Disease Listing, Brucellosis, General Information | CDC Bacterial, Mycotic Diseases

Brucellosis is an infectious disease caused by the bacteria of the genus Brucella. These bacteria are primarily passed among animals, and they cause disease in many different vertebrates. Various Brucella species affect sheep, goats, cattle, deer, elk, pigs, dogs, and several other animals. Humans become infected by coming in contact with animals or animal products that are contaminated with these bacteria. In humans brucellosis can cause a range of symptoms that are similar to the flu and may include fever, sweats, headaches, back pains, and physical weakness. Severe infections of the central nervous systems or lining of the heart may occur. Brucellosis can also cause long-lasting or chronic symptoms that include recurrent fevers, joint pain, and fatigue.

Brucellosis is not very common in the United States, where100 to 200 cases occur each year. But brucellosis can be very common in countries where animal disease control programs have not reduced the amount of disease among animals.

Although brucellosis can be found worldwide, it is more common in countries that do not have good standardized and effective public health and domestic animal health programs. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean, and the Middle East. Unpasteurized cheeses, sometimes called "village cheeses," from these areas may represent a particular risk for tourists.

How is brucellosis transmitted to humans, and who is likely to become infected?

Humans are generally infected in one of three ways: eating or drinking something that is contaminated with Brucella, breathing in the organism (inhalation), or having the bacteria enter the body through skin wounds. The most common way to be infected is by eating or drinking contaminated milk products. When sheep, goats, cows, or camels are infected, their milk is contaminated with the bacteria. If the milk is not pasteurized, these bacteria can be transmitted to persons who drink the milk or eat cheeses made it. Inhalation of Brucella organisms is not a common route of infection, but it can be a significant hazard for people in certain occupations, such as those working in laboratories where the organism is cultured. Inhalation is often responsible for a significant percentage of cases in abattoir employees. Contamination of skin wounds may be a problem for persons working in slaughterhouses or meat packing plants or for veterinarians. Hunters may be infected through skin wounds or by accidentally ingesting the bacteria after cleaning deer, elk, moose, or wild pigs that they have killed.

Direct person-to-person spread of brucellosis is extremely rare. Mothers who are breast-feeding may transmit the infection to their infants. Sexual transmission has also been reported. For both sexual and breast-feeding transmission, if the infant or person at risk is treated for brucellosis, their risk of becoming infected will probably be eliminated within 3 days. Although uncommon, transmission may also occur via contaminated tissue transplantation.

Yes. Do not consume unpasteurized milk, cheese, or ice cream while traveling. If you are not sure that the dairy product is pasteurized, don't eat it. Hunters and animal herdsman should use rubber gloves when handling viscera of animals. There is no vaccine available for humans.

B. canis is the species of Brucella species that can infect dogs. This species has occasionally been transmitted to humans, but the vast majority of dog infections do not result in human illness. Although veterinarians exposed to blood of infected animals are at risk, pet owners are not considered to be at risk for infection. This is partly because it is unlikely that they will come in contact with blood, semen, or placenta of the dog. The bacteria may be cleared from the animal within a few days of treatment; however re-infection is common and some animal body fluids may be infectious for weeks. Immunocompromised persons (cancer patients, HIV-infected individuals, or transplantation patients) should not handle dogs known to be infected with B. canis.

Brucellosis is diagnosed in a laboratory by finding Brucella organisms in samples of blood or bone marrow. Also, blood tests can be done to detect antibodies against the bacteria. If this method is used, two blood samples should be collected 2 weeks apart.

Yes, but treatment can be difficult. Doctors can prescribe effective antibiotics. Usually, doxycycline and rifampin are used in combination for 6 weeks to prevent reoccuring infection. Depending on the timing of treatment and severity of illness, recovery may take a few weeks to several months. Mortality is low (<2%), and is usually associated with endocarditis.

I am a veterinarian, and I recently accidentally jabbed myself with the animal vaccine (RB-51 or strain 19, or REV-1) while I was vaccinating cows (or sheep, goats). What do I need to do?

These are live vaccines, and strain 19 is known to cause disease in humans. Although we know less about the other vaccines, the recommendations are the same. You should see a health care provider. A baseline blood sample should be collected for testing for antibodies. We recommend that you take antibiotics (doxycycline and rifampin for strain 19 and REV-1, or doxycycline alone for RB-51) for 3 weeks. At the end of that time you should be rechecked and a second blood sample should be collected. (The sample can also be collected at 2 weeks.) The same recommendations hold true for spraying vaccine in the eyes (6 weeks of treatment in this case) or spraying onto open wounds on the skin.

