Brucellosis

Risk factors

• Ingestion of unpasteurized dairy products (especially goat cheese)
• Direct contact with cattle, goats, sheep, pigs, or their products
• Veterinary, slaughterhouse, hunting, or laboratory work
• Travel to endemic areas
• Laboratory workers handling cultures (Brucella is one of the most common laboratory-acquired infections; cultures are handled under BSL-3 precautions)

Pathophysiology

Organisms penetrate mucous membranes or broken skin, are phagocytosed by macrophages, and survive intracellularly via inhibition of phagosome-lysosome fusion. Dissemination to reticuloendothelial organs and bone produces granulomatous inflammation. Chronic and relapsing disease reflects intracellular persistence.

Clinical presentation

Differential diagnosis

• Tuberculosis — Chronic granulomatous illness with weight loss and night sweats; vertebral involvement in both — Pott disease vs Brucella spondylitis (often lumbar)
• Q fever (Coxiella burnetii) — Similar livestock exposure, hepatitis pattern; phase I/II IgG serology distinguishes
• Typhoid fever (Salmonella typhi) — Travel history, relative bradycardia, rose spots; blood culture and stool culture
• Lymphoma — Painless lymphadenopathy and B symptoms; biopsy distinguishes
• Endocarditis — Brucella is itself a cause of culture-negative endocarditis; consider when undulant fevers and a new murmur
• HIV seroconversion — Multisystem febrile illness; screen if any risk factor

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Febrile patient<br/>livestock or unpasteurized<br/>dairy exposure] --> B[Blood cultures<br/>+ alert lab<br/>+ Brucella serology]
  B --> C{Confirmed?}
  C -->|Yes - uncomplicated| D[Doxycycline 6 wk<br/>+ Rifampin 6 wk]
  C -->|Yes - focal/severe| E[Doxycycline + Rifampin<br/>+ Aminoglycoside]
  E --> F{Site}
  F -->|Spondylitis| G["Doxy + rifampin ≥12 wk<br/>aminoglycoside first 1-3 wk only"]
  F -->|Neuro| H[Add ceftriaxone<br/>≥6 months]
  F -->|Endocarditis| I[Combined therapy<br/>± valve surgery]

Treatment

Complications

• Spondylitis and sacroiliitis (most common focal complications)
• Hepatic and splenic granulomatous abscesses
• Epididymo-orchitis
• Neurobrucellosis (meningoencephalitis, cranial neuropathies)
• Endocarditis (leading cause of brucellosis mortality)
• Relapse despite adequate therapy (5-10%)

PANCE pearls

• Always ask about unpasteurized cheese in any febrile traveler from the Mediterranean or Latin America.
• Prior antibiotic therapy is the most common reason for culture-negative endocarditis; among fastidious organisms, Coxiella and Bartonella are the leading causes and Brucella is a major cause in endemic regions, all diagnosed mainly by serology or special cultures.
• Alert the laboratory before sending blood cultures — Brucella is highly infectious by aerosol and is one of the most common laboratory-acquired infections.
• Doxycycline + rifampin is the workhorse regimen; add an aminoglycoside for severe or focal disease.
• Sacroiliitis in a young patient with unexplained fevers should prompt brucellosis testing.

References

• WHO/FAO/OIE — Brucellosis in Humans and Animals (WHO/CDS/EPR/2006.7)
• CDC 2017 — CDC. Brucellosis Reference Guide: Exposures, Testing, and Prevention. Atlanta, GA: CDC; updated February 2017
• Ioannina 2007 — Ariza J, Bosilkovski M, Cascio A, et al. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med 2007;4(12):e317