Enzootic abortion of ewes (EAE), also known as chlamydial abortion or ovine enzootic abortion, is caused by Chlamydophila abortus. This bacterium has a complex lifecycle, varying between extracellular and intracellular stages. High numbers of the infectious extracellular stage are found in the aborted fetuses, fluids and membranes. Ewes become infected by ingestion or inhalation, although diagnosis is not possible until 90 days into the subsequent pregnancy, with the outcome dependent on the ewe's immune status (see Table 1).
Table 1. Ewe immune status and outcomes following infection with Chlamydophila abortus
| Ewe immune status | Outcome |
|---|---|
| Previously aborted to Chlamydophila abortus | Immune to further chlamydial abortions. May continue to shed C. abortus in vaginal discharges at subsequent lambings |
| Susceptible, infected in first half of gestation | Abortion in final 3 weeks of current gestation |
| Susceptible, infected when non-pregnant or in second half of pregnancy | Abortion in final 3 weeks of subsequent gestation |
| Surviving ewe lamb born to aborted ewe (and some ewe lambs born to ewes aborting in previous pregnancies) | Abortion in first pregnancy |
Adapted from Sargison, 2009
Clinical disease
EAE remains the most common cause of abortion in the UK, responsible for 42% of diagnosed infectious fetopathies in England in 2020 (Animal and Plant Health Agency (APHA), 2020), and has been for several decades. Lambs may be stillborn or compromised with additional losses through perinatal disease. A 2007 survey of UK sheep farmers revealed 33.8% of respondents reported cases of EAE (Longbottom et al, 2013); 40.7%, 16.7% and 8.6% of lowland, hill and pedigree flocks respectively reported cases. 47.6% of larger flocks (>150 ewes) reported cases versus 9.4% of smaller flocks.
On a flock level, outbreaks of enzootic abortion can be devastating. Up to 30% of ewes in a naïve flock may abort, often in the year following incursion, with 5–10% aborting each year thereafter if no preventative measures are put in place (Scott, 2015). The major clinical sign in the ewe is abortion of well-preserved lambs in the final 3 weeks of gestation following a placentitis (Figure 1). The ewes typically display few to no signs besides a red uterine discharge for several days post-abortion; occasionally they may retain fetal membranes and develop metritis (Sargison, 2009). As well as being born dead, the lambs themselves may be born alive, dying shortly after birth. Different lambs in the same litter may be aborted, stillborn, weak, or normal. They may also present with accumulation of fluid in the abdomen (Sargison, 2009).
Consequently, the impact on the UK sheep industry is significant. Various analyses have suggested the annual costs, as between £8–35 million (Bennett, 2003) and between £11.3–48.2 million (Bennett and IJpelaar, 2005). Direct disease costs are relatively low compared with the costs of prevention, monitoring, and to human health (Bennet and Ijpelaar, 2005).
Zoonotic potential
Veterinary surgeons have responsibilities to the health of their clients as well as that of the livestock under their care. In the case of suspected EAE abortion, the risks to human pregnancy — abortion, stillbirth, as well as generalised sepsis in the mother (Walder et al, 2005) — should be reiterated and advice given on hygiene. Pregnant women, or potentially pregnant women, should never work with lambing sheep as a standard precaution, or handle live C. abortus vaccine. Thorough cleaning and disinfection of clothing, equipment and personnel is non-negotiable. Flu-like illness has also been documented following C. abortus infection (Meijer et al, 2004; Pichon et al, 2020); these case studies also highlight the potential for indirect transmission as in both cases the spouse worked with small ruminants and was the suspected vector.
Diagnosis
History and clinical presentation are important evidence in reaching a provisional diagnosis (see Tables 2 and 3). The placentitis is described by Sargison (2009) as severe with variable discolouration and necrosis of cotyledons, while the adjacent intercotyledonary tissue is oedematous and roughly thickened. This may be accompanied by a yellow-pink exudate. This gross pathology is indicative of EAE rather than pathognomic.
