Brucellosis In Cattle - Symptoms, Effects & Treatment

03/02/2023

03/02/2023

22/09/2022

The most effective prevention strategy is the elimination of infection in animals. Vaccination of cattle, goats and sheep is recommended in enzootic areas with high prevalence rates. Serological or other testing and culling can also be effective in areas with low prevalence.

22/09/2022

Control:
Efforts are directed at detection and prevention, because no practical treatment is available. Eventual eradication depends on testing and eliminating reactors. The disease has been eradicated from many individual herds and areas by this method. Herds must be tested at regular intervals until two or three successive tests are negative.
Noninfected herds must be protected. The greatest danger is from replacement animals. Additions should be vaccinated calves or nonpregnant heifers. If pregnant or fresh cows are added, they should originate from brucellosis-free areas or herds and be seronegative. Replacements should be isolated for ~30 days and retested before being added to the herd.
Vaccination of calves with B abortus Strain 19 or RB51 increases resistance to infection. Resistance may not be complete, and some vaccinated calves may become infected, depending on severity of exposure. A small percentage of vaccinated calves develop antibodies to Strain 19 that may persist for years and can confuse diagnostic test results. To minimize this problem, calves in the USA are mostly vaccinated with a vaccine of Strain RB51. It is a rough attenuated strain and does not cause production of antibodies, which are detected by most serologic tests.
Whole-herd adult cattle vaccination using Strain 19 or RB51 has been practiced in certain high-incidence areas and selected herds in the USA with much success.
Vaccination as the sole means of disease control has been effective. Reduction in the number of reactors in a herd is directly related to the percentage of vaccinated animals. However, when proceeding from a control to an eradication program, a test and slaughter program becomes necessary. B abortus has been eradicated from cattle herds in the USA, and all states are considered free of brucellosis.
Brucellosis is endemic in some nondomesticated bison and elk herds in the USA. Transmission of B abortus to domestic cattle herds is rare but has occurred in several cattle herds commingling with infected elk in the greater Yellowstone Park area.

22/09/2022

Etiology and Epidemiology:
The disease in cattle, water buffalo, and bison is caused almost exclusively by Brucella abortus; however, B suis occasionally is isolated from seropositive cows but does not appear to cause clinical signs and is not contagious from cow to cow. In some countries, the disease in cattle is caused by B melitensis. The syndrome is similar to that caused by B abortus. B melitensis is not present in the USA.
Infection spreads rapidly and causes many abortions in unvaccinated cattle. In a herd in which disease is endemic, an infected cow typically aborts only once after exposure; subsequent gestations and lactations appear normal. After exposure, cattle become bacteremic for a short period and develop agglutinins and other antibodies; some cattle resist infection, and a small percentage of infected cows spontaneously recover. A positive serum agglutination test usually precedes an abortion or a normal parturition but may be delayed in ~15% of cows. The incubation period may be variable and is inversely related to stage of gestation at time of exposure. Organisms are shed in milk and uterine discharges, and the cow may become temporarily infertile. Bacteria may be found in the uterus during pregnancy, uterine involution, and infrequently, for a prolonged time in the nongravid uterus. Shedding from the va**na largely disappears with the cessation of fluids after parturition. Some infected cows that previously aborted shed brucellae from the uterus at subsequent normal parturitions. Organisms are shed in milk for a variable length of time—in most cattle for life. B abortus can frequently be isolated from secretions of nonlactating udders.
Natural transmission occurs by ingestion of organisms, which are present in large numbers in aborted fetuses, fetal membranes, and uterine discharges. Cattle may ingest contaminated feed and water or may lick contaminated ge****ls of other animals. Venereal transmission by infected bulls to susceptible cows appears to be rare. Transmission may occur by artificial insemination when Brucella-contaminated semen is deposited in the uterus but, reportedly, not when deposited in the midcervix. Brucellae may enter the body through mucous membranes, conjunctivae, wounds, or intact skin in both people and animals.
Brucellae have been recovered from fetuses and from manure that has remained in a cool environment for >2 mo. Exposure to direct sunlight kills the organisms within a few hours.

22/09/2022

Brucellosis control policy
Brucellosis policy is based on the following principles:
quick and accurate identification of diseased animals
isolation from non-infected herd-mates
identification of high-risk contact animals
rapid removal and slaughter
rapid and accurate tracing of reactors back through contact herds
rapid and accurate tracing of animals that have moved through infected herds
identification of "at risk" herds and rapid check testing
effective cleansing and disinfection of premises
effective epidemiological investigations
good surveillance systems
co-operation of farmers
appropriate compensation and incentives to eradicate
effective enforcement procedures
removal of risk of reintroduction at herd, regional and country-wide levels

22/09/2022

Brucellosis is one of the most common contagious and communicable zoonotic diseases with high rates of morbidity and lifetime sterility. There has been a momentous increase over the recent years in intra/interspecific infection rates, due to poor management and limited resources, especially in developing countries. Abortion in the last trimester is a predominant sign, followed by reduced milk yield and high temperature in cattle, while in humans it is characterized by undulant fever, general malaise, and arthritis. While the clinical picture of brucellosis in humans and cattle is not clear and often misleading with the classical serological diagnosis, efforts have been made to overcome the limitations of current serological assays through the development of PCR-based diagnosis. Due to its complex nature, brucellosis remains a serious threat to public health and livestock in developing countries. In this review, we summarized the recent literature, significant advancements, and challenges in the treatment and vaccination against brucellosis, with a special focus on developing countries.

