Gram-negativeBacilliZoonotic

Brucella

Facultative intracellular, small Gram-negative coccobacillus transmitted from animals to humans, causing brucellosis—a systemic febrile illness characterized by undulant fever, hepatosplenomegaly, and osteoarticular complications.

Organism Card

DomainMust know
Identity
  • G−ve small coccobacilli (short rods); non-motile, non-spore-forming
  • Facultative intracellular pathogen (survives within macrophages)
  • Key species: B. melitensis (goats/sheep, most virulent), B. abortus (cattle), B. suis (pigs), B. canis (dogs)
Lab discriminator
  • Slow-growing on culture (requires prolonged incubation ≥ 7 days; inform lab if Brucella suspected)
  • Culture-negative endocarditis workup: contact microbiologists for serology/PCR if standard blood cultures negative [1]
  • Oxidase +, urease + (most species), catalase +
  • vs Francisella: Brucella urease +, larger colonies; both are BSL-3 hazards
Reservoir / transmission
  • Zoonotic: unpasteurised dairy products (milk, cheese), direct contact with infected animals (livestock, placentae)
  • Occupational: farmers, veterinarians, abattoir workers
  • Travel-associated fever: endemic in Mediterranean, Middle East, Central Asia, Latin America
  • Not a typical HK-endemic pathogen; consider in returned travellers
Key virulence
  • Facultative intracellular survival in macrophages → evades humoral immunity, causes granulomatous inflammation
  • LPS (smooth type in B. melitensis/abortus) → resists complement killing
  • Type IV secretion system (VirB) → intracellular survival and replication
  • Granuloma formation → chronicity; can seed any organ
Clinical syndromes
  • Undulant fever: prolonged/relapsing fever with drenching sweats, malaise, weight loss
  • Osteoarticular (most common focal complication): sacroiliitis, spondylitis, peripheral arthritis
  • Chronic meningitis: Brucella listed as a cause of chronic bacterial meningitis [2]
  • Culture-negative / atypical endocarditis: major cause of endocarditis in endemic areas [1]
  • Hepatosplenomegaly, orchitis/epididymitis
  • Uveitis: listed among atypical bacterial causes of posterior/panuveitis [3]
Diagnosis
  • Blood culture: prolonged incubation needed; alert lab ("? Brucella")
  • Serology: standard agglutination test (SAT) ≥ 1:160 significant; paired sera for 4-fold rise
  • For culture-negative endocarditis: serology + PCR of blood/tissue; contact microbiologists [1]
  • Bone marrow culture: higher sensitivity than blood in chronic cases
  • Histology: non-caseating granulomas (cf. TB: caseating)
Treatment
  • Combination therapy essential to prevent relapse (intracellular organism)
  • Doxycycline + streptomycin (or gentamicin) for 6 weeks (WHO first-line)
  • Alternative: doxycycline + rifampicin for 6 weeks (oral regimen)
  • Endocarditis/neurobrucellosis: triple therapy (doxycycline + rifampicin + aminoglycoside) ± surgery for endocarditis
  • Monotherapy → high relapse rate
Prevention
  • Pasteurisation of dairy products; occupational hygiene for animal handlers
  • No licensed human vaccine (live attenuated vaccines exist for animals: Rev-1, S19)
  • Notifiable disease in HK
  • Lab safety: BSL-3 organism (high risk of lab-acquired infection)
Classic traps
  • B. melitensis listed as distractor for IE: 2025 MCQ Q39 stem = Gram-positive cocci in cluster → S. aureus IE, NOT brucellosis [4]
  • Brucella appears in EMQ options for immunocompromised infections (2022 MCQ) — typically a wrong answer for HIV/chemo scenarios [5]
  • Brucella endocarditis = culture-negative unless prolonged incubation requested
  • Undulant fever + sacroiliitis + travel to endemic area = Brucella (not TB spondylitis which is more insidious, caseating)

Exam Intelligence

  1. Culture-negative endocarditis workup: GC 101 Diagnosis of Infections lecture explicitly lists Brucella among special agents requiring serology and PCR when standard blood cultures are negative in endocarditis — "contact microbiologists if special organisms are considered in the case of culture negative endocarditis … Brucella, Leptospira, Tropheryma" [1]. This is a high-yield concept for exam stems on prolonged fever + murmur + negative cultures.

  2. Brucella as a cause of chronic meningitis: Senior neurology notes list Brucella alongside Actinomyces and Listeria as bacterial causes of chronic meningitis [2]. An exam stem with chronic CSF lymphocytosis + travel to endemic area should trigger Brucella in the differential.

