Tularemia

Caused by the highly infectious, aerobic, gram-negative coccobacillus Francisella tularensis, of which there are 3 subspecies. It is a category A biodefense agent because of its prior weaponization during the Cold War and its potential use as an inhalational agent of bioterror.

It is spread by ticks (dog tick Dermacentor variabilis, wood tick D andersoni, and Lone Star tick Amblyomma americanum), biting deer flies, or direct contact with infected animals by inhalation or exposure via a break in the skin or mucous membrane. Contact with animal skin (e.g., skinning or dressing carcasses) of rabbits, mice, voles, squirrels, or beavers can cause direct cutaneous inoculation. Inhalational tularemic pneumonia may occur in people who do yard work in areas inhabited by infected animals.[2][5][6] [10]

In the first few days of infection, intracellular multiplication of the bacteria at the site of inoculation leads to a painful papule. This is followed by lymphangitic spread leading to localized lymphadenopathy of the draining nodes, often accompanied by a transient bacteremia. Caseating granulomas may be seen at sites of infection. The bacterium contains endotoxin, and endotoxic shock can be one presentation of the infection.[1] The incubation period is 3 to 5 days (range 1 to 21 days).[1]

Clinical classification

Seven distinct clinical syndromes exist, depending on subspecies of Francisella tularensis and the site of bacterial entry.[1]

Ulceroglandular tularemia:

Most common presentation (30%-40% of cases)[2]
Usually reported following an animal or a tick bite, or after handling animals
Presents with unilateral and localized tender lymphadenopathy
The ulcer site where the organism was inoculated (by a tick or fly bite, or by direct contact with an infected animal) is 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 but without a visible skin lesion
Thought to spread via the bloodstream and lymphatic system.

Pneumonic tularemia:

Due to inhalation of airborne bacteria
Presents with nonproductive cough, dyspnea, chest tightness, rales, and pleurisy
Chest x-ray can show lobar or subsegmental infiltrates; can be accompanied by exudative pleural effusions.[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, 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
Cerebrospinal fluid shows predominant mononuclear cells with elevated protein and low glucose.[9][12]

All forms of tularemia are also accompanied by systemic symptoms (e.g., chills, headache, malaise/fatigue, myalgia, anorexia, abdominal pain, vomiting, fever).[1]

Pathophysiology

Classification

Clinical classification