Tularemia
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{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = |
Caption = |
DiseasesDB = 13454 |
ICD10 = {{ICD10|A|21||a|20}} |
ICD9 = {{ICD9|021}} |
ICDO = |
OMIM = |/
MedlinePlus = 000856 |
eMedicineSubj = med |
eMedicineTopic = 2326 |
eMedicine_mult = {{eMedicine2|emerg|591}} {{eMedicine2|ped|2327}} |
MeshID = D014406 |
}}
'''Tularemia''' (also known as "rabbit fever", "deer-fly fever", "Ohara fever" and "Francis disease") is a serious [[infectious disease]] caused by the [[bacterium]] ''[[Francisella|Francisella tularensis]]''. ''F. tularensis'' is a small [[gram-negative]] non-motile [[coccobacillus]]. The bacterium has several subspecies with varying degrees of [[virulence]]. The most important of those is ''F. tularensis tularensis'' (Type A), which is found in [[lagomorphs]] in North America and is highly virulent for humans and domestic rabbits. ''F. tularensis palaearctica'' (Type B) occurs mainly in aquatic rodents ([[beaver]]s, [[muskrat]]s) in North America and in hares and small rodents in northern Eurasia. It is less virulent for humans and rabbits.<ref>Pearson, A. In Zoonoses. Edited by S.R. Palmer. New York:Oxford Press, 1998, pp. 276-279.</ref> The primary [[vector (biology)|vector]]s are [[tick]]s and [[Deer Fly|deer flies]], but the disease can also be spread through other [[arthropods]]. The disease is named after [[Tulare County, California]].
==History==
''Francisella tularensis'' was discovered in 1911 during an outburst of rabbit fever, when the disease killed a large number of ground squirrels in the area of [[Tulare Lake]] in California. Scientists determined that tularemia could be dangerous to humans; a human being may catch the infection after contacting an infected animal. The ailment soon became frequent with hunters, cooks and agricultural workers.[http://english.pravda.ru/main/18/90/363/14923_tularemia.html]
==Epidemiology==
The disease is [[endemic (epidemiology)|endemic]] in North America, and parts of Europe and Asia. The most common mode of transmission is via arthropod [[vector]]s. [[Rodent]]s, rabbits, hares often serve as [[natural reservoir|reservoir hosts]].<ref>{{cite journal | author=Morner T | title=The ecology of tularemia | journal=Rev Sci Tech | year=1992 | volume=11 | pages=1123–30 }}</ref> but waterborne infection accounts for 5 to 10% of all tularemia in the US.<ref>{{cite journal | author=Jellison WL, Owen C, Bell JF, Kohls GM | title=Tularemia and animal populations | journal=Wildl Dis | year=1961 | volume=17 | pages=1–22 }}</ref> Tularemia can also be transmitted by biting flies, particularly the deer fly ''Chrysops discalis''. Individual flies can remain infective for 14 days and ticks for over two years. Tularemia may also be spread by direct contact with contaminated animals or material, by ingestion of poorly cooked flesh of infected animals or contaminated water, or by inhalation. The most likely method for [[bioterrorist]] transmission is through an aerosol.
In the [[United States]], although records show that tularemia was never particularly common, [[incidence (epidemiology)|incidence rates]] continued to drop over the course of the 20th century so that between 1990 and 2000, the rate was less than 1 per 1,000,000, meaning the disease is extremely rare in the US today.<ref>{{cite journal | title=Tularemia—United States, 1990–2000 | author=Hayes E, Marshall S, Dennis D, ''et al.'' | journal=MMWR | year=2002 | volume=51 | issue=09 | pages=182–4 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5109a1.htm }}</ref>
==Clinical manifestations and microbiological diagnosis==
Depending on the site of infection, tularemia has six characteristic clinical syndromes: ulceroglandular (the most common type representing 75% of all forms), glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal.<ref>{{cite journal | author=Plourde PJ, Embree J, Friesen F, Lindsay G, Williams T | title=Glandular tularemia with typhoidal features in a Manitoba child | journal=Can Med Assoc J | year=1992 | volume=146 | pages=1953–5 }}</ref>
The incubation period for tularemia is 1 to 14 days; most human infections become apparent after 3 to 5 days.<ref>"Tularemia" In Manual of Standards for Diagnostic Tests and Vaccines. Paris:WOAH, 2000, pp.494-6, 1394.</ref> In most susceptible mammals, the clinical signs include fever, lethargy, anorexia, signs of septicemia, and possibly death. Animals rarely develop the skin lesions seen in people. [[Subclinical]] infections are common and animals often develop specific antibodies to the organism. Fever is moderate or very high and tularemia bacillus can be isolated from blood cultures at this stage. Face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may suppurate (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever. Death occurs in less than 1% if therapy is initiated promptly.
