Information on the following diseases can be found in the Related Disorders section of this report:

• Cat Scratch Disease
• Toxoplasmosis
• Q Fever
• Psittacosis
• Chronic Fatigue Syndrome

The symptoms of brucellosis vary greatly among affected individuals. Some individuals may have no apparent symptoms (asymptomatic); others can develop serious complications affecting various organ systems. The incubation period may range from 1-3 weeks to several months.

Cases where individuals experience the sudden onset of symptoms may be referred to as acute brucellosis. Cases where affected individuals develop the same symptoms over the course of a few weeks may be referred to as subacute brucellosis. When infection with brucellosis lasts for more than one year it may be referred to as chronic brucellosis.

Approximately 50 percent of people with brucellosis experience the sudden onset of symptoms (acute disease) over a period of one to two days. In some cases, symptoms develop over the course of a few weeks (subacute disease). The initial symptoms of brucellosis are nonspecific and resemble those of a flu-like illness. Such symptoms may include fever, chills, generalized weakness and fatigue, headache, muscle aches (myalgias), loss of appetite, weight loss, night sweats, joint pain (arthralgia) and inflammation (arthritis), back pain, constipation and/or a dry cough. In some cases, brucellosis is characterized by repeated episodes of fever that recur on and off for more than a year (undulant fever).

Additional symptoms that may occur in individuals with brucellosis include swollen lymph glands (lymphadenopathy) and/or enlargement of the spleen (splenomegaly). Enlargement of liver (hepatomegaly) occurs less frequently.

When brucellosis affects only one specific area of the body, it may be referred to as localized brucellosis. Localized brucellosis causes inflammation of affected organs including the bones, skin, liver, genitourinary and gastrointestinal tracts, central nervous system and heart.

One of the most frequent sites of localized infection is the lower back, causing inflammation and pain of the lumbar vertebrae (osteomyelitis). In rare cases brucellosis may cause various skin lesions including papules, ulcers and rashes. Abscesses may affect the liver resulting in jaundice.

Genitourinary tract infection may result in inflammation of the kidney (interstitial nephritis). In men inflammation and pain of the testes (epididymo-orchitis) and inflammation of the prostate (prostatitis) may also occur. Gastrointestinal tract infection may result in vomiting, nausea, diarrhea, constipation, abdominal pain, and weight loss.

In some cases, brucellosis may affect the central nervous system (neurobrucellosis). Symptoms of neurobrucellosis include inflammation of the membranes (meninges) surrounding the brain and spinal cord (meningitis) and inflammation of the brain (encephalitis). Less common symptoms may include increased pressure inside the skull (intracranial hypertension); leakage of cerebrospinal fluid into the optic disk of the eye may cause swelling of the disk (papilledema) potentially resulting in progressive loss of clarity of vision (visual acuity); damage of the optic nerve (optic neuropathy) potentially resulting in loss of vision; bleeding in the brain (intracranial hemorrhage), and stroke.

Another potentially serious complication of brucellosis is acute inflammation of the lining of the heart (endocarditis), which may occur in rare cases. In addition, brucellosis may cause inflammation of nerves (neuritis) in various parts of the body, as well as visual problems and impaired kidney function. Clotting problems and other abnormalities of the blood such as low levels of circulating red blood cells may also occur.

Brucellosis is caused by the infectious bacterium Brucella. Most cases result from exposure to infected animals or contaminated animal products. Humans can contract the disease by eating or drinking food or liquids contaminated by Brucella, breathing in (inhaling) the bacteria, or through direct contact through an open wound. Most cases occur from eating contaminated food products especially improperly pasteurized milk, cheese, or raw meat. Animals may carry the bacteria without any symptoms, which results in the contamination of animal food products such as meat or dairy products. Brucella is most commonly found among cattle, sheep, goats, camels, deer, elk, and pigs.

Inhalation of Brucella or direct contact through an open wound is an occupational hazard associated with slaughterhouse workers, veterinarians, farmers, and others who may come in contact with contaminated animals. Hunters may be at risk of developing brucellosis because they may come in contact with infected animals.

There are six known species of Brucella, although only four of these species cause brucellosis in humans. The four Brucella species are: Brucella abortus, which is carried by cattle; Brucella suis, which is carried by hogs; Brucella melitensis, which is transmitted by sheep and goats; and Brucella canis, which is carried by dogs. Brucella melitensis is the organism that most frequently infects humans and causes the most severe form of the disease. It is important that people drink only pasteurized milk to avoid risk of transmission from cows and goats.

