Diseases

Salmonellosis

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Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    Several commercial immuno-diagnostic kits for S. Enteritidis and S. Typhimurium are available. These kits should be validated prior to use for surveillance purposes and are not suitable for vaccinated animals. PCR and micro-array based antigen tests are available and are in use for additional voluntary monitoring for Salmonella spp., but have not been validated for statutory use.

    List of commercially available diagnostics (Diagnostics for Animals).

    GAP:

    Need for validation of diagnostic tests and kits.

  • Commercial diagnostic kits available in Europe

    Several commercial diagnostic kits for S. Enteritidis and S. Typhimurium are available. A validated ELISA diagnostic kit has been developed at the OIE Reference Laboratory at the Veterinary Laboratories Agency in Weybridge UK.

  • Diagnostic kits validated by International, European or National Standards

    A validated ELISA diagnostic kit has been developed at the OIE Reference Laboratory at the Animal Health Veterinary Laboratories Agency in Weybridge UK.Numerous commercial diagnostic kits for Salmonella detection in foodstuffs are validated according to the EN ISO 16140 standard (validation managed from Afnor Certification). A molecular serotyping tests targeting the main Salmonella serovars including Typhimurium and Enteritidis has been developed and OIE validated.

    GAP:

    Validation procedures for molecular typing methods (i.e. molecular serotyping).

  • Diagnostic method(s) described by International, European or National standards

    ISO standards exist for isolation of Salmonella from food, animal feedstuffs and samples from primary production. Testing methods are also described in the OIE Manual of Diagnostic tests.

  • Commercial potential for diagnostic kits in Europe

    There is commercial potential for validated tests in Europe.

  • DIVA tests required and/or available

    Currently not available, except for S. Gallinarum 9R vaccine but may be generated should an appropriate vaccine available.

  • Opportunities for new developments

    Opportunities for rapid diagnostic detection at the farm level by authorities or official vets to reduce diagnostic time and spread of infected eggs into the market.

  • Vaccines availability

  • Commercial vaccines availability (globally)

    Inactivated and live Salmonella vaccines are available for S. Enteritidis and Typhimurium in mono or bivalent preparations. Inactivated vaccines include bacterins and autologous vaccine. Oral attenuated live vaccines include auxotrophic and metabolic drift mutants used to prevent Salmonella infections in poultry. Mutant vaccines attenuated rationally by molecular biological gene deletion techniques have been developed, including aroA mutants and strains with mutations in the genes encoding adenylate cyclase and the cyclic adenosine monophosphate receptor protein, which is available in the United States of America.In general, it is accepted than live Salmonella vaccines are more effective against both intestinal and systemic infection than are inactivated vaccine preparations largely, because they stimulate both the cellular and humoral arms of the immune system. Homologous immunity between strains of the same serovar is considerably stronger than between strain of different serovars. Vaccination schemes using combinations of live and inactivated Salmonella vaccines have been shown to be effective.

    GAPS:

    Multi -serovar/serogroup protection.Work to define efficacy of different serovar combinations programmes.Use of attenuated and safe Salmonella strains during egg production.Use of attenuated live S. Typhimurium vaccines in pig and cattle.

  • Commercial vaccines authorised in Europe

    The EU under the advice from EFSA recommends the use of vaccination as part of a comprehensive approach to Salmonella control. Mono or bivalent S. Enteritidis and S. Typhimurium attenuated live and inactivated vaccines are commercially available. Oral attenuated vaccines include auxotrophic mutant strains and metabolic drift mutant strains used to prevent Salmonella infections in laying hens and can clearly be differentiated from field strains.

    In Europe, genetically modified organisms are not permitted for use as vaccines.

    GAPS:

    Multi -serovar/serogroup protection.

    Work to define efficacy of different serovar combinations programmes

    Use of attenuated and safe strains during egg production.

    Use of attenuated live S. Typhimurium vaccines in pig and cattle.

  • Marker vaccines available worldwide

    Live vaccines can be used safely provided that detection methods are able to differentiate the vaccine strain from other wild-type strains. DNA Extraction and Real-Time PCRs for the differentiation of Salmonella vaccine strains from field strains have been developed.

    Parenteral administration of inactivated Salmonella vaccines will induce a strong production of antibodies than interfere serological testing.

    GAP:

    Development and availability of Marker vaccines.

  • Marker vaccines authorised in Europe

    Some live vaccines (metabolic drift mutant strains) may be differentiated by using markers such as resistance to antimicrobials. DNA Extraction and Real-Time PCRs for the differentiation of S. Enteritidis vaccine strains from field strains are available.

    GAP:

    Parenteral administration of inactivated Salmonella vaccines will induce a strong production of antibodies than interfere serological testing.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    In the EU, Salmonella vaccine programmes have been successful to reduce Salmonella prevalences in Member States.

    Live vaccines are effective because: they stimulate both cell-mediated and humoral (antibody-based) immunity, they are easier to administer through water, spray or feed, they stimulate innate immunity, they colonise the gut providing an exclusion mechanism and they provide at least some cross protection between serotypes.

