Tularemia

From Wikipedia, the free encyclopedia

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

Tularemia (also known as Pahvant Valley plague,^[1] rabbit fever,^[1] deer fly fever, 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 for 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.

[edit] History

F. tularensis was discovered in 1911 during an outbreak of rabbit fever, when the disease killed a large number of ground squirrels in the area of Tulare Lake in California. The bacterium was
first isolated by GW McCoy of the US Public Health Service plague lab
and reported in 1912.^[5][6]
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.^[7]

[edit] Epidemiology

The disease is endemic in North America, and parts of Europe and Asia. The most common mode of transmission is via arthropod vectors.^{2009" style="white-space: nowrap;"">[citation needed]} Rodents,
rabbits, and hares often serve as reservoir"">reservoir hosts,^[8]
but waterborne infection accounts for 5 to 10% of all tularemia in the
US.^[9]
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. 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 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.^[10]

[edit] 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.^[11]

The incubation period for tularemia is 1 to 14 days; most human infections become apparent after 3 to 5 days.^[12] 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.

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 sulfhydryl group 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.^{reliable sources from November 2009" style="white-space: nowrap;"">[citation needed]}

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.^[13]
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.

[edit] Treatment and prevention

The drug of choice is Streptomycin.^[14] Tularemia may also be treated with gentamicin for ten days, tetracycline-class drugs such as doxycycline
for 2–3 weeks,^[15]
chloramphenicol or fluoroquinolones. An
attenuated, live vaccine is available, but its use is restricted to
high risk groups. Its use as post-exposure prophylaxis is not
recommended.

[edit] Tularemia as a biological weapon

This section appears to contradict itself. Please see its talk page for more information. (May 2009)

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.^[16]
A former Soviet biological weapons scientist, Alibek" class="mw-redirect"">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.^[17]
In the US, practical research into using tularemia as a bioweapon took place in 1954 at Arsenal"">Pine Bluff Arsenal, Arkansas,
an extension of the Camp Detrick program.^[18]
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.^{references to reliable sources from December 2007" style="white-space: nowrap;"">[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.^[19]

No vaccine is available to the general public.^[20] 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 repellent"">insect repellent to prevent tick bites.

[edit] 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.^[21]

An outbreak of tularemia occurred in Kosovo in 1999-2000.^[22]

In 2004, three researchers at Boston University Medical Center were accidentally infected with F. tularensis, after apparently failing to follow safety procedures.^[23]

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.^[24]

Tularemia is endemic in the Gori region of Eurasian country of (country)"">Georgia. The last outbreak was in 2006.^[25]

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. Another outbreak had
taken place ten years before in the same area.^[26]

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 he was diagnosed with Tularemia, despite seeking
medical treatment in Vancouver.