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Tularemia

Tularemia

BRIAN HOYLE

Tularemia is a plague-like disease caused by the bacterium Francisella tularensis. U.S. weapons stores of tularemia bacteria were reported destroyed in 1973. Until the demise of the Soviet Union, its biological weapons development program actively developed strains of the bacterium that were resistant to antibiotics and vaccines. As of March 2003, the whereabouts and disposition of some Soviet era tularemia stocks remains uncertain.

Tularemia is listed as potential bioterrorist weapon because it is easily obtained and potentially lethal.

World Health Organization (WHO) estimates hypothesize that if 50 kg of "weaponized" or highly virulent bacterium Francisella tularensis was dispersed in aerosol form over a large city, depending on weather and exposure patterns, there could be as many as 250,000 infections resulting in a projected 19,000 deaths.

Tularemia bacterium is transferred to humans from animals (i.e., a zoonosis) such as rodents, voles, mice, squirrels, and rabbits. Reflecting the natural origin of the disease, tularemia is also known as rabbit fever. Indeed, the rabbit is the most common source of the disease. Transfer of the bacterium via contaminated water and vegetation is possible as well.

The disease can easily spread from the environmental source to humans (although direct person-to-person contact has not been documented). This contagiousness and the high death rate among those who contract the disease made the bacterium an attractive bioweapon. Both the Japanese and Western armies experimented with Francisella tularensis during World War II. Experiments during and after that war established the devastating effect that aerial dispersion of the bacteria could exact on a population.

Tularemia naturally occurs over much of North America and Europe. In the United States, the disease is predominant in south-central and western states such as Missouri, Arkansas, Oklahoma, South Dakota, and Montana. The disease almost always occurs in rural regions. The animal reservoirs of the bacterium become infected typically by a bite from a blood-feeding tick, fly, or mosquito.

The causative bacterium, Francisella tularensis is a Gram-negative bacterium that, even though it does not form a spore, can survive for protracted periods of time in environments such as cold water, moist hay, soil, and decomposing carcasses.

The number of cases of tularemia in the world is not known, as accurate statistics have not been kept, and because illnesses attributable to the bacterium go unreported. In the United States, the number of cases used to be high. In the 1950s, thousands of people were infected each year. This number has dropped considerably, to less than 200 each year, and those who are infected now tend to be those who are exposed to the organism in its rural habitat (e.g., hunters, trappers, farmers, and butchers).

Humans can acquire the infection through breaks in the skin and mucous membranes, by ingesting contaminated water, or by inhaling the organism. An obligatory step in the establishment of an infection is the invasion of host cells. A prime target of invasion is the immune cell known as macrophages. Infections can initially become established in the lymph nodes, lungs, spleen, liver, and kidney. As these infections become more established, the microbe can spread to tissues throughout the body.

Symptoms of tularemia vary depending on the route of entry. Handling an infected animal or carcass can produce a slow-growing ulcer at the point of initial contact and swollen lymph nodes. When tularemia is inhaled, the symptoms include the sudden development of a headache with accompanying high fever, chills, body aches (particularly in the lower back) and fatigue. Ingestion of the organism produces a sore throat, abdominal pain, diarrhea, and vomiting. Other symptoms can include eye infection and the formation of skin ulcers. Some people also develop pneumonia-like chest pain. An especially severe pneumonia develops from the inhalation of one type of the organism, which is designated as Francisella tularensis biovar tularensis (type A). The pneumonia can progress to respiratory failure and death. The symptoms typically tend to appear three to five days after entry of the microbe into the body.

The infection responds to antibiotic treatment and recovery can be complete within a few weeks. Recovery produces a long-term immunity to re-infection. Some people experience a lingering impairment in the ability to perform physical tasks. If left untreated, tularemia can persist for weeks, even months, and can be fatal. The severe form of tularemia can kill up to 60% of those who are infected if treatment is not given.

A vaccine is available for tularemia. To date this vaccine has been administered only to those who are routinely exposed to the bacterium (e.g., researchers). The potential risks of the vaccine, which is a weakened form of the bacterium, have been viewed as being greater than the risk of acquiring the infection.

FURTHER READING:

BOOKS:

Chin, J. "Tularemia." In Control of Communicable Diseases Manual. Washington, DC: American Public Health Association, 2000.

Dennis, D. T. "Tularemia." In: Wallace, R. B. ed. Maxcy-Rosenau-Last Public Health and Preventive Medicine, 14th edition. Stamford: Appleton & Lange, 1998.