[[Image:Francisella tularensis 01.jpg|right|thumb|A culture of ''Francisella tularensis''.]]
The microbiologist must be informed when tularemia is suspected because ''F. tularensis'' requires special media for cultivation such as buffered charcoal and yeast extract (BCYE). It cannot be isolated in the routine culture media because of the need for sulphydril groups donors (such as cystein). Serological tests (detection of antibodies in the serum of the patients) are available and widely used. Cross reactivity with ''Brucella'' can confuse interpretation of the results, and for this reason diagnosis should not rely only on serology. Molecular methods such as PCR are available in reference laboratories.
The bacteria can penetrate into the body through damaged skin and mucous membranes, or through inhalation. Humans are most often infected by tick bite or through handling an infected animal. Ingesting infected water, soil, or food can also cause infection. Tularemia can also be acquired by inhalation; hunters are at a higher risk for this disease because of the potential of inhaling the bacteria during the skinning process. It has been contracted from inhaling particles from an infected rabbit ground up in a lawnmower (see below). Tularemia is not spread directly from person to person.
''Francisella tularensis'' is an intracellular bacterium, meaning that it is able to live as a parasite within host cells. It primarily infects [[macrophages]], a type of white blood cell. It is thus able to evade the immune system. The course of disease involves spread of the organism to multiple organ systems, including the lungs, liver, spleen, and lymphatic system. The course of disease is similar regardless of the route of exposure. Mortality in untreated (pre-antibiotic-era) patients has been as high as 50% in the pneumoniac and typhoidal forms of the disease, which however account for less than 10% of cases.<ref>[http://www.cidrap.umn.edu/cidrap/content/bt/tularemia/biofacts/tularemiafactsheet.html#_Overview_1 CIDRAP >> Tularemia: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis<!-- Bot generated title -->]</ref> Overall mortality was 7% for untreated cases, and the disease responds well to antibiotics with a fatality rate of about 1%. The exact cause of death is unclear, but it is thought to be a combination of multiple organ system failures.
==Treatment and prevention==
The drug of choice is [[Streptomycin]].<ref>{{cite journal | author=Enderlin G, Morales L, Jacobs RF, Cross JT | title=Streptomycin and alternative agents for the treatment of tularemia: review of the literature | journal=Clin Infect Dis | year=1994 | volume=19 | pages=42–7 }}</ref> Tularemia may also be treated with [[gentamicin]] for ten days, [[tetracycline]]-class drugs such as [[doxycycline]] for 2-3 weeks,<ref>[http://www.bt.cdc.gov/agent/tularemia/faq.asp CDC FAQs re Tularemia]</ref> [[chloramphenicol]] or [[fluoroquinolone]]s.
An attenuated, live [[vaccine]] is available, but its use is restricted to high risk groups. Its use as post-exposure prophylaxis is not recommended.
==Tularemia as a biological weapon==
Cases of tularemia should be reported to the local health authority. The [[Centers for Disease Control and Prevention]] regard ''F. tularensis'' as a viable [[bioweapons]] agent, and it has been included in the biological warfare programs of the USA, USSR and Japan at various times<ref>Dennis DT ''et al.'' (2001) [http://jama.ama-assn.org/cgi/content/full/285/21/2763| "Tularemia as a Biological Weapon: Medical and Public Health Management"]. ''JAMA'' 285:2763-2773</ref>. A former Soviet biological weapons scientist, [[Kenneth Alibek]], has alleged that an outbreak of Tularemia among German soldiers shortly before the siege of Stalingrad was due to intentional release of F. tularensis by Soviet forces, but this claim is rejected by others who have studied the outbreak <ref>Sjostedt, A (2007) [http://www.blackwell-synergy.com/doi/full/10.1196/annals.1409.009| "Tularemia: History, Epidemiology, Pathogen Physiology, and Clinical Manifestations."]
Annals of the New York Academy of Sciences 1105:1–29 </ref>. In the USA, practical research into using Tularemia as a [[bioweapon]] took place at [[Camp Detrick]] in the 1950s. It was viewed as an attractive agent because:
* it is easy to aerosolize
* it is highly infective; 10-50 bacteria are required to infect
* it is non-persistent and easy to decontaminate (unlike [[anthrax]])
* it is highly incapacitating to infected persons
* it has low lethality, which is useful where enemy soldiers are in proximity to non-combatants, e.g. civilians
By the late 1950s the US [[biological warfare]] program was focused mostly on tularemia as a biological agent. The Schu S4 strain was standardized as Agent UL for use in the M143 bursting spherical bomblet. It was a lethal biological with an anticipated fatality rate of 40 to 60 percent. The rate-of-action was around three days, with a duration-of-action of 1 to 3 weeks (treated) and 2 to 3 months (untreated) with frequent relapses. UL was streptomycin resistant. The aerobiological stability of UL was a major concern, being sensitive to sun light, and losing virulence over time after release.{{Fact|date=December 2007}}
The United States later changed the military symbol for UL to TT (wet-type) and ZZ (dry-type) in an effort to retain security on the identity of military biologicals. When the 425 strain was standardized as agent JT (an incapacitant rather than lethal agent), the Schu S4 strain's symbol was changed again to SR.{{Fact|date=December 2007}}
No [[vaccine]] is available to the general public.<ref>[http://www.niaid.nih.gov/factsheets/tularemia.htm Tularemia, NIAID Fact Sheet<!-- Bot generated title -->]</ref> The best way to prevent tularemia infection is to wear rubber gloves when handling or skinning rodents or [[lagomorpha|lagomorphs]] (as rabbits), avoid ingesting uncooked wild game and untreated water sources, and wearing long-sleeved clothes and using an [[insect repellent]] to prevent tick bites.