Recommendations for Risk Assessment, Post-Exposure Prophylaxis and Follow-up of Laboratory Personnel Exposed to Pathogenic Brucella Species

I work with Brucella in the laboratory, am I at risk for acquiring brucellosis?

Brucellosis is the most commonly reported laboratory-associated bacterial infection. A number of factors contribute to the risk of an accidental Brucella exposure. Laboratories may lack experience working with the organism, as it has become less common in the United States due to an aggressive immunization program in cattle. In addition, the organism is often “unknown” when the sample arrives for analysis. Work may be performed on an open bench before it is recognized as a gram-negative rod. Certain characteristics of the bacterium, such as its low infectious dose and the fact that it is easily aerosolized, also contribute to the risk of acquisition of the organisms in a laboratory setting.

Specifically implicated procedures or events related to pathogenic Brucella species include sniffing bacteriological cultures, direct skin contact, mouth pipetting, inoculations, and sprays into eyes, nose, and mouth. Manipulation of Brucella organisms on an open bench without use of the recommended practices has led to infections. Anyone who practiced a specifically implicated procedure (above), anyone who was within five feet of any manipulation of Brucella on an open bench, or anyone present in a laboratory during a Brucella aerosol-generating event is at risk for acquiring brucellosis.

If my lab learns we have worked with Brucella, how do we determine who is at risk for developing brucellosis?

Related to pathogenic Brucella species, specifically implicated events associated with laboratory-acquired Brucella infections include sniffing bacteriological cultures, direct skin contact, presence when aerosols have been generated (such as during catalase testing), mouth pipetting, inoculations, and sprays into eyes, nose, and mouth. Manipulation on an open bench without use of the recommended practices has led to infections. Any worker present in the laboratory during the work-up and identification of a pathogenic Brucella isolate is considered a Brucella-exposed worker.

High-risk exposure: Individuals who performed a specifically implicated practice (see above), individuals who were near (within five feet) work with Brucella on an open bench, or individuals present in the laboratory during a Brucella aerosol-generating event should be considered as having a high risk exposure.

Low-risk exposure: Others in the lab at the time of manipulation on an open bench, but who do not have high-risk exposures as defined above, have a low-risk exposure.

What are the recommendations for post-exposure prophylaxis (PEP) to prevent brucellosis?

Interim PEP recommendations are:
Doxycycline 100 mg orally twice a day plus rifampin 600 mg orally once a day for 21 days.

Note: PEP recommendations for B. abortus RB51 (attenuated vaccine strain) differ from those for fully pathogenic Brucella spp. As RB51 was derived by selection in rifampin-enriched media and is resistant to rifampin in vitro, the use of rifampin for PEP or treatment will not be effective for RB51. Post-exposure prophylaxis for those at high risk of exposure should include doxycycline 100 mg orally twice daily for at least 21 days. For those with contraindication to doxycycline, trimethoprim-sulfamethoxazole may be used.

After a potential laboratory exposure, all individuals classified as high-risk should begin PEP. PEP should be discussed with, and offered to, laboratory workers with low-risk exposures. For women who are pregnant, PEP should be considered in consultation with their obstetricians.

Serial serum specimens should be monitored for all exposed workers. Obtain baseline serum as soon as possible after the exposure has been recognized, and obtain available pre-exposure stored specimens. Arrange for serologic testing (Brucella microagglutination testing) at 2, 4, 6, and 24 weeks. These tests will monitor for the development of infection and can be performed at your state public health laboratory or CDC. Note: RB51 does not induce a measurable antibody response. Monitoring serum specimens in individuals exposed to RB51 will not provide a useful indicator of infection.

How long should exposed workers be observed for the development of illness?

All exposed individuals, regardless of risk status, should be monitored for the development of symptoms. From the last exposure, temperature should be actively monitored for fever for four weeks. Broader symptoms of brucellosis should be passively monitored for six months from the last exposure. These symptoms include:

When brucellosis is suspected, clinicians should note ‘suspect or rule out brucellosis’ on the laboratory submission.
Review laboratory containment methods and microbiological procedures to ensure compliance with recommendations in the Biosafety in Microbiological and Biomedical Laboratories (BMBL), 5th edition.
Use primary barriers: use safety centrifuge cups, personal protective equipment, and class II or higher Biological Safety Cabinets (BSCs) for procedures with a high likelihood of producing droplet splashes or aerosols.
Use secondary barriers: restrict access to the laboratory when work is being performed and maintain the integrity of the laboratory’s air handling system by keeping external doors and windows closed.
Perform all procedures on unidentified isolates carefully to minimize the creation of splashes or aerosols.
Prohibit sniffing of opened culture plates to assist in the identification of isolates.
Manipulate isolates of small gram-negative or gram-variable rods within a BSC.

