8. Brucella, Francisella, Pasteurella

Brucella, Francisella, Pasteurella: Overview

General Information

  • Tibor Pál, Department of Medical Microbiology and Immunology, University of Pécs, Hungary

Brucella

Clinical Case Example

  • Patient: 34-year-old male with lower back pain for 3 months.

  • Symptoms: Lower back pain, low-grade fever, weakness, increased RBC sedimentation.

    • Long standing, no specific symptoms

  • MRI Findings: Extradural defect at L4-L5.

  • Biopsy Results: Signs of granulomatous inflammation; ruled out tuberculosis.

  • Exposure History: Consumed raw milk from goats and camels in the Middle East.

  • Diagnosis: Elevated brucella-specific antibodies; identified as Brucella abortus via blood culture.

Microbiology

  • Small Gram-negative coccobacilli.

  • Slow-growing with 12 recognized species.

  • Main reservoirs: Wild and domestic animals.

Human Pathogenic Species

  • B. Melitensis: Mostly from sheep, goats, camels (high pathogenicity, prevalent in Mediterranean, Asia, Latin America).

  • B. suis: Pigs (high pathogenicity, in Americas, Southeast Asia).

  • B. abortus: Cattle (moderate pathogenicity, worldwide).

  • B. canis: Dogs (moderate pathogenicity, worldwide).

Global Incidence

  • Approximately 2.1 million estimated human cases/year.

  • Most prevalent bacterial zoonotic infection.

  • Major economic impact due to abortions in animals.

Pathogenecity and Spread

  • Transmission: Primarily via unpasteurized milk; less commonly by aerosol or direct contact.

  • Intracellular parasite, primarily targets macrophages, cells of the RES; survives and replicates in ER.

    • Facultative IC parasite → can live in and outside of cells

Immune Response and Clinical Presentation

  • Symptoms can be acute or chronic. Common features include undulant fever, malaise, weight loss, joint pain, and abdominal symptoms.

  • Potential organ-specific symptoms include osteomyelitis, endocarditis, and urinary tract infections.

Laboratory Diagnosis

  • Culture and serology needed, as cultures may take weeks.

  • Blood samples are preferred; specialized media for culture.

    • also bone marrow biopsy, organ specific samples

    • write your suspicion as it is slow growing → extend incubation time

  • Standard Agglutination Test (SAT) diagnostic for B. abortus, with a titre of ≥160 being significant. (≥320 in endemic areas)

  • Work in BSL II safety cabinet

  • 2-Mercaptoethanol test → treatment of serum with 2-ME eliminates cross-reacting or persisting IgM antibodies - testing serum simultaneously in SAT → IgG only!

    • main use: monitoring response to antibiotic therapy

  • Rose bengal Test

  • Coombs test

Treatment and Prevention

  • Treatment involves antibiotics such as doxycycline, rifampin, or gentamicin. Relapse potential decreases with proper treatment.

    • Children <8 years → TMP-SMZ

    • Pregnancy → Rifampin (+/- TMP-SMZ)

  • Prevention focuses on avoiding unpasteurized products and controlling animal exposure.

    • slaughtering infected animals, also vaccination of animals

Francisella

Clinical Case Example

  • Patient: 56-year-old with symptoms suggesting tularaemia after a tick bite.

  • Diagnosis: Identified as Francisella tularensis through culture.

Microbiology

  • Small, Gram-negative coccobacilli, aerobic and capsulated.

  • Multiple subspecies: Type A and Type B.

Reservoirs and Global Distribution

  • Zoonosis with reservoirs in a variety of wild and domestic animals.

  • Infection primarily occurs in the Northern Hemisphere.

Spread and Pathogenesis

  • Transmission via inhalation, mucosal surfaces, skin injuries, or ingestion.

  • Immune evasion via atypical LPS and modulation of cytokine response.

Clinical Picture

  • Depends on portal of entry: ulceroglandular, glandular, or pneumonic presentations.

    • Ulceroglandular: skin ulcer + localised lymphadenopathy

    • Glandular: lympadenopathy without skin ulcer

    • Oropharyngeal: chronic pharyngitis with or without mucosal ulcer and swollen lymph nodes

    • Oculoglandular: conjunctivitis with lymphadenopathy

    • Pneumonic: inhalation or hematogenous spread to the lungs

    • Typhoidal: Sysetmic after any portal of entry

Laboratory Diagnosis

  • BIOHAZARD! Laboratory infections !!!

  • Serology: Microagglutination, recently ELISA and Western blot

    • At presentation often negative

    • Definitive is the 4x increase of titres

  • Culture: Slow, often negative. Needs special media

  • PCR: Promising, even good for subspecies determination

  • Others: Indirect immunofluorescence

Treatment and Prevention

  • Suspected case: exposure history + consistent clinical symptoms

  • Presumptive case:

    • suggestive clinical symptoms

    • antigen or DNA detection

    • single positive serum

  • Confirmed case:

    • recovery and identification of the isolate or paired serum show ≥4 fold increase in titre

  • Therapy:

    • Aminoglycosides (streptomycin, gentamicin)

    • Fluoroquinolones (ciprofloxacin, levofloxacin)

    • Doxycycline

    • Natural resistance to beta-lacatms due to beta-lactamase production

  • Preventions:

    • Currently no licensed vaccine (perviously a live, attenuated one)

    • Prevent contact

  • NOTE: a potential biological warfare

Pasteurella

Clinical Case Example

  • Patient: 42-year-old with a dog bite experiencing swelling and inflammation.

  • Identified as Pasteurella multocida from cultures after incision and antibiotic treatment.

Microbiology

  • Found in the oral and upper respiratory tract of animals/humans.

  • Gram-negative pleomorphic coccobacillus (bipolar staining).

  • Grows on blood agar

Transmission to Humans

  • Exists in various animals, and can transfer to humans by:

    • animal bites

    • scratches

    • licks on skin abrasions

    • contacts with mucus secretion

  • Human infections:

    • swelling, cellulitis

    • bacteriaemia

    • osteomyelitis

    • endocarditis

    • line infections

    • meningitis

    • pneumonia (relatively rare)

Lab Diagnosis and Treatment

  • Culture often negative; treatment should account for mixed infections from bites.

  • Recommended antibiotics include amoxicillin or doxycycline combined with metronidazole.

Further Readings and Contact

  • Refer to "Medical Microbiology, 8th ed., 2015, Elsevier."

  • For inquiries: pal.tibor2@pte.hu