    The current vaccines are claimed to reduce the infection and mortality in poultry and other species and therefore are not guaranteed to prevent infection. On this basis it is conceivable that infection may occur and also that this could lead to a carrier state without the knowledge of the animal keeper as the animal potentially did not exhibit clinical signs

    Periodical self-control Salmonella monitoring will correct this potential risk.

    GAP:

    Quantification of potential for reduced detection and design of monitoring programmes to correct for this.

  • Commercial potential for vaccines in Europe

    Salmonella vaccine use should be mandatory in those countries where high prevalence of infection is current.

    Vaccination of poultry already occurs and therefore there will be commercial potential for vaccines particularly if they can be designed to be readily identifiable from wild strains and also prevent infection.

    In the EU, S. Infantis, a group C serovar is the most common serovar isolated from broiler flocks and meat. There is no specific vaccine against S. Infantis. However, it seems that S. Enteritidis and S. Typhimurium based live vaccines can provide some cross-protection against S. Infantis colonisation.

    GAPS:

    S. Infantis specific vaccines.

    Multivalent vaccines.

    The period of excretion of vaccine strains after administration should be reduced to avoid the risk of contamination of the food chain with vaccine strains in broiler production.

    There is great potential for development of multivalent Salmonella vector vaccines to a range of organisms if objections to GMO vaccines can be overcome.

  • Regulatory and/or policy challenges to approval

    There is currently a surveillance scheme in Europe for Salmonella in chickens and turkeys and this will be expanded to pigs over the coming years. Any vaccine that cannot be distinguished from wild strains will not be approved for use.

    GAP:

    The period of excretion of vaccine strains after administration should be reduce to avoid the risk of contamination of the food chain with vaccine strains in broiler production.

  • Commercial feasibility (e.g manufacturing)

    Vaccination of poultry already occurs.There is no reason to believe that there will be a problem with new commercial vaccines. The limitation is the size of the market in relation to development and authorisation costs.

  • Opportunity for barrier protection

    In view of the ubiquitous nature of the bacterium this is doubtful on a national scale - but can be applied to individual holdings.

    European regulations penalizes trade in positive zoonotic Salmonella poultry flocks.

  • Opportunity for new developments

    The aetiology of Salmonella is multi-factorial, and so is the solution. Feed additives as acidifier, prebiotics, probiotics, symbiotics, bacteriophages, etc., have opportunities for development.

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    Generally, antibiotic treatment of flocks of poultry is not permitted for control of Salmonella unless there is a welfare implication or rare genetic stock would be lost if culled.

    Due to the emergence of antibiotic multi-resistant Salmonella strains, the successful control of Salmonella spp. is fundamentally based on the use of Good Farming and Good Hygienic Practices from stable to table. Control of Salmonella infections starts at the farm and includes qualified management in connection with strict cleaning and disinfection, insects (red mites and Alphitobius diaperinus) and rodents control and strict biosecurity.

    Prevention may be aided by the use of prebiotics, probiotics and competitive exclusion agents of organic acids added to feed or water.

    The development of new and successful bacteriophages active against Salmonella enterica in poultry and pig production is a promising tool for food preservation and safety.

    GAP:

    Effective interventions and assays for approval of such products.

  • Future therapy

    The use of antibiotics and supportive therapy (e.g. rehydration, antisera, anti-inflammatories) will continue. However, any new antibiotics to which the bacterium has not yet developed resistance will probably be restricted to use in human medicine for the foreseeable future.Effective cleaning and disinfection procedures, new disinfectants, Competitive Exclusion products and new bacteriophage cocktail to prevent Salmonella infection in poultry, pig and cattle is necessary.

    GAP:

    Animal specific treatments.

  • Commercial potential for pharmaceuticals in Europe

    In animal production the antibiotic potential use is thought to be limited. There may be some potential for human use of antibiotics.

    GAP:

    There may be a role for immune modulators – e.g. at the onset of lay in poultry or at calving in cattle and sheep.

  • Regulatory and/or policy challenges to approval

    New antibiotics will probably be restricted to use in humans.

  • Commercial feasibility (e.g manufacturing)

    The production of new antibiotics would be commercially feasible for use in humans but is unlikely to be so for use in animal production.

  • Opportunities for new developments

    Synthetic antisera, plantibodies, bacteriocins, phage therapy.Bacteriophage to prevent Salmonella infection in poultry, pig and cattle is a promising tool.

    GAP:

    Linked to this if disinfectants can be developed that are effective in heavily contaminated environments and therefore used to treat excreta before coming into contact with outside environments this may be of assistance.

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    Multiple organism tests that can rapid detect and characterise organisms. Simple lateral flow device type penside tests.

    GAPS:

    -Rapid detection, particular species or Salmonella spp.-Set-up Whole Genome Sequencing analysis on a routine basis.

  • Time to develop new or improved diagnostics

    This is dependant on the level of research required but could be considerable.

  • Cost of developing new or improved diagnostics and their validation

    Validation would need to be done by the reference laboratories and the cost could be substantial.

  • Research requirements for new or improved diagnostics

    Better quantification, in situ detection, multiple organism tests that can rapid detect and characterise organisms. Simple lateral flow device type penside tests.

    GAP:

    Better quantification, in situ detection, multiple organism tests that can rapid detect and characterise organisms. Simple lateral flow device type penside tests.

