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Infectious Disease and Microbiology – Brucellosis
Brucellosis is a zoonotic infectious disease affecting both wild and domestic animals, with humans serving as accidental hosts. It produces a systemic illness that may have either an acute or insidious onset. Globally, approximately 500,000 new cases occur annually. Incidence varies widely: fewer than 2 cases per million population in countries such as the United States and the United Kingdom, 2–50 cases per million in many Mediterranean countries, and more than 50 cases per million in parts of the Middle East.
Brucellosis is primarily an occupational disease. High-risk groups include farm and ranch workers, abattoir workers, veterinarians, meat inspectors, and laboratory personnel. In endemic regions, ingestion of unpasteurized milk or dairy products represents the most significant risk factor. Prevention relies on eradication of Brucella species from livestock through vaccination programs and identification of infected animals. Avoidance of unpasteurized dairy products is essential; boiling milk is effective when pasteurization is not available. There is currently no safe vaccine for humans at occupational risk.
The disease is caused by Brucella species, which are small, nonmotile, gram-negative coccobacilli. Species infecting humans include Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis. After infection, a small number of organisms survive within macrophages, escaping intracellular destruction. The host immune response involves increased γ/δ lymphocytes and interferon-γ production, with altered tumor necrosis factor-alpha responses. This intracellular persistence contributes to chronicity and recurrence.
Clinically, brucellosis presents with nonspecific systemic symptoms such as fever, chills, rigors, malaise, headache, weight loss, profuse sweating, generalized aches, arthralgias, and depression. Physical examination may reveal hepatomegaly, splenomegaly, and lymphadenopathy. Osteoarticular involvement occurs in 20–50% of patients, and spondylodiscitis must be excluded. Orchitis or epididymitis is seen in 5–25% of cases. Brucellosis can involve virtually any organ and may occasionally present as a localized infection such as pneumonia.
Definitive diagnosis is established by isolating the organism from blood, bone marrow, or other tissue cultures. Laboratories should be informed when brucellosis is suspected, as optimal growth may require specific media and 5–10% CO₂. Cultures should be maintained for at least four weeks. Serologic testing using the standard tube agglutination test is useful but must be interpreted carefully due to possible false negatives (prozone phenomenon) and false positives from cross-reacting antibodies. ELISA-based antibody detection is more reliable. Polymerase chain reaction testing can detect Brucella DNA but may remain positive long after clinical cure, requiring cautious interpretation. Imaging studies such as abdominal ultrasound, CT, or MRI may reveal organomegaly or lymphadenopathy, and MRI is valuable in evaluating suspected bone involvement. Liver biopsy in cases of fever of unknown origin may show granulomatous hepatitis.
Brucellosis should be considered in patients from endemic areas presenting with prolonged febrile illness, especially with osteoarticular symptoms. The differential diagnosis includes other infectious causes of fever of unknown origin.
First-line treatment consists of combination therapy to prevent relapse. Streptomycin (1 g intramuscularly daily for 2–3 weeks) combined with doxycycline (100 mg orally every 12 hours for 6 weeks) is recommended. Gentamicin is non-inferior to streptomycin. Triple regimens that include doxycycline, an aminoglycoside, and rifampin may provide superior outcomes. An alternative regimen is doxycycline combined with rifampin for six weeks, though it is less effective in spondylitis, central nervous system involvement, and endocarditis. Quinolone combinations are considered suboptimal. In pregnant women, co-trimoxazole and/or rifampin have been used. Valve replacement is often required in cases of Brucella endocarditis.
Careful follow-up is essential due to the high risk of relapse, which is attributed to intracellular persistence rather than antimicrobial resistance. Renal and hepatic function should be monitored during aminoglycoside and rifampin therapy. Patients should be counseled that rifampin may cause orange discoloration of urine and body secretions. Prognosis is generally excellent, although endocarditis carries a poorer outcome and accounts for most fatalities. The overall case-fatality rate is approximately 2%. Recurrence is common and may require prolonged antibiotic therapy. Occasionally, a Jarisch–Herxheimer–like reaction may occur shortly after initiation of treatment.