==Documented outbreaks==
In summer 2000, an outbreak of tularemia in [[Martha's Vineyard]] resulted in one fatality, and brought the interest of the CDC as a potential investigative ground for aerosolized ''Francisella tularensis''. Over the following summers, Martha's Vineyard was identified as the only place in the world where documented cases of tularemia resulted from lawn mowing.<ref>Feldman KA, Enscore R, Lathrop S, et al. [http://content.nejm.org/cgi/content/full/345/22/1601 Outbreak of primary pneumonic tularemia on Martha's Vineyard]. N Engl J Med 2001;345:1601--6.</ref> The research may prove valuable in preventing [[bioterrorism]]{{Fact|date=October 2007}}.
An outbreak of tularemia occurred in [[Kosovo]] in 1999-2000 [http://www.cdc.gov/ncidod/eid/vol8no1/01-0131.htm].
In 2004, three researchers at Boston University Medical Center were accidentally infected with ''F. tularensis'', after apparently failing to follow safety procedures.<ref>{{cite news | author=Smith S | publisher=Boston Globe | title=City tells BU to bolster safety of its medical labs | url=http://www.boston.com/news/local/articles/2005/03/29/city_tells_bu_to_bolster_safety_of_its_medical_labs/ | date=2005-03-29 | accessdate=2007-05-09 }}</ref>
In 2005, small amounts of ''F. tularensis'' were detected in the Mall area of Washington, DC the morning after an anti-war demonstration on [[September 24]], [[2005]]. Biohazard sensors were triggered at six locations surrounding the Mall. To this date, no cases of tularemia infection have been reported as a result.<ref>{{cite news | author=Dvorak P | title=Health Officials Vigilant for Illness After Sensors Detect Bacteria on Mall: Agent Found as Protests Drew Thousands of Visitors | publisher=Washington Post | page=C13 | date=2005-10-2 | accessdate=2007-05-08
| url=http://www.washingtonpost.com/wp-dyn/content/article/2005/10/01/AR2005100101209.html | quote=A week after six bioterrorism sensors detected the presence of a dangerous bacterium on the Mall, health officials said there are no reports that any of the thousands of people in the nation's capital Sept. 24 have tularemia, the illness that results from exposure to the bacteria. }}</ref>
In 2007, a lab of Boston University's Center for Advanced Biomedical Research, where ''F. tularensis'' were being kept for research, was evacuated after smoke set off alarms. An investigation has later determined that an electrical problem was the culprit, and no bacterial contamination was found.
In July 2007, an outbreak was reported in the Spanish autonomous region of [[Castile and León]] and traced to the plague of [[voles]] infesting the region.
== External links ==
*[http://www.bt.cdc.gov/agent/tularemia/index.asp CDC Emergency Preparedness and Response index for tularemia]
*[http://english.pravda.ru/main/18/90/363/14923_tularemia.html Soviet Army used 'rat weapon' during WWII]
*[http://www.washingtonpost.com/wp-dyn/content/article/2005/10/01/AR2005100101209.html Health Officials Vigilant for Illness After Sensors Detect Bacteria on Mall Agent Found as Protests Drew Thousands of Visitors] Petula Dvorak ''Washington Post'' October 2, 2005
*[http://www.washingtonpost.com/wp-dyn/content/article/2005/10/04/AR2005100401544.html Test Results Cited in Delay of Mall Alert CDC Explains Why Local Officials Weren't Told for Days About Bacterium Detection] Susan Levine and Sari Horwitz ''Washington Post'' October 5, 2005
*[http://www.cidrap.umn.edu/cidrap/content/bt/tularemia/biofacts/tularemiafactsheet.html Detailed CIDRAP overview of tularemia, including fatality statistics]
*[http://www.biohealthbase.org/ BioHealthBase Bioinformatics Resource Center] Database of ''Francisella tularensis'' sequences and related information.
== References ==
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