Epidemiology, microbiology, and pathogenesis of tularemia
- Robert L Penn, MD
Robert L Penn, MD
- Professor of Medicine, Infectious Diseases Section
- Louisiana State University School of Medicine in Shreveport
- Overton Brooks VA Medical Center
- Section Editors
- Stephen B Calderwood, MD
Stephen B Calderwood, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine (Microbiology and Immunobiology)
- Harvard Medical School
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
Tularemia is the zoonotic infection caused by Francisella tularensis, an aerobic and fastidious gram-negative bacterium. Human infection occurs following contact with infected animals or invertebrate vectors. Synonyms include Francis' disease, deer-fly fever, rabbit fever, water-rat trappers' disease, wild hare disease (yato-byo), and Ohara's disease .
The epidemiology, microbiology, and pathogenesis of infection due to F. tularensis will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of tularemia are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of tularemia".)
Distribution — The majority of infections in humans and animals are caused by F. tularensis subspecies tularensis (the more virulent species) and F. tularensis subspecies holarctica. Human disease is rarely associated with the subspecies novicida and Francisella philomiragia [1,2].
In North America, F. tularensis has been described in the United States, Canada, and Mexico. In the United States, the majority of cases traditionally occur in the south-central states (figure 1) . As an example, over half of the reported cases in 2013 were in Arkansas, Missouri, Kansas, Nebraska, and Oklahoma (figure 2) . Over time, however, the southern border of tularemia in the United States has shifted northward . As an example, the number of reported cases in Colorado, Nebraska, South Dakota, and Wyoming dramatically increased in 2015 . This is consistent with the predicted effects of climate change on the geographic distribution of tularemia .
Other countries known to have endemic tularemia include most European countries, the former Soviet Union, Tunisia, Turkey, Israel, Iran, China, and Japan. Tularemia is relatively uncommon in African countries, Australia, England, and South American countries.
- Penn RL. Francisella tularensis (Tularemia). In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th Ed, Bennett JE, Dolin R, Blaser MJ (Eds), Elsevier Saunders, Philadelphia 2015; 2590.
- Brett ME, Respicio-Kingry LB, Yendell S, et al. Outbreak of Francisella novicida bacteremia among inmates at a louisiana correctional facility. Clin Infect Dis 2014; 59:826.
- Centers for Disease Control and Prevention (CDC). Tularemia - Missouri, 2000-2007. MMWR Morb Mortal Wkly Rep 2009; 58:744.
- Adams D, Fullerton K, Jajosky R, et al. Summary of Notifiable Infectious Diseases and Conditions - United States, 2013. MMWR Morb Mortal Wkly Rep 2015; 62:1.
- Centers for Disease Control and Prevention (CDC). Tularemia - United States, 2001-2010. MMWR Morb Mortal Wkly Rep 2013; 62:963.
- Pedati C, House J, Hancock-Allen J, et al. Notes from the Field: Increase in Human Cases of Tularemia--Colorado, Nebraska, South Dakota, and Wyoming, January-September 2015. MMWR Morb Mortal Wkly Rep 2015; 64:1317.
- Nakazawa Y, Williams R, Peterson AT, et al. Climate change effects on plague and tularemia in the United States. Vector Borne Zoonotic Dis 2007; 7:529.
- Kugeler KJ, Mead PS, Janusz AM, et al. Molecular Epidemiology of Francisella tularensis in the United States. Clin Infect Dis 2009; 48:863.
- Petersen JM, Carlson JK, Dietrich G, et al. Multiple Francisella tularensis subspecies and clades, tularemia outbreak, Utah. Emerg Infect Dis 2008; 14:1928.
- Johansson A, Lärkeryd A, Widerström M, et al. An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis. Clin Infect Dis 2014; 59:1546.
- Acha PN, Szyfres B. Tularemia. In: Zoonosis and Communicable Disease Common to Man and Animals, Pan American Health Organization, Washington DC 2001. Vol 1, p.275.
- Rydén P, Björk R, Schäfer ML, et al. Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence. J Infect Dis 2012; 205:297.
- Centers for Disease Control and Prevention (CDC). Outbreak of tularemia among commercially distributed prairie dogs, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:688, 699.
- Padeshki PI, Ivanov IN, Popov B, Kantardjiev TV. The role of birds in dissemination of Francisella tularensis: first direct molecular evidence for bird-to-human transmission. Epidemiol Infect 2010; 138:376.
- Karadenizli A, Forsman M, Şimşek H, et al. Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012. Euro Surveill 2015; 20.
- Berrada ZL, Telford Iii SR. Survival of Francisella tularensis Type A in brackish-water. Arch Microbiol 2011; 193:223.
- El-Etr SH, Margolis JJ, Monack D, et al. Francisella tularensis type A strains cause the rapid encystment of Acanthamoeba castellanii and survive in amoebal cysts for three weeks postinfection. Appl Environ Microbiol 2009; 75:7488.
- Feldman KA, Enscore RE, Lathrop SL, et al. An outbreak of primary pneumonic tularemia on Martha's Vineyard. N Engl J Med 2001; 345:1601.
- Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health management. JAMA 2001; 285:2763.
