Diseases

Environmental mastitis (E. coli, Str. uberis)

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Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    Standard laboratory procedures are available for identifying the invading pathogen and its sensitivity to antibiotics. Molecular test are also available.

    GAP: Accurate diagnosis of infected animals and tools to identify susceptible animals.

  • Commercial diagnostic kits available in Europe

    Standard laboratory procedures are available for identifying the invading pathogen and its sensitivity to antibiotics. Molecular test are also available. Pre-commercial tools under development.

    GAP: Accurate diagnosis of infected animals and tools to identify susceptible animals.

  • Diagnostic kits validated by International, European or National Standards

    None.

    GAP: Diagnostic kits validated by National or International Standards.

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

    None.

    GAP: Diagnostic method(s) described by International standards (i.e. OIE / EU).

  • Commercial potential for diagnostic kits in Europe

    No.

    GAP: Accurate cost/benefit assessment of new methods.

  • DIVA tests required and/or available

    No.

  • Opportunities for new developments

    Whilst the conventional microbiological methods are still the most efficient way to identify pathogens several other methods have been proposed and/or investigated. Molecular methods could be the future, mainly if they will enable to identify the relevant environmental strains involved in environmental mastitis.

    GAP: Standardised typing systems.

  • Vaccines availability

  • Commercial vaccines availability (globally)

    An inactivated E.coli vaccine is available commercially.

    GAP: Standardized methods to evaluate effectiveness of the vaccines under field conditions.

  • Commercial vaccines authorised in Europe

    An inactivated E.coli vaccine is available commercially coupled with S.aureus. GAPS:
    • Data on efficacy under field conditions are still missing.
    • Standardized methods to evaluate effectiveness of the vaccines under field conditions.
  • Marker vaccines available worldwide

    No.

  • Marker vaccines authorised in Europe

    No.

  • Effectiveness of vaccines / Main shortcomings of current vaccines

    The indication for the control of mastitis for the current inactivated E.coli vaccine appears to have been removed from the current SPC suggesting that the effectiveness of the vaccine is questionable.

    GAP: The effectiveness of vaccines for controlling mastitis is a question that needs addressing prior to any serious commercial involvement.

  • Commercial potential for vaccines in Europe

    GAP: The effectiveness of vaccines for controlling mastitis is a question that needs addressing prior to any serious commercial involvement.

  • Regulatory and/or policy challenges to approval

    Currently none.

  • Commercial feasibility (e.g manufacturing)

    To be determined.

  • Opportunity for barrier protection

    No.

  • Opportunity for new developments

    The role of non specific udder immune defences has been suggested to be very important in preventing new infections. Very few studies addressed these aspects.

    GAP: Methods to improve the non specific immune defences are needed (immunomodulators ?) which enable the udder to reduce its susceptibility, independently from the bacteria involved.

  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    Teat sealants based on bismuth are available for dry cow use and dry cow and lactating cow intramammary preparations of antibiotics are available. Fly repellents may be considered to be of some value.

    GAP: New therapeutical protocols which efficacy should be assessed by standardized methods.

  • Future therapy

    Currently unlikely to change from current practice.

    GAP: New therapeutical protocols which efficacy should be assessed by standardized methods.

  • Commercial potential for pharmaceuticals in Europe

    Significant.

    GAP: A precise assessment of the role of mastitis therapy on the development of resistance for human pathogens. Current information suggest that this is very low, but MRSA reports are increasing, suggesting a potential risk that should be carefully evaluated.

  • Regulatory and/or policy challenges to approval

    None.

  • Commercial feasibility (e.g manufacturing)

    Feasible.

  • Opportunities for new developments

    Significant information are available on natural and synthesized antimicrobials.

    GAPS: Methods to apply non-traditional agents (i.e,. Nisin or an antimicrobial peptide) to reduce cost of therapy (no withdrawal time) and the risk for human being.

  • New developments for diagnostic tests

  • Requirements for diagnostics development

    The development of rapid identification and sensitivity testing methods may be beneficial.

    GAP: Standardized and Internationally accepted methods to assess accuracy.

  • Time to develop new or improved diagnostics

    Such methods could be useful straight away.

  • Cost of developing new or improved diagnostics and their validation

    Significant but could be viable.