  • Technology to determine virus freedom in animals

    Not applicable.

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    The most effective vaccines would appear to be rationally defined genetically modified live vaccines that hyper-express multiple antigens but these GMOs are not permitted.

    Development of a genetically modified vaccine that would confer immunity against a multitude of serovars, other clinically relevant and zoonotic pathogens and would be distinguishable from wild strains both serologically and bacteriologically, and not mask the carrier state would be advantageous.

    Due to S. Infantis high prevalence in the EU, S. Infantis specific vaccines are required. Multi-resistant S. Kentucky is also a matter of concern. Multivalent vaccines are necessary for these emergent serovars.

    Live attenuated vaccines to be administered during the egg production cycle are of high interest.

  • Time to develop new or improved vaccines

    The time to develop a vaccine along the lines above would be considerable, not only for the development of the vaccines but also for convincing the authorities and the public to accept the principle of genetically modified organisms.

    GAP:

    Improved Programmes for best use of existing vaccines.

  • Cost of developing new or improved vaccines and their validation

    This could be substantial especially if a lot of time and energy was spent in convincing the general public regarding genetically modified organisms.

  • Research requirements for new or improved vaccines

    As above – plus social science investigation into vaccine acceptability - the GMO argument is likely to be largely old dogma now.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    The most promising development would be for an antimicrobial that was not susceptible to the development of resistance by the bacteria and one that could potentially be effective intracellularly to prevent the occurrence of membrane bound Salmonella containing vacuoles. Potentiating agents for existing products and combination therapies that avoid resistance development in the case of existing treatments would be beneficial also.

    Bacteriophages are uneffective alternative for Salmonella control. Development of new prebiotics, probiotics, bacteriocins and Competitive Exclusion products.

    New products against red mite, important Salmonella vector for the laying hen sector, are necessary.

  • Time to develop new or improved pharmaceuticals

    The development and licensing of new pharmaceuticals is a time consuming business and it is not unusual for this to take a minimum of 5 years.

    GAP:

    Investigate ways to speed up the authorisation process.

  • Cost of developing new or improved pharmaceuticals and their validation

    This could be substantial especially if a lot of time and effort was spent.

  • Research requirements for new or improved pharmaceuticals

    As above.

Disease details

  • Description and characteristics

  • Pathogen

    For named serovars, to emphasize that they are not separate species, the serovar name is not italicized and the first letter is capitalized. As for genus, species and subspecies the traditional italicized font is kept. In Salmonella enterica serovars, S. Enteritidis and S. Typhimurium are highly pathogenetic.

    GAP:

    Serovar variability in different countries and variability within a serovar.Emerging monophasic Salmonella variant of Typhimurium.Molecular identification.

  • Variability of the disease

    Among the Salmonellae there are considered to be at least 2500 serovars, although the two most commonly encountered in cases of food poisoning of humans are the two mentioned above. There are other S. enterica serovars that have specific hosts, e.g. S. Abortusovis in sheep. Others tend to be associated with certain hosts but can also infect others, including humans. For example S. Dublin infects cattle, sheep, humans and rarely poultry, but all seem capable of causing varying degrees of disease in most mammalian species. There is also a significant reservoir of antimicrobial resistance among these serovars.

    GAPS:

    Serovar variability in different countries and variability within a serovar.

    Poor knowledge of virulence factor, host-pathogen interaction in poultry.

  • Stability of the agent/pathogen in the environment

    Salmonella can survive for months outside a living body and have been found in dried excrement or contaminated feed after over 2.5 years. Ultraviolet radiation, heat and moisture accelerate their demise.

    GAP:

    Infectivity of environmental survivors

  • Species involved

  • Animal infected/carrier/disease

    Salmonellae are found worldwide in both warm and cold blooded animals but also in non-living environments. The symptoms of disease in animals vary according to the serovar involved and infection may be asymptomatic or symptoms may be mild enough to be missed, but equally may be severe enough to kill. Once infected, even if recovered, some animals may continue to shed certain serovars for years afterwards. Carriage and recycling of infection between older and younger or recently introduced animals or between livestock and wildlife vectors is common.

    GAP:

    Detailed longitudinal and quantitative data on herd infection and environmental contamination dynamics are needed.

  • Human infected/disease

    Humans are predominantly infected via ingestion of contaminated food but can also become infected as a result of direct contact with animals, especially cattle or pets, or by contact with environments contaminated with faeces, including contamination caused by infected cats and wildlife. Cross contamination of food during processing or preparation readily occurs.

    GAP:

    Risk ranking for food and contact sources, role of subclinical infection in humans and humans as a source of infection for animals and people.

  • Vector cyclical/non-cyclical

    On farms rodents, wild birds and insects may act as vectors along with the carriage of Salmonella on overalls, boots and hands of farm workers. Anyone who handles the carcasses of animals may also act as a vector along with mechanical objects used either on farm or in food processing facilities. Aquatic vertebrates may also act as vectors.

    GAP:

    Relative Risk of different vectors and infectious doses.