SEE ALSO

Bioterrorism, Protective Measures
Infectious Disease, Threats to Security

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Tularemia

Tularemia

Definition

Tularemia is an illness caused by a bacterium. It results in fever, rash, and greatly enlarged lymph nodes.

Description

Tularemia infects a variety of wild animals, including rabbits, deer, squirrels, muskrat, and beaver. Humans can acquire the bacterium directly from contact with the blood or body fluids of these animals, from the bite of a tick or fly which has previously fed on the blood of an infected animal, or from contaminated food or water.

Tularemia occurs most often in the summer months. It is most likely to infect people who come into contact with infected animals, including hunters, furriers, butchers, laboratory workers, game wardens, and veterinarians. In the United States, the vast majority of cases of tularemia occur in the southeastern and Rocky Mountain states.

Causes and symptoms

Five types of illness may occur, depending on where/how the bacteria enter the body:

  • Ulceroglandular/glandular tularemia. Seventy-five to 85% of all cases are of this type. This type is contracted through the bite of an infected tick that has defecated bacteria-laden feces in the area of the bite wound. A tender red bump appears in the area of the original wound. Over a few weeks, the bump develops a punched-out center (ulcer). Nearby lymph nodes grow hugely swollen and very tender. The lymph nodes may drain a thick, pus-like material. Other symptoms include fever, chills, and weakness. In adults, the lymph nodes in the groin are most commonly affected; in children, the lymph nodes in the neck.
  • Oculoglandular tularemia. This type accounts for only about 1% of all cases of tularemia. It occurs when a person's contaminated hand rubs his or her eye. The lining of the eyelids and the surface of the white of the eye (conjunctiva) becomes red and severely painful, with multiple small yellow bumps and pitted sores (ulcers). Lymph nodes around the ears, under the jaw, or in the neck may swell and become painful.
  • Oropharyngeal and gastrointestinal tularemia. This type occurs when contaminated meat is undercooked and then eaten, or when water from a contaminated source is drunk. Poor hygiene after skinning and cleaning an animal obtained through hunting can also lead to the bacteria entering through the mouth. Sores in the mouth and throat, as well as abdominal pain, nausea and vomiting, ulcers in the intestine, intestinal bleeding, and diarrhea may all occur.
  • Pulmonary tularemia. This rare type of tularemia occurs when a person inhales a spray of infected fluid, or when the bacteria reach the lungs through the blood circulation. A severe pneumonia follows.
  • Typhoidal tularemia. This type of tularemia is particularly hard to diagnose, because it occurs without the usual skin manifestations or swelling of lymph glands. Symptoms include continuously high fever, terrible headache, and confusion. The illness may result in a severely low blood pressure, with signs of poor blood flow to the major organs (shock).

Diagnosis

Samples from the skin lesions can be prepared with special stains, to allow identification of the causative bacteria under the microscope. Other tests are available to demonstrate the presence of antibodies (special immune cells that the body produces in response to the presence of specific foreign invaders) which would be increasing over time in an infection with tularemia.

Treatment

Streptomycin (given as a shot in a muscle) and gentamicin (given as either a shot in a muscle or through a needle in the vein) are both used to treat tularemia. Other types of antibiotics have been tested, but have often resulted in relatively high rates of relapse (20%).

Prognosis

With treatment, death rates from tularemia are under 1%. Without treatment, however, the death rate may reach 30%. The pneumonia and typhoidal types have the worst prognosis without treatment.

Prevention

Prevention involves avoiding areas known to harbor ticks and flies, or the appropriate use of insect repellents. Hunters should wear gloves when skinning animals or preparing meat. Others (butchers, game wardens, veterinarians) who work with animals or carcasses should always wear gloves. A vaccine exists, but is usually only given to people at very high risk due to their profession or hobby (veterinarians, laboratory workers, butchers, hunters, game wardens).

Resources

ORGANIZATIONS

Centers for Disease Control and Prevention. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. http://www.cdc.gov.

KEY TERMS

Conjunctiva The lining of the eyelids and the surface of the white part of the eye.

Shock A state in which drastically low blood pressure prevents adequate blood flow to the tissues and organs throughout the body.

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Tularemia

Tularemia

One aspect of forensic science is concerned with the investigation of an illness, outbreak, or death that is thought to be caused by a microorganism. Some microbes are exceptionally more adept at initiating disease than others. A good example of this is the microbe responsible for tularemia.

