Tularemia is a febrile disease caused by Francisella tularensis; it may resemble typhoid fever. Symptoms are a primary local ulcerative lesion, regional lymphadenopathy, profound systemic symptoms, and, occasionally, atypical pneumonia. Diagnosis is primarily epidemiologic and clinical and supported by serologic tests. Treatment is with streptomycin, gentamicin, chloramphenicol, or doxycycline.

There are 7 clinical syndromes associated with tularemia (see Table 2: Gram-Negative Bacilli: Types of Tularemia*. The causative organism, F. tularensis, is a small, pleomorphic, nonmotile, nonsporulating aerobic bacillus that enters the body by

• Ingestion of contaminated food or water
• Bite of an infected arthropod vector (ticks, deer flies, fleas)
• Inhalation
• Direct contact with infected tissues or material

Table 2
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Types of Tularemia* Type Frequency Comment Ulceroglandular Most common Primary lesions on the hands or fingers with regional lymphadenitis Typhoidal Common Systemic illness without indication of the site of inoculation or localized infection Oculoglandular Uncommon Inflammation of ipsilateral lymph nodes, probably caused by inoculation of an eye from an infected finger or hand Glandular Rare Regional lymphadenitis but no primary lesion and often cervical adenopathy, suggesting oral ingestion of bacteria Pneumonic Uncommon Infiltrates with asymmetric hilar adenopathy, with or without bloody pleural effusion Oropharyngeal Rare Sore throat and cervical adenopathy due to ingestion of contaminated food or water Septicemic Rare Systemic illness with hypotension, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation, and multiorgan dysfunction *Tularemic pneumonia may be primary or may complicate any form of tularemia.

The organism can penetrate apparently unbroken skin but may actually enter through microlesions.

There are 2 types of F. tularensis: type A and type B. Type A, a more virulent serotype for humans, usually occurs in rabbits and rodents in the US and Canada. Type B usually causes a mild ulceroglandular infection and occurs in water and aquatic animals in Europe and Asia.

Hunters, butchers, farmers, and fur handlers are most commonly infected. In winter months, most cases result from contact (especially during skinning) with infected wild rabbits. In summer months, infection usually follows handling of other infected animals or birds or bites of infected ticks or other arthropods. Rarely, cases result from eating undercooked infected meat, drinking contaminated water, or mowing fields in endemic areas. In the Western states, ticks, deer flies, horse flies, and direct contact with infected animals are other sources of infection. Human-to-human transmission has not been reported. Laboratory workers are at particular risk because infection is readily acquired during normal handling of infected specimens. Tularemia is considered a possible agent of bioterrorism.

In disseminated cases, characteristic focal necrotic lesions in various stages of evolution are scattered throughout the body. They are 1 mm to 8 cm and whitish yellow; they are seen externally as the primary lesions on the fingers, eyes, or mouth and commonly occur in lymph nodes, spleen, liver, kidneys, and lungs. In pneumonia, necrotic foci occur in the lungs. Although severe systemic toxicity may occur, no toxins have been demonstrated.

Symptoms and Signs

Onset occurs suddenly, 1 to 10 (usually 2 to 4) days after exposure, with headache, chills, nausea, vomiting, fever of 39.5° to 40° C, and severe prostration. Extreme weakness, recurring chills, and drenching sweats develop. Clinical manifestations depend to some extent on the type of exposure (see Table 2: Gram-Negative Bacilli: Types of Tularemia*).

Tularemia

Within 24 to 48 h, an inflamed papule appears at the site of exposure (finger, arm, eye, roof of the mouth), except in glandular or typhoidal tularemia. The papule rapidly becomes pustular and ulcerates, producing a clean ulcer crater with a scanty, thin, colorless exudate. Ulcers are usually single on the extremities but multiple in the mouth or eyes. Usually, only one eye is affected. Regional lymph nodes enlarge and may suppurate and drain profusely. A typhoid-like state frequently develops by the 5th day, and the patient may develop atypical pneumonia, sometimes accompanied by delirium.

Pneumonic tularemia can occur after inhalation or by hematogenous spread from another type of tularemia; it develops in 10 to 15% of ulceroglandular tularemia cases and in about 50% of typhoidal tularemia cases. Although signs of consolidation are frequently present, reduced breath sounds and occasional rales may be the only physical findings in tularemic pneumonia. A dry, nonproductive cough is associated with a retrosternal burning sensation. A nonspecific roseola-like rash may appear at any stage of the disease. Splenomegaly and perisplenitis may occur. In untreated cases, temperature remains elevated for 3 to 4 wk and resolves gradually. Mediastinitis, lung abscess, and meningitis are rare complications.