  • Reservoir (animal, environment)

    Salmonellae are relatively common in the natural world and therefore any animal or environment may act as a reservoir anywhere in the world. Some serovars have spread within certain animal species or production sectors (e.g. S.enteritidis in laying hens) thus permitting further spread into the environment. The act of spreading animal manure on land as fertilizer and wash water for irrigation can contaminate crops also.

    GAP:

    Genetic or management reasons for species association.

  • Description of infection & disease in natural hosts

  • Transmissibility

    Both horizontal and vertical transmission can occur. In poultry eggs may be vertically contaminated within the reproductive tract and the faecal-oral route allows horizontal spread. The bacterium has also been isolated from the litter and dust from poultry houses. Horizontal transmission to humans occurs via contaminated food, sometimes prepared by human carriers of the bacterium, excretions from carriers, inadequately cooked food and even by association with reptiles (pet tortoises and snakes). Most animal infection results from spread by carrier animals or contaminated feed. In poultry the hatchery is also an important potential source.

    GAP:

    Relative risk attributable to the different sources.

  • Pathogenic life cycle stages

    There are no specific life cycle stages involved although small numbers of organisms can survive in a dormant form that may be difficult to culture for long periods. Disease is caused by the rapid multiplication of the bacterium with secreted proteins permitting adhesion and invasion of the cells of the intestine with subsequent further proliferation causing an inflammatory reaction leading to dysentery. Invasion of intestinal cells is promoted by secreted proteins that subvert the host cells metabolic systems leading to internalisation of Salmonella cells and subsequent survival within macrophages. Systemic infection results from passage of viable organisms beyond the local lymph nodes into major lymphatics and the circulatory system. This is more likely with host-adapted strains in the relevant species.

    GAP:

    Detailed host pathogen reactions in main target species (as opposed to mice).

  • Signs/Morbidity

    Salmonellosis manifests usually as diarrhoea although clinical signs in animals can include septicaemia and abortion, as well as pneumonia and lesions of the distal extremities in calves. In humans the disease manifests itself by a watery and sometimes bloody diarrhoea, abdominal pain, fever, headache, nausea and vomiting. Acute cases in animals and poultry can lead to death and there is a serious loss of production. Death can occur in humans, especially amongst the elderly, but more normally the infected person is treated at home or occasionally in hospital. People who have been infected are not permitted to work in the preparation of food until they have been shown to no longer be excreting the bacterium.

    GAP:

    Level/cost of long term sequelae and risk of later premature death. Level of sub-clinical infection

  • Incubation period

    The incubation period is generally 12 to 72 hours.

    GAP:

    Detailed analysis of range in relation to infectious dose, matrix and strain.

  • Mortality

    Mortality may be high among acutely infected animals, particularly cattle, and also among the young and elderly of the human population. Mortality rates can vary significantly between the species infected and also the serovar involved. The type of strain within a serovar is more important than the serovar itself (virulence factors).

    GAP:

    Quantitative role of management and intercurrent disease to risk of mortality.

  • Shedding kinetic patterns

    Infection in most animals and humans resolves spontaneously within a period of weeks. Some animals that apparently recover from salmonellosis caused by certain serovars may become permanently infected and a small number may excrete the organism in their faeces for years. Others may harbour the disease in a latent form and only excrete the bacterium during periods of stress. Infection may circulate within an animal population, being passed to newly introduced animals which then excrete high numbers of organisms that may overcome the ‘immunity’ of some previously exposed animals. Infected humans are not allowed to work in food preparation until tests have confirmed that they are no longer shedding the bacterium.

    GAP:

    Details of shedding – variability, time and numbers – in food animals and in humans.

  • Mechanism of pathogenicity

    Disease is caused by the rapid multiplication of the bacterium with secreted proteins permitting adhesion and invasion of the epithelial cells of the intestine and loss of fluid and blood from the intestine. Proteins that appear to protect the bacterium from destruction by macrophages are also present. Once the bacterium has attained its intracellular state the cells metabolism is used to produce bacterial protein and bacteria can accumulate within membrane bound Salmonella containing vacuoles. Several serotypes of medical importance, including Typhimurium, Enteritidis, Newport, Dublin, and Choleraesuis, are known to harbour virulence plasmids containing genes that code for fimbriae, serum resistance, and other factors, but the full repertoire of virulence mechanisms is very complex, varying between serovars and clonal lines, and is still not fully understood. Systemic infection can result in sepsis within vital organs, bacteraemia and septic shock.

    GAP:

    Key virulence factors that could be targeted for sub-unit vaccines.

  • Zoonotic potential

  • Reported incidence in humans

    In 2005 the number of reported cases of salmonellosis in humans was 176,395 giving an incidence rate of 39.2 per 100,000 of the population in the EU. By 2008 the number of reported cases had reduced to 133,258 (131,468 confirmed; 26.4:1000 population). By 2009, it had reduced to 108,614 cases. This reduction has resulted largely from improved control of S. Enteritidis in poultry, but there has been an increase in S. Typhimurium, thought to be largely associated with increased pig meat- related cases in Denmark and in monophasic DT193 variants originating from pigs in many European countries.In 2015 the number of reported cases of salmonellosis in humans was 64,625 for the EU (European Food Safety Authority (EFSA) and European Centre for Disease Prevention and Control (ECDC) 2017).

