Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  • A number of commercially available tests exist for the detection of antibodies by ELISA.
  • A number of other tests are also available for the detection of antigens by ELISA and using fluorescent antibodies.
  • A number of commercial PCR tests are also available for the detection of C. abortus DNA.

  For specific tests see database Diagnostics for Animals.

  GAPS :

  • New tests are required for detection of persistently infected animals.
  • Tests to detect infection at point of care on farm are required.
  • Multi pathogen tests to detect infection due to the most common pathogens causing reproductive loss are required.
  • Commercial tests to distinguish natural infection in vaccinated flocks/herds should be developed (DIVA tests).
  • Companion C. pecorum-specific serological tests to determine relative incidence of both chlamydial pathogens in causing abortion.

• Diagnostic kits validated by International, European or National Standards

  Generally not.

  GAPS:

  • Test comparisons have been frequently reported in the literature, but large scale inter-laboratory comparisons are required to properly validate these tests. A big part of the problem, particularly for bovine infections is the lack of available known and validated positive and negative samples.
  • Some of the commercial serological tests claim that they are valid for use with cattle, but have not been validated for such use due to a lack of known and properly validated standardised serum samples.
  • Some of the commercial serological tests claim to be specific for detecting C. abortus when they are known to cross react with other chlamydial species, thus causing issues with regard to the detection of true positives.
  • European wide collections of standardised validated serum of known origin should be agreed and used in large scale inter-laboratory trials to properly validate commercial tests.

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

  Routine methods are described in the WOAH Manual of Diagnostic Tests and Vaccines: Chapter 3.7.5 Enzootic abortion of ewes (ovine chlamydiosis).

  1. Identification of the agent.

  a. Staining of smears of placental cotyledons, foetal stomach contents.

  b. Antigen detection ELISAs

  c. PCR and real time PCR of placental and swab samples, and/or foetal tissues/organs

  d. Isolation of C. abortus in embryonated chicken eggs or in tissue culture

  e. Immunohistochemistry

  2. Serology

  a. Complement Fixation Test

  b. ELISA

  GAPS :

  • The CFT should be replaced as the internationally recognised diagnostic standard with a more sensitive and specific serological test.
  • Need better agreement and standardisation between National Reference and other testing laboratories on the procedures and methodologies used for the routine diagnosis of C. abortus.

• Commercial potential for diagnostic kits in Europe

  As disease is endemic in Europe and throughout the world, the potential for commercial development of kits is clear.

• DIVA tests required and/or available

  • None of the existing serological tests can differentiate antibodies resulting from a natural infection and those induced by vaccination.
  • Two molecular methods (PCR-RFLP and High Resolution Melt PCR) have been developed for the differential detection of the live attenuated vaccine strain and natural wild-type isolates (differentiation of naturally infected from vaccinated animals, DIVA) based on single nucleotide polymorphisms.

  GAPS :

  • Serological tests to detect a natural infection in vaccinated flocks/herds should be developed (DIVA tests), validated through inter laboratory trials and commercialised.
  • A molecular DIVA test should be validated in inter-laboratory trials and commercialised.

• Vaccines availability

• Commercial vaccines availability (globally)

  Both inactivated and live vaccines are available, although the live vaccines are not available in all countries.

  See also section “Main means of prevention, detection and control/Vaccines”.

• Marker vaccines available worldwide

  No, although molecular markers have been identified for the C. abortus strain 1B commercial live vaccines.

  GAPS :

  This is one of the main aims in developing next generation vaccines.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  • The cost of vaccination is too expensive for many small and medium sized farmers in some countries.
  • The live vaccines have been implicated in causing abortion in some animals. However, on balance these vaccines do better than harm and continue to be recommended until safer, effective vaccines are developed.
  • The incidence and severity of abortions in ruminants can be reduced by the use of vaccines but at present these do not confer complete protective immunity nor do they completely prevent shedding at parturition. But both inactivated and live vaccinates are effective in reducing the rate of abortion and the amount of shedding post-parturition.

  See also section “Main means of prevention, detection and control/Vaccines”.

  GAPS :

  • Requirement for new, safer, cheaper vaccines to be developed based on recombinant antigen and other technologies.
  • Development of a marker vaccine than can be coupled with a new diagnostic test to enable detection of natural infections in vaccinated flocks/herds.
  • Develop a transformation system that will enable the generation of novel vaccines based on genetically modified organisms.

• Commercial potential for vaccines in Europe

  • High, particularly in those countries with endemic problems and high density of susceptible species of ruminants.
  • Pharmaceutical companies in some European countries are working with C. abortus experts to design more effective inactivated vaccines.

  GAPS :

  See section “Main means of prevention, detection and control/Vaccines”.

• Regulatory and/or policy challenges to approval

  Use of genetically modified vaccines might be problematic in some countries. The field trials may need specific regulation regarding the release of GMOs into the environment.

• Commercial feasibility (e.g manufacturing)

  Feasibility discussions are ongoing between scientific experts and some of the major animal health companies.

• Opportunity for barrier protection

  Currently used as part of a herd or flock control programme in many European countries.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  Long acting oxytetracycline is the antibiotic most commonly used. Although the drug is recommended to be given as a single dose to minimize any potential development of resistance, the aim of the treatment is to suppress multiplication of the organisms to counter an ongoing outbreak of chlamydial abortion, therefore further doses are often given until lambing is completed.

  GAPS :

  See section “Main means of prevention, detection and control/Mechanical and biological control and /Therapeutics.

• Future therapy

  Potential pharmaceuticals which will eliminate the organism in the latent and carrier state.

  GAPS :

  Development of natural biocides and bacteriophages as therapeutics?

• Commercial potential for pharmaceuticals in Europe

  Depends on price and demand. If more effective vaccines and health schemes develop then there should not be a major demand for new pharmaceuticals. Vaccination should be favoured due to selective pressures exerted by the common or prolonged use of tetracycline and the possibility of emerging antimicrobial resistance.

• Regulatory and/or policy challenges to approval

  No specific issues.

• Commercial feasibility (e.g manufacturing)

  Feasible if demand exists.

• New developments for diagnostic tests

• Requirements for diagnostics development

  • Validation of recently developed tests to identify latently infected animals and distinguish vaccinated from naturally infected animal (DIVA).
  • Comparison and evaluation of existing diagnostic tests on a pan-European scale.
  • Serological tests: Development of host species-specific serological tests.
  • Requirement for proper validated control sera in order to assess diagnostic tests and determine cut-offs for positivity.

  GAPS :

  • DIVA tests should be applicable for sheep, goats, cattle, and pigs.
  • Molecular methods to detect persistent infections in the host should be explored, as previously described in in vitro studies.

• Time to develop new or improved diagnostics

  In general, the development of tests is much faster and less expensive than developing vaccines. From development through validation to commercial availability will be time consuming and can take years.

• Cost of developing new or improved diagnostics and their validation

  The development and validation of new tests is time consuming and labour intensive which is costly. Costs cannot be specified as they will depend on the nature of the test and the cost of producing reagents and supplying reading or processing machines if necessary. Once validated there will need to be a commercial company willing to market the test.

• Research requirements for new or improved diagnostics

  • Validation of recently developed tests to identify latently infected animals and distinguish vaccinated from naturally infected animal (DIVA).
  • Comparison and evaluation of existing diagnostic tests on a pan-European scale.
  • Serological tests: Development of host species-specific serological tests for C. abortus and C. pecorum.
  • Requirement for proper validated control sera in order to assess diagnostic tests and determine cut-offs for positivity.

