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    Topic review


    Subjects: Pathology
    View times: 16
    Submitted by: Zakaria Abdellahoum


    Francisella tularensis (Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic agents of tularemia: Ft subsp. tularensis (Ftt) and Ft subsp. holarctica (Fth), mainly distributed in North America and the whole northern hemisphere, respectively.

    1. Historical Background of Francisella tularensis and Tularemia

    Ft (originally named Bacterium tularense) was first isolated in 1911 by McCoy and Chapin in Tulare County (CA, USA), during an investigation of a epizootic pseudoplague in ground squirrels[1][2]. This bacterium was isolated from humans in 1912 by Werry and Lamb from a patient suffering from deer fly fever[3]. In 1921, Francis proposed the name tularemia for the disease caused by Ft[4]. In 1924, Parker and Spencer isolated the bacterium from the tick species Dermacentor andersoni and demonstrated this arthropod species’ role as an Ft vector[5]. The genus name Francisella and species name tularensis were proposed in 1947 to honor Edward Francis[6].

    2. Francisella tularensis

    Ft is a Gram-negative, coccobacillus shaped, facultative intracellular bacteria. This species includes four subspecies distinguishable by their geographical distribution[7][8]. The most virulent subspecies are Ftt (type A) and Fth (type B), representing the etiological agents of tularemia[9][10]. The third subspecies, mediasiatica, has never been associated with human infections[11][12]. Finally, Ft subsp. novicida (Ftn) living in aquatic biotopes generally affects immunocompromised people and is used as a laboratory model due to its low virulence[13][14].

    Ft was classified by the CDC in 2002 as a biological weapon category A[15] because of its high virulence and the possibility of inducing fatal pneumonia by aerosol diffusion[16]. Indeed, 10 CFU of this bacterium can cause infection in humans[15]. No tularemia vaccine is currently authorized for human use. In the past, tularemia vaccines were mainly developed to protect human populations from Ft as a biological weapon. The live vaccine strain (LVS) of Ft has been extensively used for this purpose but then abandoned because of significant side effects and low efficacy in preventing type A tularemia[10].

    Ft is a zoonotic agent with a large animal reservoir (mammals, fish, amphibians, birds, reptiles). Lagomorphs (wild hares and rabbits) and small rodents (mice, voles, gerbils, lemmings, coypu, etc.) are the primary sources of human infections[3][10]. Humans can be infected through different ways, such as direct contact with infected animals, inhalation of contaminated dust, ingestion of contaminated food, contact with or ingestion of contaminated water, and arthropod bites (mainly the ticks Ixodidae)[17].

    3. Tularemia Geographical Distribution

    Tularemia is mainly distributed in the Northern Hemisphere of the globe[18]. In Europe, Scandinavia (Sweden and Finland) is a primary endemic area, followed by the Balkans, particularly Kosovo[19][20]. Hungary and the European part of Turkey (Thrace) also record high incidences, followed by Slovakia, the Czech Republic, Serbia, Bulgaria, Norway, Germany, Spain, Poland, Georgia, and France[6][20][21][22]. In Asia, Russia, China, Japan, Kazakhstan, and Turkmenistan are endemic areas of tularemia. Northern America is also an endemic area for tularemia (mainly Ftt), with Canada and the United States recording several human infections every year and occasional outbreaks. In the United States, most human tularemia cases are reported in central states, Arkansas, Oklahoma, South Dakota, Kansas, and Missouri[20]. The subspecies holarctica has recently been detected in southern Australia, causing human infections after bites from possums[23]. Tularemia is classically absent in the United Kingdom, Iceland, Africa, South America, and Antarctica[20].

    4. Tularemia, the Disease

    Tularemia usually manifests in humans by a flu-like syndrome occurring on average 3 to 5 days after infection, with a maximum incubation period of two weeks[6][10][24]. Then, the disease classically progresses to one of the six clinical forms (sometimes combined), depending on the route of contamination. The ulceroglandular form manifests by a skin lesion at the inoculation site of bacteria and regional lymphadenopathy. The glandular form manifests by regional lymphadenopathy without skin lesions. The oculoglandular form corresponds to the bacterium inoculation through the conjunctiva. It corresponds to conjunctivitis with satellite lymphadenopathy. The oropharyngeal form occurs after oral contamination. It corresponds to pharyngitis with submandibular or cervical lymphadenopathy. The pneumonic form is triggered by the bacteria’s inhalation and corresponds to acute, subacute, or even chronic pneumonia. Finally, the typhoidal form manifests by severe sepsis usually associated with neurological signs (confusion) and Ft bacteremia. These two last systemic infections are the most severe forms of tularemia[10].