  • Research requirements for new or improved diagnostics

    Data suggest that there strains more likely involved in environmental mastitis than others.

    GAP: Identification of relevant strains involved environmental mastitis and their virulence factors as a mean to improve diagnosis.

  • Technology to determine virus freedom in animals

    N/A

  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    Vaccination needs to develop protective immune response without the induction of clinical signs following infection. The identification of suitable vaccine targets is THE drawback eliciting an immune response in the udder.

    Vaccination would need to elicit an immune response in the udder which would substantially (>50%) reduce the incidence of new intramammary infections. At present, the current E. coli vaccine reduces severity of acute IMI and there are no approved S. uberis vaccines on the market.

    GAPS: Currently the core vaccine will minimize the severity of the disease, but it will not impact the incidence. Data on combined E.coli/S.aureus vaccines are still not available on large scale in Europe.

  • Time to develop new or improved vaccines

    From identification of suitable targets commercial timelines indicate around 10 years to market. Significant and dependant on overcoming the main drawback. From identification of suitable targets commercial timelines indicate around 10 years to market. Significant and dependant on overcoming the main drawback.

    This is dependent of a better understanding of immune response to the different types of bacteria, new delivery technology, and new antigens. Minimum time required is 7-12 years and it could be much longer.

    GAP: Substantial advances in this area will require a multi-disciplinary, multi-site approach.

  • Cost of developing new or improved vaccines and their validation

    Significant. Total development cost including research investments would be US$15-20M per pathogen.

  • Research requirements for new or improved vaccines

    Identification of effective vaccine targets. Multi-disciplinary, multi-site approach with close interactions with an industrial partner.

    GAP: Financing the development of multi-disciplinary, multi-site research groups and their interactions.

  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    Preparations which could provide effective antibiotic action potentially intracellularly to remove intramammary sub-clinical infections and anything to neutralise endotoxin would be of benefit.

    GAPS: The lack of antibacterial discovery programs in animal health companies that are responsible for finding new compounds for potential mastitis therapeutics is a substantial obstacle. Moreover, there are fewer individuals that have training specific to antibacterial discovery available to manage these programs.

  • Time to develop new or improved pharmaceuticals

    Could be significant: 10-15 years.

  • Cost of developing new or improved pharmaceuticals and their validation

    Could be significant. Average cost to develop a new lactating cow product is US$35M.

  • Research requirements for new or improved pharmaceuticals

    Research in pharmaceutical are leaded by human side and this allows to have the most update technologies available specially at the industrial level.

    GAP: There are fewer individuals that have trainings specific to antibacterial discovery available to manage these programs.

Disease details

  • Description and characteristics

  • Pathogen

    Conventionally considered to be E. coli or Str.uberis although other Gram-positive species (Str.dysgalactiae, Enterococcus faecalis and Enterococcus faecium) and Gram negative species (Klebsiella spp, Serratia spp and Pseudomonas spp) are also implicated as environmental pathogens of the bovine udder. Implication of an environmental source is more likely that direct evidence. Such data is typically exemplified by a diverse population of the pathogen within one herd.

    GAP: Standardised typing systems to establish a likely environmental transmission.

  • Variability of the disease

    E.coli pathotypes include enterotoxigenic E.coli (ETEC); enteropathogenic E.coli (EPEC); enteroinvasive E.coli (EIEC), (found only in humans); enterohaemorrhagic E.coli (EHEC); and enteroaggregative E.coli (EAEC), (found only in humans).

    EHEC is found in humans, cattle and goats and includes 0157:H7 serotype which uses bacterial fimbriae for attachment and is moderately invasive and possesses a phage encoded Shiga toxin that can elicit an intense inflammatory response.

    The genus Streptococcus consists of of Gram-positive, facultatively anaerobic cocci occurring in pairs or chains; Species within this genus are responsible for a range of different diseases in a variety of distinct species. Streptococcus uberis is only rarely associated with diseases other than mastitis in ruminants and is not considered a human pathogen. Streptococcus dysgalactiae is closely related to other species (Streptococcus equisimilis) that cause disease in other species including humans but Streptococcus dysgalactiae is rarely associated with diseases other than mastitis in ruminants and septic arthritis; typically in lambs.

