Skip to content
Download PDF

Brucellosis

Infectious Diseases | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 174

Key Clinical Points

  1. Brucellosis is a bacterial zoonosis (undulant fever) transmitted from infected animals, primarily ruminants and swine.
  2. B. melitensis is the most common cause of symptomatic human disease (from sheep, goats, camels).
  3. Clinical hallmark: Undulating fever pattern with relapses; musculoskeletal involvement in ~50% of patients.
  4. Diagnosis requires isolation of brucellae or serologic evidence (IgM followed by IgG/IgA).
  5. Standard adult treatment: Streptomycin + Doxycycline for 6 weeks.
  6. Alternative/Pregnancy treatment: Rifampin + Doxycycline for 6 weeks.
  7. Tuberculosis must be excluded in cases of vertebral osteomyelitis due to overlapping treatment regimens.
  8. Brucellae are 'stealth' pathogens; they evade immune detection and survive within macrophages.
  9. Radiographic distinction from TB: Brucellosis features 'parrot beak' (anterolateral) osteophytes and late diskitis.
  10. Relapse occurs in 5–10% of cases, making treatment adherence critical.

1. DEFINITION & OVERVIEW

• Definition (Harrison's 22e): Brucellosis is a bacterial zoonosis caused by Brucella species, characterized by fever, malaise, and multisystem involvement. • Clinical Character: Known as "undulant fever" due to its remittent/undulating pattern. • Pathogen Profile: ◦ Gram-negative, unencapsulated rods or coccobacilli. ◦ Facultative intracellular parasites in vivo. ◦ Environmental resilience: Resistant to freezing/drying; sensitive to heat (boiling/pasteurization) and sunlight.

1.1 Etiologic Agents

• Species & Sources: ◦ B. melitensis: Sheep, goats, camels (most common cause of human disease). ◦ B. abortus: Cattle, buffalo. ◦ B. suis: Swine, rodents. ◦ B. canis: Dogs. ◦ B. ovis: Sheep (not human pathogenic). ◦ Other species: B. neotomae (rodents), B. ceti/pinnipedialis (marine mammals), B. microti (voles), B. papionis (baboons), B. vulpis (foxes), B. inopinata (breast implant). • Environmental Survival: ◦ Soft cheeses: Up to 2 months. ◦ Dry soil: 6 weeks. ◦ Damp soil/liquid manure: 6 months.

2. EPIDEMIOLOGY

• Global Impact: ◦ >2 million human cases annually. ◦ Prevalence linked to animal reservoirs; less common in high-GDP areas (e.g., Northern Europe, Australia). • Transmission Routes: ◦ Occupational: Farmers, shepherds, veterinarians, slaughterhouse workers. ◦ Domestic: Family members of animal handlers. ◦ Foodborne: Unpasteurized dairy (soft cheese, ice cream), raw meat/bone marrow. ◦ Laboratory: Exposure to cultures/infected samples. ◦ Travelers: Consumption of contaminated food in endemic areas. • Risk Factors: No evidence of increased severity in immunocompromised patients.

3. ETIOLOGY & PATHOGENESIS

• Virulence Factors: ◦ Smooth LPS (low endotoxin activity) → evades phagocytosis. ◦ Type IV secretion system (Vir) → evasion of lysosomal fusion. ◦ Acid-stable proteins, Cu-Zn superoxide dismutase, hemolysin-like protein. • Immune Evasion ("Stealth" Strategy): ◦ Inhibits macrophage apoptosis. ◦ Suppresses dendritic cell maturation and T-cell activation. ◦ Redirects replication to endoplasmic reticulum via suppressed phagosome-lysosome fusion. • Host Response: ◦ TNF-α stimulates cytotoxic lymphocytes/macrophages. ◦ IFN-γ production driven by IL-12. ◦ Inhibitory cytokines (IL-4, IL-6, IL-10) can downregulate protective responses.

4. CLINICAL FEATURES

• General Symptoms: ◦ Fever: Undulating pattern with relapses; night sweats. ◦ Incubation: 1 week to several months (abrupt or insidious). ◦ Systemic: Fatigue, anorexia, weight loss, myalgia, headache, chills. • Organ Involvement: ◦ Musculoskeletal (~50%): Osteomyelitis (lumbar/low thoracic), septic arthritis (knee, hip, sacroiliac, shoulder, sternoclavicular). ◦ Respiratory (25%): Dry cough, pneumonia, empyema, lung abscess. ◦ Hepatosplenomegaly (25%), Lymphadenopathy (10–20%). ◦ Genitourinary: Epididymo-orchitis (10% of men), prostatitis, salpingitis, pyelonephritis. ◦ Neurologic: Depression, lethargy, intracranial abscess, cranial nerve deficits, mycotic aneurysms. ◦ Cardiovascular: Endocarditis (~1%, aortic valve). ◦ Metastatic: Breast, thyroid. • Diagnostic Clues: ◦ Travel to endemic areas (Middle East, Mediterranean, Asia, Africa). ◦ Occupational exposure or consumption of unpasteurized dairy. ◦ Family history of brucellosis (50% of cases).

