Chlamydiosis (C. Abortus) - available

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Control Tools

Diagnostics availability

Commercial diagnostic kits available worldwide

A number of commercially available tests exist for the detection of antibodies using ELISA. A number of tests are also available for the detection of genus level antigen using ELISA and fluorescent antibody tests.

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 positive and negative samples.

Commercial diagnostic kits available in Europe

A number of commercially available tests exist.

Diagnostic kits validated by International, European or National Standards

No.

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

Routine methods are described in the OIE Manual of Diagnostic Tests and Vaccines: Chapter 2.7.7 on enzootic abortion of ewes (ovine chlamydiosis)

1 Identification of the agent.

  • Smears from cotyledon, foetal stomach.
  • Antigen detection tests-ELISA
  • PCR and real time PCR
  • Isolation of C.abortus in embryonated chicken eggs or in tissue culture

2. Serology

  • Complement Fixation Test
  • ELISA

The manual also mentions the ArrayTube microarray platform for detection, and IHC for antigen detection. 

 

Commercial potential for diagnostic kits in Europe

Potential exists.

DIVA tests required and/or available

Molecular methods now available for this - publications appearing in 2010 in the journal Vaccine.

Opportunities for new developments

 

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.

Vaccines availability

Commercial vaccines availability (globally)

Yes with both killed and live vaccine although live vaccines may not be available in all countries.

Commercial vaccines authorised in Europe

Only 2 live vaccines currently available in Europe, the inactivated vaccine (Mydiavac) was withdrawn from production in 2009.

Marker vaccines available worldwide

No.

GAP: This is a goal with next generation vaccines.

Marker vaccines authorised in Europe

No.

Effectiveness of vaccines / Main shortcomings of current vaccines

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 prevent shedding at parturition. 

Commercial potential for vaccines in Europe

High particularly in those countries with endemic problems and high density of susceptible species of ruminants.

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)

Feasible.

Opportunity for barrier protection

Used as part of a herd or flock control programme.

Opportunity for new developments

Requirement of next generation multi-component marker vaccines based on recombinant protein technology that can be coupled with serological test to differentially distinguish vaccinated from wild-type infected animals (DIVA).

Pharmaceutical availability

Current therapy (curative and preventive)

Long acting oxytetracycline.

Future therapy

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

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.

Regulatory and/or policy challenges to approval

No specific issues.

Commercial feasibility (e.g manufacturing)

Feasible if demand exists.

Opportunities for new developments

No demand for improvements here.

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 species-specific antibody tests. Requirement for proper validated control sera in order to assess diagnostic tests and determine cut-offs for positivity.

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 species-specific antibody tests. 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. Best bet is to identify serologically following initial infection, although this may not be possible.

GAP: would require routine multiple screening which is not practical.

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 vaccines.

Time to develop new or improved vaccines

Depending on when a candidate vaccine could be identified the timescale will be 5-10 years. This will involve development, clinical trials and licensing. Potential vaccines need to be identified and subjected to initial trials and depending on the outcome will depend the time to commercial availability.

Cost of developing new or improved vaccines and their validation

Expensive with the need to develop and undertake all the relevant tests to provide data to enable the product to be authorised. Field trial will be difficult as will evaluating the results

Research requirements for new or improved vaccines

Identification of relevant protective antigens, through genomic, bioinformatic, proteomic, immunological and biological approaches.

New developments for pharmaceuticals

Requirements for pharmaceuticals development

No requirement.

Time to develop new or improved pharmaceuticals

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

Research requirements for new or improved pharmaceuticals

No requirement.

Disease details

Description and characteristics.

Pathogen

The order Chlamydiales was reclassified in 1999 into two genera Chlamydia and Chlamydophila based on sequence analysis. The genus Chlamydia contains 3 species C. trachomatis affecting humans, C.suis in pigs and C.muridarum affecting the mouse and hamster. The genus Chlamydophila includes  C.abortus (sheep and goat, cattle, pigs), C.psittaci (avian), C.pecorum (sheep, goats, cattle, pigs) C.pneumoniae (humans), C.felis (cat) C.caviae (guinea pig)

Variability of the disease

‘Chlamydiosis’ and ‘chlamydia(e)’ are terms more universally used to describe infections in birds, mammals and man. The full names are used when referring to a specific species.  There is good correlation between the species of Chlamydia and their virulence, disease syndrome and host range. Chlamydiales are widespread in nature. They cause a range of diseases in man, birds, wild and domestic animals. Diseases include eye, lung and reproductive infections.

Stability of the agent/pathogen in the environment

The organism is relatively stable in the environment can survive for long periods in freezing temperatures and for days during the spring.

GAP: more work needs to be done on this as it is important with regards to risk of transmission and period of viability.

Species involved

Animal infected/carrier/disease

Chlamydophila abortus (C.abortus) is a cause of abortion and foetal loss in sheep, cattle, goats and pigs.