Table 2. Aspects of history
| History |
|---|
| Flock buys in replacement females |
| Flock is unvaccinated for EAE |
| Abortion rate equal to, or greater than, 1% OR cluster within a short period. |
| Surviving ewe lamb born to aborted ewe (and some ewe lambs born to ewes aborting in previous pregnancies) |
Table 3. Clinical presentation suggestive of enzootic abortion
| Clinical presentation |
|---|
| Abortion of well preserved lambs in the final 2–3 weeks of pregnancy |
| Necrotic placentitis |
| Ewe with bright demeanour |
In the face of an outbreak
Provision of placental samples, including both cotyledon and intercotyledonary area, to a laboratory should be the first step of the veterinary surgeon. Infection with C. abortus can be quickly confirmed using a modified Ziehl-Neelsen technique. Positive samples demonstrate numerous inclusion bodies on a placental smear. Placenta samples should be provided fresh and free of gross contamination. Aitken and Longbottom (2008) described a sucrose-phosphate-glutamate (SPG) buffer supplemented with bovine serum and antibiotics, which may prolong sample viability. While placental tissue is the best source, farmers may not always have or provide this material. In this case, C. abortus may be obtained from vaginal swabs of the affected ewe or the wet fleece of recently aborted lambs, although the presence is less abundant and less consistent in these sources (Aitken and Longbottom, 2008). Other samples, such as fetal fluid and fetal liver, may be taken, as usually alternative causes of infectious abortion are tested for in tandem with EAE. Given the zoonotic potential of C. abortus, samples should be handled and packaged in accordance with Carriage of Dangerous Goods Regulations (United Nations Economic Commission for Europe, 2016).
Paired serology of affected ewes can also be used to confirm active infection and involvement of C. abortus in an abortion. The initial sample should be taken just after the abortion, and the second 2 to 4 weeks later. A rising titre is suggestive of recent, rather than historical, infection (Aitken and Longbottom, 2008).
Currently in the UK, results of a modified Ziehl-Neelsen smear from an external laboratory may be expected within 24 hours in the working week. However this does not account for non-working days or other logistical complications. In the face of these and assuming a reasonable clinical suspicion based on history and clinical presentation, antimicrobial therapy and other preventative measures may be justified before infection is confirmed using histology or serology, to limit further losses and transmission.
If the opportunity is missed to sample fetal material, a representative sample of breeding females may be blood sampled for C. abortus serology. Blood should be taken from at least six breeding females from each separately managed flock, e.g. hill and in-bye.
Control and prevention
In the face of an outbreak
Once a diagnosis has been confirmed by histology or serology, or on the basis of strong clinical suspicion, treatment should be instituted without delay. The focus should be on limiting further spread, and to promote the viability of lambs.
Ewes can receive a metaphylactic dose of long-acting oxytetra-cycline (20 mg/kg via intramuscular route) to reduce the number of bacteria shed and the severity of placentitis. Greig and Linklater (1985) found this treatment reduced abortion rate in the face of an outbreak relative to untreated controls, but not in known infected flocks. This emphasises the use of oxytetracyline as a treatment rather than a preventative measure.
This treatment may be repeated every 10–14 days for ewes yet to lamb (Aitken and Longbottom, 2008). In the past, an inactivated C. abortus vaccine (‘Mydiavac’, Benchmark Holdings) was available, which could be used in the face of an outbreak. At the time of writing this vaccine is unavailable; another inactivated vaccine is available (Table 4) although this vaccine is not recommended for use in the final month of gestation.
