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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Question 1Infectious DiseaseMedium
A 38-year-old man who recently traveled to the Mediterranean and ate fresh unpasteurized goat cheese presents with several weeks of fevers that rise and fall in an undulating pattern, drenching night sweats, malaise, and arthralgias. On exam he has hepatosplenomegaly and sacroiliac tenderness. Blood cultures held for prolonged incubation grow a small gram-negative coccobacillus. Which of the following is the most likely diagnosis?
  • ATyphoid fever
  • BQ fever
  • CLeptospirosis
  • DBrucellosis
Reveal answer & full explanation
Correct answer: D — Brucellosis
  • ATyphoid fever
  • BQ fever
  • CLeptospirosis
  • DBrucellosis

Why Brucellosis is correct

  • Brucellosis is a zoonosis caused by Brucella species, most often acquired from unpasteurized dairy or direct livestock contact in the Mediterranean, Middle East, and Central Asia.
  • The insidious 'undulant' fever, drenching sweats, arthralgias, hepatosplenomegaly, and a predilection for sacroiliitis and vertebral osteomyelitis are classic.
  • Diagnosis rests on serology and blood cultures, which grow slowly and must be held for prolonged incubation, yielding a small gram-negative coccobacillus.

Why the others are wrong

  • Typhoid fever — follows fecal-oral Salmonella Typhi exposure with rose spots and relative bradycardia, not unpasteurized-dairy exposure with undulant fever.
  • Q fever — is also livestock-associated but presents with atypical pneumonia and hepatitis rather than undulant fever with sacroiliitis.
  • Leptospirosis — follows freshwater or animal-urine exposure with conjunctival suffusion and myalgias, not the dairy exposure and undulant pattern here.
Question 2Infectious DiseaseEasy
A public-health clinician is counseling travelers about preventing brucellosis. Which of the following exposures is the strongest risk factor for acquiring the infection?
  • AConsuming unpasteurized dairy products
  • BWading through contaminated fresh water
  • CSleeping in a rodent-infested cabin
  • DBeing bitten by an Ixodes tick
Reveal answer & full explanation
Correct answer: A — Consuming unpasteurized dairy products
  • AConsuming unpasteurized dairy products
  • BWading through contaminated fresh water
  • CSleeping in a rodent-infested cabin
  • DBeing bitten by an Ixodes tick

Why Consuming unpasteurized dairy products is correct

  • Brucella is transmitted to humans chiefly through consumption of unpasteurized dairy products (soft cheeses, raw milk) and through direct contact with infected livestock or their birth products, making dietary and occupational exposure the strongest risk factors; it is a classic infection of herders, veterinarians, and abattoir workers.

Why the others are wrong

  • Wading through contaminated fresh water — is the exposure for leptospirosis and schistosomiasis, not brucellosis.
  • Sleeping in a rodent-infested cabin — is the risk for hantavirus and leptospirosis.
  • Being bitten by an Ixodes tick — transmits Lyme disease, babesiosis, and anaplasmosis, not Brucella.
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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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