• Technology to determine virus freedom in animals

  Currently the technology does not exist to identify the latent carrier. This is a real technological challenge as the site of latency is unknown and may be difficult to sample routinely in a live animal. Accreditation schemes do exist where animals are monitored on a yearly basis to determine on a flock/herd basis whether infection is present on farm. This works well although anomalies do arise which can create difficulties for the farmer. Experimental studies show that following entry of infection into an animal a rise in antibody titre does occur, however this subsides as the organism latently persists in the non-pregnant animal. Catching this rise would require constant monitoring, which is impractical, but on a flock/herd basis it may be more feasible.

  GAPS :

  More robust serological based testing that will detect whether animals on a farm or flock/herd basis have become infected is needed as part of an accreditation scheme.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  There is a requirement for safer, more stable, cheaper alternatives to the current vaccines. These will likely be based on recombinant protein technology, as multi-component subunit vaccines.

  GAPS :

  Although various virulence associated antigens have been described for C. abortus, further research is needed to obtain a better understanding of the molecular mechanisms involved in infection, including the molecular functions behind the newly described ultrastructures in the organism’s developmental cycle. This may offer new perspectives for development of novel vaccine strategies as well as for diagnosis.

• Time to develop new or improved vaccines

  This would depend on the technology being employed, the identification of suitable candidate antigens, adjuvants and appropriate routes of delivery. Generally, once all of these issues have been resolved a timescale of 5-10 years to conduct efficacy and stability trials in pregnant animals, as well as licensing and marketing, would not be unreasonable.Employment of reverse vaccinology approaches to vaccine development could save money, time and labour and therefore enable faster movement to the clinical trial stages.

  GAPS :

  The big question is what do the pharmaceutical companies want in their next generation products, taking into consideration what is actually feasible from a scientific perspective? Discussions are ongoing between some scientific experts and the companies on this issue.

• Cost of developing new or improved vaccines and their validation

  This is difficult to quantify as it involves, in addition to the technological antigen discovery and proof of concept work, trials in pregnant sheep to determine efficacy, reduction of abortions, pathology and shedding. A single typical sheep vaccine trials costs in excess of €400,000 and takes over 9 months to complete. Following a series of such trials, safety field trials would need to be conducted in order to enable the product to be authorised. So, costs in excess of €2M would not be unreasonable.

• Research requirements for new or improved vaccines

  • Identification of relevant protective antigens, through genomic, bioinformatic, proteomic, immunological and biological approaches.
  • Novel adjuvants that promote an effective cellular immune response should be included in inactivated vaccine formulations together with a protective antigen.
  • Development of new approaches to vaccine development.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  No specific requirement.

• Time to develop new or improved pharmaceuticals

  Time to develop would depend on the product and the trials necessary to validate efficacy and safety. Commercial production would then take further time. Five to 10 years is a realistic timeframe.

• Cost of developing new or improved pharmaceuticals and their validation

  Expensive but difficult to assess as it will depend on the product and the trials necessary to validate and licence.

• Research requirements for new or improved pharmaceuticals

  No specific requirement.

Disease details

• Description and characteristics

• Pathogen

  • Chlamydia abortus(formerly Chlamydia psittaci serotype-1 or Chlamydophila abortus) is an obligate intracellular Gram-negative bacterium belonging to the family Chlamydiaceae.
  • The family Chlamydiaceae has undergone further reclassification since 2011, and currently comprises the reunified genus Chlamydia (formerly Chlamydia and Chlamydophila) which is composed of 13 species (plus four Candidatus species) in addition to C. abortus, including (affecting sheep, goats, cattle and pigs),
  • Chlamydia abortus is one of the most common causes of infectious abortion in small ruminants (sheep and goats) throughout Europe. The organism can also infect other animal species, including cattle, horses, pigs and wild ruminants.
  • has also been isolated from avian species, with such strains being classified into a newly recognised avian subtype by the International Chlamydiae Taxonomy Subcommittee in Aug 2022, with the ruminant/porcine strains classified into the newly recognised mammalian subtype.
  • Chlamydia abortus is also zoonotic and poses a significant risk during pregnancy for both the developing foetus and the pregnant mother.
  • Genetic diversity of C. abortus in different host species has been found to be very low with little of evidence of recombination compared to other chlamydial species.

  GAPS :

  • Extent of co-infections with other chlamydial species and effect on disease pathogenesis.
  • Impact of C. pecorum on abortion in sheep and goats in Europe (known to cause abortions in USA and Australia).

• Variability of the disease

  • The disease associated with C. abortus infection is variously known as ‘ovine enzootic abortion’, ‘enzootic abortion of ewes’ and ‘ovine chlamydiosis’.
  • Host range includes sheep, goats and cattle. Farmed game, wild and zoo ruminants, and pigs are also natural hosts. Sporadic infections have been described in the horse, mouse, guinea pig and rabbit.
  • Chlamydia abortus infection can cause severe reproductive disease in all affected species worldwide.
  • The pathogen can also result in spontaneous abortion or miscarriage if women are exposed to the organism during pregnancy and infection can also be fatal for the mother.
  • Sophisticated molecular typing tools, namely AFLP, MLVA, MLST and whole-genome specific SNP analysis have allowed the differentiation of genotypes partly related to geographical origin, but not to host.
  • Tphenotypic, genotypic and pathotypic traits) from other C. abortus strains, even among strains circulating in the same area. This LLG-variant represents one distinct lineage that has selectively maintained its genetic background for decades evolving independently from other C. abortus strains to such an extent that "subspecies" status has been suggested for it.
  • A number of avian strains, previously referred to as C. abortus-C. psittaci intermediate strains, have recently been suggested to be close evolutionary ancestors of C. abortus. These strains have been recently classified as a new avian C. abortus subspecies and that they may represent a missing link in the divergence of C. psittaci into C. abortus.

  GAPS :

  • Require greater information on strain and genotype diversity and how this relates to pathology.
  • Only a proportion of an infected naïve flock will abort. Why do some animals appear resistant to infection and disease?
  • Most research has been conducted on ovine disease. Need to determine the full host range and pathogenic potential in other domestic, farmed and wild animal species.
  • Ruminants are commonly infected with C. pecorum, which complicates the diagnosis of C. abortus infection. C. pecorum infections of sheep are generally subclinical whereas C. abortus infections generally give rise to clinical disease. What is the genetic and mechanistic basis for these wide differences in pathogenicity?
  • Role of C. pecorum in sheep and goat abortions in Europe compared to C. abortus?
  • Genome analyses of C. abortus isolates recovered from herds with mixed C. pecorum intestinal infections should be performed to reveal potential recombination events and potential emergence of admixture chlamydiae presenting differences in abortion dynamics and pathogenicity.
  • What factors underlie the geographic "specificity" of C. abortus variants/genotypes?
  • Determine whether the expansion of certain genotypes relate to some level of vaccine escape in countries where vaccination has been introduced.
  • Determine population dynamics of C. abortus through genetic investigation of isolatescollected locally over a long period.
  • Determine whether the pathogenic potential of the newly classified avian C. abortus strains in ruminant species.

• Stability of the agent/pathogen in the environment

  The organism is reported to be relatively stable in the environment and can survive for long periods (weeks to months) in freezing temperatures and for days during spring weather conditions.

  GAPS :

  • This requires further investigation due to limited published data and the importance of this question with regard to risks for transmission.
  • Need to investigate the viability of the pathogen (survival and stability) in potential transmission vehicles (bedding, water troughs, water courses, pasture, soil, abortion material), as well as under different climatic conditions (temperature, humidity).

• Species involved

• Animal infected/carrier/disease

  • Chlamydia abortus is a cause of abortion, stillbirth and premature birth of weak offspring in all affected species. Among livestock, sheep and goats are more severely affected.
  • Infections are persistent in non-pregnant animals, only manifesting clinically during pregnancy.
  • Generally, the first signs of any problem occur with the expulsion of a dead foetus 1-3 weeks prior to expected full term of parturition.
  • Higher rates of abortion occur in younger naïve animals.
  • After abortion, ewes and goats can remain persistently infected and be carriers of the organism for long periods but without suffering new abortions.