Brucellosis affects males and females in equal numbers. The disorder is rare in the United States since pasteurization of milk is routine and cattle are vaccinated against this disease. Fewer than 100 new cases are reported each year in the United States. These are thought to be brought into this country from areas where the infection is present (endemic) or they may be related to the consumption of unpasteurized cow and goat milk

Around the world, approximately 500,000 cases of this disease are reported to the World Health Organization (WHO) each year. As an infection in livestock, brucellosis occurs worldwide, and domestic livestock is the major source of human infection in parts of the world where livestock is not routinely vaccinated. It is most common in Russia, Africa, South America, and the Middle East.

Symptoms of the following disorders can be similar to those of brucellosis. Comparisons may be useful for a differential diagnosis:

Brucellosis must be differentiated from other, more common causes of fever, chronic fatigue, weakness, and other nonspecific flu-like symptoms, especially in individuals in endemic regions. These causes include other infectious diseases and various autoimmune diseases.

Diagnosis
A diagnosis of brucellosis is made based upon a thorough clinical evaluation, a detailed patient history and certain tests called cultures that can detect the presence of the bacterium Brucella in the blood, bone marrow, or tissue of affected organs. Cultures of blood, bone marrow, cerebrospinal fluid (when meningitis is present), or the tissue of any affected organ system may be performed to identify whether the bacterium Brucella is present.

The body’s immune system may create antibodies against the bacterium. Tests may be performed to detect the presence of these antibodies in the body. The most common test performed is called the serum agglutination test (SAT).

Certain x-ray tests such as computed tomography (CT) scan or magnetic resonance imaging (MRI) might be used to detect skeletal changes sometimes associated with brucellosis.

Treatment
The treatment of choice for brucellosis is antibiotic drugs, usually the combination of doxycycline and streptomycin. These medications are usually administered for about 6 weeks. Rifampin may be used as an alternative to streptomycin but is usually less effective.

The drugs trimethoprim/sulfamethoxazole is an adequate alternative, but are not as effective as doxycycline and either rifampin or streptomycin. There is debate in the medical literature as to which is the more effective combination therapy. If serious complications develop, such as acute inflammation of either the membranes that line the brain (meningitis) or the lining of the heart (endocarditis), rifampin may be added to the combination of trimethoprim/sulfamethoxazole. People with endocarditis associated with brucellosis generally require heart valve replacement in addition to antibiotic therapy. Other treatment is symptomatic and supportive.

Less than 10 percent of people with brucellosis experience a relapse of the disease after antibiotic treatment. Steroid medications (e.g., prednisone) may be administered to those affected individuals who have severe symptoms associated with the release of toxins into the blood (toxemia). Severe pain, especially in the spine, may require pain management with drugs such as codeine.

People with acute brucellosis should restrict their daily activity to avoid fatigue. Complete bed rest is recommended during periods of fever.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Research on infectious diseases such as brucellosis is ongoing. For more information about these disorders, contact the World Health Organization (WHO) listed in the Resources section below.

TEXTBOOKS
Lillibridge KM, Ashford D. Brucellosis. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:280.

Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1678-80.

Fauci AS, et al., eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:969-71.

Mandell GL, et al., eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone Inc; 1995:2053-60.

JOURNAL ARTICLES
Tunc M, Durukan H. Bilateral severe vision loss in brucellosis. Ocul Immunol Inflamm. 2004;12:233-6.

Ozisik J, Ersoy Y, Refik Tevfik M, Kizkin S, Ozcan C. Isolated intracranial hypertension: a rare presentation of neurobrucellosis. Microbes Infect. 2004;6:861-3.

Hatipoglu CA, Yetkin A, Ertem GT, Tulek N. Unusual clinical presentations of brucellosis. Scand J Infect Dis. 2004;36:694-7.

Mantur BD, Akki AS, Mangalgi SS, Patil SV, Gobbur RH, Peerapur BV. Childhood-brucellosis – a microbiological, epidemiological and clinical study. J Trop Pediatr. 2004;50:153-7.

Al-Sous MW, Bohlega S, Al-Kawi MZ, Alwatban J, McLean DR. Neurobrucellosis: clinical and neuroimaging correlation. AJNR Am J Neuroradiol. 2004;25:395-401.

Koussa S, Tohme A, Ghayad E, Nasnas R, El Kallab K, Chemaly R. Neurobrucellosis: clinical features and therapeutic responses in 15 patients. Rev Neurol. 2003;159:1148-55.

El Miedany YM, El Gaafary M, Baddour M, Ahmed I. Human brucellosis: do we need to revise our therapeutic policy? J Rheumatol. 2003;30:2666-72.

FROM THE INTERNET
Maloney Jr GE. CBRNE - Brucellosis. Emedicine. 2004. Available at: http://www.emedicine.com/emerg/topic883.htm. Accessed on: December 5, 2004.

Abuhammour W. Brucellosis. Emedicine. 2004. Available at: http://www.emedicine.com/emerg/topic883.htm. Accessed on: December 5, 2004.

Centers for Disease Control (CDC) Website. Brucellosis. Available at: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm. Accessed on: December 5, 2003.