5. DIFFERENTIAL DIAGNOSIS

• Primary Differentials: Tuberculosis (critical due to overlapping treatment), typhoid fever, malaria, glandular fever (EBV, Toxoplasma, CMV, HIV, TB), septic arthritis, endocarditis. • Laboratory Findings: ◦ Leukocytes: Normal/low with relative lymphocytosis. ◦ Hematology: Mild anemia, thrombocytopenia, DIC. ◦ Inflammatory: ESR/CRP may be normal or elevated. ◦ CSF/Joint Fluid: Lymphocytosis, low glucose. ◦ Biopsy: Noncaseating granulomas (no AFB).

6. INVESTIGATIONS & DIAGNOSIS

  1. Culture:
  2. Samples: Blood, CSF, bone marrow, joint fluid, tissue aspirate.
  3. Yield: 50–70% with modern systems (e.g., Bactec).
  4. Requirement: Biosafety level 3 containment.
  5. MALDI-TOF MS:
  6. Emerging tool for identification; note that it may misclassify Ochrobactrum as Brucella species.
  7. PCR:
  8. Detects Brucella DNA using primers targeting rrs-rrl spacer, outer-membrane proteins (OMPs), IS711, and BCSP31.
  9. Value: More sensitive than culture; predicts relapse; excludes chronic cases.
  10. Serology:
  11. Screening: Rose Bengal test.
  12. Confirmation: Microagglutination (Standard agglutination test).
  13. Criteria: ≥ 1:320 in endemic areas; ≥ 1:160 in nonendemic areas.
  14. Timing: Rising titers after 2–4 weeks confirm acute infection.
  15. Imaging:
  16. Plain x-ray: Less sensitive for early detection.
  17. Isotope scanning: More sensitive than plain x-ray.

7. MANAGEMENT & TREATMENT

  1. Adult Standard Regimen:
  2. Streptomycin (0.75–1 g IM daily imes 14–21 days) + Doxycycline (100 mg PO BID imes 6 weeks).
  3. Alternative/Pregnancy Regimen:
  4. Rifampin (600–900 mg PO daily) + Doxycycline (100 mg PO BID imes 6 weeks).
  5. Pediatric Regimen (<8 years):
  6. Rifampin + Doxycycline (Avoid tetracyclines).
  7. Monitoring & Follow-up:
  8. Adherence: Critical to prevent relapse (5–10% risk).
  9. Tuberculosis Exclusion: Mandatory in vertebral osteomyelitis cases due to overlapping treatment regimens.
  10. Renal Adjustment: Adjust aminoglycoside dosing for renal impairment.
  11. Pregnancy: Use Rifampin + Doxycycline (avoid streptomycin due to ototoxicity).

8. PROGNOSIS & COMPLICATIONS

• Prognosis: Excellent with appropriate treatment; relapse risk 5–10% if non-adherent. • Complications: ◦ Chronic infection (persistent fever, joint pain). ◦ Neurologic: Depression, cranial nerve deficits, mycotic aneurysms. ◦ Cardiovascular: Endocarditis (~1%). ◦ Metastatic abscesses: Breast, thyroid. ◦ Pregnancy: Fetal loss (less common than in animals).

9. SPECIAL CONSIDERATIONS

• Occupational Exposure: Post-exposure prophylaxis (Doxycycline + Rifampin for 6 weeks) for farmers, vets, slaughterhouse workers. • Biological Warfare: B. melitensis used historically; consider in unexplained outbreaks. • Public Health: Focus on animal vaccination (less successful for B. melitensis).

10. KEY PEARLS & CLINICAL TRAPS

• Undulant fever is pathognomonic. • Musculoskeletal involvement in ~50% of patients. • Tuberculosis must be excluded in vertebral osteomyelitis. • Radiology (Table 174-1): Brucellosis shows 'parrot beak' anterolateral osteophytes and late diskitis, whereas TB shows early diskitis and common canal compression. • PCR vs Culture: PCR is more sensitive but may miss chronic cases; culture requires BSL-3. • Clinical Traps: - Misdiagnosis as typhoid/malaria due to similar fever profiles. - Overlooking foodborne transmission (unpasteurized dairy products). - Confusing Brucella with Ochrobactrum in MALDI-TOF results. - Underestimating relapse risk with incomplete treatment.

Reference Tables

TABLE 174-1 Radiology of the Spine: Differentiation of Brucellosis from Tuberculosis Site Vertebrae Diskitis Body Canal…

Harrison's 22e, p.1333

BRUCELLOSIS TUBERCULOSIS
Site Lumbar and others Dorsolumbar
Multiple or contiguous
Diskitis Late Early
Intact until late
Canal compression Rare Common
Anterosuperior
Osteophyte Anterolateral (parrot beak) Unusual
Wedging uncommon
Recovery Sclerosis, whole-body Variable
Small, well-localized
Psoas abscess Rare More likely