22/09/2022

Bovine Brucellosis
The project assisted the Veterinary Directorate to shift the approach to the control of bovine brucellosis from the previous sporadic testing of cattle initiated at the regional level – without central collation of results – to a planned national programme for bovine brucellosis control. This approach is presented in detail in the Bovine Brucellosis Control Programme (BBCP) wich was approved and adopted by the Albanian State Veterinary Service (ShVSh) and is now under implementation by the ShVSh.
Stepwise introduction of the national bovine brucellosis control programme
For introduction of the programme the focus was put on the four-monthly screening of all herds with more than 20 cattle by means of bulk milk tests. This aspect of the programme is based on a step by step approach, starting with screening, then testing of all cattle in positive herds, identifying and removing for supervised slaughter all reactor animals.
The additional implementation of brucellosis surveillance in the bovine population is foreseen, i.e., following up all cases of abortions in cattle: collection of samples for diagnosis, with the supervised slaughter of all Brucella-positive cattle at approved slaughterhouses.
Assistance in developing standard procedures
In this reporting period, after a considerable delay, the project assisted the removal of cattle from infected premises and supervised their slaughter at an approved abattoir, in accordance with the procedures described in the strategy.
The PAZA Disease Surveillance Expert (DSE) and junior experts made field visits to the brucellosis-infected farms identified during the BBCP implementation in Durres, Lezha and Korca regions. The aim of the field visits was to investigate positive bovine brucellosis results on these farms and to discuss with and demonstrate to the staff of the regional veterinary service standard operating procedures (SOPs), including cleaning and disinfection, which hitherto the veterinary service had not routinely enforced.
NOTE: Importantly, for the sake of efficiency, this approach to screening all larger herds of cattle could, and should, be combined with a tuberculin testing programme for the control of bovine tuberculosis.
Sustained training programme needed
Whilst the theoretical training delivered to OVs has increased their understanding of the BBCP, further practical training is required to transfer knowledge and skills related to each of the activities, and to facilitate reflection on the experiences that were gained in the process, with the aim of improving the efficiency of the activity.
Overall, a sustained theoretical and practical training programme is essential in order to establish an effective bovine brucellosis control programme.
Conclusion for viable control of bovine brucellosis
The findings of the case study of bovine tuberculosis (BTB) in a village in Diber region have indicated that the only economically, and practically viable approach to the control of this disease is through the establishment of an abattoir surveillance programme but this in turn depends on the institutional responsibilities for abattoir-based inspection duties
The demonstration of the right way to clean and disinfect a stable and premises was filmed and finally compiled in a training video, which can be viewed here.

12/09/2022

A global surveillance and control system cannot (and should not!) be improvised for endemic zoonotic diseases. Indeed, endemic and epidemic diseases are in essence different and do require tailored approaches. For example, the implementation of an early detection/warning system, which is the first stage of any control program of epidemicc diseases is meaningless in the context of endemic diseases having reached the stage of endemic stability, which is often the case under traditional husbandry systems in the developing world. In 2013, we wrote a paper titled: “A One Health surveillance and control of brucellosis in developing countries: Moving away from improvisation” . Human brucellosis remains the commonest zoonotic disease worldwide with more than 500 000 new cases annually. The disease is caused by various Brucella species, which mainly infect cattle, swine, goats, sheep. Humans generally acquire the infection through direct contact with infected animals, by eating or drinking contaminated animal products, or by inhaling airborne agents. The most rational approach for preventing human brucellosis is the control and elimination of the infection in animals and the pasteurization of milk . The aim of the aforementioned publication was to highlighting knowledge gaps and misunderstandings about the biology of Brucella infections. Understanding the biology of Brucella infections and the transmission patterns at the wildlife/livestock/human interface is of paramount importance before implementing any control or eradication program in animals, even more so should interventions be justified within One Health (OH) label. Indeed, in addition to calling for transdisciplinary collaboration, and in contrast to the standard common (veterinary) public health paradigm, which is anthropocentric, the OH paradigm aims to promote the well-being of animals and natural resourse conservation and management . Unfortunately, many authors seem to view OH as nothing more than a call for interdisciplinary collaboration, the latter often being only informal. OH is much more than cost saving by sharing transport, software, communication systems and laboratory infrastructure: it requires core competencies . A new curriculum developing transdisciplinary core OH competencies, beyond the discipline-specific area of expertise, is therefore needed in order to design and implement true OH approaches. Unfortunately, up to this day, education remains often segregated between human health, animal health and environmental health (discipline-specific silos)
The aim of this opinion paper is to review the OH approach to brucellosis interventions implemented in industrialized and in low and middle income countries (LMICs) and to question whether, standard-culling practices are efficient and ethically sound OH measures, both for brucellosis control and more generally in health interventions.

12/09/2022

Human brucellosis remains the commonest zoonotic disease worldwide with more than 500 000 new cases annually. Understanding the biology of Brucella infections and the transmission patterns at the wildlife/livestock/human interface is of paramount importance before implementing any brucellosis control or eradication program in animals, even more so should interventions be justified within One Health. In addition to calling for transdisciplinary collaboration, One Health formally aims to conserve the environment and to promote the well-being of animals. In this opinion paper, the One Health approach of brucellosis is reviewed in the industrialized and the low and middle income countries, highlighting pitfalls and shortcomings of serological studies and discussing the role of urban and peri-urban farming for the re-emergence of brucellosis in the developing world. The role of wildlife as a potential reservoir is highlighted and different management strategies are discussed. Lastly, beyond its role in the control of brucellosis, the ethical dimension of culling wildlife to control disease emergence or spill-back of infections in livestock is discussed. Core transdisciplinary competencies such as values and ethics are critically important in guiding the development of One Health curricula and in continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A conceptual framework needs to be developed from inception to knowledge translation. Importantly, transdisciplinary competencies should be developed as an adjunct to discipline-specific areas of expertise, not as a replacement. A profound understanding of the biology of infectious agents is and will always remain a pre-requisite for any sound One Health approach.