Mortality is almost nil in treated cases and about 6% in untreated cases of ulceroglandular tularemia. Mortality rates are higher for type A infection and for typhoidal, septicemic, and pneumonic tularemia; they are as high as 33% for untreated cases. Death usually results from overwhelming infection, pneumonia, meningitis, or peritonitis. Relapses can occur in inadequately treated cases. One attack confers immunity.

Diagnosis

• Cultures
• Acute and convalescent serologic testing

Diagnosis is suspected based on a history of contact with rabbits or wild rodents or exposure to arthropod vectors, the sudden onset of symptoms, and the characteristic primary lesion.

Patients should have cultures of blood and relevant clinical material (eg, sputum, lesions); routine cultures may be negative, and the laboratory should be notified that tularemia is suspected so that appropriate media can be used (and appropriate safety precautions ensured). Acute and convalescent antibody titers should be done 2 wk apart. A 4-fold rise or a single titer > 1:128 is diagnostic. The serum of patients with brucellosis may cross-react to F. tularensis antigens but usually in much lower titers. Fluorescent antibody staining is used by some laboratories. Leukocytosis is common, but the WBC count may be normal with an increase only in the proportion of PMNs.

Because this organism is highly infectious, samples and culture media suspected of tularemia should be handled with extreme caution and, if possible, processed by a high-level biosafety containment-equipped laboratory with a level 3 rating.

Treatment

• StreptomycinSome Trade Names
  No US trade name
  Click for Drug Monograph
  (plus chloramphenicolSome Trade Names
  CHLOROMYCETIN
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  for meningitis)

The preferred drug is streptomycinSome Trade Names
No US trade name
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7.5 to 10 mg/kg (up to 1 g) IM q 12 h for 7 to 14 days or, if in a bioterrorism setting, 15 mg/kg IM q 12 h. For children, the streptomycinSome Trade Names
No US trade name
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dose is 10 to 15 mg/kg IM q 12 h. ChloramphenicolSome Trade Names
CHLOROMYCETIN
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12.5 to 25 mg/kg IV q 6 h is added if there is evidence of meningitis.

Alternatives to streptomycinSome Trade Names
No US trade name
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include gentamicinSome Trade Names
GARAMYCIN
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1 to 2 mg/kg IM or IV q 8 h, doxycyclineSome Trade Names
PERIOSTAT
VIBRAMYCIN
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100 mg po q 12 h, chloramphenicolSome Trade Names
CHLOROMYCETIN
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12.5 to 25 mg/kg IV q 6 h (oral form not available in US), and ciprofloxacinSome Trade Names
CILOXAN
CIPRO
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500 mg po q 12 h. However, relapses occasionally occur with these drugs, and they may not prevent node suppuration.

Continuous wet saline dressings are beneficial for primary skin lesions and may diminish the severity of lymphangitis and lymphadenitis. Surgical drainage of large abscesses is rarely necessary unless therapy is delayed. In ocular tularemia, applying warm saline compresses and using dark glasses give some relief. In severe cases, 2% homatropineSome Trade Names
ISOPTO
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1 to 2 drops q 4 h may relieve symptoms. Intense headache usually responds to oral opioids (eg, oxycodoneSome Trade Names
OXYCONTIN
OXYIR
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or hydrocodone with acetaminophenSome Trade Names
GENAPAP
TYLENOL
VALORIN
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).

Prevention

When entering endemic areas, people should use tick-proof clothing and repellents. A thorough search for ticks should be done after leaving tick-infested areas. Ticks should be removed at once (see Sidebar 1: Rickettsiae and Related Organisms: Tick Bite Prevention). When handling rabbits and rodents, especially in endemic areas, people should wear protective clothing, including rubber gloves and face masks, because organisms may be present in the animal and in tick feces on the animal's fur. Wild birds and game must be thoroughly cooked before eating. Water that may be contaminated must be disinfected before use.

No vaccine is currently available. Antibiotic prophylaxis with 14 days of oral doxycyclineSome Trade Names
PERIOSTAT
VIBRAMYCIN
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or ciprofloxacinSome Trade Names
CILOXAN
CIPRO
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is recommended after high-risk exposure (eg, a laboratory accident).

Last full review/revision August 2009 by Burke A. Cunha, MD

Content last modified February 2012