Tularemia¶
Chapter 175 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Tularemia is a zoonotic disease caused by Francisella tularensis, transmitted via arthropods, aerosols, or direct contact with infected animals.
- Clinical forms include ulceroglandular, oropharyngeal, oculoglandular, respiratory/pneumonic, and typhoidal, with varying presentations and treatment needs.
- Antimicrobial therapy is the mainstay of treatment, with fluoroquinolones, doxycycline, gentamicin, and streptomycin as first-line options.
- Prognosis is generally favorable, but mortality can reach 3% in severe cases, particularly with respiratory/pneumonic forms.
- Diagnosis requires laboratory confirmation via culture, nucleic acid detection, or serology, with specialized biosafety level 3 laboratories needed for culture.
1. DEFINITION & OVERVIEW¶
Tularemia is a zoonotic disease transmitted from vertebrate animals to humans, causing a febrile illness. Synonyms include deer-fly fever, rabbit fever, and market men’s disease. Relapse occurs in up to 30% of poorly compliant patients, requiring prolonged therapy. Immunity is not solid, and reinfection is possible.
Table 175-1: Clinical Forms of Tularemia¶
| FORMa | F. TULARENSIS INFECTION ROUTE |
|---|---|
| Ulceroglandular or glandular | Skin inoculation by blood-feeding arthropods or direct contact (touching infected animal or F. tularensis contaminated material) |
| Oropharyngeal | Ingestion of contaminated water or food |
| Oculoglandular | Touching the eye with contaminated fingers or exposure to contaminated aerosol |
| Respiratory/pneumonic | Inhalation of contaminated aerosol |
| Typhoidal | Unknown (likely by inhalation, rarely by ingestion) |
1.1 Clinical Forms¶
Clinical manifestations depend on the route of infection: ulceroglandular (skin inoculation), oropharyngeal (ingestion), oculoglandular (eye contact), respiratory/pneumonic (inhalation), and typhoidal (unknown route).
1.2 Prognosis¶
Mortality is low (<1%), but severe cases (especially respiratory/pneumonic) can have higher fatality rates. Recovery is slow, with prolonged inactivity and economic consequences.
2. EPIDEMIOLOGY¶
F. tularensis is endemic in the Northern Hemisphere, with seasonal variation. In the U.S., cases dropped from thousands annually pre-1950 to 200–300 annually (2010–2020). Type A (North America) and type B (Europe/Asia) strains have distinct ecologies. In Turkey, winter outbreaks are linked to contaminated water. In Sweden and Finland, summer peaks correlate with arthropod exposure.
2.1 Risk Factors¶
Occupational exposure (e.g., hunters, veterinarians), wildlife contact, and aerosol exposure. Immunocompromised individuals and the elderly are at higher risk for severe disease.
2.2 Demographics¶
Most U.S. cases occur in Arkansas, Kansas, Missouri, and Oklahoma. In Europe, Finland, Sweden, and Turkey have seasonal peaks. Type A is more lethal in experimental models, but type B strains show geographic variability in virulence.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
F. tularensis is a gram-negative, facultatively intracellular bacterium. It evades immune detection by manipulating host cell signaling, allowing systemic spread. Infection routes include arthropod bites, aerosols, or direct contact. The bacterium replicates in macrophages and escapes phagosomes to disseminate systemically.
Table 175-2: Treatment and Postexposure Prophylaxis Recommendations¶
| ADULTS, INCLUDING PREGNANT WOMEN | DRUG | DOSEa | DURATION (DAYS) |
|---|---|---|---|
| Preferred choices | Ciprofloxacin | 400 mg every 8 hrs IV or 750 mg every 12 hrs PO | 10 |
| Preferred choices | Levofloxacin | 750 mg every 24 hrs IV or PO | 10 |
| Preferred choices | Gentamicin | 5–7 mg/kg IV or IM per day, given every 12 hrs or 24 hrs | 10 |
| Preferred choices | Doxycyclinec | 200 mg loading dose, then 100 mg every 12 hrs IV or PO | |
| Postexposure prophylaxisd | Doxycycline | 100 mg PO twice daily | 14 |
| Postexposure prophylaxisd | Ciprofloxacin | 500 mg every 12 hrs PO | 10 |
3.1 Subspecies¶
Two clinically important subspecies: F. tularensis subspecies tularensis (type A, North America) and subspecies holarctica (type B, global). A third subspecies, mediasiatica, is found in Central Asia but lacks human disease documentation.
