American College of Physicians: Internal Medicine — Doctors for Adults ®



From the May ACP Observer, copyright 2004 by the American College of Physicians.

Tularemia is caused by Francisella tularensis, one of the most infectious pathogenic bacteria known. Inoculation with or inhalation of just 10 organisms can cause disease.

The microbe is an aerobic, gram-negative coccobacillus that can survive for weeks at low temperatures in water, moist soil, vegetation and decaying animal carcasses. Natural reservoirs of infection include rodents, squirrels, rabbits and hares.

Francisella tularensis

Tularemia cases have been reported in every state except Hawaii, with the majority occurring in south-central and western states. Most U.S. cases are reported between June and September, when arthropod-borne transmission is most common. Winter cases do occur, usually among hunters and trappers who handle infected animal carcasses.

Humans can also become infected through direct contact with or ingestion of contaminated food, water or soil, and by inhalation of infective aerosols. Person-to-person transmission does not occur. Natural cases of tularemia are relatively rare, with less than 200 cases reported every year in the United States.

Tularemia has several forms, depending on the exposure route. Most naturally-occurring cases are ulceroglandular, although oculoglandular, glandular, oropharyngeal, pneumonic, typhoidal or septic forms also occur.

While F. tularensis could be used in a number of ways as a bioweapon, an aerosol release is most likely. Airborne F. tularensis would be expected to principally cause pneumonic tularemia or oropharyngeal disease with cervical lymphadenitis.

Some aerosol exposures, however, might contaminate the eye (resulting in ocular tularemia) or penetrate broken skin, causing ulceroglandular or glandular disease. Pneumonic tularemia is rare, and you should suspect bioterrorism if you encounter the pneumonic form.

Clinical presentation and diagnosis

General symptoms of tularemia include abrupt onset of fever (38 C to 40 C; 100.4 F to 104 F), headache, chills, rigors, myalgias, coryza and sore throat. Nearly half of all patients demonstrate a pulse-temperature dissociation.

A dry or slightly productive cough and substernal chest pain are common, even in the absence of pneumonia. Nausea, vomiting and diarrhea sometimes occur.

With ulceroglandular tularemia, a papule appears at the inoculation site with the onset of generalized symptoms. It quickly becomes pustular, ulcerates and may develop an eschar. Regional lymphadenopathy also develops and may suppurate and rupture.

With oculoglandular tularemia, ulceration occurs on the conjunctiva, accompanied by chemosis, vasculitis and regional lymphadenitis. Glandular tularemia is typified by lymphadenopathy and generalized symptoms, without an ulcer.

With oropharyngeal tularemia, the patient may develop stomatitis, but exudative pharangitis or tonsillitis with ulceration is more common. Cervical or retropharyngeal lymphadenopathy may also occur.

The signs of pneumonic tularemia include one or more of the following: pharyngitis, bronchiolitis, pleuritis with adhesions and effusion, hemorrhagic inflammation of the airways, or hilar lymphadenitis.

In the clinical setting, the presence of nodular infiltrates with a pleural effusion suggests either tularemia or plague pneumonia. A substantial number of patients may have minimal or absent pulmonary signs, and generalized constitutional symptoms may predominate. Report any suspicion of pneumonic tularemia immediately to state or local public health officials.

Typhoidal tularemia is a systemic illness in the absence of signs that indicate either an inoculation site or anatomic localization of infection. Patients may also present with gastrointestinal manifestations, including abdominal pain and diarrhea.

Early symptoms of tularemia sepsis are nonspecific and include fever, abdominal pain, diarrhea and vomiting. Patients may progress to septic shock with complications of the systemic inflammatory response, including disseminated intravascular coagulation, adult respiratory distress syndrome and multiple organ failure.

The diagnosis of tularemia is supported when microscopic examination of respiratory secretions or blood reveals a characteristically small, pleomorphic and faint staining, gram-negative coccobacillus. It does not show the bipolar staining characteristic of Yersinia pestis, the agent of plague, and it is distinguishable from the large gram-positive rods characteristic of Bacillus anthracis.

Diagnosis of tularemia is usually confirmed by growth of F. tularensis on cysteine-enriched culture media at a biological safety level two or three facility, or by acute and convalescent serologic studies. Examination of cultures in which F. tularensis is suspected should be done in a biological safety cabinet.

Any testing that might produce aerosols or droplets should be conducted under biological safety level 3 conditions. Laboratory personnel should be alerted when tularemia is suspected.

Positive blood cultures are rare. Rapid diagnostic tests, such as polymerase chain reaction or fluorescent-labeled antibody assays, are not widely available. However, they can be performed in some research or reference laboratories on sputum, secretions, exudates or biopsy specimens. If alerted and prepared, laboratories can have test results available within several hours of receiving the specimens.

Differential diagnosis

Tularemia becomes more likely as a cause of pneumonia (as opposed to more common forms of pneumonia) if patients have a severe, atypical pneumonia with pleuritis, hilar lymphadenopathy and negative blood cultures that do not respond to beta-lactam antibiotics.

You should also suspect tularemia if there is a clustering of acute, severe respiratory illness in previously healthy persons. Tularemia would be expected to progress more slowly and cause fewer fatalities than either inhalation plague or anthrax.


The standard treatments for tularemia are streptomycin or gentamicin. Tetracycline and chloramphenicol are also effective.

Fluoroquinolones have been shown to be effective in vitro and in animal studies, but they are not approved by the FDA for treating tularemia. For more specific prescribing information, see "Tularemia: treatment and post-exposure prophylaxis."

Drug-resistant strains might be used in a bioterrorist attack. Consequently, you should conduct antimicrobial susceptibility testing of isolates and adjust your choice of antibiotic accordingly. The case fatality rate is 30% to 60% for untreated patients and less than 2% for those patients receiving treatment.

Post-exposure containment

The incubation period for tularemia ranges from one to 14 days. The recommended post-exposure prophylaxis is doxycycline or ciprofloxacin for 14 days.

Close contacts of patients with documented tularemia do not require prophylaxis, as person-to-person transmission has not been reported. You do not need to isolate patients with tularemia, although standard hospital precautions should be taken.

A live, attenuated vaccine derived from an avirulent strain is available as an investigational new drug. The vaccine has been used to protect laboratory workers who routinely handle the bacteria. Immunity develops over two weeks but does not completely protect against inhalational exposure, making the vaccine inappropriate for post-exposure prophylaxis.


Tularemia: treatment and post-exposure prophylaxis

This information is based upon the recommendations of the Center for Civilian Biodefense Studies, Johns Hopkins University Schools of Medicine.


Adults: preferred choices

  • Streptomycin 1 g IM BID x 10 days
  • Gentamicin 5 mg/kg IM or IV once daily x 10 days

Adults: alternative choices

  • Doxycycline 100 mg IV BID or 200 mg IV. once daily x 14-21 days
  • Ciprofloxacin 400 mg IV BID x 10 days
  • Chloramphenicol 15 mg/kg IV QID x 14-21 days

Children: preferred choices

  • Streptomycin 15 mg/kg IM BID, maximum dose 2 g x 10 days
  • Gentamicin 2.5 mg/kg IM or IV TID x 10 days

Children: alternative choices

  • Doxycycline: If greater than or equal to 45 kg, give adult dose. If < 45 kg, give 2.2 mg/kg IV BID (maximum dose 200 mg/day) x 14-21 days
  • Ciprofloxacin 15 mg/kg IV BID not to exceed 1g/d x 10 days
  • Chloramphenicol 25 mg/kg IV QID x 14-21 days

Pregnant women: preferred choice

  • Gentamicin 5 mg/kg IM or IV once daily x 10 days

Pregnant women: alternative choices

  • Doxycycline 100 mg IV BID x 14-21 days
  • Ciprofloxacin 400 mg IV BID x 10 days

Post-exposure prophylaxis for asymptomatic persons (during early incubation period)

  • Adults: oral doxycycline 100 mg BID x 14 days
  • Children: If greater than 45 kg, give adult oral doxycycline dosage. If less than 45 kg, give oral doxycycline 2.2 mg/kg BID x 14 days
  • Pregnant women: oral doxycycline 100 mg BID x 14 days OR ciprofloxacin 500 mg orally x 14 days.


This is a printer-friendly version of this page

Print this page  |  Close the preview




Internist Archives Quick Links

Not an ACP Member?

Join today and discover the benefits waiting for you.

Not an ACP Member? Join today and discover the benefits waiting for you

ACP offers different categories of membership depending on your career stage and professional status. View options, pricing and benefits.

A New Way to Ace the Boards!

A New Way to Ace the Boards!

Ensure you're board-exam ready with ACP's Board Prep Ace - a multifaceted, self-study program that prepares you to pass the ABIM Certification Exam in internal medicine. Learn more.