{{infobox disease | name	Tularemia | Image Tularemia lesion.jpg | Caption A tularemia lesion on the dorsal skin of right hand. | DiseasesDB 13454 | ICD10 | ICD9 | ICDO | OMIM | MedlinePlus 000856 | eMedicineSubj med | eMedicineTopic 2326 | eMedicine_mult | MeshID D014406 }}

Tularemia (also known as Pahvant Valley plague, rabbit fever, deer fly fever, Ohara's fever) is a serious infectious disease caused by the bacterium Francisella tularensis. 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. The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. 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. 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.

Epidemiology

The disease is endemic in North America, and parts of Europe and Asia. The most common mode of transmission is via arthropod vectors. Ticks involved include Amblyomma, Dermacentor, Haemaphysalis, and Ixodes. Rodents, rabbits, and hares often serve as reservoir hosts, but waterborne infection accounts for 5 to 10% of all tularemia in the US. 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 2 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.

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.

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.

The incubation period for tularemia is 1 to 14 days; most human infections become apparent after 3 to 5 days. In most susceptible mammals, the clinical signs include fever, lethargy, anorexia, signs of septicemia, and possibly death. Non-human 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 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.

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, 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 different depending on 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. 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. Tularemia may also be treated with gentamicin for ten days, tetracycline-class drugs such as doxycycline for 2–3 weeks, chloramphenicol or fluoroquinolones. An attenuated, live vaccine is available, but its use is only for high risk groups. Its use as post-exposure prophylaxis is not recommended.

Tularemia as a biological weapon

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. 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, but this claim is rejected by others who have studied the outbreak. In the US, practical research into using rabbit fever as a bioweapon took place in 1954 at Pine Bluff Arsenal, Arkansas, an extension of the Camp Detrick program. 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 comparatively low lethality, which is useful where enemy soldiers are in proximity to non-combatants, e.g. civilians

The Schu S4 strain was standardized as Agent UL for use in the U.S. 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. 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.

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.

No vaccine is available to the general public. The best way to prevent tularemia infection is to wear rubber gloves when handling or skinning lagomorphs (such as rabbits), avoid ingesting uncooked wild game and untreated water sources, wear long-sleeved clothes, and use an insect repellent to prevent tick bites.

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.

An outbreak of tularemia occurred in Kosovo in 1999-2000.

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

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. While thousands of people were potentially exposed, no infections were reported.

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

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.

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.

In June 2011, in Armenia, Mrgahovit village of Lori Marz two people were infected.

References

External links

Category:Bacterium-related cutaneous conditions Category:Zoonotic bacterial diseases Category:Biological weapons Category:Central Valley of California Category:Zoonoses Category:Tick-borne diseases Category:Insect-borne diseases Category:Rabbit diseases

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