12/09/2022

Forty-five brucella infected cows were studied 15 to 30 days following abortion. Eighteen cows were slaughtered and autopsied for examination of Brucella in the organs and lymph nodes. The remaining 27 cows were treated during two and one-half months and then slaughtered after undergoing a treatment with 0, 1, 2 or 3 intraperitoneal injections of oxytetracycline dissolved in 100 ml of physiological saline. The treatment modified only slightly the natural evolution of antibody titers. The levels of infection were similar for all cows which received no treatment. Cows treated with oxytetracycline had less severe infection than the non treated animals and four were infection-free at slaughter. The level of infection of treated cows was independant of the treatment regime. The advantages of treating non pregnant cows to reduce the level of infection and risk of abortion were discussed.

12/09/2022

The disease in cattle, water buffalo, and bison is caused almost exclusively by Brucella abortus; however, B suis occasionally is isolated from seropositive cows but does not appear to cause clinical signs and is not contagious from cow to cow. In some countries, the disease in cattle is caused by B melitensis. The syndrome is similar to that caused by B abortus. B melitensis is not present in the USA.
Infection spreads rapidly and causes many abortions in unvaccinated cattle. In a herd in which disease is endemic, an infected cow typically aborts only once after exposure; subsequent gestations and lactations appear normal. After exposure, cattle become bacteremic for a short period and develop agglutinins and other antibodies; some cattle resist infection, and a small percentage of infected cows spontaneously recover. A positive serum agglutination test usually precedes an abortion or a normal parturition but may be delayed in ~15% of cows. The incubation period may be variable and is inversely related to stage of gestation at time of exposure. Organisms are shed in milk and uterine discharges, and the cow may become temporarily infertile. Bacteria may be found in the uterus during pregnancy, uterine involution, and infrequently, for a prolonged time in the nongravid uterus. Shedding from the va**na largely disappears with the cessation of fluids after parturition. Some infected cows that previously aborted shed brucellae from the uterus at subsequent normal parturitions. Organisms are shed in milk for a variable length of time—in most cattle for life. B abortus can frequently be isolated from secretions of nonlactating udders.
Natural transmission occurs by ingestion of organisms, which are present in large numbers in aborted fetuses, fetal membranes, and uterine discharges. Cattle may ingest contaminated feed and water or may lick contaminated ge****ls of other animals. Venereal transmission by infected bulls to susceptible cows appears to be rare. Transmission may occur by artificial insemination when Brucella-contaminated semen is deposited in the uterus but, reportedly, not when deposited in the midcervix. Brucellae may enter the body through mucous membranes, conjunctivae, wounds, or intact skin in both people and animals.
Brucellae have been recovered from fetuses and from manure that has remained in a cool environment for >2 mo. Exposure to direct sunlight kills the organisms within a few hours.

31/07/2022

Brucellosis can be transmitted from animals to humans in many ways: ingestion of infected meat or unpasteurized dairy products; direct contact of broken skin or mucous membrane with infected animal tissues; and inhalation of infectious aerosols. Except for possible cases of transmission after blood transfusion, parenteral drug use and bone marrow transplant brucellosis is still considered not to be transmissible from person to person via close contact However, a few cases of Brucella melitensis infection in spouses of patients with serologically or culture-proven brucellosis have been reported in the past decade We describe a well documented case of transmission of B melitensis biotype 3 to a spouse, which adds to the growing evidence of interhuman transmissibility of this infection.

11/07/2022

Brucellosis is a zoonotic infectious disease caused by invading the body and causing infection-allergy by Brucella. In China, it belongs to category b infectious diseases, and sheep are the main source of infection in most areas Human is the opportunistic host of this disease. Prior to onset, most of the patients had close contact with livestock and animal products suspected to be infected with brucellosis, or had eaten raw cow's, sheep's milk and meat products, or lived in brucellosis epidemic areas, or engaged in brucella culture, detection or brucella vaccine production and use. As brucella is ubiquitous in the bodily fluids and f***s of infected patients s*xual transmission has become a potential transmission mode of brucella. The two patients reported in this case are couples, highly suspected of s*xual transmission between husband and wife.
Case presentation
In September 2019, a 46-year-old female was hospitalized at First Affiliated Hospital of Chongqing Medical University due to "recurrent fever for one month, up to 38.9 ℃ accompanied by chills and sweating", but otherwise no complaints. She was treated with meroxicillin sulbactam sodium + ribavirin locally and her temperature back to normal. However, 1 week after treatment, the patient's temperature increased again, with the highest value of 39 ℃.
After admission to our hospital, besides high body temperature, through laboratorial inspection, she had leucopenia and low neutrophils, slightly elevated hypersensitive C - reactive protein, procalcitonin and other inflammatory parameters (Table 1). Blood culture was positive for Gram-negative bacillus biochemically identified as Brucella melitensis. Simultaneously, serum agglutination test was positive. The patient was treated with intravenous aminoglycoside etimicin 300 mg (once a day for 14 days) plus minocycline 100 mg (first dosage 200 mg, then once every 12 h) in combination. Her temperature rapidly returned and maintained to normal and she was discharged and continued to take minocycline for 6 months without any recurrent signs during the follow-ups.

