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==Pathophysiology==
==Overview==
Tularemia is caused by the bacterium ''Francisella tularensis'' found in animals (especially rodents, rabbits, and hares). ''Francisella tularensis'' (''F. tularensis'') is a tiny, pleomorphic, nonmotile, [[gram-negative]], facultative intracellular coccobacillus (0.2 to 0.5 μm by 0.7 to 1.0 μm). It is a fastidious organism and may require cysteine supplementation for good growth on general laboratory media.
''[[Francisella|Francisella tularensis]]'' is an extremely infectious bacteria; fewer than ten organisms can cause disease leading to severe illness. The bacteria penetrate into the body through damaged skin and [[Mucous membrane|mucous membranes]], or through inhalation. ''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 cells|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|liver,]] [[spleen]], and [[Lymphatic system|lymphatic system.]]


*''F. tularensis'' can infect humans through the [[skin]], [[mucous membranes]], [[gastrointestinal tract]], and [[lungs]]. It is a facultative intracellular bacterium that multiplies within macrophages. The major target organs are the [[lymph nodes]], [[lungs]] and [[pleura]], [[spleen]], [[liver]], and [[kidney]]. Untreated, bacilli inoculated into skin or mucous membranes multiply, spread to regional lymph nodes and further multiply, and then may disseminate to organs throughout the body.  
==Pathogenesis==
*[[Bacteremia]] may be common in the early phase of infection. The initial tissue reaction to infection is a focal, intensely suppurative [[necrosis]] consisting largely of accumulations of polymorphonuclear [[leukocyte]]s, followed by invasion of [[macrophage]]s, [[epithelioid]] cells, and [[lymphocytes]].  
===Transmission===
*Suppurative lesions become [[granulomatous]], and [[histopathological]] examination of the [[granulomas]] shows a central necrotic, sometimes caseating, zone surrounded by a layer of epithelioid cells, [[multinucleated giant cell]]s, and [[fibroblast]]s in a radial arrangement, typical of other granulomatous conditions such as [[tuberculosis]] and [[sarcoidosis]].  
*[[Bacteremia|Bacteremic]] phase initiates the spread of disease into [[reticuloendothelial]] tissue.  
*Humans with inhalational exposures also develop hemorrhagic [[inflammation]] of the airways early in the course of illness, which may progress to [[bronchopneumonia]]. Histopathological examination of the lungs shows alveolar spaces filled with an exudate of mononuclear cells. [[Pleuritis]] with adhesions and effusion and [[hilar]] [[lymphadenopathy]] are common in radiological and pathological findings.
*This evokes an [[Immunology|immunological]] reaction resulting in a flurry of [[Tumor necrosis factor-alpha|tumor necrosis factor alpha]], [[interleukin-10]] and [[Interleukin 12|12]], as well as [[IFN|IFN-gamma]].  
*Primary clinical forms vary in severity and presentation according to virulence of the infecting organism, dose, and site of inoculum.  
*[[T-cells]] become involved as the disease progresses.  
*The onset of tularemia is usually abrupt, with [[fever]] (38oC–40oC), [[headache]], [[chills]] and rigors, generalized body aches (often prominent in the low back), [[coryza]], and sore throat. A pulse-temperature dissociation has been noted in as many as 42% of patients. A dry or slightly productive cough and substernal pain or tightness frequently occur with or without objective signs of [[pneumonia]], such as purulent sputum, [[dyspnea]], [[tachypnea]], pleuritic pain, or [[hemoptysis]]. [[Nausea]], [[vomiting]], and [[diarrhea]] may occur.
*Studies show that [[T-cells]] are necessary in stopping the reaction, but not controlling it.  
*Sweats, [[fever]], [[chills]], progressive weakness, [[malaise]], [[anorexia]], and [[weight loss]] characterize the continuing illness.
*A successful tularemia infection is the ultimate result of the disease's ability to survive within [[macrophage]] host cells. <ref name= "Tul Pub"> Tularemia. Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clin Microbiol Rev. 2002;15(4):631-46. http://www.ncbi.nlm.nih.gov/pubmed/12364373 Accessed March 28, 2016 </ref>  
*In general, tularemia would be expected to have a slower progression of illness and a lower case-fatality rate than either inhalational [[plague]] or [[anthrax]]. Milder forms of inhalational tularemia would be indistinguishable from [[Q fever]]; another potential bioterrorism agent; establishing a diagnosis of either would be problematic without reference laboratory testing.<ref>http://www.bt.cdc.gov/agent/tularemia/facts.asp</ref><ref>http://www.asm.org/ASM/files/LEFTMARGINHEADERLIST/DOWNLOADFILENAME/0000000525/tularemiaprotocol%5B1%5D.pdf</ref><ref>http://www.bt.cdc.gov/agent/tularemia/tularemia-biological-weapon-abstract.asp#2
</ref>


===Mechanism of infection===
===Mechanism of infection===
''[[Francisella|Francisella tularensis]]'' is one of the most infective bacteria known; fewer than ten organisms can cause disease leading to severe illness. The bacteria 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|Francisella tularensis]]'' is one of the most infectious [[bacteria]] known; fewer than ten organisms can cause disease leading to severe illness.
 
* The [[Bacterial Endocarditis|bacteria]] penetrate into the body through damaged skin and [[mucous membranes]], or through inhalation.
''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</ref> Overall mortality was 7% for untreated cases, and the disease responds well to antibiotics with a fatality rate of about 2%. The exact cause of death is unclear, but it is thought be a combination of multiple organ system failures.
* Humans are most often infected by tick bite or through handling an infected animal.
* Ingesting infected water, soil, or food can also cause infection. <ref> Francisella tularensis Bacteria Associated with Feline Tularemia in the United States. Larson MA, Fey PD, Hinrichs SH, Iwen PC. Francisella tularensis bacteria associated with feline tularemia in the United States. Emerging Infect Dis. 2014;20(12):2068-71. Accessed March 28, 2016 </ref>
* 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.  
* Tularemia is not spread directly from person to person.  
* ''Francisella tularensis'' is an [[Intracellular|intracellular bacterium]], meaning that it is able to live as a parasite within host cells.
* It primarily infects [[macrophages]], a type of [[White blood cells|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]]. <ref name= "Tul Pub"> Tularemia. Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clin Microbiol Rev. 2002;15(4):631-46. http://www.ncbi.nlm.nih.gov/pubmed/12364373 Accessed March 28, 2016 </ref>


==References==
==References==
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[[Category:Zoonoses]]
[[Category:Zoonoses]]
[[Category:Biological weapons]]
[[Category:Biological weapons]]
[[Category:Infectious disease]]
 
[[Category:Needs overview]]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Francisella tularensis is an extremely infectious bacteria; fewer than ten organisms can cause disease leading to severe illness. The bacteria penetrate into the body through damaged skin and mucous membranes, or through inhalation. 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.

Pathogenesis

Transmission

Mechanism of infection

  • Francisella tularensis is one of the most infectious bacteria known; fewer than ten organisms can cause disease leading to severe illness.
  • The bacteria 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. [2]
  • 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.
  • 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. [1]

References

  1. ↑ 1.0 1.1 Tularemia. Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clin Microbiol Rev. 2002;15(4):631-46. http://www.ncbi.nlm.nih.gov/pubmed/12364373 Accessed March 28, 2016
  2. ↑ Francisella tularensis Bacteria Associated with Feline Tularemia in the United States. Larson MA, Fey PD, Hinrichs SH, Iwen PC. Francisella tularensis bacteria associated with feline tularemia in the United States. Emerging Infect Dis. 2014;20(12):2068-71. Accessed March 28, 2016

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