Tularemia is a plague-like disease caused by the Gram-negative bacterium Francisella tularensis. The organism is transferred to man from animals (i.e., a zoonosis) such as rodents, voles, mice, squirrels, and rabbits. Reflecting the natural origin of the disease, tularemia is also known as rabbit fever. Indeed, the rabbit is the most common source of the disease. Transfer of the bacterium via contaminated water and vegetation is possible as well.

The disease can easily spread from the environmental source to humans (although direct person-to-person contact has not been documented). This contagiousness and the potential high death rate among those who contract the disease made the bacterium an attractive bioweapon. Both the Japanese and Western armies experimented with Francisella tularensis during World War II. Experiments during and after that war established the devastating effect that aerial dispersion of the bacteria could exact on a population.

Tularemia naturally occurs over much of North America and Europe. In the United States, the disease is predominant in south-central and western states such as Missouri, Arkansas, Oklahoma, South Dakota, and Montana. The disease almost always occurs in rural regions. The animal reservoirs of the bacterium become infected typically by a bite from a blood-feeding tick, fly, or mosquito.

Francisella tularensis does not form a spore. Nevertheless, it can survive for protracted periods of time in environments such as cold water, moist hay, soil, and decomposing carcasses.

The number of cases of tularemia in the world is not known, since accurate statistics have not been kept and illnesses attributable to the bacterium go unreported. In the United States, the number of cases used to be high. In the 1950s thousands of people were infected each year. This number has dropped considerably, to less than 200 each year. Those who are infected now tend to be those who are exposed to the organism in its rural habitat (e.g., hunters, trappers, farmers, and butchers).

Humans can acquire the infection through breaks in the skin and mucous membranes, by ingesting contaminated water, or by inhaling the organism. An obligatory step in the establishment of an infection is the invasion of host cells. A prime target of invasion is the immune cell known as a macrophage. Infections can initially become established in the lymph nodes, lungs, spleen, liver, and kidney. As these infections become more established, the microbe can spread to tissues throughout the body.

Symptoms of tularemia vary depending on the route of entry. Handling an infected animal or carcass can produce a slow-growing ulcer at the point of initial contact and swollen lymph nodes. When inhaled, the symptoms include the sudden development of a headache with accompanying high fever, chills, body aches (particularly in the lower back), and fatigue. Ingestion of the organism produces a sore throat, abdominal pain, diarrhea, and vomiting. Other symptoms can include eye infection and the formation of skin ulcers. Some people also develop pneumonia-like chest pain. An especially severe pneumonia develops from the inhalation of one type of the organism, which is designated as Francisella tularensis biovar tularensis (type A). The pneumonia can progress to respiratory failure and death. The symptoms typically tend to appear three to five days after entry of the microbe into the body.

The infection responds to antibiotic treatment and recovery can be complete within a few weeks. Recovery produces a long-term immunity to re-infection. Some people experience a lingering impairment in the ability to perform physical tasks. If left untreated, tularemia can persist for weeks, even months, and can be fatal. The severe form of tularemia can kill up to 60% of those who are infected if treatment is not given.

A vaccine consisting of a living, but weakened form of the bacterium is available for tularemia. To date it has been administered only to those who are routinely exposed to the bacterium (e.g., researchers). This is because the potential risks of the vaccine are statistically greater than the risk of acquiring the infection.

see also Bacterial biology; Bioterrorism; Vaccines.

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Tularemia

Tularemia

Tularemia is a plague-like disease caused by the bacterium Francisella tularensis that can transferred to man from animals such as rodents, voles, mice, squirrels, and rabbits. Reflecting the natural origin of the disease, tularemia is also known as rabbit fever. Indeed, the rabbit is the most common source of the disease. Transfer of the bacterium via contaminated water and vegetation is possible as well.

The disease can easily spread from the environmental source to humans (although direct person-to-person contact has not been documented). This contagiousness and the high death rate among those who contract the disease made the bacterium an attractive bioweapon. Both the Japanese and Western armies experimented with Francisella tularensis during World War II. Experiments during and after that war established the devastating effect that aerial dispersion of the bacteria could exact on a population. Until the demise of the Soviet Union, its biological weapons development program actively developed strains of the bacterium that were resistant to antibiotics and vaccines.