    GAP:

    True level of under-diagnoses in most MS. Possible role of sero-surveillance and sentinel groups.

  • Risk of occurence in humans, populations at risk, specific risk factors

    The whole human population is at risk including those who work closely with cattle, have companion animals or are involved in the processing of food. The most serious cases are generally among infants, small children, the elderly and those with suppressed immunity. A more specific risk factor would appear to be an apparent lack of understanding of the need to maintain safe handling and storage of food, kitchen hygiene and proper cooking.

    GAP:

    Level of contact infections – esp. via environment versus food.

  • Symptoms described in humans

    In humans the disease manifests itself by a watery and sometimes bloody diarrhoea, abdominal pain, fever, headache, nausea and vomiting. In severe cases a septicaemia may develop and this can lead to complications which can give rise to conditions such as arthritis, septic aneurisms or other localised infections and osteomyelitis. Reactive arthritis and irritable bowel syndrome may also be sequels to enteric infection.

    GAPS:

    Quantitative distribution of such symptoms in comparison with other causes of intestinal infectious disease (IID).

    Signs and symptoms of Salmonella infection generally last two to seven days. Diarrhea may last up to 10 days, although it may take several months before bowels return to normal.

  • Estimated level of under-reporting in humans

    Since in its mildest forms the onset of diarrhoea may be relatively long and the duration short (up to 7 days) it is considered that the level of unreported cases may be as high as 30 times the number of reported cases in some countries. An overall rate of 10 cases per reported case is considered likely in the EU.

    GAP:

    As above – also – how significant are mild unreported cases in further spread and economic loss?Need for a harmonised notification system in EU.

  • Likelihood of spread in humans

    This is dependent on the level of hygiene among the population and spread of infection has been reported in care homes. Meticulous hygiene may prevent the spread from infected humans and animals, but it is not uncommon for a breakdown in the hygiene to occur and for cases to become apparent. This is emphasised in Europe by the need to prevent people known to be infected from working in the food preparation industry. In less developed countries the likelihood of spread is significantly greater especially where the sanitary treatment of human excrement is lacking. Salmonella can also survive in water and thus drinking supplies may also become contaminated.

    GAP:

    Detailed mechanisms of spread and doses involved

    - Iveson JB et al. (2014). Epidemiol Infect. 142(11): 2281-96 (Human migration)- Benschop J et al. (2010). Zoonoses Public Health. 57 Suppl 1:60-70. (Bayesian model)- Gal-Mor O. (2018) Clin Microbiol Rev. 32(1).

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    Salmonellosis control measures, disinfection, removal of excrement, spreading of manure only on fields that are not going to be grazed for a significant period, will help to control outbreaks and also improve the welfare of animals. Statutory monitoring of the situation in breeding and production flocks of poultry also effects control of the disease. Vaccination and culling of infected flocks are also important control measures in poultry.

    GAP:

    Lack of welfare studies in sick animals, assessment of pain and pain relief.

  • Endangered wild species affected or not (estimation for Europe / worldwide)

    Salmonellosis is widespread and worldwide and therefore there is no reason to believe endangered wild species would not be susceptible. However, the disease is usually associated with intensively reared livestock and the aftermath of such systems so it may be argued that wild species may not often come into contact with intensively reared livestock so the risk is minimised. Some wild animals, particularly reptiles, pigeons, small garden birds, badgers and hedgehogs carry specific types of Salmonella and there have been outbreaks of disease and deaths in finches caused by salmonellosis

    GAP:

    Role in wild bird fluctuationsRole of rodents in contamination of endangered species consuming rodents.

  • Slaughter necessity according to EU rules or other regions

    During outbreaks, especially if humans are infected, those animals that are harbouring the disease and acting as a reservoir are often subject of compulsory slaughter, but the disease itself is not normally associated with compulsory slaughter of large numbers of animals or birds, except in the case of breeding chickens or turkeys when S. Enteritidis or S. Typhimurium is confirmed or in certain countries where there is a ‘stamping out’ policy for most Salmonella infections in most food animal species.

    GAP:

    Impact of culling versus restrictions.

  • Geographical distribution and spread

  • Current occurence/distribution

    Worldwide.

    GAP:

    Reason for global spread of some strains but not others.

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Endemic – with periodic emergence of specific epidemic strains about every 10 years.

    GAP:

    Reason for rise and fall of epidemic strains. Source identification of new emerging strains.

  • Seasonality

    There is no true seasonality in the risk of outbreaks of the disease although the very young and young animals/birds are considered more susceptible and therefore there may be a perceived seasonality corresponding to the period when the young are particularly vulnerable. In some cases there may be an association with seasonal events, e.g. use of new season grain or movement of rodents from hedgerows. Human infection is greatest in the summer and this is thought to be associated with difficulties in maintaining low temperatures of food and use of undercooked meat after outdoor cooking.

    GAP:

    Good quality logitudinal studies on infection in relation to environmental temperature.

  • Speed of spatial spread during an outbreak

    Dependant on animal welfare and the removal or minimising of risk factors in the environment. Among young animals, especially those in intensive rearing situations, the spread of the disease is rapid. Spread between holdings can also be rapid if carrier animals, e,g, replacement breeding pigs, are distributed widely. Spread within a flock and sensitivity of the flock to high level of healthy carriage is dependant from the density in laying hens.

