Background
Tularemia is an acute, febrile, granulomatous, infectious zoonosis caused by the aerobic gram-negative pleomorphic bacillus Francisella tularensis. Although tularemia has likely existed since ancient times,[1] the disease was first described in Japan in 1837. In 1911, a plaguelike disease in ground squirrels was described in Tulare County, California (tulare is an Aztec word for the tule reed, a marsh plant commonly found in that area), and was later found to be caused by the bacterium now known as F tularensis. Edward Francis studied the causative organism further, named the disease, and, in 1928, described his experience.[2]
Worldwide, more than 100 species of animals, birds, amphibians, and arthropods host F tularensis. The bacillus may also be found in mud and water. F tularensis produces acute infectious illness in humans. The mode of transmission and factors related to the host and organism influence the clinical presentation (ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, typhoidal).
Pathophysiology
Humans become infected with F tularensis after introduction of the bacillus by inhalation, intradermal injection, or oral ingestion. The clinical form of tularemia reflects the mode of transmission. Some authors classify the disease as typhoidal (predominance of systemic symptoms), pneumonic (pulmonary findings), or ulceroglandular (regional symptoms).
To cause tularemia in humans via intradermal injection or inhalation, 10-50 bacilli are required. To transmit the disease orally, 100 million organisms are required.
Ulceroglandular tularemia (80% of reported cases) usually occurs after F tularensis enters through the skin. Reportedly, bacilli can penetrate intact skin, but an abrasion (which may be clinically inapparent), a tick bite, or an insect bite is more likely to allow entry. Inoculation of the oral mucosa or conjunctiva may follow (1) contact with hands or fingers contaminated with tissue fluids or (2) contact with infectious aerosols.
Following an incubation period of 3-5 days (range, 1-14 d), a papule develops. In 2-4 more days, the papule may ulcerate, usually accompanied by fever and regional lymphadenopathy. Humans are probably bacteremic during this phase. The bacilli become entrapped in the reticuloendothelial system, where they may survive for a prolonged period. Caseating granulomata, with or without multinucleated giant cells, may develop.
Many animals and arthropods may carry F tularensis; however, ticks (especially Dermatocentor and Amblyomma species) and rabbits are the most common vectors implicated in cases of human tularemia. Domestic cats are increasingly recognized as associated with human tularemia. The deer fly is also a classic vector, although a less commonly reported one.
Inhalation of F tularensis may lead to pulmonic tularemia, while oral ingestion may cause oropharyngeal tularemia. Conjunctival inoculation may follow contact with contaminated tissue fluids. The portal of entry is unknown in most cases of typhoidal tularemia.
Epidemiology
Frequency
United States
A few hundred cases of tularemia are reported annually. Many cases are probably undiagnosed, misdiagnosed, or unreported. Tularemia has been reported in all states except Hawaii. Most reported cases occur in Arkansas, Tennessee, Texas, Oklahoma, Kansas, Utah, and Missouri.
In the past, tularemia infections reportedly occurred more frequently during the cold-weather months (eg, rabbit-associated disease); however, recently, tularemia has been reported more frequently during warm-weather months (eg, tick-associated disease).
International
Tularemia occurs throughout the Northern Hemisphere, except for in the United Kingdom. Cases have been reported in the United States, the former Soviet Union, Japan, Canada, Mexico, and Europe.[3, 4, 5] Tularemia has not been reported in Africa and South America.
Mortality/Morbidity
Overall, untreated tularemia carries a mortality rate of approximately 8%. The mortality rate of untreated typhoidal tularemia is 2-3 times higher. With early diagnosis and appropriate treatment, the mortality rate is less than 1%.
Race
All races are equally susceptible to tularemia.
Sex
Both sexes are equally susceptible to tularemia; however, societal activities common to young men may predispose them to F tularensis exposure.
Age
People of all ages are susceptible to the tularemia; however, young-to-middle-aged people are more likely to participate in activities that predispose them to exposure.
Trevisanato SI. The 'Hittite plague', an epidemic of tularemia and the first record of biological warfare. Med Hypotheses. May 11 2007;[Medline].
Francis E. A summary of present knowledge of Tularaemia. Medicine. 1928;7:411-32.
Hauri AM, Hofstetter I, Seibold E, Kaysser P, Eckert J, Neubauer H, et al. Investigating an airborne tularemia outbreak, Germany. Emerg Infect Dis. Feb 2010;16(2):238-43. [Medline]. [Full Text].
Rydén P, Björk R, Schäfer ML, Lundström JO, Petersén B, Lindblom A, et al. Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence. J Infect Dis. Jan 2012;205(2):297-304. [Medline]. [Full Text].
