Brucellosis


Clinical Overview

Brucellosis is an infectious disease caused by the bacteria of the genusBrucella often known as undulant fever. Brucella species are gram-negative cocco-bacillary organisms, of which four are pathogenic in humans (Brucella melitensis, B. abortus, B. canis and B. suis). They are highly infectious, especially B. melitensis and B. suis. Most human cases of brucellosis are caused by the B. abortus strain, while the most common cause of clinically significant disease is caused by the B. melitensis strain. The annual incidence of natural infection is <0,5 cases per 100,000 population. Most cases are reported from California, Florida, Texas and Virginia.

These bacteria cause disease primarily in domestic, feral and some wild animals, such as sheep, goats, cattle, deer, elk, pigs and dogs. Consumption of contaminated foods and occupational contact remain the major sources of infection for humans. It is a true zoonosis in that virtually all naturally occurring human infections are acquired from animals. Human brucellosis manifests as an acute febrile disease or as a persistent disease with a wide variety of symptoms. The CDC classifies Brucellosis as a class B bioterrorism agent. In the event of deliberate exposure to Brucella species, the respiratory route of exposure will be most likely, although food-borne exposure is possible.

Prevention of human brucellosis depends on the control of the disease in animals. Disease control includes routine pasteurization of milk and dairy products, as well as comprehensive campaigns to eradicate the disease by destroying domestic animals that exhibit positive serologic reactions to brucellae. Live, attenuated vaccines are available only for domestic animals and provide some protection to cattle, sheep and goats.

Clinical Presentation

Brucellosis presents as a nonspecific febrile illness with a long and variable incubation period, usually 2 to 4 weeks in about 50% of patients, and as an acute systemic febrile illness in the remainder. Respiratory brucellosis tends to have a shorter incubation period than food-borne brucellosis but the symptoms are the same with the most common manifestations being the characteristic “undulant” fever, headache, chills, myalgias, arthralgias, weakness and malaise. Psychiatric symptoms, such as depression and irritability, and gastrointestinal symptoms such as constipation, anorexia, nausea, and diarrhea may also occur. Respiratory symptoms may occur in as many as a quarter of patients with brucellosis. One or both sacroiliac joints may become infected causing low back and buttock pain that is intensified by stressing the sacroiliac joints on physical exam. Peripheral joint involvement may occur and vary from pain on range of motion testing to joint immobility and effusion. Hepatomegaly or splenomegaly may occur in up to 45-63% of cases and lymphadenopathy may be noted on physical exam. Lab results may show a relative lymphocytosis, anemia and thrombocytopenia.

Most affected persons recover entirely within 3 to 12 months but some will develop complications marked by involvement of various organs, and a few may enter an ill-defined chronic syndrome. Possible complications include arthritis, sacroiliitis, spondylitis (in about 10% of cases), central nervous system effects including meningitis (in about 5%), uveitis and epididymoorchitis. In contrast to animals, abortion is not a feature of brucellosis in pregnant women.

Diagnosis

The diagnosis of brucellosis is primarily dependent on clinical suspicion, which can be challenging since the presentation can be highly atypical. Unequivocal diagnosis requires isolation of the organism either from blood (15-70% positive) or bone marrow (92% positive). In addition, blood tests can be done to detect antibodies against the bacteria.

Blood culture is the method of choice and is often effective during the acute phase. However, specimens need to be obtained early in the disease since cultures may need to be incubated for up to four weeks. Even so, failure to grow the organism is common, especially in cases of B abortus infection, and isolation rates of only 20-50% are reported even from experienced laboratories. Culture from bone marrow and from presenting foci may be successful.

Serology is useful in laboratory diagnosis, and a serum agglutination test (SAT) is available to detect both IgM and IgG antibodies. A titer of 1:160 or greater is indicative of active disease, although cross-reaction to Francisella tularensis may occur. ELISA and PCR on blood samples are rapid tests at any stage of disease. Nasal swabs, sputum, and respiratory secretions may also be positive by PCR in the first 24 hours after exposure. The standard serum agglutination test (SAT) has been augmented by the modified Coombs’ (antiglobulin) technique and the use of 2-mercaptoethanol to separate the actions of specific IgG and IgM. While the SAT titers commonly decline after recovery from infection and antiglobulin test levels are maintained much longer, the IgM antibody that is commonly measured by the SAT does not fall away as regularly as in some infections. Nevertheless, persisting levels of antibody may indicate a remaining focus of infection and specific IgG levels rise again with a true relapse. Because cases often are investigated late in their course, rising titers are frequently missed and the variability of individual responses and the frequency of subclinical infections make the interpretation of single high titers subject to error. All serologic tests have to be interpreted with caution in the light of clinical data and in the context of the local prevalence of brucellosis.

