Tularemia

Tularemia
Classification and external resources
A tularemia lesion on the dorsal skin of the right hand
ICD-10	A21
ICD-9	021
DiseasesDB	13454
MedlinePlus	000856
eMedicine	med/2326 emerg/591 ped/2327
MeSH	D014406

Tularemia (also known as Pahvant Valley plague,^[1] rabbit fever,^[1] deer fly fever, and Ohara's fever^[2]:286) is a serious infectious disease caused by the bacterium Francisella tularensis.^[3] A Gram-negative, nonmotile 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 in humans and domestic rabbits. F. tularensis palaearctica (Type B) occurs mainly in aquatic rodents (beavers, muskrats) in North America and in hares and small rodents in northern Eurasia. It is less virulent for humans and rabbits.^[4] The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods.^[3] The disease is named after Tulare County, California.

History

The bacterium was first isolated by GW McCoy of the US Public Health Service plague lab and reported in 1912.^[5][6] Scientists determined 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.^[7]

Epidemiology

The disease is endemic in North America, and parts of Europe and Asia. The most common mode of transmission is via arthropod vectors.^{[citation needed]} Ticks involved include Amblyomma, Dermacentor, Haemaphysalis, and Ixodes.^[8] Rodents, rabbits, and hares often serve as reservoir hosts,^[9] but waterborne infection accounts for 5 to 10% of all tularemia in the US.^[10] 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.^{[citation needed]}

In the United States, although records show that tularemia was never particularly common, incidence rates continued to drop over the course of the 20th century, so between 1990 and 2000, the rate was less than 1 per 1,000,000, meaning the disease is extremely rare in the US today.^[11]

Clinical manifestations and microbiological diagnosis

A culture of Francisella tularensis

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.^[12]

The incubation period for tularemia is one to 14 days; most human infections become apparent after three to five days.^[13] In most susceptible mammals, the clinical signs include fever, lethargy, anorexia, signs of septicemia, and possibly death. Nonhuman mammals 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 bacilli can be isolated from blood cultures at this stage. The 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.

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 sulfhydryl group donors (such as cysteine). 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, so 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.^{[citation needed]}

Francisella tularensis is an intracellular bacterium, meaning it is able to live as a parasite within host cells. It primarily infects macrophages, a type of white blood cell, thus is able to evade the immune system. The course of disease involves the spread of the organism to multiple organ systems, including the lungs, liver, spleen, and lymphatic system. The course of disease is different depending on the route of exposure. Mortality in untreated (before the 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.^[14] 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.^[15] Tularemia may also be treated with gentamicin for ten days, tetracycline-class drugs such as doxycycline for two to three weeks,^[16] chloramphenicol or fluoroquinolones. An attenuated, live vaccine is available, but its use is only for high risk groups. Its use as postexposure prophylaxis is not recommended.

Tularemia as a biological weapon

The Centers for Disease Control and Prevention regard F. tularensis as a viable biological warfare agent, and it has been included in the biological warfare programs of the United States, Soviet Union and Japan at various times.^[17] 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 the release of F. tularensis by Soviet forces. Others who have studied the pathogen "propose that an outbreak resulting from natural causes is more likely".^[18][19] In the US, practical research into using rabbit fever as a biological warfare agent took place in 1954 at Pine Bluff Arsenal, Arkansas, an extension of the Camp Detrick program.^[20] 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 nonpersistent and easy to decontaminate (unlike anthrax),
• it is highly incapacitating to infected persons, and
• it has comparatively low lethality, which is useful where enemy soldiers are in proximity to noncombatants, e.g. civilians.

The Schu S4 strain was standardized as "Agent UL" for use in the United States M143 bursting spherical bomblet. It was a lethal biological warfare agent with an anticipated fatality rate of 40 – 60%. The rate-of-action was around three days, with a duration-of-action of one to three weeks (treated) and two to three months (untreated), with frequent relapses. UL was streptomycin resistant. The aerobiological stability of UL was a major concern, being sensitive to sunlight, and losing virulence over time after release. 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.^{[citation needed]}

Both wet and dry types of F. tularensis (identified by the codes TT and ZZ) were examined during the "Red Cloud" tests, which took place from November 1966 to February 1967 in the Tanana Valley, Alaska.^[21]

No vaccine is available to the general public.^[22] The best way to prevent tularemia infection is to wear rubber gloves when handling or skinning wild lagomorphs and rodents, avoid ingesting uncooked wild game and untreated water sources, wear long-sleeved clothes, and use an insect repellent to prevent tick bites.^{[citation needed]}

Documented outbreaks

In the summer of 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.^[23]

An outbreak of tularemia occurred in Kosovo in 1999-2000.^[24]

In 2004, three researchers at Boston University Medical Center were accidentally infected with F. tularensis, after apparently failing to follow safety procedures.^[25]

In 2005, small amounts of F. tularensis were detected in the Mall area of Washington, DC the morning after an antiwar demonstration on September 24, 2005. Biohazard sensors were triggered at six locations surrounding the Mall. While thousands of people were potentially exposed, no infections were reported. The detected bacteria likely originated from a natural source, not from a bioterror attempt.^[26]

Tularemia is endemic in the Gori region of the Eurasian country of Georgia. The last outbreak was in 2006.^[27]

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. Another outbreak had taken place ten years before in the same area.^[28]

In August 2009, a Swedish tourist was bitten by an unidentified insect at Point Grey, Vancouver, BC, Canada. It was not until after return to Sweden that he was diagnosed with tularemia, despite seeking medical treatment in Vancouver.^{[citation needed]}

In June 2011, in Armenia, Mrgahovit village of Lori Marz two people were infected.^{[citation needed]}

In November 2011, it was detected for the first time in the Southern Hemisphere - in Tasmania, Australia.^[29]