Table 4. Vaccines currently available for EAE in the UK
| Vaccine | Manufacturer | Primary course | Booster | Notes |
|---|---|---|---|---|
| CEVAC Chlamydophila (Ceva Animal Health Ltd) | <10 000 | Single IM or SC injection from 5 months of ageGiven between 4 months and 4 weeks pre-mating | In practice commonly used as a ‘one-off’ vaccine | Contraindicated in pregnant ewes, or within 4 weeks of matingDo not use in conjunction with antimicrobials |
| Enzovax (MSD Animal Health) | <10 000 | Single IM or SC injection from 5 months of ageGiven between 4 months and 4 weeks pre-mating | In practice commonly used as a ‘one-off’ vaccineProtection from, and excretion of, Chlamydophila abortus appears to be undiminished for at least 3 years following vaccination. For endemically infected flocks vaccinating incoming ewes, levels of EAE remain low in ewes vaccinated 4 years previously | Contraindicated in pregnant ewes, or within 4 weeks of matingDo not use in conjunction with antimicrobial |
| INMEVA (HIPRA UK and Ireland Ltd) | Hipra | Subcutaneous injection: two doses, 3 weeks apartFirst dose should be given at least 5 weeks pre-mating or AI | A single subcutaneous injection given 2 weeks before subsequent pre-mating or AI, no later than 1 year after initial vaccination | Also provides protection against Salmonella Abortusovis |
IM = intramuscular, SC = subcutaneous, AI = artificial insemmination
The fundamentals of biocontainment should be practised. All aborted material and contaminated bedding should be collected comprehensively for disposal. The affected area should have disinfectant and fresh bedding applied. The aborting ewes and surviving lambs should be isolated immediately from any other age of sheep, and kept isolated for 3 weeks. Colostrum should not be harvested from aborting ewes in case of contamination of teats by uterine discharge. If aborting ewes have lambs adopted onto them, these should be castrated male lambs only to prevent latent infection establishing in future flock replacements. At all times when handling recently aborted ewes, appropriate personal protective equipment (PPE) including arm length gloves should be worn.
Routine
If a flock is free from EAE, biosecurity and vaccination are the mainstays of disease prevention.
The most likely point of incursion into a naïve flock is through latently infected female sheep. Therefore, any flock that can breed its own replacements should consider this (Figure 2), even if only a proportion of replacements can be home-bred as reducing the number of females bought-in should reduce the risk of disease incursion. Orphan lambs can introduce EAE as well as breeding sheep, so their purchase should be avoided.
Home-breeding replacements is not a viable option for many sheep farms in the UK. Purchase policies should be designed to minimise the risk of buying in disease. Purchasers should enquire with vendors if the origin flock is routinely tested or vaccinated. Flocks accredited under schemes such as the Premium Sheep and Goat Health Schemes (PSGHS) and Highland and Island Sheep Association (HISHA) are a low-risk source of replacements.
While entry of sheep is easy to monitor and control, infection may also be introduced by wildlife through carriage of aborted material across farm boundaries. Except for geographically isolated flocks, this means there is a small chance of even fully closed flocks encountering infection. While the risk is small relative to that from bought-in sheep, the impact for naïve flocks would be severe.
Hence, vaccination is common even in flocks with strong biosecurity. A summary of the vaccines available in the UK at time of writing can be found in Table 4. Two live attenuated vaccines and one inactivated vaccine (in combination with Salmonella Abortusovis) are currently used in the UK to good effect experimentally (Rodolakis and Souriau, 1983) and in the field. Given the risk from wildlife incursion, strong consideration should be given to vaccination of homebred replacements. If replacements are wholly or partially bought-in, unless these originate from flocks that are accredited or already vaccinating replacements, they should be assumed to be infected and vaccinated in quarantine; this means date of purchase should be carefully planned to fit with vaccine schedules (see Table 4).
When vaccines are used, they should be used strictly in accordance with the datasheet. Likewise, the veterinary surgeon should impress on farmers using an EAE vaccine the generic best practice for transit, handling, storage and administration of vaccines. Unfortunately, while many farms use a fridge for medicines, these are frequently not fit for purpose (Williams and Paixão, 2018).
Where practical, bought-in replacements should be lambed separately from the rest of the flock in the first year after purchase. Assuming they are unvaccinated, serology taken from bought-in sheep in quarantine may provide evidence of exposure in the origin flock and so provide support for vaccination. However, latently infected ewes may not have seroconverted (Jones et al, 1995; Sachse et al, 2009) and therefore negative serology in bought-in sheep should not be used to suggest freedom from disease.
Annual whole-flock use of long-acting oxytetracyclines are still used by some flockmasters to control enzootic abortion. This was identified by the Responsible Use of Medicines in Agriculture Alliance (RUMA) in their Targets Task Force Report (RUMA, 2017) as a ‘hotspot’ for reducing inappropriate use of antibiotics in the sheep sector; they quote an unpublished report from a survey questionnaire suggesting around 10% of flocks give all breeding ewes a prophylactic dose of antibiotics pre-lambing. With several vaccines available, this practice should no longer be common-place; it represents scope for veterinary surgeons to engage further with this segment of their sheep clients.
