Tularemia and Other Francisella Infections

Definition

Tularemia is an infectious zoonosis caused by Francisella tularensis , which is an aerobic, pleomorphic, gram-negative bacillus. Many animal species harbor this organism, most prominently rabbits, squirrels, and muskrats. Humans acquire the infection by various means, including direct contact with infected animal tissues, ingestion of contaminated water or meat, the bite of an infected tick or deer fly, or inhalation of aerosolized bacteria. F. tularensis is highly infectious and is a well-recognized risk to laboratory personnel who manipulate culture plates of the organism. Deer flies can transmit the infection from animals to humans, and colloquially the disease is often referred to as rabbit fever or deer fly fever .

Epidemiology

Tularemia has been reported in the United States, Canada, Mexico, Japan, and Europe. In Iran, seroprevalence ranges from 2 to 14%, with the highest rates in farmers. It has not been reported in the United Kingdom or the Southern Hemisphere. In the United States, reported cases declined from a high of 2291 cases in 1939 to fewer than 300 cases per year now ( E-Fig. 287-1 ). In the United States, the highest annual incidence rates are in Arkansas (3.1 per 100,000), South Dakota (1.9 per 100,000), and Nebraska (0.9 per 100,000).

In the United States, tularemia is usually acquired from tick bites or from contact with infected animals, especially rabbits. Tick-associated cases, which now constitute the most common route of transmission, primarily occur during the summer. The most common vectors in the United States are the wood tick ( Dermacentor andersoni ), the dog tick ( Dermacentor variabilis ), and the Lone Star tick ( Amblyomma americanum ). A smaller peak of autumn and winter cases is a consequence of rabbit hunters skinning and eviscerating their game. Public health education materials aimed at decreasing the hazards of handling wild animals have contributed to the reduction of tularemia in hunters. Mosquitoes are common vectors in Northern Europe. Occasionally infections occur following the bite of an infected animal or, more likely, from the bite of an animal whose mouth was contaminated from recently eating a diseased animal. The latter likely explains most instances of cat-bite tularemia. Contaminated fresh water is another source of infection.

Males experience a higher incidence of disease than females in all age groups, probably owing to greater exposure to the outdoors and animal-related activities. Persons in all age groups are affected, with children 5 to 14 years of age and older adults most prominently infected. In the United States, Native American and Alaska Natives experience the highest annual incidence (0.5 per 100,000); Whites have a lower risk (0.04 per 100,000), but Blacks and Asians/Pacific Islanders have the lowest risks (≤0.01 per 100,000).

Although tularemia is usually a sporadic infection, outbreaks of disease have been traced to laboratory exposure, contaminated groundwater, muskrat handling, dressing a dead hare, lawn mowing, and brush cutting. In the latter two cases, pneumonic tularemia occurred following creation of an environmental aerosol of organic material that had been contaminated with F. tularensis excreted in the urine and feces of infected rodents. An outbreak of oropharyngeal tularemia in Turkey affecting 55 patients was ultimately traced to contaminated tap water. Epidemiologic evaluation following diagnosis of oropharyngeal tularemia in six grape harvesters identified inadvertent crushing of an infected rodent in the freshly pressed grape must with subsequent ingestion as the route of transmission. The organism can survive in water, mud, and straw for weeks to months. Human-to-human transmission has not been reported.

Tularemia’s high infectivity (as few as 10 organisms induces pneumonic disease), its ease of dissemination, and the difficulty of rapidly diagnosing acute illness are characteristics that make tularemia a Tier 1 bioterrorism agent ( Chapter 19 ). Infections must be reported immediately to local public health authorities to investigate both conventional and bioterrorist sources.

Pathobiology

F. tularensis can infect humans through several portals of entry, including the skin, the mucous membranes, and the gastrointestinal and respiratory tracts. The organism persists intracellularly and can multiply within macrophages and other cells. After inoculation into the skin and subcutaneous tissue, local bacterial multiplication evokes a suppurative necrotic reaction, which is characterized by an initial polymorphonuclear response followed by an influx of macrophages and lymphocytes. These suppurative lesions evolve into granulomas. Bacteremia can occur both early and late during this process. The infection can disseminate to the lymph nodes, liver, spleen, lungs, and pleura. Viable F. tularensis can persist in tissues for long periods, thereby contributing to the tendency to relapse after treatment.

Clinical Manifestations

Classically, the clinical manifestations of tularemia have been separated into six categories: ulceroglandular, glandular, oculoglandular, typhoidal, oropharyngeal, and pneumonic. However, many patients have features of several types. The course of illness is determined by the portal of entry, the degree of systemic involvement, and the dose and virulence of the infecting strain of F. tularensis .

The general features of tularemia are similar regardless of the portal of entry. After exposure, the usual incubation period is 3 to 5 days (range, 1 to 21 days). The disease begins abruptly with the onset of fever (≥101° F), chills, malaise, and headache. Myalgia, vomiting, sore throat, and abdominal pain can also occur. Almost 50% of patients have a pulse rate that is substantially slower than would be anticipated based on the degree of fever (pulse-temperature dissociation). The fever may abate somewhat after 1 to 3 days, only to recur and continue, accompanied by other symptoms, for 2 to 3 weeks. Lymphadenopathy, usually cervical, is nearly always noted. Untreated, weight loss, easy fatigability, and lymphadenopathy may persist for weeks longer.