Yes, but kits for c-ELISA. Complement Fixation Test (CFT) for use in main laboratories slowly getting into disuse due to logistic challenges and variable results. Commercial diagnostic kits (c-ELISA kits) are available from different manufacturers.
GAP: Development of a pen-side test could facilitate diagnostics for CBPP outside main laboratories.
Diagnostic kits have been validated by CIRAD/EMVT (Reference: OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals).
Routine methods are described in the OIE Manual of diagnostic tests and vaccines such as:
Required in Africa to enable differentiation of vaccinated cattle from infected cattle.
GAP: DIVA technology a critical gap in CBPP prevention and control tools.
The CF test and ELISAs can be used in screening and eradication programmes, but the highly specific Immunoblotting (IB) test should be used as a confirmatory test. However, the IB test is not fit for mass screening and may be difficult to standardise in countries with marginal laboratory facilities so IB testing should be performed in a reference laboratory.
The c-ELISA is easy to use and regarded as highly practical under the prevailing laboratory conditions. The test appears to be robust and can be used on hemolysed or "anti-complementary" sera.
The CFT performs well provided that the laboratories use it on a regular basis. Problems were encountered in the availability of reagents. At present there is no single source of reagents. The repeatability and reproducibility of the CFT is affected by the differences in quality of the antigen and the combination of the reagents used.
A rapid latex agglutination test (LAT), which gives results in less than two minutes, using sera or whole blood, has been developed for screening cattle in the field.
PCR methodology is also used to confirm outbreaks of CBPP.
GAP:
Both CFT and c-ELISA highly specific and sensitive in detecting CBPP infection in acutely infected cattle. Detection of chronically infected cattle is weak especially with CFT.
Strain T1/44 confers protection for approximately 1 year (21), but the protection conferred by the T1sr strain may only be 6 months long. Serological conversion (CF test) takes place in some animals. The antibodies disappear 3 months after vaccination.
Current vaccines are only stable for a few hours at ambient temperatures. Freeze-dried vaccine must be stored at –20°C and at this temperature its storage life is more than 1 year. Viability may even be conserved for many years without loss of titre allowing for the constitution of emergency stocks.
Intense reactions may appear when infected animals are vaccinated, as occurred recently following emergency vaccination campaigns in East Africa. These reactions usually occur within 2–3 days. Local reactions may also appear at the site of injection after 2–3 weeks with strain T1/44 in some animals. These reactions consist of an invading oedema that leads to death if antibiotic treatment, such as tetracycline is not given. (Use of antibiotics in CBPP infection is not permitted by the OIE or FAO.
The sequence of the complete genome of the reference strain PG1 has been published. Further technical development will allow for a finer characterisation of strains.
Multi-locus sequence analysis of Mycoplama mycoides subsp. mycoides identifies 3 main lineages that correlate with the geographical origins (Europe, Southern Africa, rest of Africa).It may be possible to produce modified live vaccines using various antigenic components from the Mycoplasma mycoides subsp. mycoides.
Improved and more effective anti mycoplasma drugs may be developed.
GAPS:
Possible.
New tests are being developed with a need for improved sensitivity, specificity, reproducibility, robustness, low cost and ease of use in difficult environments. Tests to detect chronic infection and carrier animals are important requirement.
There is a need for a sensitive screening test such as ELISA to be applied for CBPP diagnosis. However, both standardised antigens and reference sera need urgently to be developed.
The CFT and cELISA are relatively expensive, slow (tests took 2-3 hours plus all the transport times/costs) and usually need to be conducted in a laboratory. New tests which are inexpensive, easy to operate and pen side in nature, are required for use in Africa. These tests need high sensitivity and specificity. The sensitivity of the Latex Agglutination test was comparable to the internationally recognised CFT but is far simpler and more rapid to perform. This test may have great potential in parts of Africa where there are great distances between the outbreaks, usually in nomadic herds, and diagnostic laboratories enabling control measures to be implemented rapidly.
A safer, more effective and better characterised vaccine is needed to allow more effective disease control strategies to be implemented.
The development and validation of new types of vaccines composed either of adjuvanted, subunit preparations of defined antigens or live, attenuated mutants created by specific knockout of virulence genes.