Human infected/disease

Rare in humans but can affect pregnant women or cause respiratory problems in non pregnant persons.

GAP: it also affects immunocompromised persons. When it affects pregnant women the disease can be life-threatening.

Vector cyclical/non-cyclical

None.

Reservoir (animal, environmental)

Asymptomatic carrier animals infected with C.abortus are the main reservoir. Ewes can remain persistently infected after the initial abortion and can excrete the organism.

GAP: infective dose is currently unknown, again this is important for transmission resulting from excretion, and how long the organisms are viable in fluids and placenta.

Description of infection & disease in natural hosts

Transmissibility

Most infection occurs by ingestion. Aerosol transmission may occur.

GAP: there is no real evidence that rams transmit this disease venereally – it is all conjecture based on experimental evidence and not field evidence! This is not considered a sexually-transmitted disease.

Biggest source of infection is the placenta, vaginal fluids and the lambs themselves. Aerosol transmission is likely as the pathogen has been found in air samples from sheep stables.

Pathogenic life cycle stages

Chlamydiae comprise two developmental forms. The elementary body is relatively inactive and is the infectious particle. The reticulate body is the active replicating stage but is non- infectious. The elementary body attaches to the host cell and then enters. Once inside they differentiate into the reticulate body. Many reticulate bodies develop in the chlamydial inclusion and after a period the reticulate bodies differentiate into elementary bodies which are released when the cell lyses.

Signs/Morbidity

Clinical signs are primarily associated with outbreaks of abortions in sheep and goats in the last month of pregnancy. In cattle, abortions tend to be sporadic, occurring near or at term. Infections sometimes results in the birth of dead lambs, goats, calves at term, or delivery of weak animals which may die later. In sheep, goats and cattle there is usually no overt evidence of clinical disease prior to abortion although in the case of cattle a serous uterine discharge may be present. In sheep, a vagina discharge is sometimes observed up to 2 days prior to abortion occurring.

Incubation period

Abortions occur in the last few weeks of pregnancy irrespective of when infection occurred. The incubation period depends on the stage at which the animal was infected. Sheep infected late in pregnancy may not abort until late in the next pregnancy. If ewes are not too advanced in pregnancy when exposed to infection they may also abort. A similar situation occurs when goats become infected.

GAP: It must also be remembered that in an extended lambing season it is possible for a ewe to pick up infection from an aborted ewe and also abort. A ewe picking up infection in the last 5-6 weeks of pregnancy is thought to become latently infected, aborting in the following lambing period, although this has not been adequately investigated.

Mortality

Mortality of the dam is very low and usually associated with retained placenta and secondary infection.

Shedding kinetic patterns

C. abortus is excreted in dead lambs, placenta, uterine discharges, and faeces of aborting ruminants. The organism has also been found in goat milk.

GAP: C. abortus does not appear to be shed in large numbers from the faeces. This requires more investigation.

Mechanism of pathogenicity

Abortion is considered to be the result of several factors which have a direct and indirect effect on the foetus. There is destruction of placental tissue by C. abortus, vascular thrombosis, and an inflammatory response both in the foetal organs and the uterus.

GAP: The destruction of the trophoblast cells has an impact on hormonal imbalance and it is likely that this is responsible for the premature expulsion of the foetus.

Zoonotic potential

Reported incidence in humans

Whilst C.abortus is a zoonosis, reports of human cases are rare.

Estimated level of under-reporting in humans

As this is a rare condition in humans the level of under reporting is probably very low.

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

Human infection can result from contact with infected sheep and goats although this is less clear in the case of cattle. The risk to humans is mainly limited to pregnant women who have contact with C.abortus through pregnant sheep or goats especially during the lambing or kidding season. Infection can occur as the result of the inhalation of infected material and also because of inadequate hygiene, i.e washing of hands after touching infected materials..

Symptoms described in humans

Abortion and severe illness have been reported in pregnant women. In non pregnant humans chlamydial respiratory diseases has been reported on a number of occasions.

Likelihood of spread in humans

GAP: The likelihood of human to human spread of C.abortus is unknown.

Impact on animal welfare and biodiversity

Both disease and prevention/control measures related

None except death of the lambs.

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

None.

Slaughter necessity according to EU rules or other regions

No.

Geographical distribution and spread

Current occurence/distribution

C abortus occurs world wide.

GAP: thought not to be an issue in Australia and NZ.

Epizootic/endemic- if epidemic frequency of outbreaks

Infection is most likely to be acquired at the time of parturition by the ingestion of the elementary bodies of C.abortus. Abortion storms can occur in sheep flocks following the introduction of infected ewes which abort and result in the remainder of the flock becoming infected. The infection then lies dormant until the next lambing season when abortions will occur. A similar picture can be seen in goats but not cattle.

Seasonal cycle (seasonality)

Any seasonality is related to the breeding cycle of the affected ruminants.