The role of male sheep is generally regarded as minor or negligible, although this is debated (Aitken and Longbottom, 2008; Sargison, 2009). Venereal spread has been generated experimentally (Papp and Schewen, 1996). Scott (2015) suggested maintaining separate ‘carrier’ and ‘clean’ groups (Scott, 2015), although in many commercial settings this may be impractical.
Discussion
EAE is a very common disease of sheep in the UK with significant consequences for health and welfare, both ovine and human. The impact on farm economics can also be severe. The disease is highly preventable through biosecurity and vaccination. Minimising purchase of female replacements should be a priority. A generalised improvement in biosecurity would likely also yield benefits for other diseases; flocks with a history of EAE were also likely to have other infectious agents of abortion diagnosed (Longbottom et al, 2013).
Biosecurity alone would be sufficient were it not for the risk from wildlife carriage. Unless flocks operate in an ‘island’ setting — literal or figurative — vaccination remains a sensible insurance policy to avoid catastrophic outbreaks in naïve flocks. For truly isolated flocks producing replacement breeding females, this could represent a ‘unique selling point’, for which they should be able to command a premium. Outwith these, uptake of accreditation schemes is limited because it prohibits the use of vaccines as there is no commercially available test which differentiates between naturally-infected and vaccinated sheep. Additionally, subclinical enteric infections of C. abortus are recognised, and C. abortus has been isolated from flocks with no history of abortion but marginal antibody titres (Sachse et al, 2009).
For England in 2019, vaccination of first-time breeding ewes had a mean uptake of 41% over 5 years, remaining steady at 33–44% between 2012 and 2019 (Agriculture and Horticulture Development Board (AHDB), 2019). There are several barriers to further uptake of vaccination including farmer education: veterinary surgeons may wish to focus efforts initially on large lowland flocks (Longbottom et al, 2013). Supply issues have been noted as another barrier to uptake (AHDB, 2019). It appears that for many farmers, it takes experience of the disease to start vaccinating; Longbottom et al (2013) revealed that 76.8% of flocks with history of EAE vaccinated their flocks, versus just 15% of those without a similar history. There are concerns about the potential for live vaccines to trigger abortion, which has been documented rarely (Wheelhouse et al, 2010; Laroucau et al, 2018). Natural transmission to a naïve flock remains a bigger risk, and vaccination remains the most effective means of prevention. If vaccination is instituted in a seronegative flock, the risk may be mitigated by vaccinating all breeding females in the first year rather than only replacements as they enter the flock. The arrival of a novel inactivated vaccine to the UK market arms veterinary surgeons with an alternative for flocks where this is a barrier to uptake, although this would require an annual booster.
On a national scale, the costs of EAE are heavily weighted towards prevention (Bennett and IJpelaar, 2005). In addition, EAE has some key traits that make it a candidate for nationwide or regional elimination: there are sensitive and specific serological tests; there are several effective and widely available vaccines; and, unlike many other infectious agents of ovine abortion, there is no significant reservoir outside of small ruminants.
British agriculture is now expected to contend with that of other major sheep farming nations, alongside the dual and imminent possibilities of reduced financial support and greater access to the domestic market by these nations. Elimination of EAE from the national flock would be one step towards becoming more competitive, while improving animal and human health.
Conclusion
Enzootic abortion represents a challenge to responsible antibiotic use, farm economics and animal welfare. Between vaccination and biosecurity measures, it is eminently preventable.
KEY POINTS
- Enzootic abortion of ewes (EAE) caused by Chlamydia abortus is consistently the most common cause of ovine abortion in the UK.
- Latent infection has a key role in the transmission and propagation of this bacterial disease.
- There is a significant zoonotic risk that veterinary surgeons must make clients aware of.
- The submission of placenta and fetus is the best diagnostic tool, if this opportunity is missed serology is very useful.
- The use of vaccines alongside biosecurity is key to control.
- Better control of this disease is important to the reduction of antimicrobial use and the future of the UK sheep industry.