Tularemia

Tularemia is a rare but potentially life-threatening zoonotic infection caused by the gram-negative coccobacillus Francisella tularensis. It is a CDC Category A bioterrorism agent due to its extremely low infectious dose (as few as 10 organisms), ease of aerosolization, and high mortality if untreated (up to 60% for pneumonic/typhoidal forms).[1-2] The disease is frequently initially misdiagnosed; a thorough exposure history is the single most important factor in raising clinical suspicion.[3]

• Exposure history is critical: Ask about tick bites, deer fly bites, handling rabbits/hares/rodents, skinning or butchering wild game, mowing over animal carcasses, contact with sick/dead animals, and contaminated water ingestion[2][4]
• Outdoor activities: hunting, trapping, farming, landscaping, hiking in endemic areas[5]
• Occupational exposures: laboratory workers, veterinarians, farmers[2]
• Incubation period: typically 3–5 days (range 1–14 days)[3][6]
• Symptom onset is usually abrupt: high fever (38–40°C), chills, rigors, headache, malaise, myalgias (often prominent in the low back), sore throat, coryza[2]
• Ask about skin lesion/ulcer at inoculation site, painful swollen lymph nodes, eye redness/pain, sore throat, cough, chest pain, dyspnea[7]
• Pulse-temperature dissociation noted in up to 42% of patients[2][8]
• Timing: most US cases occur in summer (tick season) or winter (hunting season)[6]

• Pneumonic tularemia: cough, dyspnea, pleuritic chest pain, hemoptysis — mortality up to 30–60% untreated[1][5]
• Typhoidal tularemia: high fever, confusion, stupor, behavioral changes, no localizing signs — high mortality[6]
• Sepsis/bacteremia: hemodynamic instability, multiorgan dysfunction
• Meningitis: altered mental status, nuchal rigidity (rare but reported)[6]
• Rapidly progressive lymphadenopathy with suppuration
• Immunocompromised patients: unusual and severe manifestations[7]
• Delayed treatment (>2–3 weeks after onset) is associated with significantly worse outcomes and higher treatment failure rates[9]

• Effective antimicrobials (three classes with proven survival benefit):[10-11]
• Severe disease (first-line): Gentamicin 5 mg/kg/day IV (or 1.5 mg/kg q8h) or streptomycin 15 mg/kg q12h IM for 10–14 days[4]
• Mild-moderate disease (first-line per 2025 CDC): Ciprofloxacin 500–750 mg PO BID or levofloxacin 500 mg PO daily, OR doxycycline 100 mg PO BID for 14–21 days[6][11]
• Fluoroquinolones have lower relapse rates (~5–10%) compared to tetracyclines (~10–15%)[6]
• Step-down from IV aminoglycoside to oral fluoroquinolone or doxycycline is reasonable once clinically improved[4]

Contraindicated/ineffective

• Beta-lactams: F. tularensis is intrinsically resistant — avoid empiric beta-lactam monotherapy[4][9]
• Most macrolides and anti-TB agents are ineffective[9]
• Chloramphenicol: higher relapse rates, rarely used[4]

Special populations

• Pregnancy: gentamicin for severe disease; azithromycin may be considered for mild type B infections in western Europe
• Children: gentamicin preferred for severe disease; ciprofloxacin has been used safely in children ages 1–10
• Renal impairment: dose-adjust aminoglycosides

• No specific dietary triggers or restrictions
• Avoid consumption of undercooked wild game (especially rabbit) and untreated water from endemic areas — these are transmission routes for oropharyngeal tularemia[2]
• Maintain adequate hydration during febrile illness
• Prolonged illness may cause significant weight loss and anorexia — nutritional support may be needed[2]

• Constitutional: fever, chills, rigors, night sweats, fatigue, weight loss, anorexia[2][7]
• Skin: ulcer or papule at inoculation site, rash, erythema nodosum[6]
• Lymphatic: painful swollen lymph nodes (location correlates with inoculation site)[12]
• Pulmonary: cough (dry or productive), dyspnea, pleuritic pain, hemoptysis, substernal tightness[2]
• GI: nausea, vomiting, diarrhea, abdominal pain, sore throat, pharyngitis[2][7]
• Ophthalmologic: eye pain, photophobia, tearing, conjunctival injection[7]
• Neurologic: headache, confusion, stupor (typhoidal form)[6]
• MSK: myalgias, arthralgias[6]

• No person-to-person transmission — household contacts are not at risk from the patient[2]
• Collateral from family/companions regarding shared outdoor exposures (hunting trips, tick-endemic areas, animal contact)
• Ask about sick or dead animals in the area (epizootics may herald human outbreaks)[2]
• Occupational history of family members (farming, veterinary work)
• No known hereditary susceptibility; immunocompromised status (HIV, transplant, chemotherapy) increases severity[6]