11/07/2022

Brucellosis, a bacterial zoonosis, is transmitted directly or indirectly from infected animals (mainly domesticated ruminants and pigs) to humans. People are generally susceptible to brucella, which is mainly transmitted by direct contact, digestive tract and respiratory tract. Since brucella can be discharged from various secretions and f***s after human infection, s*xual transmission has become a potential mode of transmission. We report a case of highly suspected s*xually transmitted brucellosis infection patient, which was discharged after treatment with etimicin + minocycline.

29/06/2022

Bovine Mastitis
Mastitis in cows is one of the most common diseases plaguing the dairy industry. Bovine mastitis is an inflammation of the mammary gland caused from trauma or an infection, leading to abnormal and decreased milk production.
Apart from antibiotics, dairy farmers have few tools to treat the common and costly udder infection mastitis. To add to their tool kit, a team led by Dr. Gerlinde Van de Walle of the Baker Institute is exploring compounds secreted by stem cells as a potential therapy that may kill the bacteria while healing the damage they leave behind.
Dr. Gerlinde Van de Walle in her Baker Institute Lab photo by Rachel Philipson
The new project stems from a unique collaboration between the Baker Institute for Animal Health, part of the Cornell College of Veterinary Medicine (CVM), and Elanco, a leading animal health company. Funding for the work comes from the Foundation for Food and Agriculture Research (FFAR), the New York Farm Viability Institute (NYFVI) and Elanco. All together, the project will receive $1.38 million, with about half coming from FFAR. While the research is still in early stages, the team hopes it will provide proof of concept that stem cell compounds have potential for treating mastitis and perhaps other diseases as well. “The long-term goal would be a natural product that could be an adjunct or even a replacement for antibiotics,” said Van de Walle, “that in itself would be huge.”
In addition, Dr. Laura Goodman of the Baker Institute is collaborating with scientists at the University of New Hampshire to study genetics of this costly dairy cow disease. Even with this heavy cost, there is limited information about the genetics of the bacteria that cause mastitis. Now researchers at the New Hampshire Veterinary Diagnostic Laboratory at the University of New Hampshire in collaboration with colleagues at Cornell University have received a four-year $650,000 grant from the USDA National Institute of Food and Agriculture (NIFA) to conduct genetic research to unravel how these bacteria cause these costly infections.
"I’m looking forward to continuing this partnership to characterize genetic patterns in mastitis and develop better molecular characterization tools that can help us understand antimicrobial resistance in a One Health context. This work will have excellent synergy with my project on natural diets and antimicrobial resistance with the Cornell Feline Health Center," states Goodman.
See the latest developments
Dairy Global - August 5, 2021 - A cure for mastitis?
"By and large, however, it is antibiotics that veterinarians and dairy farmers have historically relied on to treat mastitis – and they still do. But while antibiotics do work, any treated cow must be taken out of the milking pool for a period of time to prevent contamination of the milk supply with antibiotic residues. Antibiotics also do nothing to repair the tissue damage caused by the infection.
And with bacterial resistance to antibiotics growing each year, it is critical that a new solution be found to treat mastitis." READ MORE
UNH Scientists Receive $650,000 Grant to Study Genetics of Costly Dairy Cattle Disease - August 23, 2021
Dr. Laura Goodman is one of the Cornell
researchers collaborating on the NIFA grant.
Researchers at the New Hampshire Veterinary Diagnostic Laboratory at the University of New Hampshire in collaboration with colleagues at Cornell University have received a four-year $650,000 grant from the USDA National Institute of Food and Agriculture (NIFA) to conduct genetic analysis and research to unravel how these bacteria cause these costly infections. The grant is part of the federal agency's $14 million research investment to protect agricultural animals from disease.

30/05/2022

28/04/2022

Brucellosis is a bacterial infection that affects thousands of people worldwide. Avoiding unpasteurised dairy products and taking precautions when working with animals or in a laboratory can help prevent brucellosis.
Symptoms may include joint and muscle pain, fever, weight loss and fatigue. Some people develop stomach pain and cough.
Treatment includes antibiotics. Relapses are common.

28/04/2022

Brucellosis is an infectious disease caused by bacteria. People can get the disease when they are in contact with infected animals or animal products contaminated with the bacteria. Animals that are most commonly infected include sheep, cattle, goats, pigs, and dogs, among others. Brucellosis Worldwide.

22/04/2022

Brucellosis is a bacterial disease caused by various Brucella species, which mainly infect cattle, swine, goats, sheep and dogs
Brucellosis is a bacterial disease caused by various Brucella species, which mainly infect cattle, swine, goats, sheep and dogs. Humans generally acquire the disease through direct contact with infected animals, by eating or drinking contaminated animal products or by inhaling airborne agents. Most cases are caused by ingesting unpasteurized milk or cheese from infected goats or sheep.
Brucellosis is one of the most widespread zoonoses transmitted by animals and in endemic areas, human brucellosis has serious public health consequences. Expansion of animal industries and urbanization, and the lack of hygienic measures in animal husbandry and in food handling, partly account for brucellosis remaining a public health hazard.

