Epidemiology
- Most common zoonotic infection worldwide and an important public health problem in many developing countries:
- Endemic areas:
- Mediterranean
- Middle East
- Central Asia
- China
- Mexico
- Central and South America
- Rare in the United States, mostly seen in:
- California
- Florida
- Texas
- Virginia
- Endemic areas:
- Prevalence:
- Worldwide: approximately 500,000 cases annually
- United States: 100–200 cases annually
- Increasing due to international tourism and migration
- Affects all age groups
Etiology
Causative organism
- Brucella melitensis (most common)
- B. abortus
- B. suis
- B. canis (rare)
- Characteristics:
- Gram-negative coccobacilli
- Facultative intracellular organism that can survive in macrophages
- Cultures are oxidase- and urease-positive.
Brucellae are poorly staining, gram-negative coccobacilli. They are mostly seen as tiny, single cells with a “fine sand” appearance.
Image: “Brucella spp” by CDC. License: Public DomainReservoirs
- Sheep, goats, camels → B. melitensis
- Cattle → B. abortus
- Swine → B. suis
- Dogs → B. canis
Transmission
- Ingestion of unpasteurized animal products (most common)
- Raw milk
- Soft cheese
- Butter
- Ice cream
- Contact between skin or mucous membranes and infected animal tissues or fluids
- Placenta or miscarriage products
- Blood
- Urine
- Milk
- Inhalation of aerosolized particles (more common in laboratory workers)
- Rare human-to-human transmission:
- Blood transfusion
- Tissue transplantation
- Breastfeeding
- Sexual contact
Occupations at high risk
- Veterinarians
- Dairy farmers
- Shepherds
- Slaughterhouse workers
- Laboratory personnel
Clinical Presentation
General signs and symptoms
- Average incubation period is 2–4 weeks.
- Symptoms:
- “Undulant fever”
- Comes in waves
- Can vary in presentation
- Persists 1‒5 weeks
- Night sweats: associated with a strong, moldy odor
- Malaise
- Arthralgias
- Headache
- Loss of appetite
- Weight loss
- Symptoms may disappear and then return after weeks or months.
- “Undulant fever”
- Physical exam (nonspecific):
- Hepatomegaly
- Splenomegaly
- Painful lymphadenopathy
Complications
- Osteoarticular (70% of patients):
- Arthritis
- Sacroiliitis
- Spondylitis
- Osteomyelitis
- Genitourinary:
- Orchitis
- Epididymitis
- Cystitis
- Interstitial nephritis and glomerulonephritis
- ↑ risk of spontaneous abortion in pregnancy
- Neurobrucellosis:
- Meningitis
- Encephalitis
- Neuritis
- Brain abscess
- Cardiovascular:
- Endocarditis (main cause of death)
- Myocarditis
- Pericarditis
- Pulmonary:
- Bronchitis
- Interstitial pneumonitis
- Pneumonia
- Pleural effusion
- Abdominal:
- Cholecystitis
- Hepatic abscess
- Splenic abscess
- Pancreatitis
- Ileitis and colitis
- Ocular: uveitis
- Cutaneous: rash (varying presentation)
Relapse can occur in 4%–24% of patients, usually within 1 year.
Diagnosis
Diagnostic algorithm
As this diagram demonstrates, testing modalities that provide a definitive diagnosis usually require a considerable amount of time. In the meantime, other testing measures can be employed to provide a presumptive diagnosis.
CSF: cerebrospinal fluid
PCR: polymerase chair reaction
Diagnostic testing
- Culture
- Definitive
- Blood cultures are usually obtained in all patients.
- Bone marrow is considered the gold standard (most sensitive).
- Requires special culture techniques
- Serum tube agglutination test (SAT)
- Measures antibodies against a Brucella antigen (smooth lipopolysaccharide)
- Evolution titers (fourfold increase in the titer between acute and convalescent serum obtained ≥ 2 weeks apart)
- Provides a definitive diagnosis
- Limited by the time required
- Positive titers providing a presumptive diagnosis:
- > 1:160 outside endemic regions
- > 1:320 within endemic regions
- Cannot be used for B. canis
- Enzyme-linked immunosorbent assay (ELISA)
- Comparable sensitivity and specificity to SAT
- Tests for immunoglobulins against cytoplasmic proteins
- Rose Bengal agglutination
- Can be used as a screening tool
- Rapid
- Polymerase chain reaction (PCR)
- Detects Brucella DNA
- Can provide a presumptive diagnosis
Serum tube agglutination testing is used to detect antibodies to a Borrelia antigen. From left to right:
Image: “Serum tube agglutination test” by Department of Veterinary Medicine, Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Dantiwada, Gujarat, India. License: CC BY 2.0
Tubes 1 and 2 = positive reaction
Tubes 3 and 4 = negative reaction
Tube 5 = control
An example of an ELISA test: This test relies on antibody-enzyme complexes to create a color change. Positive tests will be a darker color.
Image: “Microtiter plate” by Department of Veterinary Medicine, Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Dantiwada, Gujarat, India. License: CC BY 2.0
Rose Bengal agglutination test: This test uses a suspension of B. abortus antigens with a pink dye. It will agglutinate with a patient sample if antibodies are present.
Image: “Rose Bengal plate test” by Department of Veterinary Medicine, Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Dantiwada, Gujarat, India. License: CC BY 2.0
Additional workup
The testing performed is guided by the patient’s clinical presentation and any concerns for complications.