• Tick exposure: Dermacentor variabilis, D. andersoni, Amblyomma americanum are primary US vectors[12-13]
• Animal contact: handling rabbits, hares, rodents, squirrels; cat bites/scratches[4][14]
• Occupational: hunters, trappers, butchers, farmers, landscapers, laboratory workers[2][5]
• Geographic: south-central US (Missouri, Arkansas, Oklahoma), Great Plains, parts of Massachusetts; all states except Hawaii[7][15]
• Seasonal: summer (arthropod-borne) and winter (hunting-related)[6]
• Age/sex: highest incidence in children 5–9 years and men >55 years[15]
• Aerosol exposure: mowing over infected animal carcasses, laboratory accidents[2][7]
• Immunocompromise: more severe and atypical presentations[7]

The differential depends on the clinical form

• Ulceroglandular: cat scratch disease (Bartonella henselae), sporotrichosis, cutaneous anthrax, plague, staphylococcal/streptococcal lymphadenitis, Mycobacterium marinum, spider bite[4]
• Glandular/lymphadenopathy: tuberculosis, lymphoma, mononucleosis, toxoplasmosis, HIV — tularemia can produce caseating granulomas mimicking TB[16]
• Pneumonic: community-acquired pneumonia, TB, Q fever, plague, psittacosis, lung malignancy, lymphoma — pulmonary tularemia on PET/CT can mimic cancer with hypermetabolic nodules[17]
• Oropharyngeal: streptococcal pharyngitis, infectious mononucleosis, diphtheria, peritonsillar abscess
• Typhoidal: typhoid fever, brucellosis, endocarditis, malaria, rickettsial diseases
• Oculoglandular: adenoviral conjunctivitis, chlamydial conjunctivitis, Parinaud oculoglandular syndrome (cat scratch disease)

• Prior tularemia episodes (cellular immunity is long-lasting; reinfection tends to be localized)[8]
• Immunocompromising conditions: HIV/AIDS, organ transplant, chemotherapy, chronic corticosteroid use — associated with more severe and atypical disease[6-7]
• Chronic lung disease (increases risk of severe pneumonic form)
• Renal impairment (affects aminoglycoside dosing)
• Prior tick-borne illness history
• Surgical history: prior lymph node excision or drainage

• Vitals: high fever (38–40°C), pulse-temperature dissociation (relative bradycardia) in up to 42%; tachypnea if pneumonic[2][8]
• Skin: look for a papule or ulcer with eschar at the inoculation site — may be on extremities (tick bite), hands/arms (animal handling), or healed/inconspicuous by presentation[4][12]
• Lymph nodes: tender, enlarged regional lymphadenopathy; may be suppurative or fluctuant; location correlates with inoculation site (inguinal/femoral for lower extremity tick bites, axillary for upper extremity contact)[12]
• Oropharynx: exudative pharyngitis/tonsillitis with cervical lymphadenopathy (oropharyngeal form)[7]
• Eyes: unilateral painful conjunctivitis with preauricular/cervical lymphadenopathy (oculoglandular form)[7]
• Lungs: may be clear or have crackles, decreased breath sounds, signs of pleural effusion (pneumonic form)
• Abdomen: hepatosplenomegaly possible in systemic disease
• Neurologic: confusion, stupor in typhoidal form[6]

• Serology (primary diagnostic method): microagglutination test for IgM/IgG — seroconversion typically occurs 2–3 weeks after symptom onset; paired acute and convalescent sera (2–3 weeks apart) are ideal; a 4-fold rise in titer or seroconversion confirms diagnosis[4][6-7]
• Culture: optimal but challenging; requires cysteine-enriched media (chocolate agar, cysteine heart agar); blood cultures often negative; MUST alert the laboratory if tularemia is suspected due to biosafety risk[4][7][18]
• PCR: useful for rapid detection from ulcer swabs, lymph node aspirates, respiratory specimens, blood; more sensitive than culture for skin/lymph node specimens[6]
• CBC: often nonspecific; may show leukocytosis or normal WBC
• CMP: mild hepatitis (elevated transaminases) is common[8]
• Inflammatory markers: elevated ESR, CRP
• Blood cultures: low yield but should be obtained in systemic/severe disease[6]

