For Clinicians

Tularemia is caused by infection with the bacteria Francisella tularensis. Naturally occurring F. tularensis infections have been reported from all states except Hawaii. Transmission routes are multiple and include tick bite, deer fly bite, inhalation, ingestion, and skin contact with infected animals. In addition, people could be exposed as a result of bioterrorism.

Ticks that transmit F. tularensis bacteria to humans include the dog tick (Dermacentor variabilis), Rocky Mountain wood tick (D. andersoni), and lone star tick (Amblyomma americanum). Disease presentation depends on how the bacteria enter the body.

Tularemia is an uncommon disease with approximately 250 cases reported to CDC each year.

Note: F. tularensis is NOT transmitted by the same ticks that transmit Borrelia burgdorferi, the agent of Lyme disease.

Incubation Period

3–5 days (range 1–21 days)

Generalized Signs and Symptoms

  • Fever, chills
  • Headache
  • Malaise, fatigue
  • Anorexia
  • Myalgia
  • Chest discomfort, cough
  • Sore throat
  • Vomiting, diarrhea
  • Abdominal pain

Specific Presentations

The clinical presentation of tularemia will depend on the route of inoculation and other factors.

(Ulcero) Glandular: Usually occurs following a tick or deer fly bite or after handling an infected animal.

  • Localized lymphadenopathy
  • Cutaneous ulcer at infection site (not always present)

Oculoglandular: Occurs when the bacteria enter through the eye, for example if infected animal fluids splash into the eye during butchering.

  • Photophobia
  • Excessive lacrimation
  • Conjunctivitis
  • Preauricular, submandibular and cervical lymphadenopathy

Oropharyngeal: Occurs after eating or drinking contaminated food or water.

  • Severe throat pain
  • Exudative pharyngitis or tonsillitis
  • Cervical, preparotid, and/or retropharyngeal lymphadenopathy

Pneumonic: Occurs after breathing dusts or aerosols containing the bacteria or secondary to other untreated forms of tularemia.

  • Non-productive cough
  • Substernal tightness
  • Pleuritic chest pain
  • Hilar adenopathy, infiltrate, or pleural effusion may be present on chest X-ray

Typhoidal:

  • Characterized by any combination of the general symptoms (without localizing symptoms of other specific presentations)

Laboratory Diagnosis

Confirmatory and supportive results for all recommended diagnostic tests for F. tularensis infection are listed below. Physicians who suspect tularemia should alert the laboratory to the possible need for special diagnostic and safety procedures.

Confirmatory

  • Isolation of F. tularensis from a clinical specimen; appropriate specimens include swabs or scrapings of ulcers, lymph node aspirates or biopsies, pharyngeal swabs, or respiratory specimens (e.g. pleural fluid), depending on the form of illness. Blood cultures may often be negative.  The laboratory should be alerted if F. tularensis is suspected so cultures can be incubated for extended periods, due to the fastidious, slow-growing nature of the bacterium.
  • Seroconversion from negative to positive IgM and/or IgG antibodies in paired sera. Ideally, the first serum sample would be collected during the acute phase of illness (within first week of onset) and the second serum sample would be collected 2-3 weeks later.

Supportive

  • Detection of F. tularensis in a clinical specimen by direct immunofluorescence assay (DFA), immunohistochemical staining, or polymerase chain reaction (PCR) assay.
  • Detection of antibodies to F. tularensis through a single serologic test. Ideally, serum would be collected at least 14 days after illness onset to ensure sufficient time for development and detection of an antibody response.

Note: Tularemia is rare; positive serologic tests should be interpreted in the context of a compatible clinical illness and exposure. The validity of a positive test result depends on the probability that a person has the disease (positive predictive value) and the sensitivity and specificity of the diagnostic test.

Diagnostic Considerations

What is the timing of the IgM and IgG antibody response to F. tularensis infection?

  • Antibodies are often not detectable until 2-3 weeks after symptom onset.
  • A rise in IgM and IgG antibodies may occur concurrently.
  • Once increased, both IgM and IgG antibodies may remain detectable for several years following resolution of disease.
  • Note: some serologic tests detect total antibody levels and do not distinguish between IgM and IgG.

What are the clinical implications?  

  • A negative serologic test soon after illness onset does not exclude the diagnosis of tularemia. A second test obtained several weeks later is needed to confirm or exclude the diagnosis.
  • Patients with acute illness should be managed based on clinical suspicion.
  • Serology is not useful for proving that a patient has been cured of tularemia.

Do serologic cross-reactions occur on F. tularensis antibody testing?

  • False-positive results may occur in patients previously or currently infected with Brucella. Other less frequent causes of cross-reactivity that have been reported include prior infection with Yersinia or Salmonella species.

When is it useful to repeat serologic testing for F. tularensis?

  • Repeat testing may be useful if testing was performed early after illness onset—before detectable levels of antibodies developed. In this case, it can be useful to document seroconversion. If seroconversion did not occur, it is possible that another condition may be responsible for the patient’s illness.
  • Repeat testing may also be useful if an initial test result falls in the equivocal or borderline range. This result may occur when testing is performed on a serum sample drawn too soon after illness onset or alternatively, may be due to a false positive. If the test result does not change with repeat testing, it is possible another condition may be responsible for the current symptoms.

Treatment

These regimens may need to be adjusted depending on a person’s age, medical history, underlying health conditions, pregnancy status, or allergies. Consult an infectious disease specialist regarding individual patient treatment decisions.

Tularemia treatment regimen
Age Category Drug Dosage Maximum Duration (Days)
Adults Streptomycin 1 g IM twice daily 2 g per day Minimum 10
Gentamicin* 5 mg/kg IM or IV daily (with desired peak serum levels of at least 5 mcg/mL) Monitor serum drug levels Minimum 10
Ciprofloxacin* 400 mg IV or 500 mg PO twice daily N/A 10–14
Doxycycline 100 mg IV or PO twice daily N/A 14–21
Children Streptomycin 15 mg/kg IM twice daily 2 g per day Minimum 10
Gentamicin* 2.5 mg/kg IM or IV 3 times daily** Monitor serum drug levels and consult a pediatric infectious disease specialist Minimum 10
Ciprofloxacin* 15 mg/kg IV or PO twice daily 800 mg per day 10
* Not a U.S. FDA-approved use, but has been used successfully to treat patients with tularemia.
** Once-daily dosing could be considered in consultation with a pediatric infectious disease specialist and a pharmacist

NOTE: Gentamicin or streptomycin is preferred for treatment of severe tularemia. Doses of both streptomycin and gentamicin should be adjusted for renal insufficiency.
NOTE: Chloramphenicol may be added to streptomycin to treat meningitis.

Infection control and environmental decontamination

  • Isolation is not recommended for tularemia patients, given the lack of person-to-person transmission. In hospitals, standard precautions are recommended.
  • Laboratory personnel should be alerted when tularemia is suspected. Standard diagnostic procedures with clinical materials can be performed in biosafety level 2 conditions. All work with suspect cultures of tularensis should be performed in a biological safety cabinet. Manipulation of cultures and other procedures that might produce aerosols or droplets (e.g., grinding, centrifuging, or vigorous shaking) should be conducted under biosafety level 3 conditions.
  • Bodies of patients who die of tularemia should be handled using standard precautions. Autopsy procedures likely to produce aerosols or droplets should be avoided.
  • Clothing or linens contaminated with body fluids of patients with tularemia should be disinfected per standard hospital procedure.

Vaccination

  • Vaccination for tularemia is not generally available in the United States, nor is it useful in management of ill patients.

References

Centers for Disease Control and Prevention. Tularemia—United States, 2001-2010MMWR 62(47): 963–966.

Dennis D, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health managementexternal iconJAMA 2001. 285(21): 2763–2773.

Dietrich EA and Petersen JM: Francisella.  In: Carroll KC, Pfaller MA, Landry ML, et al, eds. Manual of Clinical Microbiology. 12th ed. ASM Press; 2019.

Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak of primary pneumonic tularemia on Martha’s Vineyardexternal iconNEJM 2001; 345: 1601–1606.

Johansson A, Berglund L, Sjöstedt A, et al. Ciprofloxacin for treatment of tularemiaexternal iconClin Infect Dis 2001;33:267–8.

Maurin M. Francisella tularensis, tularemia and serological diagnosisexternal icon. Review Front Cell Infect Microbiol. 2020 Oct 26;10:512090.

Nigrovic LE, Wingerter SL. Tularemiaexternal icon. Infect Dis Clin North Am. 2008;22(3):489-504.

Penn RL. Francisella tularensis (Tularemia). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA:Elsevier/Saunders; 2015. p. 2590–2602.

Tarnvik A. WHO Guidelines on tularaemia pdf icon[PDF – 125 pages]external icon. Vol. WHO/CDS/EPR/2007.7. Geneva: World Health Organization, 2007.