The mechanisms involved in the invading process after the first contact of mycoplasmas with host cells are unknown. In depth study of immunopathology will not only facilitate the development of new diagnostic tests, but at the same time will yield useful information for vaccine development.
To study the immunopathology of CBPP and to elucidate the pathogenic mechanisms by identifying the role of the microorganism and its immunogenic components in eliciting pro-inflammatory and inflammatory reactions. The cellular elements of inflammatory nature: macrophages, monocytes, lymphocytes, neutrophils that may liberate inflammatory products such as NO2, myeloperoxidases or cytokines need to be identified. Data on the T cell responses should form the scientific basis to the development of a safe vaccine conferring long lasting immune protection.
The route of administration for the vaccines might also affect immunity: an aerosol through the nose appears more effective than the current tail or subcutaneous injections.
Review of potential mycoplasmacidal agents.
GAP: In vivo studies in cattle.
M. mycoides subsp. mycoides is very sensitive to the environment with a short survival time outside the host.
Infected animals can have peracute, acute, subacute or chronic disease. Subclinical infections also occur
The main signs of the disease are fever and coughing with signs of chest pain. Some affected animals may lose a lot of weight and die. Others may appear to recover but continue to spread the disease to other animals in the herd. Many cattle that survive remain chronic carriers.
GAP: The role played by chronic carriers (lungers) is still an unclarified issue and remains a major scientific gap in the spread of the disease.
Carrier cattle may shed Mycoplasma intermittently possibly related to stress and breakdown of sequestra although this is questioned and has not been proved conclusively.
GAP: Shedding kinetic patterns are a gap that needs further investigation.
Little is known about the pathogenic mechanisms of CBPP. It has been suggested that auto immune and hypersensitive reactions are essential in the development of pathological lesions. The immunological mechanism involved during infection and ability of the pathogen to evade the immune system, must also be elucidated This lack of knowledge has consequences for diagnostic tests, for assessing immune response and for developing an appropriate vaccine.
GAP: The pathogenic mechanism of Mmm still remains a critical gap in knowledge. Production of hydrogen peroxide at tissue level and its cytotoxic effects are yet to be elucidated. It is known that certain strains of Mmm organisms have different capsular contents. Whether this is related to the levels of antibody production and ability to resist infection and hence pathogenicity, are not known. Attachment organelles as have been described for other mycoplasmas such as M. pulmonis not yet identified for MmmSC. It is important that the pathogenic mechanisms of CBPP disease be given the highest priority in terms of research activities, so as to underpin the development of vaccines and diagnostic tools.
Humans are not susceptible to Mycoplasma mycoides subsp. mycoides.
Clinical CBPP is a severe welfare problem. Both Bos indicus and Bos taurus are equally affected, with significant biodiversity implications.
GAP: Reports indicate that B. taurus and crosses more susceptible to post-vaccinal skin reactions. Possible genetic predisposition?
CBPP is widespread in Africa (south of the Sahara) except in the Republic of South Africa, Swaziland, Botswana and southern Namibia. The disease is also suspected to be present in other regions of the world, including the Middle East and parts of Asia although the situation in Asia is unclear. There have been no reported outbreaks of CBPP in Europe since 1999.
GAP: Presence of CBPP in Middle Eastern countries requires verification. In parts of Asia, similarities in both clinical signs of CBPP and Haemorrhagic Septicaemia which is highly prevalent in some Asian countries may be confused with CBPP, if bacteriologic isolation of Mmm and PCR techniques are not employed to determine the cause(s) of pulmonary pathology.
Only based on rainfall and availability of food. CBPP is a disease of cattle movement.
GAP: Seasonality of outbreaks is not clearly defined since in countries where the disease occurs; there are two basic seasons- wet and dry seasons. However, the paucity of official CBPP disease reporting to international organizations (OIE, FAO, AU-IBAR) makes the definition of this aspect of CBPP epidemiology weak.Aerosol, mostly by direct contact; droplets emitted by coughing animals, saliva, and urine. Transmission up to several kilometres has been suspected under favourable climatic conditions. Inapparent carriers are a major source of infection. Possible breakdown of sequestra.
