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]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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