• Chest X-ray: first-line for pneumonic symptoms; findings are nonspecific — infiltrates, hilar lymphadenopathy, pleural effusion[18]
• Chest CT: more sensitive; typical findings include mediastinal lymphadenopathy, pulmonary nodules, subpleural round consolidations, and pleural effusion[17][19]
• PET/CT: can show intensely hypermetabolic lesions mimicking malignancy — important pitfall[17]
• Ultrasound: useful for evaluating suppurative lymph nodes and guiding aspiration
• Imaging is unnecessary for uncomplicated ulceroglandular/glandular disease without respiratory symptoms

• Direct immunofluorescence assay (DFA): can be performed on tissue specimens[7]
• Immunohistochemical staining: useful on biopsy specimens[7]
• MALDI-TOF mass spectrometry: can identify F. tularensis from culture isolates[6]
• CT-guided biopsy: may show necrotizing granulomatous inflammation — nonspecific, can mimic TB or malignancy[16-17]
• Lymph node aspiration/biopsy: for suppurative nodes; send for culture, PCR, and histopathology
• No validated clinical scoring system specific to tularemia; diagnosis relies on clinical suspicion + exposure history + laboratory confirmation

• ECG is not routinely indicated for tularemia
• Cardiac involvement is very rare: anecdotal reports of pericarditis (usually with concomitant pneumonia), extremely rare myocarditis, and a single reported case of endocarditis[14][20-21]
• Consider ECG if substernal chest pain, dyspnea, or signs of myocarditis/pericarditis are present
• Monitor for QTc prolongation if using fluoroquinolones

Six clinical forms based on route of inoculation

Export Form Frequency Key Features Ulceroglandular ~37% (most common) Skin ulcer + regional lymphadenopathy Glandular ~25% Lymphadenopathy without visible ulcer Pneumonic ~12% Cough, dyspnea, infiltrates — highest mortality Typhoidal ~10% Systemic illness, no localizing signs — high mortality Oculoglandular ~3% Painful conjunctivitis + preauricular nodes Oropharyngeal ~2% Pharyngitis/tonsillitis + cervical nodes

• (Frequencies from Missouri surveillance data)[3]
• Severity stratification: Type A strains (North America) are more virulent than type B (holarctica); subtype A1b carries the highest case fatality (~24%).[6] Overall US case fatality with treatment is approximately 2.3%.[10] Lymph node suppuration occurs in ~30% and may require surgical drainage.[6][9] Delayed diagnosis (>2–3 weeks) significantly worsens prognosis.[9]

• Initial stabilization: IV access, fluid resuscitation, antipyretics for severe/systemic disease.
• Antimicrobial therapy (per 2025 CDC recommendations and IDSA guidelines):[4][11]
• Severe disease (pneumonic, typhoidal, septic, or acutely ill):
• Gentamicin 5 mg/kg/day IV (traditional dosing: 1.5 mg/kg q8h) or streptomycin 15 mg/kg q12h IM
• Duration: 10–14 days
• Step-down to oral fluoroquinolone or doxycycline once clinically improved

Mild-moderate disease (ulceroglandular, glandular)

• Ciprofloxacin 500–750 mg PO BID or levofloxacin 500 mg PO daily
• OR doxycycline 100 mg PO BID
• Duration: 14–21 days (minimum 14 days to reduce relapse risk)
• Postexposure prophylaxis: doxycycline 100 mg PO BID or ciprofloxacin 500 mg PO BID for 14 days[11][18]
• Surgical intervention: drainage or excision of suppurative lymph nodes when antibiotics alone are insufficient — especially common in delayed presentations[9]
• Key pearl: F. tularensis is resistant to beta-lactams. If a patient with an ulcer and lymphadenopathy fails empiric beta-lactam therapy, tularemia should be strongly considered.[4][9]

Admit for

• Pneumonic or typhoidal tularemia
• Sepsis or hemodynamic instability
• Need for IV aminoglycoside therapy
• Significant comorbidities or immunocompromise
• Inability to tolerate oral medications
• Diagnostic uncertainty with concerning features

Discharge with outpatient management for

• Mild ulceroglandular or glandular disease in immunocompetent patients
• Able to tolerate oral antibiotics (fluoroquinolone or doxycycline)
• Reliable follow-up ensured
• Observation: consider for moderate illness pending culture/serology results and clinical trajectory
• Consult infectious disease for: atypical presentations, treatment failure, immunocompromised patients, suspected bioterrorism exposure, or need for surgical management of suppurative nodes[11]
• Notify public health: tularemia is a nationally notifiable disease — report to local/state health department[15]
• Standard precautions are adequate; no person-to-person transmission[2][18]