    GAP:

    Quantitative data to populate transmission models.

  • Transboundary potential of the disease

    Salmonellosis has been readily spread across boundaries, for example from breeder birds to layers and broilers and among calves taken to market and sold to calf rearers. Contract spreaders of manure may also be responsible for the spread of Salmonellosis if the manure has not been treated or the machinery carefully disinfected between farms. Spread between holdings and countries can also be rapid if carrier animals, e,g, replacement breeding pigs or hatching eggs, are distributed widely. Some cases related to exchange between EU member states, of contaminated straw used for animal litter were identified as a source of infection with SE in poultry flocks.

    GAP:

    Strain variation in spread.

  • Route of Transmission

  • Usual mode of transmission (introduction, means of spread)

    The faecal-oral route is the normal mode of transmission among animals and for humans this route may also be important but the more accepted route of transmission to humans is via the consumption of contaminated food.

    GAP:

    Quantification of infectious doses from different matrices and exposure routes.

  • Occasional mode of transmission

    Among intensive poultry in particular vertical transmission via the egg is a recognised route of transmission, probably due to a special affinity of some strains to the uterine mucosa of hens. Contamination of collected semen, e.g. from turkeys is also possible. Airborne spread may also occur via contaminated dust or aerosols.

    GAP:

    Relative risk of airborne spread.

  • Conditions that favour spread

    Intensive rearing of animals and poultry and lack of suitable hygiene procedures, especially all-in/all-out production and disinfection of housing between batches are the conditions favouring spread.

    GAP:

    Validated procedures for establishing and maintaining minimal Salmonella populations on large farms – especially pig farms.

  • Detection and Immune response to infection

  • Mechanism of host response

    The innate immune system is involved initially and this is followed by both humoral and cellular immune responses although Salmonella can survive in macrophages. Immunoglobulins are produced and it is these which may eventually aid the clearance of the bacterium. It should be borne in mind that the clearance is often not complete and stress situations can elicit a recrudescence of the bacterium suggesting that it has adapted to maintaining an intracellular presence despite the immune responses.

    GAP:

    Best approach to immunostimulation, vaccine routes, combination approaches, adjuvants.

  • Immunological basis of diagnosis

    A number of serological tests are available for the diagnosis of Salmonellosis. Whole blood tests and serum agglutination tests have been used for long periods and ELISAs are now in routine use. Dependant on the antigen and tests used serological cross reactions between different serovars and even with some non-Salmonella organisms can occur so bacterial isolation must be used for confirmatory diagnosis.

    GAP:

    Differential test for infected vs. vaccinated animals.Tool to assess cellular and local response.

  • Main means of prevention, detection and control

  • Sanitary measures

    Feed, food and water should be treated prior to consumption. Manure should be composted or effectively treated prior to being spread on the ground. Disinfection of the environment where animals are kept and of items coming into contact with either the animals or their excreta should be practised. Rigorous adherence to sanitation will minimise the risk but not prevent it completely. General biosecurity measures remained a good mean to avoid entrance of Salmonella into buildings.

    GAPS:

    Potential for applying competitive exclusion principles to overcome environmental contamination.Enhanced cleaning and disinfection.Biogas.

  • Mechanical and biological control

    The isolation or elimination of carriers and the prevention of cross contamination together with adequate disinfection permits a good but incomplete degree of control.

    GAP:

    What is best way to identify latent carriers?

    - Milho C et al. (2018). Biofouling. 30:1-16 (Use of bacteriophage)- Helke KL et al. (2017). Crit Rev Food Sci Nutr. 11;57(3):472-488 (drug resistance)

  • Diagnostic tools

    Whole blood tests and serum agglutination tests are still used along with ELISAs which have been validated. Cross reactivity among the serovars often occurs and therefore a definitive diagnosis of the serovar concerned involves isolation of the organism using bacterial culture methods. Antimicrobial susceptibility testing also should be performed.

    GAP:

    Better biomic methods to simultaneously and rapidly detect, type and characterise organisms:- Detection scheme according to the ISO 6579-1 standard- Semi-quantification by qPCR- 3M Molecular Detection System and ANSR Pathogen

    Detection System for rapid detection of Salmonella: Hu L, et al. (2017). Poult Sci. 1;96(5):1410-1418-Metagenomics (diagnostic signatures) : Huang et al. (2017) Appl Environ Microbiol. 17;83(3)).

  • Vaccines

    Many inactivated vaccines are used against salmonellosis which are often multivalent. Live vaccines have also been used in some countries. Mutant vaccines attenuated rationally by molecular biological gene deletion techniques have also been developed. EU legislation dictates that live vaccines shall not be used unless an appropriate method is provided to distinguish bacteriologically wild type strains of Salmonella from vaccine strains. Vaccination programmes shall be used during rearing to all laying hens in EU countries with more than 20% S. Enteritidis and S. Typhimurium prevalence in laying hens flocks (EU baseline study 2004).

    GAP:

    As above – plus potential for vaccination via spray.