Tularemia naturally occurs over much of North America and Europe. In the United States, the disease is predominant in south-central and western states such as Missouri, Arkansas, Oklahoma, South Dakota, and Montana. The disease almost always occurs in rural regions. The animal reservoirs of the bacterium become infected typically by a bite from a blood-feeding tick, fly, or mosquito.

The causative bacterium, Francisella tularensis, is a Gram-negative bacterium that, even though it does not form a spore, can survive for protracted periods of time in environments such as cold water, moist hay, soil, and decomposing carcasses.

The number of cases of tularemia in the world is not known, as accurate statistics have not been kept, and because illnesses attributable to the bacterium go unreported. In the United States, the number of cases used to be high. In the 1950s thousands of people were infected each year. This number has dropped considerable, to less than 200 each year in the 1990s and those who are infected now tend to be those who are exposed to the organism in its rural habitat (e.g., hunters, trappers, farmers, and butchers).

Humans can acquire the infection through breaks in the skin and mucous membranes, by ingesting contaminated water, or by inhaling the organism. An obligatory step in the establishment of an infection is the invasion of host cells. A prime target of invasion is the immune cell known as macrophages. Infections can initially become established in the lymph nodes, lungs, spleen, liver, and kidney. As these infections become more established, the microbe can spread to tissues throughout the body.

Symptoms of tularemia vary depending on the route of entry. Handling an infected animal or carcass can produce a slow-growing ulcer at the point of initial contact and swollen lymph nodes. When inhaled, the symptoms include the sudden development of a headache with accompanying high fever, chills, body aches (particularly in the lower back), and fatigue. Ingestion of the organism produces a sore throat, abdominal pain diarrhea, and vomiting. Other symptoms can include eye infection and the formation of skin ulcers. Some people also develop pneumonia -like chest pain. An especially severe pneumonia develops from the inhalation of one type of the organism, which is designated as Francisella tularensis biovar tularensis (type A). The pneumonia can progress to respiratory failure and death. The symptoms typically tend to appear three to five days after entry of the microbe into the body.

The infection responds to antibiotic treatment and recovery can be complete within a few weeks. Recovery produces a long-term immunity to re-infection. Some people experience a lingering impairment in the ability to perform physical tasks. If left untreated, tularemia can persist for weeks, even months, and can be fatal. The severe form of tularemia can kill up to 60% of those who are infected if treatment is not given.

A vaccine is available for tularemia. To date this vaccine has been administered only to those who are routinely exposed to the bacterium (e.g., researchers). The potential risks of the vaccine, which is a weakened form of the bacterium, have been viewed as being greater than the risk of acquiring the infection.

See also Bacteria and bacterial infection; Bioterrorism, protective measures; Infection control; Zoonoses

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Tularemia

TULAREMIA

Tularemia is a potentially severe and fatal bacterial zoonosis caused by a gram-negative coccobacillus, Francisella tularensis. Tularemia occurs only in the Northern Hemisphere, most commonly in the United States and Europe. In nature, infection occurs mostly in rodents, rabbits, and hares. Humans become infected by handling infectious animal carcasses; eating or drinking contaminated food or water; being bitten by infective ticks, flies, or mosquitoes; or by inhaling contaminated aerosols. The disease is not transmitted person-to-person. The more severe F. tularensis strain A occurs only in the United States and Canada, while the milder strain B occurs throughout the Northern Hemisphere.

Tularemia in humans is relatively rare, and it takes several forms, depending on the route of inoculation. The ulceroglandular form is the most common. It is characterized by an ulcer that develops where infection has penetrated the skin, accompanied by painful swelling of nearby lymph glands. Other forms include the glandular, oculoglandular, oropharyngeal, pneumonic, intestinal, and septic ("typhoidal") types. Following a usual incubation period of three to five days (sometimes longer), all forms have similar acute onsets of fever, headache, musculoskeletal pain, progressive weakness, and weight loss. Patients with tularemia pneumonia typically develop a cough with minimal or no sputum production, chest pain, and difficulty in breathing. Patients with the septic form sometimes develop complications of bleeding, respiratory failure, and shock. All forms can be cured by treatment with antibiotics such as streptomycin, gentamicin, or tetracyclines. The disease can be fatal if not treated early with appropriate antibiotics.

Tularemia is best prevented by avoiding sick or dead animals, protecting against tick and insect bites, and by sanitary practices that protect against contamination of food and water by infected animals.

David T. Dennis

(see also: Vector-Borne Diseases; Zoonoses )

Bibliography

Beran, G. W. (1994). Handbook of Zoonoses, 2nd edition. Boca Raton, FL: CRC Press.