  GAPS :

  • What is the role of wildlife (foxes, rabbits, rodents, wild ungulates etc.) and birds (carrion, game, etc.) as carriers and/or reservoirs?
  • Investigate and compare host susceptibility and its determining factors for C. abortus infection: sheep and goat (enzootic abortions) vs. cattle and pigs (sporadic abortion cases); goats more susceptible than sheep.
  • Require further investigations to determine the anatomical site of latency or persistence.

• Human infected/disease

  • Literature suggests that cases in humans are relatively rare. However, infection can affect pregnant women resulting in spontaneous abortion or stillbirths depending on period of pregnancy when exposed. Such infections are most likely to result from direct or indirect exposure during the lambing or kidding season.
  • There are also reports of atypical pneumonia in laboratory staff. One human case of pelvic inflammatory disease in a woman resulting from C. abortus infection has been published.
  • During the COVID-19 pandemic, more cases of respiratory illness due to C. abortus have been reported. This is due to increased awareness, more testing and reporting.

  GAPS :

  • It is unclear if cases of abortion or respiratory illness in humans are under reported. Further epidemiological evidence and seroprevalence data is required to determine the true extent of exposure in contact persons (
  • Epidemiological studies on human cases are needed to investigate if chronic infection with C. abortus may be involved in the pathogenesis of tubal infertility and chlamydial pelvic inflammatory disease similar to the human pathogen C. trachomatis.
  • Diagnostic tools that allow the rapid and reliable detection of C. abortus in human specimens are needed.
  • Strengthen collaboration between human and veterinary medicine (One Health approaches).

• Vector cyclical/non-cyclical

  • Recent work reports the finding of chlamydial species in ticks. It is not unreasonable to expect that C. abortus is carried at some level in ticks from infected flocks/herds, although there is no direct evidence for vector transmission (most likely mechanical transmission) of this disease.
  • The role of ticks as vectors for transmission of C. abortus is considered to be negligible.

  GAPS :

  Determine whether vectors such as ticks, mites or fleas are involved as vectors (mechanical or otherwise) for transmitting infection.

• Reservoir (animal, environment)

  • Asymptomatic carrier animals infected with C. abortus are the main reservoir of infection.
  • Ewes can remain persistently infected after the initial abortion and limited evidence suggests they can excrete the organism and infect other naïve animals in a subsequent lambing/kidding season.
  • can persist in the environment for days to months, depending on weather conditions (temperature and humidity).
  • Transmission of C. abortus may occur between wild and domestic animals through sharing of grazing pastures.
  • The main sources of environmental contamination and transmission to susceptible animals are the aborting placentas, the foetuses and the vaginal discharges.
  • Vaginal excretions have been shown to be infective for up to around 7-10 days post abortion/lambing.
  • A lower level of infection may give rise to the premature birth of weak lambs of low weight that frequently die during the perinatal period or survive, possibly playing a role in the epidemiology of this disease.
  • Aborting animals may shed the microorganism during the following per-ovulatory period and at subsequent lambing, although evidence is limited.

  GAPS :

  • Determine the site of persistence of C. abortus in asymptomatic carrier animals (body/tissues site).
  • The main period of transmission is believed to be lambing time. Transmission may also occur outside of this period but is poorly documented and quantified. Therefore, does excretion and transmission occur to any significant extent outside of the lambing period? Investigate other potential routes of excretion, such as faecal, ocular or mammary secretions.
  • In flocks that have experienced chlamydial abortion, it is common to find evidence of intermittent faecal shedding. Indeed, intestinal infections have been observed, even in the absence of elevated abortion rates. This raise questions about the significance of this reservoir for animal and human health and underlines the necessity for further investigation and regular monitoring.
  • Determine the proportion of infected animals that fail to clear infection following abortion and the proportion that excrete EBs at subsequent parturitions.
  • Determine the length of time infection can persist in animals post abortion.
  • Can the pathogen be shed in colostrum/milk or survive/propagate in milk after secondary contamination?

• Description of infection & disease in natural hosts

• Transmissibility

  • The main routes of transmission are through contact and ingestion of microorganisms shed with the aborted materials (vaginal fluids, dead foetuses, coats of weak and surviving lambs), as well as through inhalation of aerosols from the environment.
  • There is also limited evidence of vertical transmission from mother to lamb, as well as transmission resulting from shedding in faecal material. Thus, horizontal transmission remains the greatest risk for other naive animals.
  • Venereal transmission by males is not thought to play an important role in the spread of infection, although direct intra-vaginal infection of ewes has been demonstrated suggesting that it is possible, while infection of rams or semen failed to establish infection in ewes or result in abortion.

  GAPS :

  • Pathogen transmission and stability in the environment (bedding, soil, water, air) is currently unclear as well as role in the epidemiology of infection.
  • Investigate other potential sources and routes of infection, for example artificial insemination, milk, colostrum.
  • Further evidence for transmission through faeces.
  • Further evidence for horizontal transmission of infection to lambs and disease outcome.
  • Further evidence required of the possible role of rams in transmission of infection from infected to naïve ewes.

• Pathogenic life cycle stages

  • C. abortus, like other chlamydial species, undergoes a developmental cycle involving two developmental forms, the extracellular metabolically inactive infectious form (elementary body or EB) and the intracellular metabolically active form (reticulate body or RB). Both forms play an important role in the pathogenesis of the organism. The EB attaches to the host cell, enters and differentiates to the RB within a chlamydial inclusion. The RB multiplies within this inclusion, which fills most of the cells extranuclear space. At the end of the cycle the RBs re-differentiate back into EBs and the cell is lysed releasing the infectious organisms, which go on to infect neighbouring cells and thus causing the tissue damage that is characteristic of this disease.
  • C. abortus possesses a strong predilection for the placenta. Specifically, it is currently thought that infection is established first in the tonsils, from where it is disseminated by blood or lymph to other organs (possibly lymph nodes), where it may remain in a latent or persistent form until the animal becomes pregnant. Possibly key to this persistent stage is the discovery of aberrant forms of the organism. Infection establishes in the placenta and is thought to pass from the maternal to foetal side at around 60 days coinciding with the development of hematomas at the placental villous tips. From this point infection develops and spreads from the trophoblastic chorionic epithelial cells. Ensuing tissue damage, changes in key pregnancy hormones and possible changes in immune responses ultimately lead to placental insufficiency and the death and abortion of the foetus, or the birth of weak lambs. In multiparous pregnancies a combination of live/dead outcomes are possible.

  GAPS :

  • Determine the role of the aberrant bodies in chlamydial persistence using in vivo models?
  • What is the site of persistence in asymptomatic animals?
  • What is the trigger for release of the organism from a persistent state to a replicating state?
  • Role of antibiotics (e.g. too low a dose) in inducing a persistent state.

• Signs/Morbidity

  • In sheep and goats, clinical signs primarily consist of abortion occurring in the last 1-3 weeks of gestation. In cattle, abortions tend to be sporadic, occurring near or at term.
  • Infections can result in the birth of almost fully developed dead animals at term, or the delivery of weak and underweight animals which may subsequently die.
  • In sheep, goats and cattle there is usually no overt evidence of clinical disease prior to abortion although uterine discharge can be observed 1-2 days prior to abortion occurring. In the case of goats this vaginal discharge may be observed for up to 2 weeks prior to and following the abortion.
  • Placentas may be retained following delivery, with an increased frequency of placental retention being described for goats.
  • Chlamydial infections have been reported to have a substantial and quantifiable impact on cattle productivity with chronic, recurrent infections associated with pulmonary disease in calves and with infertility and sub-clinical mastitis in dairy cows.

