Tularemia (Francisella tularensis)

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Chapter 198 Tularemia (Francisella tularensis)

Gordon E. Schutze, Richard F. Jacobs

Tularemia is a zoonotic infection caused by the gram-negative bacterium Francisella tularensis. Tularemia is primarily a disease of wild animals; human disease is incidental and usually results from contact with blood-sucking insects or live or dead wild animals. The illness caused by F. tularensis is manifested by different clinical syndromes, the most common of which consists of an ulcerative lesion at the site of inoculation with regional lymphadenopathy or lymphadenitis. It is also a potential agent of bioterrorism (Chapter 704).

Etiology

F. tularensis, the causative agent of tularemia, is a small, nonmotile, pleomorphic, gram-negative coccobacillus that can be classified into 4 main subspecies (F. tularensis tularensis [type A], F. tularensis holarctica [type B], F. tularensis mediasiatica, and F. tularensis novicida). Type A can be further subdivided into 4 distinct genotypes (A1a, A1b, A2a, A2b) with A1b appearing to produce more serious disease in humans. Type A is found exclusively in North America and is associated with wild rabbits, ticks, and tabanid flies (e.g., deer flies), whereas type B may be found in North America, Europe, and Asia and is associated with semiaquatic rodents, hares, mosquitoes, ticks, tabanid flies, water (e.g., ponds, rivers), and marine animals. Human infections with type B are usually milder and have lower mortality rates compared to infections with type A.

Epidemiology

During 1990-2000, a total of 1,368 cases of tularemia were reported in the USA from 44 states, averaging 124 cases (range 86-193) per year (Fig. 198-1). Four states accounted for 56% of all reported tularemia cases: Arkansas, 315 cases (23%); Missouri, 265 cases (19%); South Dakota, 96 cases (7%); and Oklahoma, 90 cases (7%).

Figure 198-1 Reported cases of tularemia in the USA from 1990-2000, based on 1,347 patients reporting county of residence in the continental USA. Alaska reported 10 cases in 4 counties during 1990-2000. The circle size is proportional to the number of cases, ranging from 1 to 39 cases.

(From the Centers for Disease Control and Prevention: Tularemia—United States, 1990-2000, MMWR Morb Mortal Wkly Rep 51:181–184, 2002.)

Transmission

Of all the zoonotic diseases, tularemia is unusual because of the different modes of transmission of disease. A large number of animals serve as a reservoir for this organism, which can penetrate both intact skin and mucous membranes. Transmission can occur through the bite of infected ticks or other biting insects, by contact with infected animals or their carcasses, by consumption of contaminated foods or water, or through inhalation, as might occur in a laboratory setting. This organism is not, however, transmitted from person to person. In the USA, rabbits and ticks are the principal reservoirs. Most disease due to rabbit exposure occurs in the winter, and disease due to tick exposure occurs in the warmer months (April-September). Amblyomma americanum (Lone Star tick), Dermacentor variabilis (dog tick), and Dermacentor andersoni (wood tick) are the most common tick vectors. These ticks usually feed on infected small rodents and later feed on humans. Taking that blood meal through a fecally contaminated field transmits the infection.

Pathogenesis

The most common portal of entry for human infection is through the skin or mucous membrane. This may occur through the bite of an infected insect or by way of unapparent abrasions. Inhalation or ingestion of F. tularensis can also result in infection. Usually >10⁸ organisms are required to produce infection if they are ingested, but as few as 10 organisms may cause disease if they are inhaled or injected into the skin. Within 48-72 hr after injection into the skin, an erythematous, tender, or pruritic papule may appear at the portal of entry. This papule may enlarge and form an ulcer with a black base, followed by regional lymphadenopathy. Once F. tularensis reaches the lymph nodes, the organism may multiply and form granulomas. Bacteremia may also be present, and although any organ of the body may be involved, the reticuloendothelial system is the most commonly affected.

Conjunctival inoculation may result in infection of the eye with preauricular lymphadenopathy. Inhalation, aerosolization, or hematogenous spread of the organisms can result in pneumonia. Chest roentgenograms of such patients may reveal patchy infiltrates rather than areas of consolidation. Pleural effusions may also be present and may contain blood. In pulmonary infections, mediastinal adenopathy may be present; in oropharyngeal disease, patients may develop cervical lymphadenopathy. Typhoidal tularemia may be used to describe severe bacteremic disease, regardless of the mode of transmission or portal of entry.

Infection with tularemia stimulates the host to produce antibodies. This antibody response, however, has only a minor role in fighting this infection. The body is dependent on cell-mediated immunity to contain and eradicate this infection. Infection is usually followed by specific protection; thus, chronic infection or reinfection is unlikely.

Clinical Manifestations

Although it may vary, the average incubation period from infection until clinical symptoms appear is 3 days (range, 1-21 days). A sudden onset of fever with other associated symptoms is common (Table 198-1

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