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'Tularemia' (also known as "rabbit fever") is a serious infectious disease caused by the bacterium ''Francisella tularensis''. The disease is endemic in North America, and parts of Europe and Asia. The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. Animals such as rabbits, prairie dogs, hares and muskrats serve as reservoir hosts. The disease is named after Tulare County, California.

Contents

History

Epidemiology

Clinical manifestations

Mechanism of infection

Treatment

Tularemia as a biological weapon

Documented outbreaks

Biological Warfare

External links

References

History

''Franciscella tularensis'' was discovered in 1911 during an outburst of rabbit fever, when the disease killed a large number 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.[1]

Epidemiology

The disease is endemic in North America, and parts of Europe and Asia. The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. Rodents, rabbits, hares often serve as reservoir hosts,^[1] but waterborne infection accounts for 5 to 10% of all tularemia in the US.^[2]
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 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.^[3]

Clinical manifestations

Depending on the site of infection, tularemia has six characteristic clinical syndromes: ulceroglandular, glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal.^[4]
The disease has a very rapid onset, with headache, fatigue, dizziness, muscle pains, loss of appetite and nausea. 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 may result.[2]

Mechanism of infection

''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 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.^[5] 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.

Treatment

The drug of choice is Streptomycin.^[6] Tularemia may also be treated with gentamicin, tetracycline, chloramphenicol or fluoroquinolones.

Tularemia as a biological weapon

The Centers for Disease Control and Prevention regard ''F. tularensis'' as a viable bioweapons agent for use by terrorists. The disease was used as a weapon by the Russians during World War II.[3] 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; fewer than 10 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, eg civilians
No vaccine is available to the general public.^[7] The best way to prevent tularemia infection is to wear rubber gloves when handling or skinning rodents or lagomorphs (as rabbits), avoid ingesting uncooked wild game and untreated water sources, and wearing long-sleeved clothes and using an insect repellant 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.^[8] The research may prove valuable in preventing bioterrorism.
An outbreak of tularemia occurred in Kosovo in 1999-2000 [4].
In 2004, three researchers at Boston University Medical Center were accidentally infected with ''F. tularensis'', after apparently failing to follow safety procedures.^[9]
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.^[10]
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.

Biological Warfare

By the late 1950's 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.
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.

External links

★ CDC Emergency Preparedness and Response index for tularemia

★ Soviet Army used 'rat weapon' during WWII

★ Biohazard Sensors Triggered Mall Germ Levels Likely Not a ThreatMartin Weil and Susan Levine ''Washington Post'' October 1, 2005

★ 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

★ US finds fever bacteria during war protest weekend ''Reuters'' Oct 3, 2005

★ 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

★ Detailed CIDRAP overview of tularemia, including fatality statistics

★ BioHealthBase Bioinformatics Resource Center Database of ''Francisella tularensis'' sequences and related information.

References

1. The ecology of tularemia, Morner T, , , Rev Sci Tech, 1992
2. Tularemia and animal populations, Jellison WL, Owen C, Bell JF, Kohls GM, , , Wildl Dis, 1961
3. Tularemia—United States, 1990–2000, Hayes E, Marshall S, Dennis D, ''et al.'', , , MMWR, 2002
4. Glandular tularemia with typhoidal features in a Manitoba child, Plourde PJ, Embree J, Friesen F, Lindsay G, Williams T, , , Can Med Assoc J, 1992
5. http://www.cidrap.umn.edu/cidrap/content/bt/tularemia/biofacts/tularemiafactsheet.html#_Overview_1
6. Streptomycin and alternative agents for the treatment of tularemia: review of the literature, Enderlin G, Morales L, Jacobs RF, Cross JT, , , Clin Infect Dis, 1994
7. http://www.niaid.nih.gov/factsheets/tularemia.htm
8. Feldman KA, Enscore R, Lathrop S, et al. Outbreak of primary pneumonic tularemia on Martha's Vineyard. N Engl J Med 2001;345:1601--6.
9. City tells BU to bolster safety of its medical labs
10. Health Officials Vigilant for Illness After Sensors Detect Bacteria on Mall: Agent Found as Protests Drew Thousands of Visitors


★ Tularemia, NIAID Fact Sheet, April 2005