  GAPS :

  What is the role of chronic/subclinical C. abortus infections in cases of infertility in both pigs and cattle?

• Incubation period

  • Sheep and goats infected early in pregnancy (generally prior to 110 days in the case of sheep) abort late in the same pregnancy. However, infection of non-pregnant females (lambs, kids) or females in late pregnancy (last 5-6 weeks) will most likely lead to the development of a latent or sub-clinical infection, where the animals appear to be uninfected until the subsequent pregnancy.
  • In an extended lambing season it is possible for a naive pregnant ewe to pick up infection from an aborted ewe and then abort in the same season.

  GAPS :

  • The localization of the pathogen (body/tissues site) during the incubation period should be investigated.
  • What is the situation in cattle and pigs? This is currently unknown and should be investigated.

• Mortality

  • Mortality of infected ewes and goats is very low and if it occurs it is usually associated with retained placentas and the development of secondary bacterial infections.
  • This is principally a disease of offspring, with up to 30-40% of pregnant ewes and 60% of pregnant goats affected during an abortion storm resulting in abortion, stillbirths and weak progeny. Following an abortion storm the disease becomes enzootic in nature, with an annual abortion incidence of 5-10% occurring in younger females and replacement naïve animals.

• Shedding kinetic patterns

  • C. abortus is excreted in large numbers in the products of abortion (aborted foetuses and placentas) and post-abortion uterine discharges, as well as contaminating the coats of weak lambs and surviving offspring.
  • Infectious organisms may also be shed in the faeces of animals, although it is unclear as to the extent of such shedding and the role this might play in the epidemiology of infection.
  • The organism has also been found in goats’ milk, but again it is unclear as to the significance of this in terms of spread of infection.

  GAPS :

  • Faecal shedding of C. abortus should be investigated quantitatively and over a longer time period as well as a potential role in causing infection and abortion.
  • The role of the GI tract as a potential reservoir for genital re-infection should be investigated (analogous to C. trachomatis rectal infection in humans as a source of genital re-infection).
  • Data on shedding (including duration of shedding) for cattle and pigs is required.
  • Evidence has not been found for significant post abortion excretion of microorganisms in colostrum and milk, although it has been detected in the milk of asymptomatic cattle. This requires further investigation. Any etiological involvement with subclinical mastitis in ruminants?

• Mechanism of pathogenicity

  • The destruction of the chorionic epithelium and associated placental damage and vascular thrombosis impair the functional integrity of the placentomes that are responsible for the maternal-foetal exchange of nutrients and oxygen, as well as affecting hormonal balance.
  • Progesterone which is responsible for the maintenance of pregnancy is produced by the trophoblast cells of the chorionic epithelium in the latter stages of pregnancy and these are the cells targeted and destroyed by the pathogen.
  • The production of TNF-alpha and other pro-inflammatory mediators, probably triggered by chlamydial lipopolysaccharide, has also been postulated to be responsible for placental inflammation and damage.
  • All of these changes combine ultimately to result in the death and subsequent expulsion of the foetus.

  GAPS :

  • It is necessary to increase our understanding of the role and influence of reproductive hormones on the pathogenicity of C. abortus.
  • Is there any effect of different C. abortus strains and different transmission routes on pathogenicity?
  • Studies have shown that low doses of organisms can result in classical disease and pathology. But what is the lowest infectious dose that elicits these effects?
  • Why does the disease present differently in different animal species, sheep vs. goat vs. cattle vs. pigs?
  • What differences are there in mechanisms of pathogenicity?

• Zoonotic potential

• Reported incidence in humans

  While C. abortus is recognised as a zoonotic agent, reports of human cases are rare, although this might be because they remain undetected/underreported and because the disease is not notifiable in humans.

  GAPS :

  • An epidemiological survey in hospitals of areas in which chlamydial abortion is endemic could reveal the incidence amongst pregnant women or other persons engaged in sheep production, in comparison with other types of farming or non-agricultural activities.
  • It would be worthwhile investigating human abortion cases and respiratory infections (occupational disease) in humans. Consideration should be given to making the disease notifiable as this would help such investigations.

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

  Human infection can result from contact with infected sheep and goats. The risk of infection from contact with cattle is less clear. The risk to humans is mainly limited to pregnant women who have contact with C. abortus through assisting pregnant sheep or goats especially during the lambing or kidding season. Indeed, there are several reports of human abortion resulting from contact with lambing/aborting sheep and although relatively few cases occur annually, the potential danger to the pregnant woman and her developing foetus is considerable. Infection can occur as the result of direct contact with animals and their secretions, the inhalation of aerosols from contaminated material or the accidental ingestion of contaminated material through poor hygiene and biosafety/biosecurity practices.

  GAPS :

  • Investigate the zoonotic risk arising from C. abortus infection in cattle and pigs.
  • Identify risk populations (farmers, veterinarians, laboratory workers, abattoir workers, etc.): determine their exposure risk by serology.
  • Investigate risk and association with respiratory diseases resulting from zoonotic infections in both males and non-pregnant females.

• Symptoms described in humans

  • There are a number of reports of pregnant women having severe infections, including spontaneous abortion, stillbirth and septicaemia, following exposure to animals infected with C. abortus. These are likely to follow several days of acute influenza-like illness. Infection in pregnant women also typically causes renal failure, hepatic dysfunction and disseminated intravascular coagulation, and may result in death.
  • In males and non-pregnant women chlamydial respiratory disease has been reported on a number of occasions.

  GAPS :

  Investigate cases of respiratory infections in humans and any association with exposure to C. abortus.

• Likelihood of spread in humans

  • The likelihood of human-to-human spread of C. abortus is unknown. However, evidence from reported cases would suggest that human-to-human transmission is rare or unlikely.
  • Reports also suggest that there is no evidence of persistence in humans as occurs in sheep.

  GAPS :

  As human-to-human transmission has been recently confirmed to occur with C. psittaci it would be worthwhile to investigate possible cases of transmission involving C. abortus.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Aborted, stillborn or weak lambs/kids/calves/piglets that fail to survive are considered welfare issues for the mothers.

  GAPS :

  Any behavioural changes in the animals as a result of the loss of their young.

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

  This is not known but is probably of low importance.

  GAPS :

  Investigate infection and disease in endangered ruminant species that are subject to ex-situ breeding programmes in captivity.

• Slaughter necessity according to EU rules or other regions

  • It is not usually necessary to slaughter animals that have aborted, although some livestock keepers choose this as a method of controlling spread of infection.
  • Secondary infections after abortion, especially in extensive or semi-extensive system, may end up receiving late treatment and consequently animals will die or have to be culled.

• Geographical distribution and spread

• Current occurence/distribution

  • Chlamydial abortion resulting from C. abortus infection occurs in most sheep- and goat-rearing countries worldwide.
  • It is not thought to be an issue in Australia and New Zealand.

• Epizootic/endemic- if epidemic frequency of outbreaks

  • As the name implies ("enzootic abortion"), the disease exhibits an enzootic character and is endemic is most sheep-rearing countries of the world, apart from New Zealand and Australia.
  • After the introduction of C. abortus to a fully susceptible breeding flock, infection can spread to other naïve ewes resulting in an abortion storm. Thereafter the disease becomes enzootic in nature with an annual incidence of 5-10%, principally among younger females and new flock entrants. A similar picture is observed in goats but not in cattle where infections are more epizootic in nature.

  GAPS :

  Infection kinetics should be investigated in cattle and pigs (in comparison to sheep and goats).

• Speed of spatial spread during an outbreak

  Spread of infection can be rapid depending on the amount of infectious material in the environment. However, the consequence of infection is not seen until the next pregnancy.

