Tularemia

Abstract

Francisella tularensis is the etiological agent of tularemia, a serious and occasionally fatal disease of humans and animals. In humans, ulceroglandular tularemia is the most common form of the disease and is usually a consequence of a bite from an arthropod vector which has previously fed on an infected animal. The pneumonic form of the disease occurs rarely but is the likely form of the disease should this bacterium be used as a bioterrorism agent. The diagnosis of disease is not straightforward. F. tularensis is difficult to culture, and the handling of this bacterium poses a significant risk of infection to laboratory personnel. Enzyme-linked immunosorbent assay- and PCR-based methods have been used to detect bacteria in clinical samples, but these methods have not been adequately evaluated for the diagnosis of pneumonic tularemia. Little is known about the virulence mechanisms of F. tularensis, though there is a large body of evidence indicating that it is an intracellular pathogen, surviving mainly in macrophages. An unlicensed live attenuated vaccine is available, which does appear to offer protection against ulceroglandular and pneumonic tularemia. Although an improved vaccine against tularemia is highly desirable, attempts to devise such a vaccine have been limited by the inability to construct defined allelic replacement mutants and by the lack of information on the mechanisms of virulence of F. tularensis. In the absence of a licensed vaccine, aminoglycoside antibiotics play a key role in the prevention and treatment of tularemia.

FIG. 1.

World map showing areas where F. tularensis is endemic (shaded).

FIG. 2.

Evolutionary distance tree, based on 16S rDNA sequences, showing the relationship of F. tularensis with other putative members of the Francisellaceae and with other closely related members of the γ subclass of the Proteobacteria. Agrobacterium tumefaciens was included as an outgroup. Reproduced from Forsman et al. (50) with the kind permission of the International Union of Microbiological Societies.

FIG. 3.

Preliminary annotation of the F. tularensis strain Schu S4 genome sequence; comparison of the number of F. tularensis genes in 15 functional categories (solid bars). The mean number of genes in these categories in 20 other bacterial species is shown as open bars, with error bars indicating the lowest and highest numbers of genes in each category. Reproduced from Prior et al. (138) with the kind permission of Blackwell Scientific Limited.

FIG. 4.

Enlarged lymph node in a tularemia patient.