaccine and that the vaccine is of good quality. Consequently, the shortcomings of current vaccines are the need to vaccinate well ahead of virus exposure and the need of either knowing the antigenic characteristics of the outbreak virus strain or instead add multiple antigens to the vaccine, thereby increasing the costs significantly. In endemic settings, the need for regular booster vaccinations is a major constraint to maintaining protective levels of immunity, as is the heat labile nature of the vaccine, necessitating provision of a cold chain. There is a danger of virus escape from vaccine plants and from inadequately inactivated vaccines. GAPS:
The commercial potential for FMD vaccines in Europe appears to be low. A number of challenges including the current requirement for market authorisation and for potency testing in live animals. GAPS:
Commercially feasible but return on investment for expensive new vaccines may be limited. Multistrain registration has become possible in Europe and would make registration more affordable. GAP: governments should support the development of new vaccines, as there is no market in Europe and America for new products that might help developing countries to control FMD more easily. Feasible to produce buffer zones with vaccination to protect free areas from endemic areas. GAP: information on the cost effective application of buffer zones scanty. In the USA, adenovirus vectored vaccines may become commercially available within the next five years with potential advantages in their speed of onset of protection and with a reduced risk for FMDV escape during production or from incomplete inactivation. Another promising line of research is the development of recombinant empty capsids which may have enhanced stability and can be produced without the need to handle live FMDV. There is potential to create master seed vaccines for production of inactivated vaccines using recombinant technology to facilitate rapid changes in the vaccine, e.g. to alter antigenicity to better match emerging strains of FMD virus. Pharmaceutical availabilityNone. Interferons such as INF-alpha or gamma. Inhibitors of FMD virus replication, e.g. inhibitors of the viral RNA polymerase. Very low at present. Not applicable at present. Not applicable at present. Possible developments of antivirals or immune system stimulants. New developments for diagnostic testsBetter methods are needed for strain typing and vaccine selection. This may be done by e.g. hybridisation methods such as SNAP-ELISA or Micro-array or by rapid sequencing using e.g. pyrosequencing. New approaches to genetic characterisation allow tracing of the origin of infection down to the farm level. 2-5 years. Medium. Economical support for animal studies is essential. Such studies are very costly and it is of utmost importance that funding is available in order to get significant progress. GAP: new internationally validated (trade) methodologies for confirming freedom from virus are required. New developments for vaccinesVaccines can be improved in relation to several different properties. One could hope to increase the heat stability of the vaccines, or to e.g. make the response wider and thus covering more outbreak strains (subtypes) or even covering several serotypes. Vaccines may also be improved to provide a more rapid response and to include e.g. components of the innate of cellular immunity in order to potentially also protect against persistent infection. Mucosal vaccination might block virus entry. GAPS: FMD Vaccine needs for the future:
Long term. High. Limited at present. New developments for pharmaceuticalsAntivirals although problems are likely with resistance. Immunostimulants to complement existing vaccines to improve effectiveness. Long term. High. Limited at present. Disease detailsDescription and characteristics.A virus of the family Picornaviridae, genus Aphthovirus. GAP: FMD has been studied for many years, but despite this there are still significant areas of uncertainty in relation to pathogenesis, immunology, vaccinology, epidemiology and control. This is partly due to the limited number of places where such research can be performed under suitable containment conditions as well as limited field investigations in endemic areas. Consequently, significant research contributions are still needed to prove or disprove a number of dogmas on FMD before rational disease control, including vaccination, can be optimised. More research is now being done in economically emerging countries such as China and India. A wide range of variants is seen within the distinct serotypes. Different serotypes and strains are associated with different regions; some have a restricted distribution and others are widespread, differences occur between isolates in terms of pathogenesis, virulence and host range. Some serotypes such as the SAT types are less well understood from the antigenic variability and epidemiological aspects. GAPS:
Preserved by refrigeration and freezing and progressively inactivated by temperatures above 50°C. Inactivated by pH <6.0 or >9.0. Inactivated by sodium hydroxide (2%), sodium carbonate (4%), and citric acid (0.2%). Relatively resistant to iodophores, quaternary ammonium compounds, hypoclorite and phenol, especially in the presence of organic matter. Survives in lymph nodes and bone marrow at neutral pH, but destroyed in muscle when is pH <6.0 i.e. after rigor mortis. Can persist in contaminated fodder and the environment for up to 1 month, depending on the temperature and pH conditions. Humidity and other specific climatic, host and virus isolate conditions favour long distance aerosol spread. GAPS:
Species involvedFMD virus has a very broad host range and may infect both large and small ruminants as well as porcine species including both domestic and wildlife species. Ruminants, especially large ruminants, appear to play a special role as long time carriers of the virus and wildlife such as the African Buffalo are likely to play a significant role in maintaining the SAT serotypes of FMD virus. Other wildlife reservoirs may include various gazelles such as impala and Ugandan kop although these species are more likely to play a role in transmission of acute infection. Various species of deer can also be infected but do not usually play a significant role in viral maintenance. Pigs appear not to become carriers, however, during acute infection the excretion of virus from pigs are at a very high level and they are likely to play an important role as amplifiers of virus during acute infection. There are breed differences in susceptibility to FMD within a particular host species. Different husbandry systems and contact networks also influence the likelihood of virus transmission and persistence. GAPS:
Human infection is extremely rare. A number of cases associated with mild illness have been reported but very few are fully documented by isolation of virus and an increase in antibody titre. In one such case in 1966, the infection only resulted in a transient and mild disease with minor blisters which quickly healed. During the 2001and 2007 FMD outbreaks in the UK, there were cases of people suspected of being infected with FMD virus, however, where samples were evaluated using sensitive RT-PCR the virus was not detected. Transmission by e.g. stable flies is unlikely but has not been studied extensively and can therefore not completely be excluded. GAP: studies on mechanical transmission by vectors. Impala and buffalo can be involved in the epidemiology of FMD especially SAT strains in Southern Africa. Wildlife can become infected with FMD virus: buffalo, antelope, feral swine, deer, wild boar, Bactrian camels. GAPS:
Description of infection & disease in natural hostsDirect or indirect contact (droplets), Animate vectors (humans, etc.), Inanimate vectors (vehicles, implements), food-borne via contaminated animal products (swill). Airborne, especially in temperate zones (importance of long distant spread is controversial but up to 60 km overland and 300 km by sea have been reported). GAP: more studies are still needed to describe infection and disease in various hosts including role of different livestock species within different ecosystems as well as for various species of the camelidae and a number of wildlife, including the interplay among African buffalo, small and large wildlife ruminants (such as impala, Kop, kudu, blue wildebeest) and domestic cattle and small ruminants. Not applicable. Cattle
Sheep and goats Lesions in mouth and on feet are less pronounced and may go unrecognised. Agalactia in milking sheep and goats is a feature. Death of young stock. Pigs May develop severe foot lesions particularly when housed on concrete. Lesions form on areas of friction such as elbows and snout. High mortality in piglets a frequent occurrence GAP: the clinical signs are well understood, with the possible exception of the so-called “hairy panter” condition that has been ascribed to FMD. Short incubation period; generally 2 to 14 days, but can be as short as 1 day if pigs are infected through skin abrasions. GAP: limited knowledge on effect of infectious dose, virus isolate and adaption during outbreaks on incubation period. Frequently non-fatal disease for adult animals (2-5% mortality), though young animals can have a high mortality. GAP: limited knowledge on effect of infection on foetuses and abortion. Incubating and clinically affected animals Breath, saliva, faeces, and urine; milk and semen (up to 4 days before clinical signs) ; some animal products from animals killed during acute infection (including incubation period). GAP: transmission potential of infected aborted carcasses not known. Rapidly replicating lytic virus and damage from inflammatory immune response. GAP: mechanisms not fully understood, especially innate immune response component. Zoonotic potentialExtremely rare. No indication of human infection playing any role in the epidemiology of FMD. Probably low. Extremely low. Mild vesicular condition. Extremely low. Impact on animal welfare and biodiversityVery high impact on animal welfare which is intolerable in modern highly productive breeds of livestock. Control measures severely disrupt the care and movement of animals leading to significant welfare problems. Mass slaughter may be used for control. The severity of trade restrictions has more impact on animal welfare than the disease by itself. GAPS:
Potential to affect zoo animals and endangered species if these are culled as part of a control programme. GAP: we do not know how vaccines perform in most wild species. Slaughter of infected, recovered, and FMD-susceptible contact animals. Trade restrictions due to vaccination are still much more severe than after culling. Culling remains the preferred option in many countries. GAPS:
Geographical distribution and spreadFMD is widely distributed with only the rich (exporting) countries of Northern Europe, North America and Australia/New Zealand being completely free while many developing countries in Asia, the Middle East and in Africa, in particular, have significant problems with endemic FMD. GAPS: limited knowledge of circulating isolates in endemic countries, especially in Africa, and the potential for new variants to arise and spread. Can be a high frequency but with controls can be limited. Ro may be from 4 to 80 depending on circumstances. GAPS:
Not specifically related to season but in Europe often worse during the winter months and outbreaks may be linked to seasonal animal movements and trade practices, e.g. religious festivals in the Middle East. Climatic conditions such as drought and floods with subsequent changes in wildlife movement patterns and contact with domestic animals could lead to seasonal cycles especially in sub-Saharan Africa. GAPS:
High. GAP: conditions that favour the spatial spread not fully elucidated. High. GAP: movement patterns (both animal and human) and the factors that drive those not clear in endemic regions. Not specifically related to season but in Europe often worse during the winter months and outbreaks may be linked to seasonal animal movements and trade practices, e.g. religious festivals in the Middle East. Climatic conditions such as drought and floods with subsequent changes in wildlife movement patterns and contact with domestic animals could lead to seasonal cycles especially in sub-Saharan Africa. Not known at present. Not known but unlikely. Not known. Route of TransmissionFMD virus can be transmitted by a number of routes including movement of infected animals (and possibly by movement of carrier animals), by contaminated animal products e.g. by contaminated straw and fodder or by swill feeding, or by physical transfer on any contaminated surface including vehicles and people. GAP:
In addition to these routes of transfer, FMD virus can occasionally be transferred as an infectious aerosol from the breath of an infected animal. Infected pigs are the most likely to emit sufficient virus for the infectious aerosol to be transported by the wind for long distances under favourable epidemiological and climatic conditions. GAP: Very difficult to prove causation for airborne long-distance spread of FMD virus. Trade patterns induce price differences, which lead to more and longer distance transport of animals and animal products. Relatively high humidity, cold inversion conditions, little wind and relatively smooth geography. GAP:
Detection and Immune response to infectionSerum antibody appears quickly after infection and is associated with virus clearance. Furthermore, protection can be transferred between animals by antibody transfusion. Similarly, current vaccines elicit an antibody response that correlates quite well with protection. GAPS:
Antibody responses can be used to identify past infection and to help differentiate between previous infection and vaccination. GAP: Assays to distinguish between vaccinated and infected animals with improved sensitivity are needed. Mucosal IgA responses are starting to be studied as indicators of ongoing viral replication and IgM responses might help to identify recent infection. Main means of prevention, detection and controlProtection of free zones by border animal movement control and surveillance; Slaughter of infected, recovered, and FMD-susceptible contact animals; Disinfection of premises and all infected material (implements, cars, clothes, etc.); Destruction of cadavers, litter, and susceptible animal products in the infected area; Quarantine measures (Code Chapter 2.1.1.); swill feeding restrictions. GAP: Protection prior to vaccine induced immunity (0-7 days) is needed. Not applicable. Identification of the agent
- Virus isolation: inoculation of primary bovine thyroid cells and primary pig, calf and lamb kidney cells; inoculation of BHK-21 and IB-RS-2 cell lines; inoculation of mice Serological tests
GAP: Pen-side tests under development/evaluation. Gap in availability of commercialised tests for antibodies and for virus and tests that can serotype across all the variants within serotypes. Inactivated virus vaccine containing an adjuvant. GAPS:
Potential for e.g. interferons or specific inhibitors of viral replication. GAP: Little data available. More therapeutics should be identified. Advice given by Defra:
GAP: Quantitative analysis of secretion and excretion would help to identify the importance of different indirect transmission routes. Protection of free zones by border animal movement control and surveillance and restrictions on trade in animal products.
