Basics
Description
- Tularemia is an acute febrile illness caused by the small aerobic gram-negative pleomorphic intracellular coccobacillus Francisella tularensis:
- Organism is highly infectious.
- Person-to-person transmission has not been reported.
- Humans become infected through different environmental exposures:
- Bites from infected tick, deerfly, mosquito, or other infected insect
- Direct contact with infectious animal tissue or fluid
- Contact with or ingestion of contaminated food, water, or soil
- Inhalation of infected aerosols (e.g., cutting grass with power mowers, which may aerosolize the organism)
- The 4 major strains of the bacterium have different virulence and geographic location:
- 2 subspecies cause human infection in North America: F. tularensis subspecies tularensis (type A, more virulent) and F. tularensis subspecies holartica (type B, less virulent)
- Natural hosts:
- Lagomorphs and other rodents
- Found in species of wild animals (insects, rabbits, hares, ticks, flies, muskrats, beavers, mice), domestic animals (sheep, cattle, cats), ticks, and water and soil contaminated by infected animals
- Natural vectors:
- Ticks
- Biting flies
- Mosquitoes
- Wild rabbits
- Weaponization of tularemia was accomplished during the Cold War:
- Because of its virulence and ability to be aerosolized, it remains a potential biologic agent for mass destruction.
- Lab technicians handling culture specimens are at high risk:
- F. tularensis cultures should be manipulated only in a biosafety level 3 facility.
- Also known as "rabbit fever " or "deerfly fever "
Etiology
- Individuals who spend time outdoors in endemic areas are at higher risk:
- Farmers
- Hunters
- Forest workers
- Those who handle animal carcasses are at highest risk (taxidermists and butchers).
- Two-thirds of cases occur in males.
- Although tularemia can occur worldwide, it is endemic in the northern hemisphere:
- Reported nationwide except in Hawaii
- States with the highest incidence include Missouri, Arkansas, Kansas, South Dakota, and Oklahoma.
- Few hundred cases annually in US, although probably underreported
- Peak season is June " October.
- Mortality is 5 " 15%. Appropriately treated patients have mortality as low as 1%.
- 25% of cases occur in children 1 " 14 yr of age.
- Children who spend time outdoors in endemic rural areas are at highest risk.
Diagnosis
Signs and Symptoms
- Tularemia has different presentations based on route of entry:
- Primary route of entry is through skin; most often a cutaneous ulcer develops.
- Incubation is 3 " 5 days, range 1 " 14 days. Lesion usually begins as papule, often with fever.
- 6 forms of illness:
- Ulceroglandular:
- Most common presentation (70 " 80% of cases)
- Inoculated cutaneously (scratch, abrasion, insect bite) with as few as 50 organisms
- Initially, a local cutaneous papule at point of entry
- Followed by tender regional adenopathy and constitutional symptoms to include fever, chills, myalgias, and headaches
- Associated with pneumonia in 30% of cases
- Glandular:
- Rare form
- Gains access to lymphatic system or bloodstream through inapparent abrasion
- Tender regional lymphadenopathy with no local lesions
- Oculoglandular:
- Rare form
- Organism enters through a splash of infected blood/fluid to the eye or is introduced by eye rubbing after handling infectious materials (e.g., rabbit carcass).
- Edema, conjunctivitis, injection, chemosis with periauricular, submandibular, or cervical lymphadenopathy
- Pharyngeal:
- Rare form
- From ingestion of contaminated food or water
- Severe throat pain with exudative pharyngitis and regional lymphadenitis
- Pneumonic:
- Secondary to inhalation
- Seen in sheep shearers, farmers, landscapers, and lab technicians
- Fever, dry cough, and pleuritic chest pain develop.
- Pneumonia can occur in 30% of patients with ulceroglandular tularemia
- Typhoidal:
- Historically, the typhoidal form defined as devoid of skin or mucous membrane lesion or remarkable lymph node enlargement.
- No known point of entry (probably oral or respiratory).
- Only when no route of infection can be established may the term still be acceptable.
- In North America, where type A is prevalent, fulminant manifestations are reported, including severe sepsis, meningitis, endocarditis, hepatic failure, and renal failure.
- Septicemia associated with type A tularemia is usually extremely severe and potentially fatal. High fever, abdominal pain, and diarrhea may occur early in the course of disease.
History
- Exposure and epidemiologic risk factors can be helpful.
- Sudden fever, chills, headaches
- Progression of components of signs and symptoms may be useful in defining form of illness.
Physical Exam
- Fever
- Tender, well-demarcated cutaneous ulcer
- Tender regional lymphadenopathy; lymph nodes can develop fluctuance and spontaneously drain.
- Exudative pharyngitis (with pharyngeal tularemia)
- Ulcerations of the conjunctiva with pronounced chemosis (with oculoglandular tularemia)
Diagnosis Tests & Interpretation
Lab
- No rapid diagnostic test available
- Routine lab studies nonspecific:
- CBC can be normal.
- ESR might be slightly elevated.
- CSF: May have increased protein or mild pleocytosis
- LFTs are often abnormal.
- Gram stain, cultures, and tissue biopsies:
- Blood cultures usually negative because of specific growth requirements
- Enzyme-linked immunosorbent assay and polymerase chain reaction are available through reference labs.
- Serum antibody titers:
- Typically do not reach diagnostic levels until ≥10 days after the onset of illness
- A single titer of at least 1:160 for tube agglutination is diagnostic for F. tularensis infection.
- May not be elevated before day 11 of illness and generally are diagnostic after 16th day.
