Brucellosis

Patricia Cristofaro, M.D.

Basic Information

Definition

Brucellosis is a zoonotic infection caused by one of four species of Brucella. It commonly presents as a nondescript febrile illness.

Synonyms

Malta fever, undulant fever
Bang’s disease

ICD-10CM CODES
A23.9	Brucellosis, unspecified

Epidemiology & Demographics

Incidence (In U.S.)

About 100 to 200 cases/yr (may be underreported) (Fig. E1), predominantly B. melitensis. The number of cases is increasing worldwide due to travel and globalization.

FIG.E1

Brucellosis.

Number of reported cases—United States and U.S. territories, 2010.

From Centers for Disease Control and Prevention: Summary of notifiable diseases—United States, 2010, *MMWR Morb Mortal Wkly Rep* 59:1–111, 2012.

Predominant Sex

Male

Predominant Age

Adult

Congenital Infection

Recent evidence suggests a high rate of spontaneous abortions in untreated pregnant women during the first and second trimesters.

Neonatal Infection

Can occur if mother is infected during pregnancy.

Physical Findings & Clinical Presentation

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Incubation period is 1 wk to 3 mo.
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Patients may be asymptomatic or have nonspecific symptoms such as fever, sweats, malaise, weight loss, depression, arthralgia, and arthritis.
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Fever is the most common finding (Fig. E2).

FIG.E2

Brucellosis.

Several small noncaseating granulomas are present in the bone marrow of a patient with an unexplained febrile disease. He was not aware of exposure to Brucella in over 30 years (HANDE, ×40, Brucella suis isolated from blood cultures).

From Scott MA, et al.: Infectious disease pathology. Silverberg SG, ed.: Principles and practice of surgical pathology and cytopathology, ed 4, Philadelphia, 2006, Churchill Livingstone, p 101.
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Hepatomegaly, splenomegaly, or lymphadenopathy is possible.
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Localized disease includes endocarditis, meningitis, spondylitis, sacroiliitis, and osteomyelitis (especially vertebral).
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Chronic hepatosplenic suppurative brucellosis (CHSB) presents with hepatic or splenic abscesses. This form is thought to be a reactivation and can occur years after the acute infection.
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Table E1 describes a clinical classification of human brucellosis.

TABLEE1 Clinical Classification of Human BrucellosisFrom Goldman L, Schafer AI: Goldman’s Cecil medicine, ed 24, Philadelphia, 2012, Saunders.

Classification	Duration of Symptoms Before Diagnosis	Major Symptoms and Signs	Diagnosis	Comments
Subclinical	—	Asymptomatic	Positive (low titer) serology, negative cultures	Occurs in abattoir workers, farmers, and veterinarians
Acute and subacute	Up to 2-3 mo and 3 mo to 1 yr	Malaise, chills, sweats, fatigue, headache, anorexia, arthralgias, fever, splenomegaly, lymphadenopathy, hepatomegaly	Positive serology, positive blood or bone marrow cultures	Presentation can be mild, self-limited (B. abortus) or fulminant with severe complications (B. melitensis)
Localized	Occurs with acute or chronic untreated disease	Related to involved organs	Positive serology, positive cultures in specific tissues	Bone or joint, genitourinary, hepatosplenic involvement most common
Relapsing	2-3 mo after initial episode	Same as acute illness but may have higher fever and more fatigue, weakness, chills, and sweats	Positive serology, positive cultures	May be extremely difficult to distinguish relapse from reinfection
Chronic	>1 yr	Nonspecific presentation but neuropsychiatric symptoms and low-grade fever most common	Low titer or negative serology, negative cultures	Most controversial classification; localized disease may be associated

Etiology

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Caused by infection with Brucella species:
1. 1.
  
  Most commonly B. melitensis but also B. suis, B. abortus, or B. canis
2. 2.
  
  A small, gram-negative coccobacillus
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Acquired through ingestion of organisms (unpasteurized goat or cow’s milk) or breaks in the skin or by inhalation.
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Most cases occur after exposure to animals (sheep, goats, swine, cattle, or dogs) or animal products (i.e., milk, cheese, hides, tissue).
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Most cases (in the U.S.) occur in men with occupational exposure to animals (e.g., farmers, ranchers, laboratory workers, veterinarians, abattoir workers). Accidental animal vaccine exposure warrants evaluation for a full therapeutic antibiotic regimen.
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Laboratory workers, especially those in microbiology, are also at increased risk. Guidelines for postexposure prophylaxis are available from MMWR Surveill Summ 57:39, 2009.

Diagnosis

Differential Diagnosis

Many febrile conditions without localizing manifestations (i.e., TB, endocarditis, typhoid fever, malaria, autoimmune diseases)

Workup

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Cultures of blood, bone marrow, or other tissue (e.g., lymph node, liver) should be sent and held for 4 wk because Brucella spp. grow slowly in vitro.
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Granulomas on biopsy are suggestive of diagnosis.
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Serum agglutination test (see the following)

Laboratory Tests

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WBC count: normal or low
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Serology:
1. 1.
  
  Serum agglutination test (SAT) to detect antibodies to B. abortus, B. melitensis, and B. suis. An elevated initial titer of ≥1:160 or demonstration of a fourfold increase from acute to convalescent titers is considered diagnostic. Positive test results warrant confirmatory testing with specific Brucella agglutination tests.
2. 2.
  
  Specific antibody test to identify antibodies to B. canis.
3. 3.
  
  False-negative SAT possibly resulting from a prozone effect.
4. 4.
  
  PCR (polymerase chain reaction) for Brucella spp. specific 16S rRNA or DNA sequences are increasingly used for the diagnosis of brucellosis from blood, tissue samples, and bone marrow.

Imaging Studies

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Radiographs to show splenic or hepatic calcifications in chronic disease
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Bone scan, MRI, and radiographs of the spine to suggest osteomyelitis
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Ultrasound or CT scan of the abdomen to show an enlarged liver or spleen
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Echocardiogram to reveal vegetations in endocarditis

Treatment

Nonpharmacologic Therapy

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Drainage of abscesses
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Valve replacement for endocarditis

Acute General Rx

Combination antibiotics required:

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Major options:
1. 1.
  
  Doxycycline 100 mg PO bid for 6 wk plus rifampin plus gentamycin 5 mg/kg qd for 7 days
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Alternative therapies:
1. 1.
  
  Doxycycline 100 mg PO bid plus rifampin 600 to 900 mg PO qd for 6 wk plus streptomycin.
2. 2.
  
  Sulfamethoxazole 800 mg/trimethoprim 160 mg one DS tablet PO qid, ciprofloxacin 500 mg bid for 6 wk along with doxycycline or rifampin as an alternative regimen.
3. 3.
  
  Courses <6 wk are associated with higher relapse rates; longer courses are recommended for complicated disease (e.g., osteomyelitis, endocarditis, and neurobrucellosis).

Disposition

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Relapse is possible weeks to months after the completion of therapy.
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Reactivation with CHSB has been reported up to 35 yr after initial illness.

Referral

For all cases to an infectious disease specialist

Pearls & Considerations

Comments

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Alert the microbiology laboratory to the possibility of Brucella spp. (prolonged incubation needed and biohazard for laboratory personnel).
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Do not use doxycycline in children or pregnant women.
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Avoid aminoglycosides in pregnant women.
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Fluoroquinolones have good in vitro activity against Brucella spp. and are under study as components of complex regimens. Monotherapy is not effective.

Ferri – Brucellosis