Approach

Diagnosis requires a high index of suspicion as the clinical presentation (except for ulceroglandular disease) is relatively nonspecific and the disease itself is rare. Culture, polymerase chain reaction (PCR), and serologic testing are all helpful in making a laboratory diagnosis. Tularemia is a reportable disease in the US.

Clinical presentation

Tularemia is most common in children, although it can occur in all ages.[13]​ It is more common in spring and summer, as it is often a tick-borne disease, and this is when tick exposure is at its peak.[1]​ Infection occurs predominantly in the northern hemisphere.

Patients may present with a history of tick bite, fly bite, or direct contact with infected animals or animal skins. A history of yard work or lawn mowing in areas where infected animals live may also be noted.[16]

Clinical presentation depends on many factors including the subspecies of Francisella tularensis and the route of inoculation.[1]​​ All forms of tularemia are accompanied by systemic symptoms, including chills, headache, malaise/fatigue, myalgia, anorexia, abdominal pain, and vomiting. Fever, with a pulse-temperature deficit, is seen in one half of cases, remitting only after several days and with a high chance of relapse.[1]​​​​

Additional, more specific signs and symptoms will also be seen, depending on the type of tularemia.[1]​​

Ulceroglandular tularemia:

  • The most common presentation, usually reported after handling animals, or after an animal or tick bite

  • Presents with unilateral and localized tender lymphadenopathy

  • A painful ulcer where the organism was inoculated (by a tick or fly bite, or by direct contact with an infected animal) is found distal to the draining lymph nodes that are enlarged, and starts as a painful papule before ulcerating.[2]​​[3]​​[4]​​[5]​​[6]​​

Glandular tularemia:

  • As for ulceroglandular tularemia, except without a visible skin lesion

  • Is thought to spread via the bloodstream and lymphatic system.

Pneumonic tularemia:

  • Spreads by airborne route

  • Presents with nonproductive cough, dyspnea, chest tightness, rales on auscultation, and pleurisy.​[4][7]​​​​[8]​​[9]​​[10]​​[11]​​

Pharyngeal tularemia:

  • Can occur after ingestion of contaminated meat or water

  • Presents with sore throat and exudative pharyngitis or tonsillitis

  • May be accompanied by regional lymphadenopathy.

Oculoglandular tularemia:

  • Unilateral conjunctivitis secondary to direct inoculation into the eye (e.g., from a contaminated finger)

  • Often accompanied by photophobia, vision impairment/loss, and submandibular, cervical, or preauricular lymphadenopathy.

Typhoidal tularemia:

  • Possibly due to septic spread of organism

  • Without skin lesions or lymphadenopathy but with diarrhea

  • Can be accompanied by jaundice and cholestasis, and with hepatosplenomegaly in chronic presentations.

Tularemic meningitis or brain abscess:

  • Rare presentation of tularemia, with symptoms of acute headache, stiff neck, and Kernig and Brudzinski signs.[12][9]​​

Laboratory investigations

CBC, electrolytes, LFTs, and blood culture should be evaluated in patients with suspected tularemia. Hyponatremia, leukocytosis, thrombocytopenia, elevated LFTs, elevated creatine kinase, myoglobinuria, and elevated erythrocyte sedimentation rate may be suggestive of tularemia; however, the absence of any of these does not exclude the diagnosis.[15]

Serologic testing using enzyme immunoassay (EIA) or immunofluorescence assay (IFA) is diagnostic for tularemia. The clinical microbiology laboratory should be notified if tularemia is suspected, so that proper precautions can be taken. A 4-fold rise in titer of antibodies against Francisella tularensis between acute and convalescence serums is considered diagnostic. This diagnostic increase in antibody titer usually occurs 2 to 3 weeks after onset of symptoms.[15]​ A single elevated serum antibody titer is supportive of the diagnosis; however, a single antibody titer should be confirmed by serologic tests or isolation of the organism from a clinical specimen.​[19]

Blood culture, specimen cultures, and PCR for F tularensis should be ordered on clinical presentation. Culture is optimal for diagnosis, but can be challenging as F tularensis is slow growing.[15]​ Although modern blood cultures (nonradiometric) detect bacteria, this is an insensitive test, as bacteremia is only transient.[1]​ PCR on swab of ulcer or lymph node aspirate seems to be a more sensitive test, although experience in its use is limited.[1]​​F tularensis may also be cultured from clinical specimens (e.g., lymph node aspirate, ulcer scraping, pharyngeal swab, or respiratory specimens, depending on the type of illness) using special media.[15]​ Culture must be performed under biosafety level 3 conditions because of infection risk to laboratory personnel.

Chest x-ray is ordered in suspected cases of pneumonic tularemia (indicated by respiratory signs and symptoms) and can show lobar or subsegmental infiltrates or exudative pleural effusions.​​[4][7]​​[8]​​[9]​​[10]​​[11] Infiltrates may be present in typhoidal tularemia in the absence of respiratory symptoms.​[15]

Cerebrospinal fluid shows predominant mononuclear cells with elevated protein and low glucose in patients with tularemic meningitis.[9][12]​​ Lumbar puncture is required only for patients who present with signs and symptoms of meningitis.

Histopathology should be ordered after initial tests; however, it is limited by the fact that caseating granulomas are not specific for tularemia, as they can be seen with other infectious and inflammatory conditions. Despite this, it is useful to exclude other infectious and inflammatory conditions.

Current methods of antigen testing in urine have proved insensitive for the detection of F tularensis, and further investigations are needed in establishing it as a diagnostic tool.

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