Microbiology and Epidemiology

Tularemia is the only disease caused by Francisella tularensis, a small, gram-negative, aerobic bacillus that is a potential agent of bioterrorism.

• Humans are infected incidentally through various exposure routes (i.e., via the skin, mouth, lungs, or eyes) by the bite of an insect (e.g., tick, deerfly), handling of infected wildlife (e.g., while hunting or skinning), consumption of undercooked infected meat, drinking of contaminated water, or inhalation of contaminated aerosols.
  • As few as ≤25 inhaled organisms can result in infection.
• A disproportionate number of U.S. cases occur in Arkansas, Kansas, Oklahoma, and Missouri.

Clinical Manifestations

After an incubation period of 3-7 days, tularemia generally starts with an acute onset of fever, chills, headache, fatigue, arthralgias, and myalgias. The ulceroglandular/glandular forms of tularemia are most common, but several other syndromes involving systemic manifestations can occur.

• Ulceroglandular/glandular tularemia: The hallmark of ulceroglandular tularemia is a small papule that evolves into an ulcer and is accompanied by painful regional lymphadenopathy.
  • Skin manifestations (e.g., erythema nodosum, papular/maculopapular rash) occur in 30% of cases.
  • Glandular tularemia presents with similar lymphadenopathy but lacks the ulcer.
  • If either syndrome is untreated for >2 weeks, the lymph nodes may suppurate.
• Oropharyngeal and oculoglandular tularemia: Oropharyngeal infection presents as fever, sore throat, marked cervical adenopathy (typically unilateral), and pharyngitis (which may be exudative or accompanied by a small ulcer). Oculoglandular tularemia is rare and results from touching of the conjunctival sac with contaminated fingers or possibly by exposure to infectious aerosols. Pts present with fever, unilateral conjunctivitis with mucopurulent discharge, eyelid swelling, and ulcers or pustules on the palpebral conjunctivae. Pts may have tender lymphadenopathy in the preauricular, submandibular, or cervical regions.
• Pneumonic tularemia: Primary pneumonic tularemia, the most severe form of the disease, is acquired via inhalation of F. tularensis. Pneumonic tularemia can also develop as a secondary complication of other clinical forms of tularemia.
  • Pts present with signs and symptoms similar to those of pneumonia of other etiologies (e.g., dry paroxysmal cough, dyspnea, pleuritic or retrosternal pain, CXR with lobar or multilobar infiltrates).
  • Exudative pleural effusions occur in 20-30% of cases.
• Typhoidal tularemia: This designation originally categorized pts with systemic infections where the portal of entry was unclear, particularly before the recognition of ingestion and inhalation as routes of exposure to F. tularensis. This term is outdated and rarely used.

Diagnosis

The diagnosis of tularemia requires a culture yielding F. tularensis or a rise in antibody titer between paired acute- and convalescent-phase sera.

• Serology is useful for diagnosing all clinical presentations of tularemia. However, it is of limited utility in acute illness, given that detectable antibody titers are not present for ∼10 days after illness onset.
• Clinical specimens for culture must be collected before antibiotic treatment. The sample type (e.g., respiratory secretions, pleural fluid, swabs of lesions, lymph node biopsies) depends on the disease presentation, although blood can be used in all clinical forms. The laboratory must be notified that tularemia is being considered as a diagnosis so that the exposure risk to laboratory staff is minimized.
• PCR and direct fluorescence assays are F. tularensis-specific assays that can be used to aid diagnosis.