Recommendations for Surveillance and Post-Exposure Prophylaxis for
Laboratory Exposure to Brucella isolates

1. Determine number of workers exposed to Brucella isolates and classify exposures into high- and low-risk

4. Obtain baseline serum samples from all workers as soon as possible after a potential Brucella exposure is recognized. If available, obtain pre-exposure stored specimens.

5. Arrange for sequential serologic testing on all workers exposed to Brucella (e.g. 2, 4, 6, and 24 weeks post exposure) using agglutination test at state public health laboratory or CDC.

6. Arrange for regular (e.g. weekly) active surveillance for development of febrile illness or other signs and symptoms of brucellosis among all workers exposed to Brucella isolates for 6 months following last exposure.

What is Brucella abortus RB-51?

Brucella abortus is a bacterium that causes disease in cattle (and other animals), and also in humans. B. abortus RB-51 (RB51) is a strain of this bacterium developed specifically for an immunization for cattle against brucellosis. RB51 was selected because it is less likely to cause severe disease in cattle than other strains of B. abortus and is presumed to be less likely to cause severe disease in humans. Cattle immunizations against brucellosis started in1941. The RB51 immunization represents a safer immunization both for cattle and for the veterinarians administering it. The vaccine was conditionally licensed for use in cattle in 1996 and received full licensure in March 2003 and is used in 49 states, Puerto Rico, and the US Virgin Islands. RB51 does not induce an antibody response measurable with standard assays. This means that testing cattle for brucellosis will correctly identify naturally occurring cases that could affect other cattle and humans, and not identify antibody response resulting from immunization.

Can RB51 cause infections in people?

Accidental human exposure to RB51, although uncommon, has resulted in disease. Exposures have included needle sticks, eye and wound splashes, and exposure to infected material. In a series of exposures reported to CDC, described below, most of those exposed developed local symptoms of brucellosis infection; and of those ill, most exhibited some systemic symptoms.
In the CDC review, 26 individuals reported exposure to the RB51 vaccine from January 1998 through December 1999. Of these, 21 (81%) reported needlestick injuries; of 5 patients (19%) who were splashed with the RB51 vaccine, 4 were splashed in their conjunctiva and 1 was splashed in an open wound. Even though most individuals (69%) reported receiving prophylactic antibiotics, 19 (73%) reported at least 1 systemic symptom. Of those ill, three (12%) reported persistent local reactions with systemic involvement, and 7 (27%) had persistent symptoms for 16 months. One patient required surgery and RB51 was isolated from the patient’s surgical wound. Very limited published information is available regarding laboratory exposures to RB51.

What laboratory activities are considered high risk exposures to RB51?

Laboratories working specifically with RB51 isolates should perform all manipulations in a class II biological safety cabinet, utilizing biosafety level 3 (BSL-3) practices as described in Biosafety in Microbiological and Biomedical Laboratories, 5th edition. The risk for accidental exposure is highest for procedures or manipulations that would have occurred outside the class II biological safety cabinet and that have the potential for creating aerosols or splashes; examples of such procedures include pipetting, centrifuging, grinding, blending, shaking, mixing, sonicating, and opening containers of infectious materials.

What can those exposed do to decrease their risk of developing brucellosis?

Although RB51 was developed as a less pathogenic strain, it does retain pathogenicity for humans so exposures can pose a human health risk. Post-exposure prophylaxis should therefore be considered for persons with RB51 exposure. RB51 was derived by selection in rifampin-enriched media and is resistant to rifampin in vitro. Use of rifampin for post-exposure prophylaxis or treatment, a recommended choice for other pathogenic bacteria, will not be effective for RB51. Post-exposure prophylaxis for those at high risk of exposure should include doxycycline 100 mg orally twice daily for at least 21 days. For those with contraindication to doxycycline, trimethoprim-sulfamethoxazole 160 mg/800 mg orally twice daily for at least 21 days may be used. Persons with contraindications to these antimicrobial agents should consult with their health care provider for alternative post-exposure prophylaxis. Should brucellosis occur despite prophylaxis, treatment regimens would need to be selected based on antimicrobial susceptibility results. Those with low risk exposures may also opt to take post-exposure prophylaxis.

Both those with high and low risk exposures should be monitored for the development of symptoms of brucellosis. Routine serologic tests for brucellosis will not be effective in monitoring for infection. From the last exposure, temperature should be actively monitored for fever for four weeks. Broader symptoms of brucellosis should be passively monitored for six months from the last exposure. Persons potentially exposed to RB51 who develop symptoms should consult with a health care provider. These symptoms include:

In individuals who exhibit clinical symptoms, bacteriologic isolation may be possible using blood culture.