    The genus Enterococcus contains a variety of species capable of opportunistic infection in a number of species including humans.

    The genus Lactococcus is considered avirulent in most circumstances and its involvement in mastitis is limited and its role as a primary cause of infection should be questioned.

    In no instance have specific groups or phylogenetic clusters of strains with any of the Gram positive or negative species been shown to be predisposed to cause infection.

    GAPS: Country and regional differences in the types of pathogens found. There is a significant need in a better understanding of the epidemiology of S uberis. Recent data using PFGE analysis has suggested that some strains are capable of acting as contagious pathogens. Standardised typing systems are needed to establish a likely environmental transmission and to study Streptococcus mastitis molecular epidemiology.

  • Stability of the agent/pathogen in the environment

    S. uberis has been detected in soil for up to 2 weeks after grazing in winter. Experiments have shown that when faeces containing E coli have been deposited on grass the organism was transferred to the soil where it was detected even after the faeces had decomposed. On soil cores containing rooted grass E coli have been demonstrated to persist for several months.

    GAP: The importance of stability of the organism and repopulation. Are there many types of environmental mastitis pathogens that can cause IMI and are constantly repopulated? Or are there a select few types and thus stability is of importance.

  • Species involved

  • Animal infected/carrier/disease

    Bovine; goats may also be affected by these organisms as can humans and any one of these species may be a carrier. Limited circumstantial evidence that pasture used for sheep grazing may be contaminated with S. uberis resulting in infection of cattle.

    GAP: It has been suggested the presence of chronic E. coli mastitis, but this should be confirmed by standardized typing methods and by additional information on genetic differences in chronic and acute strains.

  • Human infected/disease

    Yes. Infection with these organisms is potentially serious and can, in the case of E coli EHEC be fatal. S. uberis only very rarely implicated in human disease most of those reported to date have been misidentified as uberis and are another organism. Enterococcus is a known agent of opportunistic infection in human population links with cattle not yet established.

    GAP: Risk assessment of transmission of E.coli EHEC among cattle in dairy herds as a potential risk for human.

  • Vector cyclical/non-cyclical

    These are environmental pathogens that may be transmitted by contact with the environment but may also be carried, for example, by insects.

    Survival of S.uberis in the environment eg in pasture has been shown to be affected by climate (humidity, UV exposure etc).

    GAP: The importance of other animal vectors, such as insects, in transmission of this complex disease.

  • Reservoir (animal, environment)

    There is a significant environmental reservoir but there are also animal reservoirs. S. uberis has been isolated from many sites on the cow including the skin surface, genital tract, intestinal tract and tonsils. E coli lives in the gut of ruminant animals, including cattle, goats, sheep, deer, and elk.

    GAP: Full knowledge of the environmental reservoirs of other streptococci, coliforms and enterobacteriaceae is lacking.

  • Description of infection & disease in natural hosts

  • Transmissibility

    Horizontal transmission via contact with other infected animals or the environment. Teat injuries, wet bedding and contamination with faecal material are important risk factors. It is also postulated that increased milk flow capacity in cows is leading to increased milk leakage which is seen as another risk factor. The rate of new infections is higher during the dry period and the rate of infection is higher during the first 75 days post partum and increases as the lactation number increases.

    S. uberis may be shed form milk in high numbers without overt signs of disease (pre-clinical phase or subclinical infection) during this time the organism may be present in numbers such that an infectious dose for another quarter may be contained within less than 1 μl of secretion. (thus S.uberis can appear to act as a contagious pathogen even after acquisition from an environmental source)

    GAP:

    • The genetic predilection for transmission and establishment of environmental mastitis is lacking.
    • The role of host in susceptibility has been suggested (at teat, udder and animal level), but a there several gaps in environmental mastitis pathogenesis to be filled.
  • Pathogenic life cycle stages

    N/A.