Dennis, D. T. (1998). "Tularemia." In Maxcy-Rosenau-Last Public Health and Preventive Medicine, 14th edition, ed. R. B. Wallace. Stamford, CT: Appleton & Lange.

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tularemia

tularemia (tōōlərē´mēə) or rabbit fever, acute, infectious disease caused by Francisella tularensis (Pasteurella tularensis). The greatest incidence is among people who handle infected wild rabbits. Tularemia may also be transmitted by other infected animals, ticks, or contaminated food or water. Within 10 days of contact the disease begins suddenly with high fever and severe constitutional symptoms. An ulcerating lesion (or several lesions) develops at the site of infection, such as the arm, eye, or mouth. The regional lymph nodes enlarge, suppurate, and drain. The infection may be complicated by pneumonia, meningitis, or peritonitis, and the mortality rate is about 6%. Treatment is with antibiotics. Continuous wet saline dressings can be beneficial for primary skin lesion.

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Tularemia

Tularemia

Do Rabbits Cause Rabbit Fever?

How Do People Contract Rabbit Fever?

Is Tularemia Common?

What Are the Symptoms of Tularemia?

How Can a Doctor Tell if a Person Has Tularemia?

How Is Tularemia Treated?

Is There Any Way to Prevent Tularemia?

Resources

Tularemia (too-lah-REE-me-uh), sometimes called rabbit fever, is an infection caused by bacteria that can be spread to humans by wild animals.

KEYWORDS

for searching the Internet and other reference sources

Biological weapons

Bioterrorism

Francisella tularensis

Rabbit fever

Tick-borne diseases

Zoonoses

Do Rabbits Cause Rabbit Fever?

Tularemia is caused by the bacterium Francisella tularensis (fran-sih-SEL-uh too-lah-REN-sis). Most cases in the United States come from contact with infected rabbits and deer, although the bacterium also lives in other small mammals and birds, and it can be found in soil.

Tularemia bacteria enter the body through the mucous membranes*, the skin, the lungs, or the digestive system. There are seven different forms of the disease:

*mucous membranes
are the moist linings of the mouth, nose, eyes, and throat.
  • Ulceroglandular tularemia comes from handling an infected animal or from the bite of a tick or deer fly. An ulcer (an open sore) forms on the skin.
  • Glandular tularemia causes symptoms similar to those of the ulceroglandular form but an ulcer does not form. The bacteria may enter the body through small cuts in the skin. Most cases of rabbit fever in the United States are glandular or ulceroglandular tularemia.
  • Oculoglandular tularemia comes from touching the eye with infected fingers. The eye becomes red and painful and has a discharge.
  • Oropharyngeal tularemia comes from eating the undercooked meat of an infected animal or from drinking water contaminated by the bacterium. It causes digestive system symptoms, such as vomiting or diarrhea.
  • Pneumonic tularemia is caused by inhaling spores (an inactive form of the germ enclosed in a protective shell) in dust from a contaminated area into the lungs. Other types of tularemia also may spread to the lungs.
  • Typhoidal tularemia affects many organs of the body. This rare form of the disease occurs without any previous signs of infection in any specific part of the body.
  • Septic tularemia is a severe form of the disease that affects the whole body. Someone with this form may go into shock* and experience serious complications.
*shock
is a serious condition in which blood pressure is very low and not enough blood flows to the bodys organs and tissues. Untreated, shock may result in death.

Is Tularemia the Next Anthrax?

It takes as few as 10 spores of the Francisella tularensis bacterium to infect someone with tularemia. The bacterium is hard to destroy and can be easily released into the air. For these reasons, experts on biological warfare fear that some groups might use tularemia as a weapon.

The United States stockpiled the bacteria during the 1960s but destroyed its stores in the 1970s at the order of the president. Russia, too, stockpiled and produced the bacteria through the mid-1990s.

There is no vaccine currently available in the United States. In the event of a bioterrorist attack, swift and widespread use of antibiotics could reduce the harmful effects of the disease.

How Do People Contract Rabbit Fever?

People cannot catch tularemia from one another. Most cases in the United States occur when someone gets a bite from a tick or deer fly that has previously bitten an infected rabbit or deer. Those in contact with infected animals may be infected by the bacterium through small cuts on the skin. Hunters contract tularemia from handling or eating undercooked, contaminated meat. In rare cases, bacterial spores survive in the soil and are released into the air; people then breathe the spores into their lungs. Drinking contaminated water is another rare but possible way to contract the disease.