Hansen CM, Vogler AJ, Keim P, Wagner DM, Hueffer K. Tularemia in alaska, 1938 - 2010. Acta Vet Scand. Nov 18 2011;53:61. [Medline]. [Full Text].
Thomas LD, Schaffner W. Tularemia pneumonia. Infect Dis Clin North Am. Mar 2010;24(1):43-55. [Medline].
van de Beek D, Steckelberg JM, Marshall WF, Kijpittayarit S, Wijdicks EF. Tularemia with brain abscesses. Neurology. Feb 13 2007;68(7):531. [Medline].
Mitchell LA, Bradsher RW Jr, Paden TC, Malak SF, Warmack TS, Nazarian SM. Tularemia induced bilateral optic neuritis. J Ark Med Soc. Mar 2006;102(9):246-9. [Medline].
Gelfand MS, Slade W, Abolnik IZ. Tularemia serology: Differentiating true-positive and false-positive titers. Inf Dis Clin Pract. 1992;1:105-8.
Tärnvik A, Chu MC. New approaches to diagnosis and therapy of tularemia. Ann N Y Acad Sci. Apr 27 2007;[Medline].
Cronquist SD. Tularemia: the disease and the weapon. Dermatol Clin. Jul 2004;22(3):313-20, vi-vii. [Medline].
Gallagher-Smith M, Kim J, Al-Bawardy R, Josko D. Francisella tularensis: possible agent in bioterrorism. Clin Lab Sci. 2004;17(1):35-9. [Medline].
Choi E. Tularemia and Q fever. Med Clin North Am. Mar 2002;86(2):393-416. [Medline].
Cunha BA. Bioterrorism in the Emergency Room: Anthrax, Tularemia, Plague, Ebola, and Smallpox. Clin Microbiol Infect. 2002;8:489-503.
Cunha BA. Tularemia. In: Tickborne Infectious Diseases: Diagnosis and Management. Marcel Dekker; 2000:251-68.
Dienst FT. Tularemia: a perusal of three hundred thirty-nine cases. J La State Med Soc. Apr 1963;115:114-27. [Medline].
Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clin Microbiol Rev. Oct 2002;15(4):631-46. [Medline].
Evans ME, Gregory DW, Schaffner W, McGee ZA. Tularemia: a 30-year experience with 88 cases. Medicine (Baltimore). Jul 1985;64(4):251-69. [Medline].
Farlow J, Wagner DM, Dukerich M, Stanley M, Chu M, Kubota K. Francisella tularensis in the United States. Emerg Infect Dis. Dec 2005;11(12):1835-41. [Medline].
Gill MV, Cunha BA. Tularemia Pneumonia. Sem Respir Infect. 1997;13:61-67.
Guffey MB, Dalzell A, Kelly DR, Cassady KA. Ulceroglandular tularemia in a nonendemic area. South Med J. Mar 2007;100(3):304-8. [Medline].
Kandemir B, Erayman I, Bitirgen M, Aribas ET, Guler S. Tularemia presenting with tonsillopharyngitis and cervical lymphadenitis: report of two cases. Scand J Infect Dis. 2007;39(6-7):620-2. [Medline].
Leblebicioglu H, Esen S, Turan D, Tanyeri Y, Karadenizli A, Ziyagil F, et al. Outbreak of tularemia: a case-control study and environmental investigation in Turkey. Int J Infect Dis. May 2008;12(3):265-9. [Medline].
Markowitz LE, Hynes NA, de la Cruz P, et al. Tick-borne tularemia. An outbreak of lymphadenopathy in children. JAMA. Nov 22-29 1985;254(20):2922-5. [Medline].
Matyas BT, Nieder HS, Telford SR 3rd. Pneumonic tularemia on Martha's Vineyard: clinical, epidemiologic, and ecological characteristics. Ann N Y Acad Sci. Jun 2007;1105:351-77. [Medline].
Nigrovic LE, Wingerter SL. Tularemia. Infect Dis Clin North Am. Sep 2008;22(3):489-504. [Medline].
Penn RL, Kinasewitz GT. Factors associated with a poor outcome in tularemia. Arch Intern Med. Feb 1987;147(2):265-8. [Medline].
Sinclair JR, Newton A, Hinshaw K, Fraser G, Ross P, Chernak E, et al. Tularemia in a park, Philadelphia, Pennsylvania. Emerg Infect Dis. Sep 2008;14(9):1482-3. [Medline].
Sjöstedt A. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. Jun 2007;1105:1-29. [Medline].