  • Signs/Morbidity

    There are 3 main clinical presentations:- acute toxic mastitis where the cow is acutely sick and may be recumbent. The udder may show a variety of changes including swelling, heat, pain and the milk may look watery and discoloured. Endotoxin producing Gram negative bacteria are often the pathogens involved

    Mild/Moderate Clinical Mastitis commonly recognised as a clinical case usually treated by the farmer whereby the udder becomes swollen and clots appear in the milk. A number of pathogens may be involved. In moderate clinical mastitis the cow will be systemically ill as noted by reduced milk production, reduced feed intake, and inflamed affected mammary quarter. In mild clinical mastitis the mammary gland may or may not be clinically inflamed but the milk will be demonstrably abnormal with visible changes in milk composition.

    Subclinical Mastitis does not cause obvious visible changes to the milk. An increased somatic cell count (SCC) occurs. This type of mastitis is commonly associated with S. uberis and is important as the cows may become a reservoir of infection. Subclinical mastitis due to the Gram negative bacteria is more rare than the clinical forms of the disease, relative to the streptococci.

    GAP: Longevity of animals in the milking herd after they have been treated for environmental mastitis, as delineated by pathogen type and severity of infection.

  • Incubation period

    Once the pathogen has gained entry to the udder a matter of hours may be involved. Experimentally induced E coli mastitis has been induced within 12 hours of infection.

    Experimental challenge with virulent S. uberis in early lactation animals induces overt disease typically within 5 milking post infusion. Later lactation animal may harbour the same strain for longer periods (i.e. 14 days) before signs appear. Other, less virulent strains may be present within the secretion for longer periods even at high numbers (>106 /ml milk) before clinical signs are evident. These strains are typically equally infective as more virulent strains and may be a source of infection within a herd.

    GAP: The incubation period for environmental streptococci under field condition is a matter of discussion and more information are needed to improve preventive and therapeutical protocols.

  • Mortality

    Generally not considered as a cause of death except in the case of acute toxic mastitis although culling may be carried out of cows showing repeated episodes as these may be carriers of the environmental pathogens.

  • Shedding kinetic patterns

    Pathogenic organisms shed during infection and, in the case of sub-clinical mastitis, may continue to be shed during a prolonged period either continually or intermittently.

    GAP: The information coupled with genetic predilection for transmission and the role of host in susceptibility are needed to improve control programs.

  • Mechanism of pathogenicity

    Multiplication and potentially also via endotoxin production. Various virulence factors from S.uberis have been investigated in vivo capsule, plasminogen activator were found not to be required. High affinity Mn uptake system was essential. Generally S.uberis replicates in the secretion and resists innate defences and phagocytosis by PMN; mechanisms underlying this are uncertain.

    GAPS: More data on environmental streptococci pathogenesis and on their suggested capability to invade epithelial cells are needed.

  • Zoonotic potential

  • Reported incidence in humans

    E coli EHEC are ubiquitous and zoonotic. S. uberis has occasionally been reported associated with human infection in most cases this was misidentification an unrelated bacterium. S. uberis is not considered to be a human pathogen.

    GAP: The potential for other zoonoses by other pathogens (Serratia sp., Pseudomonas) exists and could be investigated.

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

    The incidence of EHEC infections varies by age group, with the highest incidence of reported cases occurring in children aged under 15 years (0.7 cases per 100 000 in the United States). Contaminated food and contact with contaminated environments during farm visits are risk factors. There is no link between S. uberis in humans and contact with cattle or unprocessed milk products.

    GAP: Specific risk factors for E.coli EHEC in dairy cattle should be investigated to reduce risks for humans.

  • Symptoms described in humans

    Normally associated with severe diarrhoea which can lead on in the case of E.coli EHEC to severe and life threatening disease of other organs due to ingestion by the means of contaminated food.

  • Estimated level of under-reporting in humans

    Most cases reported in the EU but possibly under-reported in developing countries.

    GAP: Standardized reporting protocols.

  • Likelihood of spread in humans

    Highly likely if normal hygiene is not strictly followed.

    GAP: Specific risk factors for E.coli EHEC in dairy cattle should be investigated to reduce risks for humans.

  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    Animal welfare can have a profound affect on the incidence – for example by maintaining the areas for cattle to lay down by removing moisture and faecal matter, ensuring there is room enough to avoid trampling of teats, breeding for udder conformation.

    GAP: Mechanisms on how machine milking is affecting teat tissues, reducing cow welfare and increasing mastitis risks.

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

    No.

  • Slaughter necessity according to EU rules or other regions

    No. Culling used to remove persistently affected animals.