Speed of spatial spread during an outbreak

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

Transboundary potential of the disease

Spread by infected incubating ruminants or carrier recovered animals.

GAP: We do not know the role if any in spread of infection through wild-life species such as rabbits.

Seasonal cycle linked to climate

No.

Distribution of disease or vector linked to climate

No.

Outbreaks linked to extreme weather

GAP: Could be though, the cooler the weather the longer the organisms remain viable in the environment.

Sensitivity of disease or vectors to the effects of climate change (environmental changes/land use)

GAP: The organism is affected by weather and temperature, therefore this is likely to impact on disease, but currently unknown.

Route of Transmission

Usual mode of transmission (introduction, means of spread)

Ingestion of infectious agent through oral-nasal route.

Occasional mode of transmission

Inhalation.

Conditions that favour spread

The introduction of asymptomatic C. abortus carriers into a flock or herd can result in infection. Poor hygiene at lambing, kidding or calving can allow infection to spread rapidly.

Detection and Immune response to infection

Mechanism of host response

Effective 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.

Immunological basis of diagnosis

Detection of antibodies.

Main means of prevention, detection and control

Sanitary measures

  • Biosecurity.
  • Care in the purchase of replacement stock from known disease free sources.
  • Vaccinate all replacement animals being introduced into a clean flock.

Mechanical and biological control

  • Dispose of abortion material and contaminated bedding effectively by burning
  • Isolate aborting ewes/goats
  • Clean and disinfect lambing/calving pens
  • Personal hygiene to prevent spread
  • Prevent exposure to C.abortus
  • Routine vaccination if C.abortus infection is established in the flock or where there is a high level of infection in an area.
  • Use of antibiotics to limit losses in non-vaccinated flocks where problem becomes evident.

Diagnostic tools

Identification of the organisms and serological tests. Current serological tests will not detect latent carriers. Molecular detection of specific DNA (by PCR) is clearly superior over serology for being more sensitive and specific. Serology can be useful only for herd screening and identification of acute clinical disease.

Vaccines

Currently inactivated and attenuated live vaccines are available for use in sheep but not cattle. They should be administered at least 4 weeks before breeding as a preventative measure, but can also be administered during pregnancy.

Therapeutics

Long acting tetracyclines given at the correct period will reduce the severity of infections and prevent abortions. C.abortus may still be shed at birth. Antibiotic treatment has been considered as the most practical measure for control of disease in cattle where the abortions are more sporadic.

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 newborn lambs. Immuno-compromised or immuno-suppressed individuals should avoid potential contact with infection. Care should be taken in the use of live vaccines.

Border/trade/movement control sufficient for control

Standards laid down in the OIE Terrestrial Animal Health Code.

Prevention tools

Vaccination, husbandry and biosecurity.

Surveillance

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

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

Vaccination is effective at reducing the clinical picture but not for the eradication of infection.

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 and to possible treatment.

Disease information from the OIE

Disease notifiable to the OIE

Ovine and Avian Chlamydiosis are notifiable.

OIE disease card available

No.

OIE Terrestrial Animal Health Code (reference)

Enzoonotic abortion of ewes: http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_1.14.5.htm

Avian chlamydiosis: http://www.oie.int/index.php?id=169&L=0&htmfile=chapitre_1.10.1.htm

OIE Terrestrial Manual (reference)

Enzoonotic abortion of ewes: http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.07.07_ENZ_ABOR.pdf

Avian chlamydiosis: http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.03.01_AVIAN_CHLAMYD.pdf

Socio-economic impact

Zoonosis: Impact on affected individuals and/or aggregated DALY figures

Not known but will be low.

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

Negligible.

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.

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

Costs of vaccine and application. Use of antibiotics add to the costs.

Indirect impact

Reduced production of lambs and kids.

Trade implications

Impact on international trade/exports from the EU due to existing regulations

International standards for trade are contained in the OIE 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.

Impact on EU intra-community trade due to existing EU regulations

None.

Impact on national trade due to existing regulations

None.

Main perceived obstacles for effective prevention and control

1. Detecting the presence of the organism is difficult as one of the characteristics of ovine abortion is the persistence of subclinical C. abortus infection in non-pregnant sheep.

2.Vaccine does not give complete protection

3. Vaccinated animals may still excrete C.abortus at lambing.

4. Vaccination will not eradicate infection from a flock.

Main perceived facilitators for effective prevention and control

1. Improved diagnostic tests

2. Better understanding of the immune response of sheep to infection and too the vaccines.

3. Recognition of latent infection.

4. Improved second generation vaccines

Risk

Risks to production and rare risk of infection in humans. Across the world the infection poses problems in the main sheep rearing areas and can also impact on goats.

Main critical gaps

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 recombinants.

Sources of information

Name of expert group leader

Dr. Konrad Sachse - Friedrich-Loeffler-Institut

Name of reviewers

PMB

Date of preliminary approval

17th September 2010

Date of final approval

1st October 2010