  GAPS :

  What is the situation in cattle and pigs?

• Transboundary potential of the disease

  Spread by C. abortus-infected incubating or carrier recovered animals. Some reports show high anti-C. abortus antibody titres in wild ungulates, but little is known about their role as carriers or reservoirs of infection.

  GAPS :

  What is the role of wildlife species as carriers or reservoirs of infection?

• Route of Transmission

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

  Ingestion or inhalation of infectious microorganisms (EBs), through contact with infected placentas, aborted foetuses, post-abortion uterine discharges and the soiled hindquarters of aborted ewes.

• Occasional mode of transmission

  • Possible mechanical transmission from infected to naïve ewes may occur by the ram (male sheep).
  • Faecal-oral and rectal-genital transmission might be possible.
  • There is no strong evidence for venereal transmission, although this cannot be completely ruled out and may occasionally occur.

  GAPS :

  • Investigate other non-classical routes of transmission (such as venereal transmission) and estimate impact on epidemiology of infection.
  • Investigate the potential role of vectors such as ticks and other parasites on transmission.

• Conditions that favour spread

  • The introduction of asymptomatic C. abortus carriers as replacement animals into a naïve unvaccinated flock or herd can result in the rapid spread of infection.
  • Lambing indoors with close contact between animals at lambing increases risk of spread of infection to naïve animals.
  • Poor hygiene at lambing, kidding or calving can also allow spread of infection.

  GAPS :

  • What is the effect of different management and housing systems on the spread of infection?
  • What impact does inter-species transmission have on the spread of infection amongst co-housed animals (sheep-goat, cattle-goat, cattle-sheep and vice versa, pigs).

• Detection and Immune response to infection

• Mechanism of host response

  • Both innate, as a first line of defence, and adaptive immune responses are important in the control of chlamydial infections.
  • Following infection in the non-pregnant animal, the pathogen persists until the animal becomes pregnant. This persistence is thought to be mediated through the cytokine interferon-gamma.
  • An important characteristic of the disease is the long-term immunity it confers to affected ewes, which do not suffer any more from instances of chlamydial abortion.
  • Protective immunity following abortion in sheep results from the high levels of antigenic stimulation due to C. abortus replication in the placenta.
  • Both cellular and humoral immunity have been demonstrated, although cellular responses appear more important in terms of a primary infection.
  • The primary infectious dose appears to be an important factor that determines disease outcome.

  GAPS :

  • Is immunity and immune responses similar in goats and sheep?
  • Requirement to investigate immunity in both cattle and pigs.

• Immunological basis of diagnosis

  Diagnosis of infection is generally based on antibody responses at the time of abortion, which correlate very well with infection in sheep. This also applies to goats, but the situation in pigs and particularly cattle is much less clear.

  GAPS :

  • Determine whether antibody is a good correlate of infection in cattle and pigs, which will aid the development of specific diagnostic tests for these species.
  • Immune mechanisms of persistent infections should be further investigated.

• Main means of prevention, detection and control

• Sanitary measures

  • Effective biosafety and biosecurity measures.
  • Care in the purchase of replacement animals from known disease free sources, for example from accredited flocks/herds.
  • Keep a flock/herd closed.
  • Vaccinate all replacements, although it should be remembered that vaccination of animals already infected may not protect them from disease and shedding of infectious organisms.

  GAPS :

  Determine sanitary measures for cattle and pigs.

• Mechanical and biological control

  When chlamydial abortion occurs attention must be paid to reduce the risk of within-flock transmission by:

  • Removal and destruction of the products of conception as well as contaminated bedding by burning or incineration.
  • Cleaning and disinfection procedures could have an important impact on persistence and environmental contamination in the areas where the abortion occurred.
  • Isolating ewes which have aborted for 2-3 weeks, or at least until vaginal discharges have dried up (organisms in fluids have been demonstrated to be infective for up to 7-10 days post-partum). If the number of aborting animals is large, they may be retained for further breeding, preferably as a separately managed group.
  • Operating basic standards of hygiene (e.g. hand washing) and obligatory use of personal protective equipment (clothing, boots, gloves) to prevent spread of infection

  The use of long-acting tetracycline’s can be administered as an emergency treatment to reduce further potential losses, but should not routinely be used as a means of controlling infection due to issues of potential antibiotic resistance. Antibiotics should not be used in combination with the live vaccines.

  Initiate a vaccination programme for the next breeding season where abortion has occurred in a flock, if infection becomes established in a flock or where there is a high level of infection in neighbouring farms (although this depends on provision of adequate biosecurity measures).

  GAPS :

  What are the recommendations for cattle and pigs?

• Prevention through breeding

  There is currently no evidence for this.

• Diagnostic tools

  A range of tools are available for diagnosing C. abortus infection in sheep and goats and these are well documented in the WOAH Manual of Diagnostic Tests and Vaccines: Chapter 3.8.5:

  • Serological tests – ELISAs, CFT (no longer preferred as lacks specificity and sensitivity)
  • Detection of the microorganism, PCR, real-time PCR, High-Resolution Melt PCR (HRM), immunohistochemistry, chemical staining (e.g. Giemsa and Macchiavello stains) of smears (useful for a provisional diagnosis)

  There are advantages and disadvantages to the use of some of these tests. Some serological tests (CFT, some ELISAs) detect antibodies induced by infection with other chlamydiae, including C. pecorum, which can be widespread in ruminants and can result in false positive test results. New ELISAs that are more sensitive and specific have been developed and commercialised.Molecular detection of organism DNA is generally superior over serology, being more sensitive and specific, although requiring more specialist equipment and is generally more expensive.A molecular DIVA has been developed based on PCR-RFLP and another based on High Resolution Melt (HRM) PCR that differentiate the live vaccinal 1B strain from wild-type strains.None of the current tests can detect persistently-infected carriers.

  GAPS :

  • Develop diagnostic tools that are able to detect persistently-infected animals.
  • Develop serological tests for differentiating between vaccinated (using live or inactivated vaccines) animals and those naturally infected.
  • Develop point-of-care tests for diagnosing infections in the field.
  • Develop and validate approved tests for certifying animals free of disease for export purposes.
  • Develop species-specific serological tests for diagnosing infections in cattle and pigs.
  • Develop and evaluate tests for detection of C. abortus infection in other farmed species (e.g. European bison, water buffalos, yaks, zebus, reindeer, South American camelids).

• Vaccines

  Currently both inactivated and live vaccines are available for use in sheep and goats but not cattle [not officially recommended but cattle can be administered twice the dose of live vaccine given to small ruminants].

  • The live commercialized vaccine (C. abortus strain 1B; Enzovax, MSD Animal Health & Cevac Chlamydia vaccine, CEVA Animal Health) is available in several countries worldwide. This must be administered at least 4 weeks prior to mating and not in combination with antibiotic treatment. Vaccination should be repeated every 2–3 years.
  • Inactivated vaccines are also commercialized (e.g. Clasovax, MSD Animal Health in Italy and Chlamysure, Onderspoort Biologicals Products in South Africa). These vaccines can be administered during pregnancy, but not until 4 weeks after breeding. A recent inactivated vaccine (INMEVA; HIPRA, S.A.) can be administered at any time, although it is not recommended in the last month of pregnancy. Vaccination should be repeated annually.