21/04/2022

BrucellosisMany commercial diagnostic kits are available worldwide. These include iELISA, cELISA and FPA which all detect antibodies to S-LPS components of Brucella. In addition many diagnostic antigens are also commercially available worldwide such as Rose Bengal, complement fixation and serum agglutination antigens. Other assays are coming onto the market such as the Brucellacapt agglutination assay and lateral flow assays. Protein preparations for use in skin tests and in-vitro IFNg assays are available commercially but only through one company and supply is limited and vulnerable.
For list of commercially available diagnostics see here (DiagnosticsForAnimals).
Reagents for the cultural identification and typing of Brucella are also available commercially and from OIE laboratories. These include phages and anti-sera. These are on a test/test basis more expensive than the serological reagents. There are commercially available PCR kits for typing isolates at species level.
GAPS:
–Although costs of tests are generally competitive, they are out of reach for many areas in Africa orAsia.
–Almost all kits require cold storage to maintain effectiveness. This may be a problem in some resource poorer regions.
–There are no commercially available PCR kits that claim to diagnose brucellosis.
Commercial diagnostic kits available in Europe
Most if not all of the kits available globally are also available in Europe (certainly those that are most well known in the brucellosis community are available).
For list of commercially available diagnostics see here (DiagnosticsForAnimals).
Diagnostic kits validated by International, European or National Standards
Many of the kits available have been tested against International standards. Indeed in some cases, such as the development of the (Brucella abortus) OIE ELISA Standard Sera, the standards were set on the basis of the results obtained from commercially available diagnostic kits with good validation data and provenance.
Diagnostic method(s) described by International, European or National standards
These are well described in the last Edition of the OIE Manual for Diagnostic Tests and Vaccines: CFT, iELISA, cELISA and FPA are the currently prescribed tests for international trade in cattle. RBT, CFT, FPA and brucellin skin tests are the prescribed tests for international trade in small ruminants (B. melitensis infection). Only the CFT is the prescribed tests for B. ovis in sheep. RBT, iELISA, cELISA and FPA are the prescribed tests for B. suis in pigs.
GAPS:
–Updated regularly but criteria for inclusion-exclusion are not clear and properly documented. Probably lobbies and commercial interests, rather than intrinsically technical features of tests, play a major role.
–Some of the methodological descriptions are open to a variety of interpretations. Whilst this is advantageous in some respects, it can also lead to some drift in techniques between laboratories.
Commercial potential for diagnostic kits in Europe
Very high since eradication-surveillance is compulsory in the EU in most animal species.
The market for standard commercial kits that meet the usual requirements (i.e. as already available) is fairly full. There may be an opportunity for niche kits to be developed to meet specific needs such as addressing false positives that arise from standard methods. However, such a market would be relatively small and research problems would need to be overcome before developing such a kit.
GAP: Possibly some space in the market for niche assays based on non-OPS antigens.
DIVA tests required and/or available
A suitable and effective DIVA test would be of help in completing B. abortus eradication in countries that need vaccination (in the EU or elsewhere). The cELISA kit sold by Svanova markets itself as being able to differentiate between infected and vaccinated animals but this is not true in many cases and there is also information to indicate that this assay lacks sensitivity. A DIVA test would be more necessary for eradicating B. melitensis, since most infected countries need vaccination. Enabling a combined vaccination and test and slaughter programme would undoubtedly enhance the efficiency of disease eradication.
Rev 1 vaccine (or other new vaccine to be developed) and an associated DIVA would be of interest in the case of B. ovis in the EU, which is an increasing problem in countries -regions in which B. melitensis has been eradicated and Rev 1 vaccine abandoned.
Opportunities for new developments
Good. Classical vaccines adequately tagged, new vaccine to be developed, both associated with an adequate DIVA tests; a B. ovis vaccine; a human vaccine; improved therapies for human brucellosis.
Vaccines availability
Commercial vaccines availability (globally)
Live attenuated vaccines S19, Rev 1 and RB51 and are the only vaccines recognised for use by the OIE. S19 and Rev 1 vaccines can be produced without commercial infringement but should be extensively tested for efficacy and safety by recognised protocols before use. Whereas Rev 1 and RB51 are available globally, marketing of S19 has been discontinued in some countries.
GAP: No S19 for conjunctival route has been ever produced and marketed internationally.
Commercial vaccines authorised in Europe
Rev 1 (small ruminants) and S19 and RB51 (cattle) are authorised in the EU.
GAP: No B. ovis specific vaccine available in the EU (or elsewhere).
Marker vaccines available worldwide
None. Rev 1 vaccine and S19 have been deleted in a diagnostic marker (i.e. protein BP26) but associated DIVA tests are not sensitive enough. Since it interferes in iELISA, cELISA tests, R vaccines cannot be considered as marked vaccines.
Marker vaccines authorised in Europe
None. Rev 1 vaccine and S19 have been deleted in a diagnostic marker (i.e. protein BP26) but associated DIVA tests are not sensitive enough. Since it interferes in iELISA, cELISA tests, R vaccines cannot be considered as marked vaccines.
Effectiveness of vaccines / Main shortcomings of current vaccines
Small ruminant vaccines:
B. melitensis Rev 1 induces strong immunity in sheep (against both B. melitensis and B. ovis infections) and goats (B. melitensis) and is safe enough when applied to young replacement animals but Induces a serological response that interferes in serological tests, more markedly when applied by the subcutaneous route and to adult animals. Vaccination during pregnancy results in high numbers of abortions and vaccine excretion in milk. This is a serious inconvenient for applying mass vaccination campaigns, frequently the only suitable alternative in developing countries. Conjunctival vaccination of young (3-4 month old) animals minimise the diagnostic interferences and abortion and is the method of choice. Rev 1 is safe enough also in young rams or billy goats. Quality control is strictly necessary (Rev 1 shows instability). It is virulent in humans and is streptomycin resistant.
R vaccines against B. melitensis in sheep have been investigated to solve the problem of the serological interference. None is as efficacious as Rev 1 and, although they do not interfere in RBT or CF, they elicit anti-core-oligosaccharide antibodies in (at least) iELISA and interfere in B. ovis serodiagnostic tests.
Cattle vaccines:
B. abortus S19. Is the best effective vaccine in cattle against B. abortus infection but provides no absolute protection (possibly less than Rev1 in sheep). It is also effective against B. melitensis infection in cattle, a relative frequent event in developing countries. The vaccine is safe enough when applied to young replacement females but not in males. Vaccination interferes with the diagnosis and complicates eradication. Conjunctival vaccination of young (3-4 month old) animals minimise diagnostic interferences and is the method of choice. Proven effective in many countries having eradicated B. abortus infection in cattle.
Quality control is strictly necessary since S19 shows some instability. Not safe enough in bulls. Infectious for humans but less than Rev 1. Significantly safer than Rev 1 when used in adult cattle, including pregnant and lactating animals, but safety is not absolute.
B. abortus RB51. R LPS mutant obtained to avoid the interference of vaccination in serological tests but, although it does not interfere in RBT or CF, it elicits anti-core-oligosaccharide antibodies in (at least) iELISA, cELISA and LFA. Considerably more expensive than S19. Lower protection than S19 against B. abortus in cattle. Ineffective in sheep, pigs and wildlife tested. Efficacy against B. melitensis in cattle unknown. Induces abortion and milk excretion when used in pregnant cattle. Not safe in bulls. It is virulent in humans and is rifampin resistant. Never proven more effective than S19 for eradicating B. abortus infection in cattle in any country.
Other animal vaccines:
B. abortus 45/20 and B. melitensis H38 (others) killed vaccines abandoned.
B. suis Strain 2 (a biovar 1 strain attenuated in guinea pigs) has been used inChina. In controlled experiments, S2 was inefficacious against B. melitensis or B. ovis. Information on alternative vaccines used in the formerSoviet Union difficult to contrast.
Many attempts to develop a B. ovis subcellular vaccine based on outer membrane components in different formulations (adjuvants, encapsulation, DNA, etc).
Human vaccines:
Several unsuccessful/doubtful/obscure attempts, including attenuated, subcellular or DNA based vaccines.
GAPS: There is a critical need for new vaccines that are:
more protective.
able to generate immune responses easily differentiable from those of infected animals (DIVA assays required).
less pathogenic for livestock (not abortifacient, etc.).
attenuated in humans.
more stable.
affordable.
Commercial potential for vaccines in Europe
In most EU countries B. abortus has been eradicated and no vaccines are required. However, the S19 for conjunctival use (associated or not with potential DIVA tests) would be of great help (see 16.1.) and interest in completing B. abortus eradication in PT, IT, ES and GR, since some regions in these countries need adequate vaccination programs.
New vaccines associated or not with DIVA tests would be necessary for eradicating B. melitensis, since most infected countries (P, IT, GR, ES) need vaccination. Rev 1 vaccine (or other new vaccines to be developed) and an associated DIVA would be of interest also in the case of B. ovis infection, an increasing problem in regions in which B. melitensis has been eradicated and Rev 1 vaccine forbidden.
Vaccines against B. suis are not required for industrial indoor breeding systems, but should be of great interest for outdoor breeding systems (at least in P and ES).
GAP: No possibilities for vaccines that do not solve the DIVA problem. New vaccines (see 9.4.) would be necessary to open the market.
Regulatory and/or policy challenges to approval
It is estimated that a good vaccine would not face any unusual regulatory barriers.
Commercial feasibility (e.g manufacturing)
Significantly improved vaccines would be very commercially feasible.
For attenuated live vaccines, technology & experience gained in Rev 1 and S 19 production in the EU.
After the production of the Master Seed Lot by the manufacturer a thorough control in vitro and in vivo of this pivotal biological starting material must be performed by a Reference Laboratory.
After satisfactory control, the Master Seed Lot can be used by the manufacturer for the production of Brucella vaccines. However some basic processes must be respected.
1. The seedlot system must be respected in order to have a robust and validated technology to avoid qualitative difference from batch to batch.
2. These vaccines have to be produced in Category 3 confined area with adequate equipments as fermentor, centrifuge and negative pressure freeze -drier.
3. Beside the technology of production, rigour in process and batch release controls must be applied. This last test should be performed internally by the manufacturer and externally by Reference Laboratory. The question is how many batches have to be controlled in parallel by the manufacturer and the reference laboratory.(10 first consecutive Industrial batches?).
Opportunity for barrier protection
N.A.
Opportunity for new developments
Vaccines that solve 9.4 would have a good opportunity. These include tagged classical vaccines or new attenuated vaccines subunit vaccines (plus improved adjuvants and delivery systems), and DNA vaccines, all associated with DIVA system.
A specific need is a B. ovis vaccine; a B. suis vaccine may be useful under some circumstances in EU.
Some reformulations of classical vaccines (i.e. S19 conjunctival) may have a chance as well.
GAPS:
Available resources