  3. Brucella as a cause of uveitis: Ryan Ho Ophthalmology notes list Brucella among atypical bacterial causes of uveitis (alongside syphilis, TB, Bartonella) [3]. Posterior uveitis + travel history = consider Brucella.

  4. Infective spondylitis: The 2023 Minicase Q9 asks for "three microorganisms that can commonly cause infective spondylitis" — acceptable answers include S. aureus, Mycobacterium tuberculosis, and Brucella [6]. Brucella spondylitis classically involves the lumbar spine and sacroiliac joints in young adults from endemic regions.

  5. Prolonged blood culture incubation: Standard automated blood culture systems may detect Brucella, but informing the lab to hold cultures for ≥ 7 days and use biphasic media increases yield. This is a practical exam point tested via "how to improve diagnostic yield" questions.

  • Brucellosis vs Infective Endocarditis (IE): Both cause prolonged fever. If the stem says "Gram-positive cocci in cluster" on blood culture, this is S. aureus → IE, not brucellosis. Brucella is a G−ve coccobacillus and grows slowly. The 2025 MCQ Q39 uses Brucellosis as a distractor for IE [4].
  • Brucella vs Typhoid fever: Both cause prolonged fever in returned travellers. Typhoid: stepwise fever, relative bradycardia (Faget sign), rose spots, fecal-oral transmission, Salmonella on culture. Brucella: undulant fever pattern, sacroiliitis/spondylitis, exposure to unpasteurised dairy or livestock.
  • Brucella vs TB spondylitis: Both cause vertebral osteomyelitis. TB: caseating granulomas, Pott's disease (thoracic spine, kyphosis, cold abscess). Brucella: non-caseating granulomas, lumbar/sacroiliac involvement, positive Brucella serology.
  • Brucella in EMQ lists: In the 2022 Fourth Summative MCQ Section B, B. melitensis appears as an option for opportunistic infections in immunocompromised patients (Q19–21) but is NOT the answer for any of those stems (HIV → Talaromyces; post-chemo mucositis → Streptococcus mitis; post-transplant colitis → CMV) [5]. Brucella is not a classic opportunistic pathogen — it is a zoonotic pathogen of immunocompetent hosts.

2025 Fourth Summative MCQ Q39 [4]:

"A 36-year-old man presented to the hospital for fever which persisted for 2 weeks. He did not have any other symptoms. He has a history of eczema, but otherwise good past health. Physical examination showed small non-tender erythematous macular lesions over both palms. Chest X-ray did not show any abnormal infiltrates. Two sets of blood culture grew Gram-positive cocci in cluster. What is the MOST LIKELY clinical diagnosis? A. Brucellosis B. Extrapulmonary tuberculosis C. Infectious mononucleosis D. Infective endocarditis"

  • Answer: D. Infective endocarditis
  • Rationale: Gram-positive cocci in clusters = Staphylococcus aureus. Persistent fever + palmar lesions (Janeway lesions) + positive blood cultures with a typical organism = IE by Modified Duke's criteria (1 major + ≥1 minor). Brucellosis is a G−ve coccobacillus — morphology mismatch eliminates option A. Infectious mononucleosis and extrapulmonary TB do not grow Gram-positive cocci in cluster on blood culture.

2022 Fourth Summative MCQ Section B Q19–21 [5]:

Brucella melitensis is listed as option B in an EMQ matching microorganisms to immunocompromised clinical scenarios. None of the three stems (HIV with disseminated skin papules → Talaromyces marneffei; post-chemo breakthrough fever with oral mucositis → Streptococcus mitis; post-transplant sigmoid colitis with inclusion bodies → CMV) have Brucella as the correct answer.

  • Key learning: Brucella is a zoonotic, not opportunistic, pathogen. Its inclusion is a distractor for students who confuse travel-acquired infections with opportunistic infections.

2023 Fourth Summative Minicase Case 3, Section 3, Q9 [6]:

"Name three microorganisms that can commonly cause infective spondylitis."

  • Acceptable answers include: S. aureus (most common), Mycobacterium tuberculosis, Brucella species, coagulase-negative staphylococci, Gram-negative bacilli.
  • Rationale: Brucella spondylitis is a classic focal complication of brucellosis, especially affecting the lumbar spine, and is an expected answer for this type of question.

[1] Lecture slides: GC 101. Diagnosis of infections [Handouts].pdf [2] Senior notes: Ryan Ho Neurology.pdf [3] Senior notes: Ryan Ho Opthalmology.pdf [4] Past papers: 2025 Fourth Summative MCQ.pdf [5] Past papers: 2022 Fourth Summative MCQ.pdf [6] Past papers: 2023 Fourth Summative Minicase.pdf

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