    GAP: Longevity of animals in the milking herd after they have been treated for environmental mastitis, as delineated by pathogen type and severity of infection.

  • Geographical distribution and spread

  • Current occurence/distribution

    Ubiquitous worldwide and despite application of known control procedures infection for S. uberis can still be common.

    GAP: Country and regional differences in the types of pathogens found.

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Endemic.

  • Seasonality

    Seasonal associated with the calving pattern of the herds/countries of the world. Climate has a significant affect and is related to episodic outbreaks of the disease.

  • Speed of spatial spread during an outbreak

    Dependant on animal welfare and the removal or minimising of risk factors in the environment. If contagiousness will be confirmed, infected animals should, for example, be milked last and preferably with equipment not used for healthy animals.

    GAP: Country and regional differences in the types of pathogens found. There is a significant need in a better understanding of the epidemiology of S.uberis. Recent data using PFGE analysis has suggested that some strains are capable of acting as contagious pathogens. Standardised typing systems are needed to establish a likely environmental transmission and to study Streptococcus mastitis molecular epidemiology.

  • Transboundary potential of the disease

    Generally low.

  • Seasonal cycle linked to climate

    Yes.

  • Distribution of disease or vector linked to climate

    In parts of the US, outbreaks of coliform mastitis are linked to wet weather in the spring of western states, and in the summer in Midwestern states.

  • Outbreaks linked to extreme weather

    No.

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

    Yes. Climate warming may enable cattle to be kept out in the fields for longer thus reducing the need for housing and the potential for wet or soiled bedding to harbour the organisms. It has, however, been recorded that the level of these environmental pathogens increases with increasing traffic on walkways between fields and milking parlour which also may affect the incidence.

    GAP: The impact of weather related targeted control strategies. For example, what are the economic benefits and costs in changing control strategies during periods when outbreaks are common?

  • Route of Transmission

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

    Horizontally via contaminated environment or intimate contact between animals. Fomites (e.g., milking equipment, udder cloths) are also a recognised means of spreading the disease.

  • Occasional mode of transmission

    None recognised.

  • Conditions that favour spread

    Poor husbandry both in terms of layout and material of bedding areas, improper maintenance of milking equipment, unhygienic measures for udder cleaning.

  • Detection and Immune response to infection

  • Mechanism of host response

    Generally swelling and inflammation of the mammary gland and associated degradation of the secretion which can spread to a systemic infection particularly as a result of endotoxin production. The response can be peracute, acute, or chronic.

    GAP: The genetic predilection for transmission and establishment of environmental mastitis is lacking. The role of host in susceptibility has been suggested (at teat, udder and animal level), but a there several gaps in environmental mastitis pathogenesis to be filled.

  • Immunological basis of diagnosis

    None

    GAP: Immune response measures may be helpful in predicting the success in treatment and future production potential of the host.

  • Main means of prevention, detection and control

  • Sanitary measures

    The use of individual wipes for udder cleaning prior to milking along with teat dipping pre- and post- milking can be effective in preventing mastitis along with effective treatment of any physical damage to the teats.

  • Mechanical and biological control

    Attention to maintenance of the milking equipment is a priority. The use of dry cow antibiotic therapy during the dry period is also recommended. Any measure which could reduce the exposure of the teat in the dry cow period is recommended. Acute toxic mastitis should be treated with intramammary and possibly systemic antibiotics together fluids with NSAID treatment to reduce heat, pain and swelling.

  • Diagnostic tools

    By visual symptoms and bacteriology which should include antibiotic sensitivity testing.

    GAP: Rapid tests (<24h) to identify as soon as possible the etiological agents to suggest proper therapeutical protocol.

  • Vaccines

    An inactivated E coli vaccine for the prevention of mastitis is commercially available. Vaccines for S.uberis subject of intense research activity

    GAP: Vaccine development and available vaccine improvement.

  • Therapeutics

    Both dry cow and lactating cow intramammary antibiotic infusions are commercially available as are NSAID’s for systemic use.

    Antibacterial resistance is generally not an issue for E. coli but can be a problem with selected strains of S. uberis.