3.2 Pathogenesis¶
F. tularensis infects macrophages, replicates in the cytosol, and spreads via lymphatics. It causes necrotizing pneumonia and granuloma formation. Immune evasion mechanisms include suppression of proinflammatory cytokines and manipulation of host cell signaling.
4. CLINICAL FEATURES¶
The most common presentation is an influenza-like illness with high fever. Ulceroglandular form presents with skin ulcers and swollen lymph nodes. Respiratory/pneumonic form may progress to severe disease requiring hospitalization. Typhoidal form mimics typhoid fever with prolonged fever and systemic symptoms.
4.1 Clinical Forms¶
Ulceroglandular (skin ulcer + lymphadenopathy), oropharyngeal (pharyngitis + lymphadenopathy), oculoglandular (conjunctivitis + preauricular lymphadenopathy), respiratory/pneumonic (cough + mediastinal lymphadenopathy), and typhoidal (prolonged fever + systemic symptoms).
4.2 Complications¶
Lymph node abscesses, sepsis, meningitis, endocarditis, osteomyelitis, and multiorgan failure. Postinfectious fatigue and disability may persist.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include brucellosis, tuberculosis, viral infections (e.g., influenza, mononucleosis), and malignancies (e.g., lymphoma, lung cancer). Specific features like ulceroglandular lymphadenopathy or respiratory symptoms help distinguish tularemia from other febrile illnesses.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis requires laboratory confirmation via culture, nucleic acid detection, or serology. Blood cultures, lymph node aspirates, and sputum samples are critical. Serology (e.g., microagglutination test) detects IgG antibodies 10–20 days post-infection. Molecular methods (PCR) offer rapid detection.
6.1 Diagnostic Criteria¶
Clinical suspicion based on exposure history + laboratory confirmation (culture, PCR, or serology). Serology is less reliable for acute diagnosis due to prolonged antibody persistence.
6.2 Imaging¶
Chest X-ray/CT may show consolidation, nodules, or lymphadenopathy. PET scans may reveal metabolic activity in lung lesions. Bronchoscopy with biopsy is used for respiratory/pneumonic forms.
7. MANAGEMENT & TREATMENT¶
Antimicrobial therapy is the mainstay. Fluoroquinolones (ciprofloxacin, levofloxacin), doxycycline, gentamicin, and streptomycin are first-line options. Treatment duration is 10–21 days, with prolonged courses for relapse prevention. Surgical drainage is needed for abscesses.
7.1 Antimicrobial Therapy¶
Preferred drugs: ciprofloxacin (400 mg every 8 hrs IV/750 mg PO), levofloxacin (750 mg daily), gentamicin (5–7 mg/kg/day), or doxycycline (100 mg every 12 hrs). Avoid macrolides due to resistance in type B strains.
7.2 Postexposure Prophylaxis¶
Doxycycline 100 mg twice daily for 14 days for high-risk exposures (e.g., aerosol-generating procedures with F. tularensis).
8. PROGNOSIS & COMPLICATIONS¶
Mortality is <1% in most cases but can reach 3% in severe respiratory/pneumonic forms. Complications include lymph node abscesses, sepsis, and multiorgan failure. Postinfectious fatigue and disability may persist. Early treatment reduces mortality.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid tetracyclines; use doxycycline or fluoroquinolones. Immunocompromised patients require prolonged therapy. In endemic areas, prophylaxis may be considered for high-risk exposures. Laboratory work must be done in BSL-3 facilities.
10. KEY POINTS & CLINICAL PEARLS¶
- Tularemia is a zoonotic disease with diverse clinical presentations.
- Early antibiotic treatment prevents complications.
- Serology is unreliable for acute diagnosis; PCR or culture is preferred.
- Doxycycline is the preferred choice for nonsevere cases, but fluoroquinolones are better for severe disease.
- Postexposure prophylaxis is critical for high-risk exposures.