Lymphoreticular and Hematopoetic Infections
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TULAREMIA

General Goal: To know the major cause of this disease, how it is transmitted, and the major manifestations of the disease.

Specific Educational Objectives: The student should be able to:

1. recite the most common cause of tularemia (shape and gram stain?).

2. describe the common means of transmission.

3. describe the major manifestations of this infection.

4. describe how you diagnose, treat and prevent this infection.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 3rd Edition. pp. 269-271.

Lecture: Dr. Neal R. Chamberlain

References:

OVERVIEW

Tularemia is a general name for several syndromes that are caused by the same organism, Francisella tularensis. The most common form of the disease is an indolent, febrile condition manifested by a skin ulcer and tender enlargement of regional lymph nodes. Another organism frequently mentioned as a biological weapon. Tularemia was was stockpiled by the US military in the late 1960's. All of our stockpiles were destroyed by 1973. The Soviet Union continued weapons production of antibiotic and vaccine resistant strains into the early 1990s.

Francisella tularensis is a hardy non-spore forming organism that is capable of surviving for weeks at low temperatures in water, moist soil, hay, straw or decaying animal carcasses.

ETIOLOGY

All forms of tularemia are caused by Francisella (formerly, Pasteurella) tularensis, a Gram-negative coccobacillus. Two basic types of the organism - Jellison Type A (highly virulent) and Type B (mild disease).

EPIDEMIOLOGY

Tularemia is a sporadic disease that occurs in areas of high endemicity. Since 1939, there has been a steady decline in the numbers of cases reported.

Worldwide, there are almost 500,000 cases/year. In the U.S. about 150-300 cases/year are seen.

Highest incidents:

In the Midwest: during the summer months when ticks are common.

East of the Mississippi: during the winter when cottontail rabbits are hunted.

Source:
Organisms are acquired from:

Handling infected tissue, body fluids or pelts of infected cottontail rabbits
Bites of the ticks and deer flies that parasitize these rabbits
Handling specimens or cultures in the clinical lab.

PATHOGENESIS Portals:

Skin:

F. tularensis, able to pass through unbroken skin.

Incubation period = 1-21 days

Skin papule (bump) formation at the site of entry.

Ulcer formation, accompanied by fever and lymphadenopathy.

Bacteremia, entrapment of organisms in the reticuloendothelial organs, where the organisms proliferate and induce abscesses and granulomata. Bacilli survive inside monocytes, which probably contribute to relapses.

Respiratory:

Organisms are inhaled. Multiple necrotizing granulomata that destroy alveolar septa and produce a bronchopneumonia, bronchitis, or tracheitis. Bacteremia can arise when alveolar macrophages enter the hilar lymphatics. Most likely disease resulting from biological weapon release.

Ingestion:

This route requires about 1 million bacilli. Pharyngitis and cervical lymphadenopathy.

Ocular:

Wiping the eye with contaminated hands leads to infection of the conjunctival sac and nearby lymphatic glands.

MANIFESTATIONS

Ulceroglandular tularemia.

Commonest form; 80% of cases. Incubation (48 h) following skin infection.

Papule: an erythematous, pruritic (itchy) bump forms at the site. The overlying skin becomes taut, thin, and shiny, but not fluctuant (movable and compressible).

Ulcer: after about 96 h, the enlarging papule ulcerates.

Fever: abrupt onset, often with rigors (shivering), continuous or mildly remittent, lasting up to a month in the absence of treatment.

Headache: occasionally with photophobia.

Lymphadenopathy: Regional lymph nodes often become enlarged and suppuration (pus) may develop.

Buboes (enlarged lymph nodes) can form in the inguinal or axial regions.

Hepatomegaly and splenomegaly: palpation causes pain.

Pneumonic tularemia.

The most serious form of tularemia and often a complication of the typhoidal and ulceroglandular forms.

Nonproductive cough

Substernal burning

A paucity of findings on physical examination

Patchy ill-defined infiltrates on radiographs

Rhonchi (a whistling from congested airways) may be the only physical sign.

Apprehension and toxicity are marked and shock is common.

Typhoidal tularemia.

Endotoxemia produced by the bacilli lysing in the blood

Continuous fever (without chills or sweats)

Myalgias (muscle pains)

Severe headaches

Hepatosplenomegaly

Oropharyngeal tularemia.

An acute exudative or membranous pharyngotonsillitis with cervical lymphadenopathy.

Oculoglandular tularemia.

Rarest form; 1% of cases. Pain, photophobia, intense ocular congestion, itching, lacrimation, edema of the ocular conjunctiva, mucopurulent discharge.

DIAGNOSIS

Acute febrile illness rarely a leukocytosis; usually leukocyte count is normal.

Sed rate and C-reactive protein is elevated.

Contact with rabbits, ticks, or other vectors is informative, but not required.

Smears of aspirates from enlarged lymph nodes usually contain the organisms.

Skin ulcers with enlarged regional lymph nodes accompanied by fever must be diagnosed as tularemia until proven otherwise.

Agglutination test: agglutinins appear 10-14 days after infection. Some cross reactivity with Brucella antigens.

The severe forms of tularemia (pneumonic and typhoidal) are more difficult to diagnose. Gram stain of sputum is unrewarding. An immunofluorescent reagent is available for use directly on smears. Culture of F. tularensis from sputum, bronchial or gastric washings, or blood is possible in guinea pigs or on glucose-cystine-blood agar containing cycloheximide and penicillin G to suppress normal flora, but is usually not done because of danger to lab personnel.

A skin test antigen is available that gives a positive reaction in 90% of patients within the first 7 days of the disease (Forshay's test).

THERAPY

Drug of choice: streptomycin; gentamycin is also effective.

Fever usually responds to antibiotic therapy in 24-36 hours.

Tetracycline and chloramphenicol are able to control the acute phases of tularemia, but relapses occur.

Without therapy, fatality rates are 5% (ulceroglandular) to 30% (pneumonic).

PREVENTION

Infection provides lifelong partial immunity.

An attenuated strain of F. tularensis is available as a vaccine for persons at risk.

Protection is complete against small inocula, and is superior to that provided by an earlier, killed vaccine. It is not recommended for use in post-exposure prophylaxis.

Protection depends on cellular immunity.

Wear protection to deal with wild animals.

Remove ticks promptly.