  Disadvantages :

  1. Both types of vaccine do not completely eradicate the shedding of infectious organisms at lambing
  2. Some vaccinated animals can still abort (either as a direct result of using the live vaccines, which have been shown to cause abortion in some vaccinated animals, or possibly due to the vaccine being administered over an existing infection)
  3. Inactivated vaccines require large amounts of Chlamydia and thus may not be cost effective for vaccine manufacturers and sheep producers. However, for the production of a recent inactivated vaccine (INMEVA; HIPRA, S.A.) new technologies have been used to increase the production of antigen and reduce the costs of manufacture.
  4. It has been shown that some of the commercial inactivated vaccines are not fully effective in controlling abortion in the flock. Nonetheless, they do induce significant reductions in abortion numbers and in the shedding of infectious organisms post parturition.
  5. Production issues for the live vaccines that have led to availability issues across Europe.
  6. Safety concerns in using the live vaccines (potential infection in animals as well as human handlers) and inactivated vaccines (use of oily adjuvant and potential for self-injection).
  7. In general, vaccine design and development is an inherently laborious process.

  Modern vaccine research should be focused on the development of next generation vaccines that are efficacious, but safe and more stable and cheaper to produce. Improved computational techniques and combined integrative strategies have the potential to simplify the process greatly. These techniques also have the potential to identify candidate proteins that would be overlooked by conventional experimentation. In particular, reverse vaccinology has proved effective in the discovery of antigenic subunit vaccines that would otherwise remain undiscovered. If methodology of reverse vaccinology is applied appropriately in vaccine design, it can save enormous amounts of money, time and labour.

  GAPS :

  • Develop next generation vaccines that are safer, cheaper to manufacture, more stable and easier to produce.
  • Investigate differences in immunity induced by inactivated versus live attenuated vaccines to aid in the development of new vaccines.
  • Develop a transformation system that will enable the generation of novel vaccines based on genetically modified organisms.
  • The development of a subunit vaccine comprising antigens different from a corresponding diagnostic antigen will allow the detection of infected animals within a vaccinated flock.
  • Investigate the efficacy of vaccines in animals that have previously been infected but not aborted, to determine whether they can reduce abortions or shedding in these persistently-infected animals.
  • The role of sex-hormones on the protection conferred by vaccination should be investigated.

• Therapeutics

  • Long acting tetracycline’s given at the correct period (in late pregnancy) as an emergency treatment for an ongoing outbreak of chlamydial abortion will reduce the severity of infections and reduce the number of abortions. However, C. abortus may still be shed at lambing and thus pose a risk of transmission to other naïve ewes.
  • Antibiotic treatment has been considered as the most practical measure for control of disease in cattle where abortions are more sporadic.
  • It is possible that the use of antibiotics can mask pathology, inducing C. abortus to persist in reservoirs. Once antibiotic treatment is complete, the organism can then replicate again and initiate infection and pathological damage.
  • Tetracycline administration should be limited to abortion outbreaks to reduce the incidence of abortion in a flock, rather than used routinely as a prophylactic due to concerns of antimicrobial resistance worldwide.

  GAPS :

  • Based on the emergence of tetracycline-resistant (Tet^R) Chlamydia suis isolates in pig herds in several countries, it is of importance to investigate how the use of tetracycline’s in ruminants could contribute (or has contributed) to the emergence and persistence of tetracycline-resistant C. abortus strains.
  • A comprehensive genome analyses and comparisons of field C. abortus isolates originating from flocks/herds with common or prolonged use of long acting tetracycline should be performed to determine any possible occurrence of the Tet-genomic island, as found for C. suis infections in pigs.

• Biosecurity measures effective as a preventive measure

  • As C. abortus is a particular risk to pregnant women they should avoid involvement with lambing ewes and should not handle contaminated clothing from those working with lambing ewes or new-born lambs.
  • Immunocompromised or immunosuppressed individuals should avoid contact with potentially infected animals or contaminated material.
  • Care should be taken in the use of live vaccines.
  • Preventative measures should be put in place to limit the spread of infection from aborting animals and products of abortion to naïve animals.
  • Adequate personal hygiene procedures including the use of protective equipment should be put in place to additionally reduce the risks of transmission.
  • Replacement animals should be purchased from accredited sources.
  • Consider operating a closed flock to keep disease out.

  GAPS :

  • What recommendations can be made for cattle and pigs?
  • Increase public awareness of the zoonotic potential of the pathogen.
  • Knowledge of the risks arising from C. abortus exposure emphasizes the essential need for modification and adaptation of work protocols and the strict observance of best practice to protect workers from exposure during lambing.

• Border/trade/movement control sufficient for control

  Standards laid down in the WOAH Terrestrial Animal Health Code.

  GAPS :

  • Define recommended tests and sampling sites to prove that animals are free of C. abortus for trade, export etc.
  • Species-specific tests are important, because other endemic chlamydial species (C. pecorum) are of much less relevance.

• Prevention tools

  Vaccination, diagnostics, husbandry, biosafety/biosecurity and health education (e.g. leaflets focussing on occupational hazards to pregnant women).

• Surveillance

  Serological surveillance to assess the status of flocks/herds. This must be coupled with flock history as antibody is not a measure of current infection.

  GAPS :

  • Develop recommendations for direct pathogen detection and sampling site.

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

  Vaccination is effective at reducing the clinical picture but is not suitable for the eradication of infection. Nevertheless, vaccination is the best option to control the disease.There is information on non-response to oxytetracycline administration in herds with confirmed chlamydial abortion in Southern Greece.

  GAPS :

  It is necessary to work on improving the currently available vaccines and/or to design new vaccines taking into account the prevalence of C. abortus variants especially in areas where potential non-response to tetracycline has been reported.

• Costs of above measures

  Usually controls are related to the herd/flock and are not implemented at a national or regional level. Costs are related to vaccination, diagnostic investigations and to possible treatment, as well as associated costs of dealing with abortions, losses in lamb production and in purchasing more expensive premium replacement livestock from accredited sources.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  No. However, enzootic abortion is a WOAH listed disease, although no epidemiological events are officially reported as the disease is endemic in most European countries. Some European countries however operate their own disease surveillance systems with annual incidence figures provided. However, even then disease incidence is under reported. In the UK, around 44% of cases of ovine fetopathy due to an infectious cause are diagnosed as being caused by C. abortus. Figures are likely to be similar in other European countries.

  GAPS :

  • Epidemiological data is not available for all European countries and would be beneficial. Availability of data depends on disease surveillance systems in respective countries.
  • Improved monitoring of disease incidence is required.
  • Improved surveillance systems by veterinary laboratories/bodies at a local or national level.
  • Reporting of infections in cattle and pigs is likely to be much poorer than for sheep and goats.
  • Increase systematic notification and investigation of abortion cases in all species to get a better understanding of prevalence.

• WOAH disease card available

  Not available.

  GAPS :

  Not applicable.

• WOAH Terrestrial Animal Health Code

  Yes

• WOAH Terrestrial Manual

  Yes

• Socio-economic impact

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

  Not known but will be low.

  GAPS :

  Requires better data on incidence.

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

  Not known but will be low as infections are considered to be rare.

  GAPS :

  Requires better data on incidence to calculate costs of treatment.

• Direct impact (a) on production

  When introduced into non infected flocks/herds abortion may occur in up to 30% of the ewes and as many as 60-90% of pregnant goats.

  GAPS :

  Impact for cattle and pigs is unknown.

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

  Costs associated with diagnostic testing as well as use of vaccines and application and use of antibiotics contribute to the costs. Such costs can be prohibitively expensive for some small ruminant farmers.

  GAPS :

  Impact for cattle and pigs is unknown.

• Indirect impact

  Reduced production of lambs and kids affecting food supply chain and food security.

  GAPS :

  • Indirect impact for cattle and pigs is unknown.
  • Assess the zoonotic potential of raw milk products from sheep and goats.

• Trade implications

• Impact on international trade/exports from the EU

  • International standards for trade are contained in the WOAH Terrestrial Animal Health Code. These specify the recommendations for the importation of sheep/goats into a breeding flock/herd to minimise the risk of introducing infection, the mechanisms to confirm freedom in the herd/flock and the rules for the movement of semen.
  • Some countries such as Russia and China demand strict serological controls for the importation of C. abortus free sheep and pigs.

