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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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)
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
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