- Kugeler KJ, Mead PS, McGowan KL, et al. Isolation and characterization of a novel Francisella sp. from human cerebrospinal fluid and blood. J Clin Microbiol 2008; 46:2428.
- Respicio-Kingry LB, Byrd L, Allison A, et al. Cutaneous infection caused by a novel Francisella sp. J Clin Microbiol 2013; 51:3456.
- Peterson JM, Schriefer ME. Francisella. In: Manual of Clinical Microbiology, 11th Ed, Jorgensen J, Pfaller M, Carroll K, et al. (Eds), American Society for Microbiology Press, Washington DC 2015; 1:851.
- Gunnell MK, Adams BJ, Robison RA. The Genetic Diversity and Evolution of Francisella tularensis with Comments on Detection by PCR. Curr Issues Mol Biol 2016; 18:79.
- Birdsell DN, Johansson A, Öhrman C, et al. Francisella tularensis subsp. tularensis group A.I, United States. Emerg Infect Dis 2014; 20:861.
- Sjöstedt AB. Francisella. In: Bergey's Manual of Systematic Bacteriology, 2nd ed, Brenner DJ, Krieg NR, Staley JT (Eds), Springer-Verlag, New York 2005. Vol 2, p.200.
- ASM. Sentinel level clinical laboratory guidelines for suspected agents of bioterrorism and emerging infectious diseases: Francisella tularensis. http://www.asm.org/images/PSAB/LRN/Tularemia%20Aug2015.pdf. (Accessed on November 04, 2015).
- Section IV—Laboratory Biosafety Level Criteria. In: Biosafety in Microbiological and Biomedical Laboratories, 5th Ed. Chosewood LC, Wilson D (Eds), CDC, 2009; 30. https://www.cdc.gov/biosafety/publications/bmbl5/bmbl5_sect_iv.pdf#x2013;%20Laboratory%20Biosafety%20Level%20CriteriaSection%20IV—Laboratory%20Biosafety%20Level%20Criteria%20[PDF%20-%20354%20KB]</a> (Accessed on September 04, 2017).
- Geyer SJ, Burkey A, Chandler FW. Tularemia. In: Pathology of Infectious Diseases, Connor DH (Ed), Appleton & Lange, Stamford, Conn 1997. p.869.
- Clemens DL, Horwitz MA. Uptake and intracellular fate of Francisella tularensis in human macrophages. Ann N Y Acad Sci 2007; 1105:160.
- Pechous RD, McCarthy TR, Zahrt TC. Working toward the future: insights into Francisella tularensis pathogenesis and vaccine development. Microbiol Mol Biol Rev 2009; 73:684.
- Santic M, Al-Khodor S, Abu Kwaik Y. Cell biology and molecular ecology of Francisella tularensis. Cell Microbiol 2010; 12:129.
- Moreau GB, Mann BJ. Adherence and uptake of Francisella into host cells. Virulence 2013; 4:826.
- Bencurova E, Kovac A, Pulzova L, et al. Deciphering the protein interaction in adhesion of Francisella tularensis subsp. holarctica to the endothelial cells. Microb Pathog 2015; 81:6.
- Clemens DL, Lee BY, Horwitz MA. Francisella tularensis enters macrophages via a novel process involving pseudopod loops. Infect Immun 2005; 73:5892.
- McCaffrey RL, Allen LA. Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. J Leukoc Biol 2006; 80:1224.
- Oviedo-Orta E, Perreau M, Evans WH, Potolicchio I. Control of the proliferation of activated CD4+ T cells by connexins. J Leukoc Biol 2010; 88:79.
- Forestal CA, Malik M, Catlett SV, et al. Francisella tularensis has a significant extracellular phase in infected mice. J Infect Dis 2007; 196:134.
- Horzempa J, O'Dee DM, Stolz DB, et al. Invasion of erythrocytes by Francisella tularensis. J Infect Dis 2011; 204:51.
- Henry T, Brotcke A, Weiss DS, et al. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J Exp Med 2007; 204:987.
- Kirimanjeswara GS, Golden JM, Bakshi CS, Metzger DW. Prophylactic and therapeutic use of antibodies for protection against respiratory infection with Francisella tularensis. J Immunol 2007; 179:532.
- Elkins KL, Cowley SC, Bosio CM. Innate and adaptive immunity to Francisella. Ann N Y Acad Sci 2007; 1105:284.
- Forslund AL, Salomonsson EN, Golovliov I, et al. The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis. BMC Microbiol 2010; 10:227.
- Dotson RJ, Rabadi SM, Westcott EL, et al. Repression of inflammasome by Francisella tularensis during early stages of infection. J Biol Chem 2013; 288:23844.
- Bauler TJ, Chase JC, Wehrly TD, Bosio CM. Virulent Francisella tularensis destabilize host mRNA to rapidly suppress inflammation. J Innate Immun 2014; 6:793.
- Jones BD, Faron M, Rasmussen JA, Fletcher JR. Uncovering the components of the Francisella tularensis virulence stealth strategy. Front Cell Infect Microbiol 2014; 4:32.
- Steiner DJ, Furuya Y, Metzger DW. Host-pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity. Infect Drug Resist 2014; 7:239.
- Gillette DD, Curry HM, Cremer T, et al. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes. Front Cell Infect Microbiol 2014; 4:45.