  GAPS :

  Impact not known for cattle or for wild and farmed ruminants (e.g. European bison, water buffalos, yaks).

• Impact on EU intra-community trade

  None.

• Impact on national trade

  None.

• Links to climate

  Seasonal cycle linked to climate

  There is currently no evidence for this, although changes in climate will likely affect persistence of the organisms in the environment.

  GAPS :

  Investigate the persistence of the agent in the environment.

• Distribution of disease or vector linked to climate

  There is currently no evidence for this.

  GAPS :

  If vectors are involved in transmission, and vector populations vary in different regions/countries depending on climate or changes in climate, then this could affect infection rates. This should be investigated.

• Outbreaks linked to extreme weather

  There is currently no evidence for this.

  GAPS :

  Weather could impact on persistence of organisms in the environment, with cooler weather resulting in organisms remaining viable for longer. Thus, persistence and viability of the pathogen in the environment under different climatic conditions should be investigated.

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

  There is currently no evidence for this.

  GAPS :

  • The organism is affected by weather and temperature, therefore this is likely to impact on disease, but to what extent is currently unknown.
  • If vectors are involved in transmission and vector populations vary in different regions/countries depending on changes in climate, then this could affect infection rates. This should be investigated.

• Main perceived obstacles for effective prevention and control

  • Detecting the presence of the organism in subclinical persistently infected non-pregnant animals is not currently possible.
  • Identifying infected ewe lambs that will go on to abort is difficult.
  • Commercial vaccines do not give complete protection.
  • Vaccinated animals may still excrete C. abortus at lambing.
  • Vaccination will not eradicate infection from a flock.
  • Live vaccine is capable of inducing abortion.
  • Vaccines are not licenced for use in cattle and pigs.

  GAPS :

  • Better detection of latently/persistently infected animals.
  • Improved, safer vaccines.
  • Improved diagnostics.
  • Develop diagnostics and vaccines for use in cattle and pigs.
  • Develop DIVA vaccines and complementary diagnostics.

• Main perceived facilitators for effective prevention and control

  • Improved diagnostic tests.
  • Better understanding of the immune response to infection and to existing and new vaccines, in particular the protective elements of the immune response.
  • Detection of latent infections.
  • Improved next generation vaccines.

  GAPS :

  • Improve our understanding of the immune correlates of protection (cellular and antibody responses).
  • Improve existing inactivated vaccines with new adjuvants to enhance an effective cellular immune response.
  • Feasibility of screening tests for assessing infection at herd/flock level (define specimen type, number of samples, tests).

Global challenges

• Antimicrobial resistance (AMR)

• Mechanism of action

  None known.

  GAPS :

  Requires investigation to determine if present in sheep flocks and goat herds.

• Conditions that reduce need for antimicrobials

  Adequate surveillance, known flock history and management, improved diagnostics and use of vaccines all reduce need for use of antimicrobials.

• Alternatives to antimicrobials

  Good flock management and use of diagnostics and vaccines to monitor and control infections and disease.

• Impact of AMR on disease control

  Not known.

• Established links with AMR in humans

  Not known.

• Digital health

• Precision technologies available/needed

  Technologies are currently available that detect changes in the movement of animals and drinking/eating patterns that may predict early lambing and abortion. The monitoring of body temperature is possible using under the skin sensors. Detection of prolonged elevated temperature in animals may provide an early warning of disease and potential for early lambing/abortion.

  GAPS :

  Technologies need to be validated to see if they are effective in predicting abortion and cost effective for the farmer.

• Data requirements

  Continuous surveillance through use of digital cameras would be required at different key times in relation to a potential infection and subsequent pregnancy.

  GAPS :

  Requirements would need to be identified and determined.

• Data availability

  Limited data available on temperature changes following experimental oronasal infection of a flock of sheep.

  GAPS :

  Available data would need to be determined.

• Data standardisation

  Outside experimental settings, standardisation of behavioural and temperature/ immune composition changes will be difficult metabolically.

  GAPS :

  Data standardisation would need to be determined and agreed.

• Climate change

• Role of disease control for climate adaptation

  It could be assumed that improved disease control would positively impact the ability of animals to respond to climatic changes.

  GAPS :

  Direct comparisons would need to be investigated at a flock level of infected versus uninfected animals over time and potentially generations of animals. Tangible productivity would need to be measured.

• Effect of disease (control) on resource use

  If the presence of disease was lessened or eradicated, this would lead to less resource use for the same number of animals in a group with the same output.

  GAPS :

  Experimental setting comparisons would need to be determined.

• Effect of disease (control) on emissions and pollution (greenhouse gases, phosphate, nitrate, …)

  If the presence of disease was lessened or eradicated, this would likely result in less emissions and pollution for the same number of animals in a group with the same output.

  GAPS :

  Experimental setting comparisons would need to be determined.

• Preparedness

• Syndromic surveillance

  Some countries such as the UK operate surveillance schemes to routinely test animals for a range of reproductive pathogens including C. abortus, Toxoplasma gondii, Campylobacter spp, Salmonella spp, Listeria monocytogenes etc.

  GAPS :

  • Determine the most common causes of reproductive loss for each country in Europe.
  • Improve surveillance of the major pathogens responsible for reproductive loss across Europe.

• Diagnostic platforms

  Testing is generally based on individual PCR tests for different pathogens. Platforms for screening for a range of pathogens require development.

  GAPS :

  Development of multi-tandem PCR technology to test for a range of abortifacient pathogens.

• Mathematical modelling

  Epidemiological modelling of chlamydial outbreaks in sheep flocks has been published. Simulation of data revealed the importance of the transmission rate (i.e. contact) and the number of infected replacements introduced at the start of an outbreak. Depending upon the rate of transmission, the year in which the peak number of affected ewes occurs and the number of years over which a high number of animals are affected varies.

  GAPS :

  • A better understanding of the underlying processes that drive transmission of C. abortus is needed.
  • Better identification of infected ewes prior to parturition, when they shed the organism in large numbers, to reduce the impact of EAE on sheep flocks.

• Intervention platforms

  Not known.

  GAPS :

  Intervention platforms need to be agreed and validated.

• Communication strategies

  Not known.

  GAPS :

  Better coordination of strategies for communication and coordination on a local, regional, country and European basis need to agreed.

Main critical gaps

• • Greater understanding of the extent of genetic diversity of C. abortus strains
  • Greater understanding of disease pathogenesis in cattle, pigs and other farmed and wild ruminant species
  • A greater understanding of the mechanistic basis of latency and persistence, including determination of the site of latency
  • Evaluation of the resistance of the pathogen under different environmental conditions
  • Investigations of other potential sources for transmission of infection, including faeces, milk and water samples, as well as the potential for venereal transmission
  • Role of wildlife and vectors in transmission of infection
  • Improve epidemiological evidence of infections in humans
  • Improve diagnostic tools for: other animal species (cattle, pigs, wild ungulates and farmed animal species); detecting latent/persistent infections; identifying naturally-infected animals in vaccinated flocks/herds; detecting co-infections; and point-of-care use. This will require greater standardisation of fully defined sera of known origin as well as pan-European inter-laboratory trials.
  • Further knowledge on relationships between antibiotics treatment (dose) and stage of persistence in the host.
  • Investigations on the potential emergence of tetracycline-resistant C. abortus strains, especially in pig herds.
  • Vaccine development studies: define immune correlates of protection for C. abortus in ruminants; improve inactivated vaccine efficacy through the use of novel adjuvants to promote an effective cellular response; determine effect of co-infections on efficacy of vaccines; and develop a stable transformation system for C. abortus.
  • Development of safer, cheaper, more stable next generation marker vaccines, which will likely be based on subunit recombinant antigens.