Treatment

The optimum antibiotic therapy for brucellosis is controversial but the treatment includes a six week course of a combination of antibiotics. Doxycycline and rifampin form the basis, but some advocate including three weeks of daily streptomycin to decrease relapses. In children, serious infections are treated with streptomycin 15 mg/kg intramuscularly twice daily (up to 2 grams/day) or gentamicin 2.5 mg/kg every 8 hours plus ciprofloxacin 15 mg/kg/day or rifampin 20 mg/kg/day in 2 divided doses. For central nervous system infections, a third generation cephalosporin plus rifampin is appropriate. 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.

Transmissibility and Infection Control

Humans are generally infected in one of three ways: ingestion of contaminated food/water, inhalation, or contamination of skin wounds. Ingestion of contaminated milk products is the most common mode of transmission. The milk of infected animals, such as sheep, goats, cows or camels, 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 from 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. Contamination of skin wounds may be a problem for hunters, persons working in slaughterhouses or meat packing plants, or for veterinarians.

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.

Prevention consists of pasteurization of milk and dairy products, eradicating infection from herds and flocks, and observing safety precautions. Eradication of brucellosis from domestic animals via live, attenuated vaccines and eliminating infected domestic animals dramatically reduces the threat to humans and has been successful in several countries. Individuals who are occupationally exposed can be protected to some extent by wearing impermeable clothing, rubber boots, gloves and facemasks and by practicing good personal hygiene. Currently no vaccine is available against human brucellosis.

Special Thanks to Altoon Dweck, MD, MPH, Preventive Medicine Resident at Johns Hopkins University for her contribution to this material. 


Patient Handouts

What is brucellosis?
Brucellosis is an infectious disease caused by the bacteria of the genusBrucella. It is a disease that is usually transmitted from handling infected animals or consuming contaminated milk products.

How does a person get brucellosis?
There are three ways people can become infected or exposed through deliberate release.

  1. Ingestion – eating or drinking unpasteurized milk or dairy products that have been contaminated with Brucella.
  2. Inhalation – breathing in the organism. This is not a common route of infection but can be a hazard for people working in laboratories where the organism is cultured.
  3. Wound contamination – bacteria can enter the body through skin wounds. This can be a problem for hunters, people working in slaughterhouses or meat packing plants, or veterinarians.

Where can brucellosis usually be found?
Brucellosis can be found worldwide but it is more common in countries that do not have domestic animal health programs and standardized pasteurization programs. Areas that are currently considered high risk include the Mediterranean Basin, South and Central America, Eastern Europe, Asia, Africa, the Caribbean and the Middle East.

What are the symptoms of brucellosis?
Brucellosis can cause a range of flu-like symptoms and may include fever, sweats, headache, back pains and physical weakness. With time, the infection might spread to the bones, joints, kidneys, brain or the lining of the heart. In rare cases, patients might have long term fevers that come and go, joint pain and fatigue.

Can brucellosis be spread from person to person?
Brucellosis is rarely transmitted from person to person. There are reports of transmission via breast-feeding and sexual contact.

How is it diagnosed?
Your doctor can tell if you might have Brucellosis based on how you were exposed to the disease. Brucellosis can be diagnosed in a laboratory by finding Brucella organisms in samples of blood or bone marrow.

What is the treatment?
Treatment includes a combination of antibiotics for 6 weeks to prevent recurring infections. Recovery usually takes a few weeks to several months. While this infection may take a while to recover from, very few people (less than two percent) die from it.

Can it be prevented?
Milk is pasteurized to eliminate the most common source of infection in other countries. When traveling, do not consume unpasteurized milk, cheese or ice cream. If you work with live animals, extra protective precautions should be taken.

Could it be used for bioterrorism?
Yes. Brucella is a biological agent that could be used for bioterrorism. The federal Centers for Disease Control and Prevention place Brucella as a “class B” or second highest priority agent.

Where can I find more information?
Additional Brucellosis information may be obtained at Centers for Disease Control and Prevention


Trainings/Powerpoint Presentations

Brucellosis Presentation (2004) is available as a PowerPoint or a PDF.


Additional Resources

Readings

Sauret JM, Vilissova N. Human brucellosis. J Am Board Fam Pract. 2002 Sep-Oct;15(5):401-6. http://www.jabfm.org/content/15/5/401.full.pdf+html

Memish ZA, Balkhy HH.Brucellosis and international travel. J Travel Med. 2004 Jan-Feb;11(1):49-55. Review

Chomel BB, DeBess EE, Mangiamele DM, Reilly KF, Farver TB, Sun RK, Barrett LR. Changing trends in the epidemiology of human brucellosis in California from 1973 to 1992: a shift toward foodborne transmission. J Infect Dis 1994; 170:1216-1223.

Thakur SD, Kumar R, Thapliyal DC. Human brucellosis: review of an under-diagnosed animal transmitted disease. J Commun Dis. 2002 Dec;34(4):287-301. Review

Internet Resources

Centers for Disease Control and Prevention, Brucellosis

eMedicine. Warfare CBRNE – Chemical, Biological, Radiological, Nuclear and Explosives

University of Texas Medical Branch, Medmicro Chapter 28