Clinical Features

After an incubation period varying from 1-21 days (average 3-5 days), dependent upon the dose of organisms, onset is usually acute.

Tularemia typically appears in one of six forms in man depending upon the route of inoculation:

• Typhoidal
• Ulceroglandular
• Glandular
• Oculoglandular
• Oropharyngeal
• Pneumonic tularemia

In humans, as few as 10 to 50 organisms will cause disease if inhaled or injected intradermally. Approximately 108 organisms are required with oral infection.

Typhoidal tularemia (5-15% of naturally acquired cases) occurs mainly after inhalation of infectious aerosols, but can occur after intradermal or gastrointestinal contact. F. tularensis would be most likely delivered by aerosol in a bioterrorism attack and would primarily cause typhoidal tularemia.

Tularemia manifests as fever, prostration, and weight loss, but unlike most other forms of the disease, presents without glandular swelling. Pneumonia may be severe and rapid and can be associated with any form of tularemia (30% of ulceroglandular cases), but it is most common in typhoidal tularemia (80% of cases). Respiratory symptoms, chest pain and discomfort, a cough (productive and non-productive) may also be present.

Fatality rates following a bioterrorism attack may be greater than the 1-3% seen with appropriately treated natural disease. Fatality rates are about 35% in untreated, naturally acquired typhoidal cases.

Ulceroglandular tularemia (75-85% of cases) is most often acquired through inoculation of the skin or mucous membranes with blood or tissue fluids of infected animals. It is characterized by fever, chills, headache, malaise, an ulcerated skin lesion, and painful regional lymph glands. The skin lesion is usually located on the fingers or hand where contact occurs.

Glandular tularemia (5-10% of cases) results in fever and tender lymph glands but no skin ulcer.

Oculoglandular tularemia (1-2% of cases) occurs after inoculation of the conjunctivae by contaminated hands, splattering of infected tissue fluids, or by aerosols. Patients have unilateral, painful, purulent conjunctivitis with lymph gland swelling. Swelling and the accumulation of fluid around the eyes and small nodular lesions or ulcerations of the eyelids are noted in some patients.

Oropharyngeal tularemia refers to primary ulceroglandular disease confined to the throat. It produces an acute inflammation of the throat with swollen lymph glands.

Pneumonic tularemia is a severe atypical pneumonia that may appear with rapid onset with a high rate of fatality if untreated. It can be primary following inhalation of organisms or secondary following contact with bodily fluids. It is seen in 30-80% of the typhoidal cases and in 10-1% of the ulceroglandular cases.

The case fatality rate without treatment is approximately 5% for the ulceroglandular form and 35% for the typhoidal form. All ages are susceptible, and recovery is generally followed by permanent immunity.

Diagnosis

A clue to the diagnosis of tularemia subsequent to a bioterrorism attack with F. tularensis might be a large number of patients, within a short period of time, appearing with similar illnesses and a non-productive pneumonia.

The clinical presentation of tularemia may be severe, yet non-specific. Differential diagnoses include typhoidal syndromes (e.g., salmonella, rickettsia, malaria) or pneumonic processes (e.g., plague, mycoplasma, SEB).

Radiological evidence of pneumonia or glandular swelling is most common with typhoidal disease. In general, chest x-rays show that approximately 50% of patients have pneumonia, and fewer than 1% have glandular disease. Fluid build-up in the lungs is seen in 15% of patients with pneumonia.

Most diagnoses of tularemia are made from blood serum testing. Antibodies to F. tularensis appear within the first week of infection but levels adequate to allow diagnosis do not appear until more than 2 weeks after infection.

Medical Management

Since there is no known human-to-human transmission, isolation and quarantine are not necessary. Standard Precautions are appropriate for care of patients with draining lesions or pneumonia and for the disinfecting of soiled clothing, bedding, equipment, etc. Heat and disinfectants easily inactivate the organism.

Appropriate therapy includes one of the following antibiotics:

• Gentamicin 3 - 5 mg/kg IV daily for 10 to 14 days.
• Ciprofloxacin 400 mg IV every 12 hours, switch to oral ciprofloxacin (500 mg every 12 hours) after the patient is clinically improved; continue for completion of a 10- to 14-day course of therapy
• Ciprofloxacin 750 mg orally every 12 hours for 10 to 14 days
• Streptomycin 7.5 - 10 mg/kg IM every 12 hours for 10 to 14 days

Streptomycin has historically been the drug of choice for tularemia; however, since it may not be readily available immediately after a large-scale bioterrorism attack, gentamicin and other alternative drugs should be considered.

Another concern is that a fully virulent streptomycin-resistant strain of F. tularensis was developed during the 1950s and it is presumed that other countries have obtained it. The strain was sensitive to gentamicin. Gentamicin offers the advantage of providing broader coverage and may be useful when the diagnosis of tularemia is considered but in doubt.

Tetracycline and chloramphenicol are also effective antibiotics; however, they are associated with significant relapse rates.

Preventative Measures

none

Pre-exposure Prevention

Antibiotics given for anthrax or plague (ciprofloxacin, doxycycline) may provide protection against tularemia.

A 2-week course of antibiotics is effective as post-exposure prevention when given within 24 hours of aerosol exposure from a bioterrorism attack, using one of the following regimens:

• Ciprofloxacin 500 mg orally every 12 hours for 2 weeks
• Doxycycline 100 mg orally every 12 hours for 2 weeks
• Tetracycline 500 mg orally every 6 hours for 2 weeks

ChemoPrevention is not recommended following potential natural exposures tick bite, rabbit or other animal exposures.