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Tularemia is a rare zoonotic disease caused by Francisella tularensis, a Gram-negative, non-motile, non-spore forming, facultative intracellular bacterium. The genus Francisella comprises seven species, and F. tularensis can be subdivided into four subspecies, F. tularensis (type A strains), F. holartica (type B strains), F. mediasiatica, and F. novicida. F. tularensis and F. holartica are the only two subspecies to cause tularemia worldwide.

Transmission occurs via ticks, deer flies, and, in some regions (e.g., Sweden and Finland), mosquitoes. Small mammals such as rabbits, hares, and muskrats act as reservoir hosts. Modes of transmission to humans are direct transmission from the animal reservoir, arthropod bites, and through contaminated water and soil. Infection in the US and Canada is mainly due to F. tularensis while in Europe and the rest of the northern hemisphere infection is caused by F. holartica.1–3 In the United States, most of the cases are found in the northwest, and parts of Massachusetts including Martha’s Vineyard. The first case of Tularemia-like disease was reported in Norway in 1653.1 In 2008–2018 the incidence of the disease in the United States per 100,000 residents was 0.07.1–3

Occupational risk includes veterinarians, butchers, farmers, and landscapers. The first human case was reported 2 years later from a butcher suffering lymphadenopathy and conjunctival ulcer in Ohio.1,2 One study determined the seroprevalence of Tularemia as 7.57% among farmers in Ilam Province, a region in western Iran.4 Another study identified 8.6% of landscapers as having antibodies to Tularemia compared to 1.0% of the general population.5 One study noted infection mainly through contact with rodents or game (21.4%), through tick bites (12.9%), and outdoor leisure activities (20.9%).6


Francisella is a small gram-negative pleomorphic coccobacillus that is catalase-positive and an intracellular pathogen (Figure 23-1). Tularemia virulence is due to its ability to invade macrophages and replicate intracellularly. The organism escapes the phagosomal compartment of the macrophage and multiplies in the cytosol. The bacterial lipopolysaccharide (LPS) does not trigger an inflammatory response in the macrophages, and thus reduces the host immune response.

Figure 23-1

Francisella tularensis via methylene-blue stain. (Courtesy of the CDC.

Clinical Manifestations

Incubation is 3–6 days. Initial symptoms include fever myalgia, headache, and/or cough and eventually develop maculopapular lesions. Temperature-pulse dissociation is common as is gastrointestinal or pulmonary involvement. There are six known syndromes: ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal. (Figures 23-2 and 23-3) Ulceroglandular syndrome involves formation of skin ulcer at the inoculation site with localized lymphadenopathy. Glandular is an isolated tender lymphadenopathy without skin manifestations. Oropharyngeal occurs when individuals ingest the bacteria causing pharyngitis, fever, and cervical lymphadenopathy.7 Oculoglandular occurs due to direct contact of contaminated hands, or via ...

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