    The entry is from 10.3390/microorganisms9010026


    1. McCoy, G.W. A plague-like disease of rodents. Public Health Bull. 1911, 45, 53–71.
    2. McCoy, G.W.; Chapin, C.W. Further observations on a plague-like disease of rodents with a preliminary note on the causative agent, Bacterium Tularense. J. Infect. Dis. 1912, 10, 61–72.
    3. Sjostedt, A. Tularemia: History, epidemiology, pathogen physiology, and clinical manifestations. Ann. N. Y. Acad. Sci. 2007, 1105, 1–29.
    4. Francis, E. The occurrence of tularemia in nature as a disease of man. Public Health Rep. 1921, 36, 1731–1738.
    5. Green, R.G. The occurrence of Bacterium tularense in the eastern wood tick Dermacentor variabilis. Am. J. Epidemiol. 1931, 14, 600–613.
    6. Gürcan, S. Epidemiology of tularemia. Balkan. Med. J. 2014, 31, 3–10.
    7. Sjöstedt, A.B.; Brenner, D.J.; Krieg, N.R.; Staley, J.T.; Garrity, G.M. Family XVII. Francisellaceae, genus I. Francisella. In Bergey’s Manual of Systematic Bacteriology; Springer: Berlin/Heidelberg, Germany, 2005; pp. 200–210.
    8. Petersen, J.M.; Mead, P.S.; Schriefer, M.E. Francisella tularensis: An arthropod-borne pathogen. Vet. Res. 2009, 40, 7.
    9. Keim, P.; Johansson, A.; Wagner, D.M. Molecular epidemiology, evolution, and ecology of Francisella. Ann. N.Y. Acad. Sci. 2007, 1105, 30–66.
    10. Maurin, M.; Gyuranecz, M. Tularaemia: Clinical aspects in Europe. Lancet Infect. Dis. 2016, 16, 113–124.
    11. Olsufjev, N.G.; Meshcheryakova, I.S. Infraspecific taxonomy of tularemia agent Francisella tularensis McCoy et Chapin. J. Hyg. Epidemiol. Microbiol. Immunol. 1982, 26, 291–299.
    12. Petersen, J.M.; Schriefer, M.E. Tularemia: Emergence/re-emergence. Vet. Res. 2005, 36, 455–467.
    13. Hollis, D.G.; Weaver, R.E.; Steigerwalt, A.G.; Wenger, J.D.; Moss, C.W.; Brenner, D.J. Francisella philomiragia comb. nov. (formerly Yersinia philomiragia) and Francisella tularensis biogroup novicida (formerly Francisella novicida) associated with human disease. J. Clin. Microbiol. 1989, 27, 1601–1608.
    14. Triebenbach, A.N.; Vogl, S.J.; Lotspeich-Cole, L.; Sikes, D.S.; Happ, G.M.; Hueffer, K. Detection of Francisella tularensis in Alaskan mosquitoes (Diptera: Culicidae) and assessment of a laboratory model for transmission. J. Med. Entomol. 2010, 47, 639–648.
    15. Dennis, D.T.; Inglesby, T.V.; Henderson, A.; Bartlett, J.G.; Ascher, M.S.; Eitzen, E.; Fine, A.D.; Friedlander, A.M.; Hauer, J.; Layton, M.; et al. Tularemia as a biological weapon: Medical and public health management. JAMA 2001, 285, 2763–2773.
    16. Darling, R.G.; Catlett, C.L.; Huebner, K.D.; Jarrett, D.G. Threats in bioterrorism. I: CDC category a agents. Emerg. Med. Clin. N. Am. 2002, 20, 273–309.
    17. Hennebique, A.; Boisset, S.; Maurin, M. Tularemia as a waterborne disease: A review. Emerg. Microbes. Infect. 2019, 8, 1027–1042.
    18. Whipp, M.J.; Davis, J.M.; Lum, G.; De Boer, J.; Zhou, Y.; Bearden, S.W.; Petersen, J.M.; Chu, M.C.; Hogg, G. Characterization of a novicida-like subspecies of Francisella tularensis isolated in Australia. J. Med. Microbiol. 2003, 52, 839–842.
    19. Grunow, R.; Kalaveshi, A.; Kuhn, A.; Mulliqi-Osmani, G.; Ramadani, N. Surveillance of tularaemia in Kosovo, 2001 to 2010. Euro. Surveill. 2012, 17, 20217.
    20. Ulu-Kilic, A.; Doganay, M. An overview: Tularemia and travel medicine. Travel. Med. Infect. Dis. 2014, 12, 609–616.
    21. Gürcan, Ş. Epidemiology of Francisella tularensis and tularemia disease. In Proceedings of the XXXV. Turkish Microbiology Congress, Kuşadası-Aydın, Turkey, 3 November 2012.
    22. Zargar, A.; Maurin, M.; Mostafavi, E. Tularemia, a re-emerging infectious disease in Iran and neighboring countries. Epidemiol. Health 2015, 37, e2015011.
    23. Mia D. Champion; Qiandong Zeng; Eli B. Nix; Francis E. Nano; Paul Keim; Chinnappa D. Kodira; Mark Borowsky; Sarah Young; Michael Koehrsen; Reinhard Engels; et al. Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies. PLOS Pathogens 2009, 5, e1000459, 10.1371/journal.ppat.1000459.
    24. Matthew J. Hepburn; Andrew Jh Simpson; Tularemia: current diagnosis and treatment options. Expert Review of Anti-infective Therapy 2008, 6, 231-240, 10.1586/14787210.6.2.231.