Conclusion

• Better diagnostic tools are required, especially to identify the latent carrier. Improved vaccines which prevent shedding and which give 100% immunity are needed. The next generation of vaccines will be based on multi component recombinant antigens. These studies will be helped by a greater understanding of pathogenesis, understanding the extent of diversity across Europe and developing tools to identify and manipulate targets for vaccine development studies.

Sources of information

• Expert group composition

  David Longbottom (Moredun Research Institute, UK) – [Leader]

  Nicole Borel (University of Zurich, Switzerland)

  Maria Rosa Caro Vergara (University of Murcia, Spain)

  Mireia Fontseca Presta (HIPRA S.A., Amer, Girona, Spain)

  Karine Laroucau (ANSES, Paris, France)

  Bryan Markey (University College Dublin, Ireland)

  Carlos Montbrau Morcillo (HIPRA S.A., Amer, Girona, Spain)

  Laura del Rio (University of Murcia, Spain)

  Christiane Schnee (Friedrich-Loeffler Institute, Jena, Germany)

  Victoria Siarkou (Aristotle University of Thessaloniki, Greece)

  Daisy Vanrompay (University of Ghent, Belgium)

  Sean Wattegedera (Moredun Research Institute, UK)

• Date of submission by expert group

  23 November 2022

• References

  • Aitken, I. D. and Longbottom, D. (2007). Chlamydial abortion. In: Diseases of Sheep, 4th Edition, Chapter 16, pp. 105-112, Blackwell Publishing.
  • Borel, N. and Longbottom, D. (2019). Chlamydiosis. Anipedia, editors JAW Coetzer, GR Thomson, NJ Maclachlan and ML Penrith. https://anipedia.org/resources/chlamydiosis/1125
  • Entrican, G, Wheelhouse, N., Wattegedera, S.R. and Longbottom, D. (2012). New challenges for vaccination to prevent chlamydial abortion in sheep. Comparative Immunology, Microbiology and Infectious Diseases 35, 271-6.
  • Essig, A. and Longbottom, D. (2015). Chlamydia abortus: New aspects of infectious abortion in sheep and potential risk for pregnant women. Current Clinical Microbiology Reports 2, 22–34.
  • Laroucau, K., Aaziz, R., Vorimore, F., Menard, M.F, Longbottom, D., Denis, G. (2018). Abortion storm induced by the live C. abortus vaccine 1B strain in a vaccinated sheep flock, mimicking a natural wild-type infection. Veterinary Microbiology 225, 31-33.
  • Laroucau K, Vorimore F, Sachse K, Vretou E, Siarkou VI, Willems H, Magnino S, Rodolakis A, Bavoil PM. (2010). Differential identification of Chlamydophila abortus live vaccine strain 1B and C. abortus field isolates by PCR-RFLP. Vaccine 28, 5653-6.
  • Livingstone, M., Wattegedera, S.R., Palarea-Albaladejo, J., Aitchison, K., Corbett, C., Sait, M., Wilson, K., Chianini, F., Rocchi, M. S., Wheelhouse, N., Entrican, G., Longbottom, D. (2021). Efficacy of two Chlamydia abortus subcellular vaccines in a pregnant ewe challenge model for ovine enzootic abortion. Vaccines 9, 898.
  • Longbottom, D., Livingstone, M., Ribeca, P., Beeckman, DSA, van der Ende, A., Pannekoek, Y. and Vanrompay, D. (2021). Whole genome de novo sequencing and comparative genomic analyses suggests that Chlamydia psittaci strain 84/2334 should be reclassified as Chlamydia abortus species. BMC Genomics 22, 159.
  • Longbottom, D., Sait, M.L., Livingstone, M., Laroucau, K., Sachse, K., Harris, S.R., Thomson, N.R., Seth-Smith, H.M.B. (2018). Genomic evidence that the live Chlamydia abortus vaccine strain 1B is not attenuated and has the potential to cause disease. Vaccine 36, 3593-3598.
  • Milne, C.E., Gunn, G.J., Entrican, G. and Longbottom, D. (2009). Epidemiological modelling of chlamydial abortion in sheep flocks. Veterinary Microbiology 135, 128-133.
  • Montbrau, C., Fontseca, M., March, R., Sitja, M., Benavides, J., Ortega, N., Caro, M.R., Salinas, J. (2020). Evaluation of the efficacy of a new commercially available inactivated vaccine against ovine enzootic abortion. Frontiers in Veterinary Science 7, 593.
  • Murcia-Belmonte, A., Álvarez, D., Ortega, N., Navarro, J.A., Gómez-Lucia, E., Buendía, A.J., Sánchez, J., Del Río, L., Salinas, J. and Caro, M.R. (2019). Effect of progesterone on the vaccination and immune response against Chlamydia abortus in sheep. Veterinary Immunology and Immunopathology, 213, 109887.
  • Reinhold, P., Sachse, K. and Kaltenboeck, B. (2011). Chlamydiaceae in cattle: Commensals, trigger organisms or pathogens? The Veterinary Journal 189, 257-67.
  • Sachse, K., Vretou, E., Livingstone, M., Borel, N., Pospischil, A. and Longbottom, D. (2009). Recent developments in the laboratory diagnosis of chlamydial infections. Veterinary Microbiology 135, 2-21.
  • Siarkou, V. I., Vorimore, F., Vicari, N., Magnino, S., Rodolakis, A., Pannekoek, Y., Sachse, K., Longbottom, D., and Laroucau, K. (2015). Diversification and Distribution of Ruminant Chlamydia abortus Clones Assessed by MLST and MLVA. PloS one 10, e0126433.
  • Sillis, M. and Longbottom, D. (2011). Chlamydiosis. In: Zoonoses (Palmer, S.R., Soulsby, Lord, Torgerson, P.R. and Brown, D.W.G., eds.), second edition, Oxford University Press, pp.146-57.
  • Turin, L., Surini, S., Wheelhouse, N. et al. (2022). Recent advances and public health implications for environmental exposure to Chlamydia abortus: from enzootic to zoonotic disease. Veterinary Research 53, 37.
  • Vorimore F, Cavanna N, Vicari N, Magnino S, Willems H, Rodolakis A, Siarkou VI, Laroucau K. (2012). High-resolution melt PCR analysis for rapid identification of Chlamydia abortus live vaccine strain 1B among C. abortus strains and field isolates. Journal of Microbiological Methods 90, 241-4.
  • Wattegedera, S.R., Livingstone, M., Maley, S., Rocchi, M., Lee, S., Pang, Y., Wheelhouse, N.M., Aitchison, K., Palarea-Albaledejo, J., Buxton, D., Longbottom, D., Entrican, G. 2020. Defining immune correlates during latent and active chlamydial infection in sheep. Veterinary Research 51, 75.
  • World Organization for Animal Health (WOAH). WOAH Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, last updated May 2018. Chapter 3.8.5. Enzootic abortion of ewes (ovine chlamydiosis). https://www.woah.org/fileadmin/Home/eng/Health_standards/tahm/3.08.05_ENZ_ABOR.pdf. (Accessed 31 May 2022).
  • OIE World Animal Health Information System. WAHIS portal: Animal Health Data. Ovine chlamydiosis. https://www.woah.org/en/what-we-do/animal-health-and-welfare/disease-data-collection/world-animal-health-information-system. (Accessed 31 May 2022).
  • Zaręba-Marchewka, K., Szymańska-Czerwińska, M., Livingstone, M., Longbottom, D. and Niemczuk, K. 2021. Whole genome sequencing and comparative genome analyses of Chlamydia abortus strains of avian origin suggests that Chlamydia abortus species should be expanded to include avian and mammalian subgroups. Pathogens 10, 1405.