GAP: Breakdown of sequestra in the transmission of CBPP in experimental studies have shown that transmission does not occur by this route. However, studies need to be extended to the field.
Complex host response which is not fully understood involving humoral and cellular immune responses.
GAPS:
In disease-free areas: quarantine, serological tests (complement fixation and c-ELISA) and slaughtering of all animals of the herd in which positive animals have been found. Detailed epidemiological investigations.
In endemic areas diagnosis and vaccination with movement controls and slaughter of infected animals.
Identification of the agent
Serological tests
In Africa control of the disease is based on vaccination campaigns using attenuated strains such as T1/44 and T1/SR. Current vaccines, which are freeze-dried live and attenuated, are unstable and cause post-vaccinal reactions in some animals. Consistent application of CBPP vaccines has been known to reduce the prevalence of CBPP to low levels in some countries.
GAP: There is a strong scientific debate regarding
Cattle owners often use antibiotic treatments and are reluctant to declare the disease. No therapeutic treatment is effective; However, farmers resort to heavy antimicrobial treatment in an attempt to reduce disease damage and mortality rates. Recent work has shown that antibiotic treatment of cattle may greatly reduce the transmission to healthy contacts but this requires treatment of all affected cattle in a group.
GAP: Demonstration of efficacy of commonly available antibiotic treatment in vivo, can facilitate the consideration of the official policy of non-use of antibiotic therapy in CBPP disease.
Surveillance of infected zones and surrounding areas
Surveillance to demonstrate freedom for CBPP for countries with eradication programmes.
Yes. CBPP was recorded in 19 African countries in 2014 (AU-IBAR Annual Year Book -2014). The outbreaks were experienced mostly in West and Eastern Africa. In some cases only infection was reported and in others clinical disease. CBPP is restricted to specific regions in some countries e.g. Namibia.
GAP: Effective diagnostic tools especially isolation of organism and application of currently available serological tests.
http://www.oie.int/fileadmin/Home/eng/Health_standards/tahm/2.04.08_CBPP.pdf
CBPP is currently one of the most serious diseases of cattle in Africa, causing estimated losses of over US$ 2 billion per annum through loss of animals, reduced production of meat and milk.
High economic, social impact in countries with a high incidence. CBPP infected cattle have indirect effects on human activities, e.g. ploughing for crop agriculture, traction of farm produce, reduction in milk production and meat production etc. Cattle used for several social occasions such as marriages may be lost through outbreaks of the disease. Other indirect impact include:
Difficulties in identifying carrier and sub clinically infected cattle. In Africa inability to enforce movement controls for a variety of reasons. Inadequate vaccine potency. Poor diagnostic facilities. Financial constraints and lack of compensation for slaughter of whole infected herds.
GAP: Critical gap is the development of a pen-side test in live animals to support the use of other ancillary actions in CBPP prevention and control.
There is a need for further research on CBPP, especially with regard to the establishment of infection (pathogenicity factors, immunopathology, virulence factors, genomics) and the persistence of infection in chronically affected animals (e.g. reservoirs). The search for new diagnostic tests with high sensitivity and high specificity should be continued as should the objective of developing safe and efficacious vaccines.
Names of expert group members are included where permission has been given.
William Amanfu, consultant (ex-FAO), Ghana [Leader]
Project Management Board
June 2016
http://www.fao.org/DOCREP/005/Y4143E/Y4143E00.HTM
http://www.fao.org/DOCREP/005/Y4142E/Y4142E00.HTM
Centre for Food Safety and Public Health Iowa State University: http://www.cfsph.iastate.edu/DiseaseInfo/animaldiseaseindex.htm
USAHA The Seventh Edition Foreign animal diseases - Gray book: https://www.aphis.usda.gov/emergency_response/downloads/nahems/fad.pdf
Manso-Silván L, Vilei EM, Sachse K, Djordjevic SP, Thiaucourt F, Frey J., 2009. Mycoplasma leachii sp. nov. as a new species designation for Mycoplasma sp. bovine group 7 of Leach, and reclassification of Mycoplasma mycoides subsp. mycoides LC as a serovar of Mycoplasma mycoides subsp. capri”. Int J Syst Evol Microbiol.59:1353-8.