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Tularemia


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										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*).
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 painSpecific Presentations
The clinical presentation of tularemia depends 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 when a person touches their eye after handling infectious material.
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.
Cough (dry or productive)
Substernal tightness
Pleuritic chest pain
Hilar adenopathy, infiltrate, or pleural effusion may be present on chest imaging**Typhoidal:**
Characterized by any combination of the general symptoms, without localizing symptoms of other specific presentationsLaboratory 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, sequence-based technologies, 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.**Notes**: ****
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.
Some commercial laboratories perform reflex testing to improve overall specificity. Check the commercial laboratory test directory website for information to ensure that all test results, including any reflex tests, have been reported.
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 by serologic testing can occur for many diseases, including tularemia. *F. tularensis*serologic tests can cross-react with antibodies to some other bacteria, including *Brucella***.****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 soon after illness onset, before the antibody response has fully developed. An equivocal or borderline serologic test result may also be due to cross-reactivity with a different pathogen. 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**
Gentamicin*
5 mg/kg IM or IV daily (with desired peak serum levels of at least 5 mcg/mL)
Monitor serum drug levels
10 – 14Ciprofloxacin*
400 mg IV or 500 mg PO twice daily
N/A
10 – 14Doxycycline
100 mg IV or PO twice daily
N/A
14 – 21**Children**
Gentamicin*
2.5 mg/kg IM or IV 3 times daily**
Monitor serum drug levels and consult a pediatric infectious disease specialist
10 – 14Ciprofloxacin*
15 mg/kg IV or PO twice daily
800 mg per day
10 – 14Doxycycline
2.2 mg/kg IV or PO twice daily
100 mg IV or PO twice daily
14 – 21* 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.Show More
Show More
**NOTE:**Gentamicin is preferred for treatment of severe tularemia. Dose should be adjusted for renal insufficiency.**NOTE:** For tularemia meningitis, combination therapy should be considered in consultation with an infectious disease specialist.
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 *F.* *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.Prophylaxis
Tularemia post-exposure prophylaxis is recommended in cases of laboratory exposure to infectious materials. Doxycycline (100 mg orally twice daily for 10 – 14 days) is generally recommended for prophylaxis in adults. Ciprofloxacin (500 mg orally twice daily for 10 – 14 days) may be an alternative for patients unable to take doxycycline.
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, 2001-2010. *MMWR* 62(47): 963–966.
Dennis D, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health management. *JAMA* 2001. 285(21): 2763–2773.
Petersen JM and Dietrich EA. Detection of *Francisella tularensis*Antibodies. In: Leber AL and Burnham CAB, eds. *Clinical Microbiology Procedures Handbook,*4th Edition. 2021. ASM Press, Washington DC.
Dietrich EA and Petersen JM: *Francisella.*  In: Carroll KC, Pfaller MA, Landry ML, et al, eds. *Manual of Clinical Microbiology*. 12th ed. 2019. ASM Press, Washington DC.
Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak of primary pneumonic tularemia on Martha’s Vineyard. *NEJM* 2001; 345: 1601–1606.
Johansson A, Berglund L, Sjöstedt A, et al. Ciprofloxacin for treatment of tularemia. *Clin Infect Dis* 2001;33:267–8.
Maurin M. *Francisella tularensis*, tularemia and serological diagnosis. *Review Front Cell Infect Microbiol*. 2020 Oct 26;10:512090.
Nigrovic LE, Wingerter SL. Tularemia. *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 – 125 pages]. Vol. WHO/CDS/EPR/2007.7. Geneva: World Health Organization, 2007.
							
					
						Page last reviewed:  July 5, 2022					Content source: 	Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD) Tularemia Home
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