    - Oral vaccine: Renu S, et al. (2018). Int J Nanomedicine. 30;13:8195-8215- Live attenuated vaccine: Zhi Y et al. (2018). J Microbiol.- Boosted vaccination (live vaccine): Methner U. (2018).Vaccine. 17;36(21):2973-2977.

  • Therapeutics

    Generally speaking, the use of antibiotics for the treatment of animals and humans with salmonellosis in many countries is limited because of the risk of further developing the incidence of resistance in the bacterium. Antibiotic treatment is normally restricted to those cases where the disease is serious and potentially life threatening. EU legislation states that antimicrobials shall not be used as a specific method for the control of salmonellosis in poultry, but this is often interpreted to mean regulated serovars only.

    GAP:

    Role of probiotics (which?) and painkillers/anti-inflammatory for therapy.

    - Molecule anti-biofilm : Moshiri J, et al. (2018). Front Microbiol. 9:2804- Food additives (ie: organic acid), competition flora.

  • Biosecurity measures effective as a preventive measure

    The checking of feed for the presence of Salmonella and the provision of dedicated protective clothing, hygiene barriers, and disinfection together with appropriate handling of excreta is appropriate. Where possible avoiding the movement of animals or birds onto the farm and, where this cannot be avoided the isolation and monitoring of bought in animals or pre-movement testing at source is advisable.

    GAP:

    Motivation of farm staff to ensure full compliance

    - Andres and Davies. (2015). Comprehensive Reviews in Food Science and Food Safety. 14:315-335.

  • Border/trade/movement control sufficient for control

    The general prevalence of Salmonella organisms would negate any reason to prevent cross border trade but the current surveillance on poultry would suggest that any infected poultry would not be acceptable for trade and similarly animals known to be infected would not be accepted. There is still room for improvement as there are frequent breaches in control involving animals from within and outside the EU.

    GAP:

    Design of reliable testing for International trade and detection of masking by antibiotic treatment.

  • Prevention tools

    Biosecurity, the use of disinfection and normal sanitary measures can be used but no method is 100% effective at preventing salmonellosis occurring because of the common occurrence of the organism and the high cost of intensive control programmes.

    GAP:

    Cost-effective priorities for control(Gavin C, et al. (2018). Prev Vet Med. 15;160:54-62)- The industry now uses: counterflows,, multichamber scalders, etc.; The processing involves more wash steps ; The use of antimicrobial chemical spray treatments (helped to reduce Salmonella or reducing the occurrence of cross-contamination).

  • Surveillance

    The EU has a specific surveillance procedure in place for monitoring the level of S. Enteriditis and S. Typhimurium infection in poultry with specific targets in terms of the percentage reduction to be achieved for breeding chickens, laying hens, broilers and turkeys.

    GAP:

    Verification of improved prevalence across MS

    - Source attribution.

  • Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

    Surveillance and slaughter techniques with poultry have reduced the number of human infections from eggs or poultry meat considerably since the inception of this method of control but there is no means of eradicating the disease and a varying level of infection still persists in MS. Sweden, Norway and Finland have achieved a very high level of control by means of stamping out and restrictions as well as intense feed controls, but as the size of farms increases such measures become increasingly unaffordable.

    GAP:

    How to create and maintain Salmonella-free niches in mainstream production.

    - Prevention, detection and control of Salmonella in poultry – OIE (2018).

  • Costs of above measures

    The cost of the ‘Salmonella in eggs scare’ in the UK in the early 1990’s which increased the level of surveillance and slaughter of birds is estimated to have cost £70 million. Whilst the current annual cost will be lower since there are fewer flocks of infected poultry slaughtered the cost of the continued surveillance will still be considerable and since this is now EU wide may be even higher than the figure quoted above. The ongoing costs for EU, producers and competent authorities of control programmes is very large, but is necessary to maintain market confidence. Public Health gains are not translated into benefits for industry.

    GAP:

    How to reward producers for effective control of Salmonella without encouraging ‘cheating’.

    - Fraser et al. (2010) Zoonoses Public Health. 57(7-8):109-115.

  • Disease information from the WOAH

  • Disease notifiable to the WOAH

    Salmonellosis is not an OIE notifiable disease.

  • WOAH disease card available

    No.

  • WOAH Terrestrial Animal Health Code

    Not available.

  • WOAH Terrestrial Manual

    Not available.

  • Socio-economic impact

  • Zoonosis: impact on affected individuals and/or aggregated DALY figures

    In general, the impact on human individuals is merely a case of dealing with diarrhoea for a few days. Where the disease progresses, antibiotic treatment may be required and ultimately hospitalisation. Occasionally the disease may be severe enough in the very young or elderly to be the cause of death

    GAP:

    Food consumption by affected people.

  • Zoonosis: cost of treatment and control of the disease in humans

    A 2011 report from the University of Florida stated Salmonella at the first rank with a total cost of illness of $ 3,309 million in the US for the year 2009.For 2016 in the Netherlands, it has been estimated that the mean total cost of illness (COI) due to Salmonella spp. would be around € 23-21 million.

    GAP:

    A detailed breakdown of the treatment cost by Member States (MS), and differential use of antimicrobials. Treatment failure rates in MS where AMR (Anti-microbial resistance) is high.Cost benefit analysis of EU measures against S. Enteritidis and S. Thypimurium must be evaluated to convinced member states of the interest of their investment in Salmonella prophylaxis.