References

1. ^ ^{a b} Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0. 
2. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. 
3. ^ ^{a b} Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 488–90. ISBN 0838585299. 
4. ^ Pearson A (1998). Zoonoses: biology, clinical practice, and public health control (Soulsby EJ, Palmer SL eds.). Oxford [Oxfordshire]: Oxford University Press. pp. 276–9. ISBN 0-19-262380-X. 
5. ^ A. Tärnvik1 and L. Berglund, Tularaemia. Eur Respir J 2003; 21:361-373.
6. ^ McCoy GW, Chapin CW. Bacterium tularense, the cause of a plaguelike disease of rodents. Public Health Bull 1912;53:17–23.
7. ^ http://english.pravda.ru/main/18/90/363/14923_tularemia.html
8. ^ George W. Beran; James H. Steele (22 October 1994). Handbook of Zoonoses: Bacterial, rickettsial, chlamydial, and mycotic. CRC Press. pp. 117–. ISBN 9780849332050. http://books.google.com/books?id=wcE1AR_CLy8C&pg=PA117. Retrieved 28 October 2010. 
9. ^ Mörner T (December 1992). "The ecology of tularaemia". Rev. Sci. Tech. 11 (4): 1123–30. PMID 1305858. 
10. ^ Jellison WL, Owen C, Bell JF, Kohls GM (1961). "Tularemia and animal populations". Wildl Dis 17: 1–22. 
11. ^ Hayes E, Marshall S, Dennis D, et al. (March 2002). "Tularemia--United States, 1990-2000". MMWR 51 (JULIOes=181–4): 181–4. PMID 11900351. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5109a1.htm. 
12. ^ Plourde PJ, Embree J, Friesen F, Lindsay G, Williams T (June 1992). "Glandular tularemia with typhoidal features in a Manitoba child". CMAJ 146 (11): 1953–5. PMC 1490377. PMID 1596844. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1490377. 
13. ^ Office international des épizooties. (2000). Manual of standards for diagnostic tests and vaccines: lists A and B diseases of mammals, birds and bees. Paris, France: Office international des épizooties. pp. 494–6, 1394. ISBN 92-9044-510-6. 
14. ^ "Tularemia: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, treatment, and prophylaxis". CIDRAP. http://www.cidrap.umn.edu/cidrap/content/bt/tularemia/biofacts/tularemiafactsheet.html#_Overview_1+CIDRAP. Retrieved 2008-09-29. 
15. ^ Enderlin G, Morales L, Jacobs RF, Cross JT (July 1994). "Streptomycin and alternative agents for the treatment of tularemia: review of the literature". Clin. Infect. Dis. 19 (1): 42–7. doi:10.1093/clinids/19.1.42. PMID 7948556. 
16. ^ "Tularemia: FAQ About Tularemia". CDC. 2003-10-08. http://www.bt.cdc.gov/agent/tularemia/faq.asp. Retrieved 2008-09-29. 
17. ^ Dennis DT, Inglesby TV, Henderson DA, et al. (June 2001). "Tularemia as a biological weapon: medical and public health management". JAMA 285 (21): 2763–73. doi:10.1001/jama.285.21.2763. PMID 11386933. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11386933. 
18. ^ Croddy E, Krcalova S (October 2001). "Tularemia, Biological Warfare, and the Battle for Stalingrad (1942-1943)". Military Medicine 166 (10). http://cns.miis.edu/archive/cbw/tula.htm. 
19. ^ Sjöstedt A (June 2007). "Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations". Ann. N. Y. Acad. Sci. 1105: 1–29. doi:10.1196/annals.1409.009. PMID 17395726. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2007&volume=1105&spage=1. 
20. ^ Kanti Ghosh, Tushar, Prelas, Mark, Viswanath, Dabir: Science and Technology of Terrorism and Counterterrorism. CRC Press, 2002. Page 97. ISBN 0-8247-0870-9
21. ^ "Fact Sheet - Red Cloud", Office of the Assistant Secretary of Defense (Health Affairs), Deployment Health Support Directorate.
22. ^ "Medscape & eMedicine Log In". http://www.medscape.com/viewarticle/431539. 
23. ^ Feldman KA, Enscore RE, Lathrop SL, et al. (November 2001). "An outbreak of primary pneumonic tularemia on Martha's Vineyard". N. Engl. J. Med. 345 (22): 1601–6. doi:10.1056/NEJMoa011374. PMID 11757506. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=11757506&promo=ONFLNS19. 
24. ^ www.cdc.gov
25. ^ Smith S (2005-03-29). "City tells BU to bolster safety of its medical labs". Boston Globe. http://www.boston.com/news/local/articles/2005/03/29/city_tells_bu_to_bolster_safety_of_its_medical_labs/. Retrieved 2007-05-09. 
26. ^ Dvorak P (2005-10-02). "Health Officials Vigilant for Illness After Sensors Detect Bacteria on Mall: Agent Found as Protests Drew Thousands of Visitors". Washington Post. p. C13. http://www.washingtonpost.com/wp-dyn/content/article/2005/10/01/AR2005100101209.html. Retrieved 2007-05-08. "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." 
27. ^ According to staff at Georgia's National Center for Disease Control, there was an outbreak of tularemia in the village of Zemo Rene east of Gori in December 2005 and January 2006. Twenty-six persons tested positive for the bacteria, and 45 tested positive for antibodies. There were no fatal cases. The source was deemed to be a water spring. Previous outbreaks were in Tamarasheni (2005) and Ruisi (1997 and 1998).
28. ^ Diagnóstico de un brote de tularemia en Castilla-León (Spanish)
29. ^ Biological war disease found in Tasmania Australian Broadcasting Corporation - Retrieved 4 Nov 2011.

External links

• Tularemia at the Open Directory Project