    GAPS: The availability of an antibacterial therapy based on non-traditional agents (i.e,. Nisin or an antimicrobial peptide) that would not require a withdrawal period and can be used in organic herds is needed. Additionally, the availability of new traditional antibiotics would be useful.

  • Biosecurity measures effective as a preventive measure

    May be useful in preventing the incorporation of sub-clinically infected cattle into the herd but generally not thought to be important for prevention of mastitis.

    GAP: Whether outbreaks of environmental mastitis can be reduced by biosecurity measures.

  • Border/trade/movement control sufficient for control

    Mastitis is not seen as an impediment to movement.

  • Prevention tools

    The use of hygiene, teat sealants and milking equipment maintenance are important.

    GAP: Vaccine and immunomodulating agents development and available vaccine improvement.

  • Surveillance

    Limited Surveillance programs currently available.

    GAP: Long term multiyear surveillance programs that monitor pathogen prevalence and/or antibiotic resistance is needed.

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

    Reports appear to suggest that the incidence of environmental mastitis is increasing. Also, treatability of S.uberis appears to be declining, although true antibiotic resistance is not yet evident. Eradication is not a possibility.

  • Costs of above measures

    N/A.

  • Disease information from the OIE

  • Disease notifiable to the OIE

    No.

  • OIE disease card available

    No.

  • OIE Terrestrial Animal Health Code

    No.

  • OIE Terrestrial Manual

    No.

  • Socio-economic impact

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

    Endotoxin producing E.coli may have a profound effect on individuals requiring hospitalisation and occasionally may even lead to death.

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

    Significant costs are involved, particularly if hospitalisation occurs.

  • Direct impact (a) on production

    It has been estimated that mastitis costs between £69 and £228 per cow per year depending on the incidence of sub-clinical mastitis. Other estimates have placed a figure of £42 million on the disease. Estimated to be £42 million. Cost to UK alone estimated at £170M.

    GAP: Benefit cost scenarios for treatment and/or culling, relative to future production based on presentation of clinical state.

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

    Significant costs are involved, particularly if hospitalisation occurs.

  • Indirect impact

    Environmental mastitis generally not considered to impact greatly on these areas.

  • Trade implications

  • Impact on international trade/exports from the EU

    Environmental mastitis is not generally expected to impact this area.

  • Impact on EU intra-community trade

    Environmental mastitis is not generally expected to impact this area.

  • Impact on national trade

    Environmental mastitis is not generally expected to impact this area.

  • Main perceived obstacles for effective prevention and control

    Continued breeding for increased production per animal. Difficulty of establishing which animals may be sub-clinically infected.

    GAP: Accurate diagnosis of infected animals and tools to identify susceptible animals.

  • Main perceived facilitators for effective prevention and control

    Economic costs to the industry.

    GAP: Availability of preventive tools and efficient therapeutical protocols.

Risk

  • Environmental mastitis results in significant losses to the dairy industry and has the potential for transfer of endotoxin producing pathogens to be transferred to humans along with the possibility of the transfer of resistance to human pathogens.

    GAP: A precise assessment of the role of mastitis therapy on the development of resistance for human pathogens.

Main critical gaps

  • Information on host-pathogens interactions are still very few and controversial. Studies on these aspects are needed both to identify the most relevant virulent strains and to identify methods which will enable the udder to reduce its susceptibility, independently from the bacteria involved.

Conclusion

  • Whilst the use of dry cow and lactating cow intramammary antibiotics is acceptable to conventional dairy farmers it is more difficult for organic dairy farmers and their animals may well act a s a reservoir for the organisms involved. The use of the teat sealant by organic farmers is acceptable as it is with conventional dairy farmers but there is a potential problem with teat sealing if there is already a sub-clinical infection in the quarters. Stress and reduced immunity for example due to a leucopoenia caused by other infections can cause recrudescence particularly of sub-clinical cases.

Sources of information

  • Expert group composition

    Expert group members are included where permission has been given

    Alfonso Zecconi, University of Milan, Italy - [Leader]Larry Fox, College of Veterinary Medicine, Washington State University, USA Jamie Leigh, The University of Nottingham, UK Jeff Watts, Pfizer, USA

  • Reviewed by

    Project Management Board.

  • Date of submission by expert group

    17 September 2010.

  • References

    1st October 2010.