Imaging
- Chest radiograph for:
- Consolidative process, pleural effusions, and hilar adenopathy
- CT scan of chest for:
- Severe pulmonary symptoms
- Other possible etiologies of atypical pneumonia
Differential Diagnosis
- Ulceroglandular tularemia mimics include:
- Tuberculosis
- Catscratch disease
- Syphilis
- Chancroid
- Lymphogranuloma venereum
- Toxoplasmosis
- Sporotrichosis
- Rat-bite fever
- Anthrax
- Oculoglandular tularemia mimics include:
- Pharyngeal tularemia mimics include:
- Diphtheria
- Bacterial pharyngitis
- Infectious mononucleosis
- Adenoviral infection
- Typhoidal tularemia mimics include:
- Salmonellosis
- Brucellosis
- Legionnaire disease
- Q fever
- Malaria
- Disseminated fungal or mycobacterial infections
- Pulmonary tularemia mimics include:
- Mycoplasmal infection
- Legionnaire disease
- Chlamydial infection
- Tuberculosis
Treatment
Pre-Hospital
- Universal precautions
- Management of ABCs
- Treat dehydration/hypotension with boluses of normal saline.
Initial Stabilization/Therapy
- ABCs
- Supplemental oxygen for hypoxia
- Fluid resuscitation with normal saline for intravascular volume depletion or septic shock
- Central line access for unstable patients
- Vasopressors for persistent hypotension
Ed Treatment/Procedures
- Fever control with acetaminophen
- Early administration of antibiotic therapy after obtaining cultures
- Antibiotic options:
- 1st-line agents: Streptomycin or gentamicin continued for 10 days
- Ciprofloxacin if community-acquired pneumonia is in the differential diagnosis of patients ≥18 yr of age
- Tetracycline or doxycycline in those >8 yr of age; or chloramphenicol:
- Continue for 14 days, since these drugs are only bacteriostatic.
- Associated with a higher rate of treatment failures than the previously mentioned antibiotics
- 3rd tier of treatment, since they are static
- F. tularensis is resistant to ²-lactam drugs and carbapenems
Streptomycin and gentamicin are recommended as 1st-line agents.
Medication
First Line
- Gentamicin: 5 mg/kg IV or IM q24h (peds: 2.5 mg/kg IV or IM q8h) 10 days
- Streptomycin: 1 g IM (peds: 15 mg/kg, not to exceed 2 g/d) q12h 10 days
Second Line
- Ciprofloxacin: 400 mg IV q12h 10 days
- Doxycycline: 100 mg (peds: If weight ≥45 kg and child >8 yr, 100 mg; if weight ≤45 kg and child >8 yr, 2.2 mg/kg) IV q12h for at least 14 days (longer treatment needed since doxycycline is bacteriostatic); max. 200 mg/d
- Chloramphenicol is usually avoided due to the possibility of adverse reactions. However, chloramphenicol may be considered in cases of tularemic meningitis due to its ability to cross the blood " brain barrier and reach higher concentrations in the CSF.
Follow-Up
Disposition
Admission Criteria
- ICU admission for advanced age, neutropenia, severe hypoxemia, hemodynamic instability, or patients presenting with typhoidal tularemia
- Inpatient floor bed admission for mild to moderate illness:
- Isolation bed required only for the purpose of ruling out other etiology (e.g., tuberculosis)
Discharge Criteria
Outpatient therapy: Oral or IM therapy for mild illness with close follow-up
Issues for Referral
Critical care and infectious disease consultation to assist in assessment of differential considerations and manage life-threatening complications
Followup Recommendations
Infectious disease consultation to manage ongoing treatment and reduce subsequent exposures
Pearls and Pitfalls
- Patients presenting with high fever and regional lymphadenopathy, especially if there is an ulcer or conjunctivitis, should have tularemia in the differential.
- Epidemiology may be useful in pointing to this diagnosis.
- Definitive diagnosis ultimately based upon serology, which usually isnt positive until >10 days of infection.
- Vaccine currently under review by FDA; not currently available in US
- Currently listed as category A (critical agent of concern) bioterrorism agent because of pathogenicity. It can be disseminated via dispersal in food, water, or air.
Additional Reading
- American Academy of Pediatrics. Red Book 2012 Report of the Committee on Infectious Diseases. Elk Grove, IL: AAP; 2012.
- Centers for Disease Control and Prevention. Available at www.cdc.gov/tularemia. Accessed on January 2011.
- Hofinger DM, Cardona L, Mertz GJ, et al. Tularemic meningitis in the United States. Arch Neurol. 2009;66(4):523 " 527.
- Snowden J, Stovall S. Tularemia: Retrospective review of 10 years ' experience in Arkansas. Clinical Pediatrics. 2011;50(1):64 " 68.
- Treat JR, Hess SD, McGowan KL, et al. Ulceroglandular tularemia. Pediatr Dermatol. 2011;28(3):318 " 320.
- World Health Organization Guidelines on Tularemia, 2007.
Codes
ICD9
- 021.0 Ulceroglandular tularemia
- 021.3 Oculoglandular tularemia
- 021.9 Unspecified tularemia
- 021.2 Pulmonary tularemia
- 021.1 Enteric tularemia
- 021.8 Other specified tularemia
- 021 Tularemia
ICD10
- A21.0 Ulceroglandular tularemia
- A21.1 Oculoglandular tularemia
- A21.9 Tularemia, unspecified
- A21.2 Pulmonary tularemia
- A21.3 Gastrointestinal tularemia
- A21.7 Generalized tularemia
- A21.8 Other forms of tularemia
- A21 Tularemia
SNOMED
- 19265001 Tularemia (disorder)
- 37722001 Ulceroglandular tularemia (disorder)
- 73363000 Oculoglandular tularemia (disorder)
- 45556008 Pulmonary tularemia
- 34023009 Generalized tularemia (disorder)
- 398599000 Enteric tularemia