GAP: Risk of treated animal products not always known. Treatments for certain cultural products such as jerky, biltong etc not tested for virus inactivation. Vaccines, routine movement controls, animal identification, movement records. GAPS:
Notification and education, sero-surveillance in some circumstances. GAPS:
Variable. Needs good surveillance, vaccines and diagnostic tests. GAP: Critical success factors for eradication programmes in endemically infected countries. High but variable depending on the size and extent of an outbreak. Disease information from the OIEYes. http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/FOOT_AND_MOUTH_DISEASE_FINAL.pdf http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_1.8.5.htm http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.01.05_FMD.pdf Socio-economic impactNone. None. FMD causes considerable losses in livestock production by severely reducing animal productivity and reducing the value of affected animals. GAP: accurate figures on production losses especially on poor farmers are lacking. The economic impact is significant and prolonged for countries or regions with endemic FMD while epidemics, such as the UK 2001 epidemic, are extremely costly in terms of disease control, proving freedom from infection and by short or long term trade implications. GAP: The cost of vaccination campaigns and other control measures such as fences, permit systems to trace movement is not quantified in many countries and regions. Major economic impacts with disruption of food supply, constraints on production and impact on the welfare of animals subject to the controls. Control measures have a major impact. GAP: accurate figure are lacking. Trade implicationsSevere trade difficulties especially with overreaction in some circumstances. Can cause major disruption to trade within the community. The internal control measures cause major disruption especially with movement standstills and controls on animals. Main perceived obstacles for effective prevention and controlThe main obstacle for effective prevention and control, in particular in the developing world, are the availability of HIGH QUALITY and AFFORDABLE vaccines that have been accurately selected and matched to the circulating virus strains. This need to be supported by sufficient resources to the veterinary services in order to ensure an adequate and rapid response in relation to outbreak surveillance and examination and for establishing movement controls and improved biosecurity measures etc. Developing countries have many other priorities and limited resources so incentives to tackle FMD control are needed. Transboundary nature of disease requires concerted regional approaches to control. Lack of knowledge on circulating isolates in endemic regions may impact on the efficacy of vaccination campaigns. GAP: gaps regarding FMD vaccines and knowledge on circulating viruses have been mentioned. Main perceived facilitators for effective prevention and controlIncentives, regional cooperation, better vaccines, diagnostic tools. RiskSignificant funding for the above mentioned activities will clearly improve our understanding of FMD epidemiology and control and will have a very good chance of leading to improved disease control. The next 2-5 years may not necessarily lead to any significant new and improved products, but will anyhow provide a better background for using current vaccines and diagnostic methods. ConclusionFMD is a very important animal disease with a considerable impact on the economy of many developing countries with endemic infection and also having considerable trade implications when an outbreaks occur in a previously free region. Increased funding to study this infection in detail, in particular for studies focusing on improved vaccines, treatment or disease control, is likely to result in significant progress in terms of reducing the presence of endemic FMD worldwide and in reducing the risk of introduction to previously free regions. Different approaches are required for the free countries and the endemic countries. |