- Laboratory testing (nonspecific)
- Complete blood count:
- Anemia
- Leukopenia with ↑ lymphocytes
- Thrombocytopenia
- ↑ liver function tests
- Synovial fluid:
- May be tested in patients with arthritis
- White blood cell (WBC) count ≤ 15,000 cells/µL
- Culture will grow Brucella
- Cerebrospinal fluid
- May be tested in patients with neurologic involvement
- 10‒200 WBC with mononuclear cell predominance
- ↑ protein
- Antibody or agglutination testing may be done.
- Urinalysis
- ↑ WBC
- Brucella may be grown on culture.
- Complete blood count:
- Imaging
- Radiographs
- Arthritis
- Interstitial pneumonitis, pleural effusion, or pneumonia
- Computerized tomography (CT)
- Abscess
- Magnetic resonance imaging (MRI)
- Spondylitis
- Osteomyelitis
- Echocardiography
- Endocarditis
- Myocarditis
- Radiographs
A liver abscess is seen on contrast CT in a patient with brucellosis.
Image: “CT scan” by Diagnostic Radiology Department, Interbalcan Medical Center, Thessaloniki, 55236, Greece. License: CC BY 3.0
A patient diagnosed with septic arthritis caused by Brucella melitensis:
Image: “Figure 1” and “Figure 4” by Tak Man Wong et al. License: CC BY 4.0, edited by Lecturio.
(A) Normal X-ray of the left hip
(B) T2–weighted MRI coronal plane of the pelvis showing marked effusion over left hip joint
A transthoracic echocardiogram performed on a patient with brucellosis: The white arrows point to the thickened aortic valves. This thickening is secondary to vegetations.
Image: “Transthoracic echocardiogram” by Faculty of Nursing, University of Peloponnese, Orthias Artemidos & Plataion, 23100 Sparta, Greece. License: CC BY 3.0, edited by Lecturio.
Management and Prevention
Management
- Antibiotics
- Adults: doxycycline plus an aminoglycoside or rifampin
- Children < 8 years: trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampin
- Neurobrucellosis: ceftriaxone plus rifampin and doxycycline for 12 weeks
- Endocarditis: aminoglycoside plus rifampin and doxycycline for 12 weeks
- 5%–15% of patients relapse.
- All patients should have close clinical follow-up.
- Repeat serologic studies for 1 year.
- Treat relapse with a repeat course of the standard antibiotic regimen.
- Immunity lasts for only 2 years after the disease.
Prevention
- Brucellosis is a reportable disease.
- Post-exposure prophylaxis for high-risk patients: doxycycline plus rifampin
- Avoid unpasteurized dairy products.
- Wear gloves, gowns, and goggles while handling animals and carcasses.
- Vaccination of livestock (do not give to humans, as can cause infection)
Differential Diagnosis
- Malaria: an infection due to Plasmodium. Patients may also present with periodic fever similar to brucellosis. Other symptoms include rigors, night sweats, diarrhea, abdominal pain, seizure, hemolytic anemia, and splenomegaly. The diagnosis is confirmed by visualizing Plasmodium on a peripheral smear and with rapid test detection of Plasmodium antigens. Treatment with antimalarials depends on the species.
- Tuberculosis: a mycobacterial infection, most commonly affecting the lungs. Symptoms include fever, night sweats, weight loss, malaise, and cough. The diagnosis is made with a sputum smear and culture detecting acid-fast bacilli. Treatment involves combination therapy with isoniazid, rifampin, pyrazinamide, and ethambutol.
- Endocarditis: an inflammatory condition of the endocardium, usually due to an infection. The heart valves are typically affected. Patients present with fever and a new heart murmur. Endocarditis is diagnosed with blood cultures and echocardiography. Prolonged antibiotics are required for infectious causes, and surgery may be required.
- Typhoid fever: a systemic disease caused by Salmonella enterica serotype Typhi. Patients may have high fever, abdominal pain, and rose spots (rash) on the body. Unlike brucellosis, typhoid predominantly manifests with gastrointestinal symptoms. The diagnosis is based on the clinical presentation and confirmed by culture. Antibiotics are used to treat, and include ceftriaxone, fluoroquinolones, and azithromycin.
- Rheumatic fever: a nonsuppurative, inflammatory complication of streptococcal pharyngitis. The disease is rare in developed countries. Patients can have a high fever, arthritis, pancarditis, and erythema marginatum, and often have preceding symptoms of sore throat or skin infection. Diagnosis is based on the clinical presentation, modified Jones criteria, and laboratory testing. Treatment includes aspirin, corticosteroids, and antibiotics.
References
- Bosilkovski, M. (2020). Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis. In Baron, E.L. (Ed.), UpToDate. Retrieved December 8, 2020, from https://www.uptodate.com/contents/brucellosis-epidemiology-microbiology-clinical-manifestations-and-diagnosis
- Bosilkovski, M. (2019). Brucellosis: Treatment and prevention. In Baron, E.L. (Ed.), Retrieved December 8, 2020, from https://www.uptodate.com/contents/brucellosis-treatment-and-prevention
- Al-Nassir, W., Lisgaris, M.V., Salata, R.A, and Bennett, N.J. (2018). Brucellosis. In Bronze, M.S. (Ed.), Medscape. Retrieved December 8, 2020, from https://emedicine.medscape.com/article/213430-overview
- Bush, L.M., and Vazquez-Pertejo, M.T. (2020). Brucellosis. [online] MSD Manual Professional Version. Retrieved December 8, 2020, from https://www.msdmanuals.com/professional/infectious-diseases/gram-negative-bacilli/brucellosis