Brucellosis is a zoonotic infectious disease affecting both wild and domestic animals, with humans serving as accidental hosts. It produces a systemic illness that may have either an acute or insidious onset. Globally, approximately 500,000 new cases occur annually. Incidence varies widely: fewer than 2 cases per million population in countries such as the United States and the United Kingdom, 2–50 cases per million in many Mediterranean countries, and more than 50 cases per million in parts of the Middle East.
Brucellosis is primarily an occupational disease. High-risk groups include farm and ranch workers, abattoir workers, veterinarians, meat inspectors, and laboratory personnel. In endemic regions, ingestion of unpasteurized milk or dairy products represents the most significant risk factor. Prevention relies on eradication of Brucella species from livestock through vaccination programs and identification of infected animals. Avoidance of unpasteurized dairy products is essential; boiling milk is effective when pasteurization is not available. There is currently no safe vaccine for humans at occupational risk.
The disease is caused by Brucella species, which are small, nonmotile, gram-negative coccobacilli. Species infecting humans include Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis. After infection, a small number of organisms survive within macrophages, escaping intracellular destruction. The host immune response involves increased γ/δ lymphocytes and interferon-γ production, with altered tumor necrosis factor-alpha responses. This intracellular persistence contributes to chronicity and recurrence.
Clinically, brucellosis presents with nonspecific systemic symptoms such as fever, chills, rigors, malaise, headache, weight loss, profuse sweating, generalized aches, arthralgias, and depression. Physical examination may reveal hepatomegaly, splenomegaly, and lymphadenopathy. Osteoarticular involvement occurs in 20–50% of patients, and spondylodiscitis must be excluded. Orchitis or epididymitis is seen in 5–25% of cases. Brucellosis can involve virtually any organ and may occasionally present as a localized infection such as pneumonia.
Definitive diagnosis is established by isolating the organism from blood, bone marrow, or other tissue cultures. Laboratories should be informed when brucellosis is suspected, as optimal growth may require specific media and 5–10% CO₂. Cultures should be maintained for at least four weeks. Serologic testing using the standard tube agglutination test is useful but must be interpreted carefully due to possible false negatives (prozone phenomenon) and false positives from cross-reacting antibodies. ELISA-based antibody detection is more reliable. Polymerase chain reaction testing can detect Brucella DNA but may remain positive long after clinical cure, requiring cautious interpretation. Imaging studies such as abdominal ultrasound, CT, or MRI may reveal organomegaly or lymphadenopathy, and MRI is valuable in evaluating suspected bone involvement. Liver biopsy in cases of fever of unknown origin may show granulomatous hepatitis.
Brucellosis should be considered in patients from endemic areas presenting with prolonged febrile illness, especially with osteoarticular symptoms. The differential diagnosis includes other infectious causes of fever of unknown origin.
First-line treatment consists of combination therapy to prevent relapse. Streptomycin (1 g intramuscularly daily for 2–3 weeks) combined with doxycycline (100 mg orally every 12 hours for 6 weeks) is recommended. Gentamicin is non-inferior to streptomycin. Triple regimens that include doxycycline, an aminoglycoside, and rifampin may provide superior outcomes. An alternative regimen is doxycycline combined with rifampin for six weeks, though it is less effective in spondylitis, central nervous system involvement, and endocarditis. Quinolone combinations are considered suboptimal. In pregnant women, co-trimoxazole and/or rifampin have been used. Valve replacement is often required in cases of Brucella endocarditis.
Careful follow-up is essential due to the high risk of relapse, which is attributed to intracellular persistence rather than antimicrobial resistance. Renal and hepatic function should be monitored during aminoglycoside and rifampin therapy. Patients should be counseled that rifampin may cause orange discoloration of urine and body secretions. Prognosis is generally excellent, although endocarditis carries a poorer outcome and accounts for most fatalities. The overall case-fatality rate is approximately 2%. Recurrence is common and may require prolonged antibiotic therapy. Occasionally, a Jarisch–Herxheimer–like reaction may occur shortly after initiation of treatment.
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