Infectious Disease · PANCE / PANRE

Brucellosis

Undulant fever and constitutional symptoms after unpasteurized dairy or livestock exposure; insidious, multisystem zoonosis caused by Brucella spp.

Also known as: undulant fever, Mediterranean fever, Bang disease, Malta fever, Brucella melitensis

Overview

Zoonotic infection caused by small, gram-negative, intracellular coccobacilli of the Brucella genus (B. melitensis, B. abortus, B. suis, B. canis). Characterized by undulant fevers, sweats, arthralgias, and a propensity for chronic focal infections of bone, joints, and heart.

Epidemiology

Worldwide zoonosis. Highest incidence in the Mediterranean basin, Middle East, Central Asia, Mexico, and Latin America. Approximately 100-200 reported US cases annually, mostly from imported unpasteurized cheese or returning travelers. Occupational exposure in farmers, veterinarians, abattoir workers, and laboratory personnel.

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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 a CDC Tier 1 select agent and biosafety hazard)

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

Symptoms

  • Insidious onset of intermittent ('undulant') fevers, drenching night sweats with a peculiar 'wet hay' or moldy odor
  • Profound fatigue, headache, arthralgias, myalgias, low back pain
  • Anorexia and weight loss
  • Focal symptoms: low back pain (sacroiliitis, spondylitis), hip or knee pain, orchitis

Signs / physical exam

  • Fever often >39 °C with relative bradycardia
  • Hepatosplenomegaly, lymphadenopathy
  • Sacroiliac joint tenderness; vertebral percussion tenderness in spondylitis
  • New murmur if endocarditis

Classic findings

Goat herder or returning Mediterranean traveler with intermittent fevers, sweats, and sacroiliitis.

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 criteria

Compatible exposure plus positive culture OR serum agglutination titer ≥1:160 with rising titers OR PCR.

Labs

  • Blood and bone marrow cultures (alert lab — Brucella is a biosafety hazard; prolonged incubation required)
  • Serum agglutination test (SAT) titer ≥1:160 or fourfold rise supports diagnosis
  • Brucella IgG/IgM ELISA
  • PCR on blood or tissue (where available)
  • CBC: leukopenia or normal WBC with relative lymphocytosis; mild thrombocytopenia
  • LFTs: mildly elevated transaminases (granulomatous hepatitis)

Imaging

  • MRI lumbosacral spine and sacroiliac joints when focal symptoms
  • Echocardiogram if endocarditis suspected
  • Abdominal ultrasound or CT for hepatosplenomegaly and abscess

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[≥12 weeks]
  F -->|Neuro| H[Add ceftriaxone<br/>≥6 months]
  F -->|Endocarditis| I[Combined therapy<br/>± valve surgery]
Brucellosis: from exposure to tailored combination therapy by focal involvement.

Treatment

First-line

  • Doxycycline (cat scratch, Q fever, brucellosis, RMSF) 100 mg PO BID for 6 weeks PLUS rifampin 600-900 mg daily for 6 weeks — standard uncomplicated regimen
  • Doxycycline 6 weeks + streptomycin (or gentamicin) for 2-3 weeks is a more effective alternative for severe disease (lower relapse than doxycycline + rifampin)
  • TMP-SMX + rifampin in children <8 years and pregnancy

Spondylitis or sacroiliitis

  • Doxycycline + rifampin + an aminoglycoside (streptomycin or gentamicin) for ≥12 weeks
  • Surgical drainage of paraspinal abscess as needed

Neurobrucellosis

  • Doxycycline + rifampin + ceftriaxone for ≥6 months
  • Steroids if cranial nerve involvement or vasculitis

Endocarditis

  • Doxycycline + rifampin + aminoglycoside; valve replacement frequently required

Second-line / adjunct

  • Avoid monotherapy — high relapse rate
  • Public health reporting required; counsel on PEP for laboratory exposure (doxycycline + rifampin for 3 weeks)

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.
  • Brucella, Bartonella, Coxiella, and HACEK organisms together account for most culture-negative endocarditis.
  • Alert the laboratory before sending blood cultures — Brucella is highly infectious by aerosol and is a Tier 1 select agent.
  • 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 — CDC Brucellosis Reference Guide for Clinicians and Laboratorians
  • IDSA 2012 — Treatment guidance summarized in Solera J, Expert Rev Anti Infect Ther 2010 and IDSA brucellosis primers

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