General constraints: availability of research teams with complementary skills (optimally, teams from public institutions in collaboration with Industry).
Funding.
Better understanding of host immunity-pathogen interactions and the pathology of the agent
Imperfect or no knowledge on (a), Brucella virulence mechanisms and genetic regulators for adapting to intracellular life; (b), interaction with immunity; (c), underlying mechanisms for host preference/specificity; (d), the pathology of the agent within each natural host other than humans, ruminants or swine (camelids, yaks, water buffaloes, etc.). Identifying these will help to understand the virulence mechanisms which in turn could help to generate improved treatments and vaccines
Others for specific approaches: tag immunogenic enough to be used in DIVA test; identification of immunogenic/protective oligonucleotidic sequences (DNA vaccines) may be long and not necessarily successful.
Legislation
Genetically Modified Organism legislation in Europe.
Pharmaceutical availability
Current therapy (curative and preventive)
Seldom used in animals. However, B. suis infection in pigs could be treated with antibiotics when the infection affects large industrial premises since depopulation is unfeasible.
In humans, adults with acute brucellosis and no complications or focal disease should be treated with doxycycline-streptomycin or doxycycline-­gentamicin combinations. In focal forms, the preferred regimen is the same but duration of therapy must be individualized. Surgery should be considered for patients with endocarditis, cerebral, epidural, spleen, hepatic or other abscesses not resolving with antibiotic therapy. During pregnancy tetracyclines and streptomycin must be avoided and a rifampin monotherapy is considered the regimen of choice. Trimethoprim-sulfamethoxazole (cotrimoxazole) plus rifampin is an alternative regimen but it is contraindicated before week 13 or after week 36 of pregnancy. Children less than 8 years old can be treated with rifampin-cotrimoxazole, or rifampin or cotrimoxazole plus gentamicin. Antibiotics have to be administered for long (usually 6 weeks but sometimes longer) times. Treatment is expensive and may pose compliance problems. Relapses occur in 5 to 30% of patients. Rifampin must be avoided in countries where tuberculosis is endemic.
GAP: Human brucellosis
More efficacious/cheaper antibiotics would be valued that could:
avoid parental administration
shorten the administration period
avoid relapses
make treatment affordable
Future therapy
See section "Current therapy".
Commercial potential for pharmaceuticals in Europe
Reduced since brucellosis is in the process of being eradicated.
Regulatory and/or policy challenges to approval
N.A.
Commercial feasibility (e.g manufacturing)
N.A.
Opportunities for new developments
Human brucellosis: more efficacious/cheaper antibiotics would be valued that could:
avoid parental administration
shorten the administration period
avoid relapses.
make treatment affordable.
New developments for diagnostic tests
Requirements for diagnostics development
All serological tests need validation (cut-off optimization and sensitivity and specificity studies) according to local conditions (prevalence, breed, etc.) and specific animal host (both for domestic animals and wild life).
GAP: No validation studies (adequate to the particular country/conditions) for most commercial kits and animal species.
Time to develop new or improved diagnostics
Variable depending upon the animal species and resources. Optimally, gold standard serum collections should be based on bacteriological studies and these may be difficult in wildlife.
Cost of developing new or improved diagnostics and their validation
Difficult to estimate.
Research requirements for new or improved diagnostics
See also section "Main means of prevention, detection and control - Diagnostics".
More effective selective enrichment and culture media are required. Conventional typing is difficult and poses reproducibility problems. Classical methods could be advantageously replaced by molecular methods.
Methods for DNA detection on animal samples should be investigated.
Technology to determine virus freedom in animals
Vaccination is a more cost-effective policy than test and slaughter but as vaccination on its own is unlikely to eradicate disease, test and slaughter (with the associated compensation costs) is the only way to certify and maintain freedom from brucellosis.
New developments for vaccines
Requirements for vaccines development / main characteristics for improved vaccines
There is a critical need for new vaccines that are more protective, able to generate immune responses easily differentiable from those of infected animals (DIVA assays required), less pathogenic for livestock (not abortifacient, etc.), attenuated in humans, more stable and affordable.
Need for proper information on the use of Rev 1 and S19 in species other than small ruminants and cattle, respectively. Tests for specific protection and safety against infections by S brucellae in swine, camelids, yaks, water buffaloes and others are needed. Need for specific B. ovis attenuated vaccine available when Rev 1 use is discontinued after eradication of B. melitensis. Need for B. canis vaccine.
Need for classical vaccines adequately tagged, new vaccines associated with an adequate DIVA tests; a B. ovis vaccine; a human vaccine.
Time to develop new or improved vaccines
From concept to industrialisation and to EU marketing authorisation, will take 5 to 10 years depending on whether improvement or development of completely new vaccines is considered.
To develop a new vaccine (tagged, sub-unit, live modified) will take more time than the improvement of the existing Rev 1 and S19 vaccines. If the Master Seed Batch is changed, however, the registration of such an “improved” vaccine will have to go through all the development steps as for a new vaccine, and to build a registration dossier with new parts 2 (analytical), 3 (safety) and 4 (efficacy).
More attention if the vaccine is considered as Genetically Modified Organism.
Main steps for development of new vaccines:
Building project with relevant tasks. Bottle neck: Human resources and budget.
Feasibility steps. Validation of Master Seed Batch / Working Seed Batch.
Labscale technology +analytical tools IPC and potency release test. In this phase challenge trials in target animals must be performed.