• Follow-up: within 1 week of ED discharge to assess clinical response; repeat at 2–3 weeks for convalescent serology[7]
• Relapse monitoring: treatment failures and relapses occur in 5–15% of cases depending on antibiotic class; higher with doxycycline and with delayed treatment[6][9]
• Lymph node suppuration: may develop in ~30% of patients weeks to months after initial treatment — may require surgical drainage[6][9]
• Return precautions — instruct patients to return immediately for:
• Worsening or recurrent fever after initial improvement
• New or worsening shortness of breath, chest pain, or cough
• Increasing size, redness, or drainage from lymph nodes
• Confusion, altered mental status, or severe headache
• Inability to tolerate oral medications
• Expected recovery: symptoms typically improve within 48–72 hours of appropriate antibiotic therapy; complete recovery may take weeks, and progressive weakness, malaise, and weight loss can persist.[2][19] Convalescence from untreated or delayed-treatment cases may last 3–12 months.[5]

1. Tularemia for Clinicians: An Up-to-Date Review on Epidemiology, Diagnosis, Prevention and Treatment. — Antonello RM, Giacomelli A, Riccardi N. European Journal of Internal Medicine. 2025.

2. Tularemia as a Biological Weapon: Medical and Public Health Management. — Dennis DT, Inglesby TV, Henderson DA, et al. The Journal of the American Medical Association. 2001.

3. Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases. — Weber IB, Turabelidze G, Patrick S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2012.

4. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America. — Stevens DL, Bisno AL, Chambers HF, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2014.

5. Multifaceted effects of F rancisella tularensis on human neutrophil function and lifespan. — Kinkead LC, Allen LA. Immunological Reviews. 2016.

6. Tularaemia: Clinical Aspects in Europe. — Maurin M, Gyuranecz M. The Lancet. Infectious Diseases. 2016.

7. Tickborne Diseases of the United States: A Reference Manual for Healthcare Providers Sixth Edition. — Nancy Shadick MD MPH, Nancy Maher MPH, Dennis Hoak MD United States Centers for Disease Control and Prevention (2022). 2022.

8. Tularemia: A 30-Year Experience With 88 Cases. — Evans ME, Gregory DW, Schaffner W, McGee ZA. Medicine. 1985.

9. Tularemia Treatment: Experimental and Clinical Data. — Maurin M, Pondérand L, Hennebique A, et al. Frontiers in Microbiology. 2023.

10. Tularemia Clinical Manifestations, Antimicrobial Treatment, and Outcomes: An Analysis of US Surveillance Data, 2006-2021. — Wu HJ, Bostic TD, Horiuchi K, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.

11. Tularemia Antimicrobial Treatment and Prophylaxis: CDC Recommendations for Naturally Acquired Infections and Bioterrorism Response - United States, 2025. — Nelson CA, Meaney-Delman D, Fleck-Derderian S, Winberg J, Mead PS. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2025.

12. Tick-Borne Diseases in the United States. — Spach DH, Liles WC, Campbell GL, et al. The New England Journal of Medicine. 1993.

13. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States. — Ho BM, Davis HE, Forrester JD, et al. Wilderness & Environmental Medicine. 2021.

14. Tularemia: An Experience of 13 Cases Including a Rare Myocarditis in a Referral Center in Eastern Switzerland (Central Europe) and a Review of the Literature. — Frischknecht M, Meier A, Mani B, et al. Infection. 2019.

15. Tularemia - United States, 2001-2010. — MMWR. Morbidity and Mortality Weekly Report. 2013.

16. A Clinical Pitfall in Caseating Necrotizing Granulomatous Lymphadenitis: Tularemia. — Özan Köse S, Erdem H, Köse ÖC, Yılmaz Ertürk F. Diagnostic Microbiology and Infectious Disease. 2025.

17. Pulmonary Tularemia: A Diagnosis Not to Overlook. — Zaghdoudi A, Robin F, Moulinie J, et al. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. 2026.

18. Clinical Management of Potential Bioterrorism-Related Conditions. — Adalja AA, Toner E, Inglesby TV. The New England Journal of Medicine. 2015.

19. Treatment Outcome of Severe Respiratory Type B Tularemia Using Fluoroquinolones. — Widerström M, Mörtberg S, Magnusson M, Fjällström P, Johansson AF. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024.

20. ACCF/­AHA/­CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force III: Prevention and Control of Cardiovascular Complications of Emerging Infectious Diseases and Potential Biological Terrorism Agents and Diseases. — Cooper LT, Mensah GA, Baddour LM, et al. Journal of the American College of Cardiology. 2007.

21. ACCF/­AHA/­CDC Conference Report on Emerging Infectious Diseases and Biological Terrorism Threats. Task Force I: Direct Cardiovascular Implications of Emerging Infectious Diseases and Biological Terrorism Threats. — Baddour LM, Zheng ZJ, Labarthe DR, O'Connor S. Journal of the American College of Cardiology. 2007.