  • Direct impact (a) on production

    The cost of production is associated with the cost to the farm of replacing animals or birds slaughtered because they are found to be positive for Salmonella together with the cost of disinfectants and vaccination. The cost therefore may be high. Deaths and clinical disease resulting is large costs are also common in cattle, but also occur in sheep, pigs and very occasionally poultry.

    GAP:

    True cost of low level disease and wet litter.

  • Direct impact (b) cost of private and public control measures

    There are a number of estimates of the cost of surveillance depending on which country is recording the cost but generally it is thought that the cost of surveillance alone is in the region of £ 3.4 million per annum.

    GAP:

    More detail needs to be gathered from European Commission claims for reimbursement.

  • Indirect impact

    The total cost of the ‘Salmonella in eggs scare’ in the UK in 1993 has been estimated at £70 million based on the cost of slaughtering infected birds and the 90% drop in consumption of eggs. Other reports of Salmonella (e.g. in pigs) appear to not have disrupted the market in the same way.

    GAP:

    No overall cost benefit analyses of Salmonella prophylaxis have been done at an EU level.

  • Trade implications

  • Impact on international trade/exports from the EU

    Other than the obvious restriction on infected animals there are no further restrictions on the international trade for this disease. Imports into the EU must conform with EU control legislation and countries must be approved for such imports. Certain third countries have additional requirements in relation to testing of breeding stock, companion animals and horses.

    GAP:

    Role of international trade in spreading infection – e.g. in pigs.

  • Impact on EU intra-community trade

    Other than the obvious restriction on infected animals there are no further restrictions on the international trade for this disease. There are special import guarantees for Sweden, Finland and Norway on account of their very low prevalence.

  • Impact on national trade

    Other than the obvious restriction on infected animals there are no further restrictions on the international trade for this disease.

  • Main perceived obstacles for effective prevention and control

    The widespread nature of the bacteria together with its longevity and diversity in the environment will be the main obstacles to prevention and control. It could be much more effectively controlled but the cost would be prohibitive in most cases.

  • Main perceived facilitators for effective prevention and control

    Should more effective prevention and control be available, the surveillance regime in the EU may be scaled down thus saving several million Euro per year.

    GAP:

    Design of a validation procedure for randomised testing to confirm continued high levels of control in the absence of a harmonised monitoring programme.

  • Links to climate

    Seasonal cycle linked to climate

    No.

    GAP:

    Certainty about this.

  • Distribution of disease or vector linked to climate

    There are a large number of vectors and in warmer climates the activity of wild birds, rodents and flies may be greater thus increasing the risk but generally there are no major climatic factors for the spread of the disease.

    GAP:

    Certainty about this.

  • Outbreaks linked to extreme weather

    This is a possibility as extreme rainfall, for example, may cause flooding which permits the transfer of water from polluted waterways to clean waterways thus increasing the environmental burden.

    GAP:

    Detailed studies on translocation by water – including non-municipal water supplies.

  • Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

    As the climate warms the activity of potential vectors may increase and therefore the risk of spread increases and the incidence of outbreaks will also be likely to rise unless greater care is taken in general hygiene.

    GAP:

    Spread in relation to vector population density and reproduction rate.

Risk

  • Salmonellosis in animals can lead to increased environmental contamination together with infected produce (eggs or meat) which can then cause outbreaks in the human population. Whilst these are generally self limiting they can occasionally lead to hospitalisation and ultimately to death. Epidemics have occurred in countries and have caused major reductions in the consumption of the offending produce thus risking the livelihood of the farmers as well. Salmonella can be transferred from meat to plant materials during food preparation so avoidance of meat may not rule out the risk of contracting the disease. There has been considerable build-up of resistance among the bacteria and therefore it is perceived to be a greater risk should the disease develop into one requiring hospitalisation.

    GAP:

    Relative risk and attribution resources and routes.Antimicrobial resistance gene transfer

Conclusion

  • Salmonellae are widespread in the environment and salmonellosis is most prevalent in areas of intensive animal husbandry. Many animals may be infected but show no clinical illness and are therefore important in relation to the spread of the disease. There is a need for improved diagnostic methods and techniques for strain identification and typing. Whilst strain identification has traditionally relied on biochemical and serological methods, phage typing of some serovars and antibiograms, genotypic analysis by molecular fingerprinting of DNA has been used in recent years.

    Legislation is in place in the EU for surveillance of farm animals, particularly poultry, and this is to be extended over the coming years in order to minimise the chances of contaminated farm produce causing disease in the human population but also to prevent food scares which could jeopardise the livelihood of farmers.

    Vaccines are available but better and more effective products are required and more needs to be known about the best use of vaccines in control programmes.

Sources of information

  • Expert group composition

    Antonia Ricci, IZS Venezie, Italy [Leader]

    Pietro Antonelli, IZS Venezie, Italy

    Laetitia Bonifait, ANSES, France

    Felix Ponsa, Elanco

  • Reviewed by

    Project Management Board.

  • Date of submission by expert group

    7 June 2019.