Research to set the Minimal Protective Dose; production of the Pilot Batches.
Industrialisation of the technology, field trials.
GAPS:
– Available resources: Decisions concerning project management and adequate repartition of tasks between Public Institutions/Laboratories and Industry; Category 3 facilities.
- Legislation: Genetically Modified Organism legislation in Europe.
Cost of developing new or improved vaccines and their validation
Cost will depend on the decision if it will be improvement or new development of vaccines with corresponding analytical and DIVA associated tests.
Another factor which will dramatically increase the cost is if the development of new vaccine will require confined category 3 facilities (Laboratory, Industrial and challenge on target animals).
GAP: Category 3 facilities (Laboratory, Industrial and challenge on animals).
Research requirements for new or improved vaccines
Better understanding of host immunity-pathogen interactions and the pathology of the agent:
Imperfect or no knowledge on (a), Brucella virulence mechanisms and genetic regulators for adapting to intracellular life; (b), interaction with immunity; (c), underlying mechanisms for host preference/specificity; (d), the pathology of the agent within each natural host other than humans, ruminants or swine (camelids, yaks, water buffaloes, etc.). Identifying these will help to understand the virulence mechanisms which in turn could help to generate improved treatments and vaccines.
Research towards classical vaccines adequately tagged, new vaccines associated with an adequate DIVA test; a B. ovis vaccine; a human vaccine.
New developments for pharmaceuticals
Requirements for pharmaceuticals development
N.A.
Time to develop new or improved pharmaceuticals
N.A.
Cost of developing new or improved pharmaceuticals and their validation
N.A.
Research requirements for new or improved pharmaceuticals
N.A.
Disease details
Description and characteristics
Pathogen
The genus Brucella includes several recognized species: B. melitensis B. suis, B. abortus, B. neotomae, B. canis and B. ovis. Some are subdivided into biovars. In addition, isolates from marine mammals of theAtlantic have been grouped into two species: B. pinnipedialis and B. ceti; strains isolated from the common vole are proposed to belong to a new species: B. microti. Whereas B. melitensis, B. abortus, B. canis and B. ovis have well defined characteristics, B. suis shows a great internal diversity which could encompass the B. microti strains. Few isolates of B. neotomae have been studied, and the studies of the strains from marine mammals need to be complemented with additional strains from the Pacific Ocean. New Brucella strains that do not fit within the classical species have been described more recently.
GAPS: Taxonomy
The internal taxonomy of the genus needs revision.
It cannot be assumed that isolates from geographical areas other than Europe, the near East and N. and S. America fall within the previously described species and biovars.
Variability of the disease
The severity of brucellosis varies according to the host and the infective species and strain. In livestock and humans the geographical range of the disease is well known but in wildlife, although there is some knowledge, there is much less information
The brucellae are highly clonal and stable in the hosts. However, two types can be distinguished naturally: rough (R) and smooth (S). R brucellae (B. canis and B. ovis) show a narrower host range (sheep and dogs) than the remaining Brucella species that all are S. The molecules responsible for these phenotypes are the cell envelope lipopolysaccharides. In S species, these molecules carry an O-polysaccharide not present in the R species. B. abortus preferentially infects cattle (and water buffalo); B. melitensis, sheep and goats; B. ovis, sheep and B. canis dogs. B. suis can be mainly isolated from swine (including wild swine), reindeer, hares, wild rodents and some other wildlife species. Marine mammals harbour B. pinnipedialis and B. ceti. B. microti from common voles has been proposed as a new emerging pathogen, but clusters genetically with B. suis biovar 5. B. abortus, B. melitensis and some B. suis biovars can infect animals other than their primary hosts, including wildlife, depending upon the epidemiological circumstances.
GAPS:
Brucellosis in camelids, yaks, water buffaloes and other "exotic" animals.
Swine brucellosis: epidemiology (interactions with wildlife), diagnosis, vaccines.
Brucellosis in wildlife: epidemiology; role as reservoirs/carriers; diagnosis.
Stability of the agent/pathogen in the environment
The brucellae do not multiply outside the hosts but may persist in the environment, mostly associated to animal products. Adverse environmental factors are high temperature, acid pH, dryness and exposure to sunlight. In temperate climates, particularly in winter, B. abortus may survive for several months in abortions, placenta and tissues; in exudates and abortion discharges for less than a month; in liquid manure in fresh conditions for at least 8 months; in dairy products (milk, butter, cheese, cream and ice cream), and depending upon pH and refrigeration, from one week to 4-5 months. In refrigerated organs, for at least 2 months; in water for up to 2 months. The data available suggest similar persistence for B. melitensis or B. suis.
GAPS:
Information incomplete concerning non-pasteurized dairy products, particularly those obtained by traditional procedures (souring, etc.).
Stability of Brucella in seawater mostly unknown (some studies have been performed).
Species involved
Animal infected/carrier/disease
The brucellae infect a wide range of animals, especially the smooth strains, and the known range is getting wider all the time as the organism is looked for in more possible host species.
Cattle, yaks, water buffaloes, sheep, goats, reindeer, camelids, swine, horses, reindeer, hares, seals (pinnipeds), dolphins and porpoises (and other toothed whales), and dogs are susceptible. Poultry may be artificially infected but the disease is of little importance. But for hares and wild boars, these seem to be of little practical importance as reservoirs in Northern Europe,USA,Canada andMediterranean countries.
Any animal that has the disease poses a potential risk of spread to others.

Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked