Tularemia Workup

Updated: Feb 29, 2016
  • Author: Kerry O Cleveland, MD; Chief Editor: Burke A Cunha, MD  more...
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Workup

Approach Considerations

Consider tularemia in patients with fever and regional lymphadenopathy, particularly when an ulcer or conjunctivitis is present.

Routine laboratory testing is generally not helpful in tularemia, except to aid in excluding other diseases from the differential diagnoses. The following lab results may be seen in patients infected with F tularensis, but these are not specific to tularemia:

  • Serum transaminase levels are mildly elevated in about one half of patients
  • Urinalysis may show sterile pyuria in as many as one fourth of patients
  • The complete blood count (CBC) may reveal an elevated white blood cell (WBC) count in about one half of patients
  • Mild thrombocytopenia may be present
  • Hyponatremia is occasionally present
  • Elevation of creatine kinase values may be observed and is associated with rhabdomyolysis
  • Cerebrospinal fluid (CSF) may show hypoglycorrhachia, a mild elevation of protein concentration, and, almost always, a mononuclear cell pleocytosis

Updated (2014) guidelines on the diagnosis and treatment of tularemia have been published by the Infectious Diseases Society of America (IDSA) (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America). [54]

Indirect fluorescent antibody test

Indirect fluorescent antibody testing of suppurative material is rapid and specific. Microscopic examination of tissue and smear specimens is possible using fluorescently labeled antibodies at reference laboratories, possibly providing rapid confirmation of disease.

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Histology

Early tularemic lesions may demonstrate areas of focal necrosis surrounded by neutrophils and macrophages. Later, the necrotic areas become surrounded by epithelioid cells and lymphocytes. Caseating granulomata with or without multinucleated giant cells develops in some lesions.

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Serology

The diagnosis of tularemia is usually based on serology results. Tests vary from antibody detection (using latex agglutination or enzyme-linked immunosorbent assay [ELISA] testing) to the examination of a range of polymerase chain reaction (PCR) assay products. [2, 3, 4]

An agglutination titer greater than 1:160 is considered presumptively positive, and treatment may be started if this result is obtained.

A second titer, demonstrating a 4-fold increase after 2 weeks, confirms the diagnosis. Note that, although titers begin to rise within 7-10 days after exposure, early titers in the first 2 weeks of illness may be negative in the setting of infection. Detectable titers are identified in the second week of infection in more than 50% of cases.

Titers achieve maximum levels between 4-8 weeks and may remain elevated for years after infection, causing an uncertainty in individuals with a remote history of tularemia exposure.

Titers of 1:10-80 occur in 1% of the American population, especially in persons with long-term exposure to rabbits. Thus, an elevated titer in the absence of clinical tularemia does not establish a diagnosis. Moreover, tularemia serologic tests may cross-react with Salmonella, Brucella, Yersinia, Burkholderia, Pseudomonas, and Legionella species, as well as the Proteus strain OX19.

PCR assay

PCR assay tests may provide rapid and specific confirmation that tularemia is present, and may demonstrate the disease phase. [3] Real-time PCR assay for genetic typing of clinical and environmental isolates of F tularensis has been developed. [55, 56] A study on wound swabs from 40 patients with ulceroglandular tularemia found that PCR assay using 17-kDa primers was 75% sensitive, while culture was 62% sensitive. [57]

However, while PCR assay is very sensitive in artificial media, it is less sensitive when applied to biologic specimens, and false negatives may occur. Although it has been used to detect F tularensis after initiation of antibiotic therapy, it is not yet available in most laboratories.

Capture ELISA

Capture ELISA is an advancement based on monoclonal antibodies specific for lipopolysaccharide of the virulent forms of F tularensis. In animal studies, capture ELISA was more sensitive and specific than routine ELISA.

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Bacterial Culture

Although F tularensis has been cultured from sputum, pleural fluid, wounds, blood, lymph node biopsy samples, and gastric washings, the yield is extremely low and culturing poses a danger to laboratory personnel. The plates must be sealed and handled by a biosafety level-2 (BSL-2) facility, with further testing at a BSL-3 facility after a presumptive identification of F tularensis. [58]

Specimens should be maintained for at least 10 days because the slow growth of the culture may require 48-72 hours to be identified.

Blood cultures have poor sensitivity, which is probably due to the specific medium (cysteine-glucose-blood agar) needed to culture this organism.

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Imaging Studies

Chest Radiography

Chest radiography is indicated in any patient in whom the diagnosis of tularemia is suspected, to evaluate for pneumonia. As many as 30% of patients with tularemic pneumonia have no physical findings or respiratory tract symptoms.

Common findings in tularemia pneumonia include bilateral patchy infiltrates or lobar infiltrates (74%); cavitary lesions, which may be better visualized on chest computed tomography (CT) scans; hilar lymphadenopathy (32%); and a pleural effusion (30%).

The triad of oval opacities, hilar lymphadenopathy, and pleural effusion is more likely with tularemia than with other tick-borne diseases.

Ultrasonography

Ultrasonograms of infected lymph nodes may reveal findings suggestive of infection; however, these findings lack specificity.

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