Is Tularemia Common?

Tularemia occurs in the United States, Europe, and Asia, mainly in rural areas. Tularemia is highly infectious, but in the United States fewer than 200 cases are reported each year (mostly from Texas, Arkansas, and Oklahoma). Some additional cases may not be recognized and reported.

Tularemia affects people of every age, sex, and race. In spring and summer months, it occurs most often in children who become infected when playing outside. In fall and winter, hunters are more likely to contract the infection.

What Are the Symptoms of Tularemia?

Symptoms of tularemia depend on the form of the disease. Most infected people have a red spot at the site of the insect bite or cut where the bacterium entered the body. This becomes an ulcer.

Other signs and symptoms appear within 1 to 14 days (most frequently in 2 to 5 days) and may come on suddenly. They can include extreme tiredness, muscle aches, fever, headache, sweating, chills, and weight loss. Lymph nodes* in the groin and armpits may become swollen.

*lymph
(LIMF) nodes are small, bean-shaped masses of tissue that contain immune system cells that fight harmful microorganisms. Lymph nodes may swell during infections.

People who contract tularemia from inhaled bacteria usually have pneumonia*-like symptoms, such as a dry cough, shortness of breath, or discomfort in the chest area. This form can progress to shock and respiratory failure*.

*pneumonia
(nu-MO-nyah) is inflammation of the lung.
*respiratory failure
is a condition in which breathing and oxygen delivery to the body is dangerously altered. This may result from infection, nerve or muscle damage, poisoning, or other causes.

People who drink contaminated water or eat contaminated meat may experience nausea (NAW-zee-uh), vomiting, pain in the abdomen, diarrhea, sore throat, and sometimes gastrointestinal* bleeding.

*gastrointestinal
(gas-tro-in-TES-tih-nuhl) means having to do with the organs of the digestive system, the system that processes food. It includes the mouth, esophagus, stomach, intestines, colon, and rectum and other organs involved in digestion, including the liver and pancreas.

How Can a Doctor Tell if a Person Has Tularemia?

Doctors use blood tests to check for tularemia. Some tests look for antibodies* to the Francisella tularensis bacterium. Doctors also may look for evidence of the bacterium in the blood, fluid from the nose and mouth, and lymph nodes. If the person has symptoms of pneumonia, a chest X ray will be taken.

*antibodies
(AN-tih-bah-deez) are protein molecules produced by the bodys immune system to help fight specific infections caused by microorganisms, such as bacteria and viruses.

How Is Tularemia Treated?

Tularemia responds well to antibiotics, and most people can receive treatment at home. Because tularemia is not contagious, people who have it do not have to be isolated.

In more severe cases, when the disease attacks the lungs or other organs, people may require hospitalization and closer monitoring.

Most people who receive treatment recover from tularemia. The septic and pneumonic forms of the disease can be life threatening, however. Symptoms of tularemia can last for several weeks. Most people do not experience any lasting damage from the disease and may develop some degree of immunity* to it.

*immunity
(ih-MYOON-uh-tee) is the condition of being protected against an infectious disease. Immunity often develops after a germ is introduced to the body. One type of immunity occurs when the body makes special protein molecules called antibodies to fight the disease-causing germ. The next time that germ enters the body, the antibodies quickly attack it, usually preventing the germ from causing disease.

Complications of tularemia can include pneumonia, meningitis*, osteomyelitis*, kidney problems, lung abscesses*, pericarditis (inflammation of the sac surrounding the heart), shock, and, rarely, death.

*meningitis
(meh-nin-JY-tis) is an inflammation of the meninges, the membranes that surround the brain and the spinal cord. Meningitis is most often caused by infection with a virus or a bacterium.
*osteomyelitis
(ah-stee-o-my-uhLYE-tis) is a bone infection that is usually caused by bacteria. It can involve any bone in the body, but it most commonly affects the long bones in the arms and legs.
*abscess
(AB-ses) is a localized or walled off accumulation of pus caused by infection that can occur anywhere in the body.

Is There Any Way to Prevent Tularemia?

In the past, laboratory workers at risk for contracting tularemia because of frequent contact with laboratory animals were vaccinated against the disease. In 2003, the vaccine is not available for public use in the United States while the Food and Drug Administration performs further studies.

The best way to avoid contracting tularemia is to prevent tick bites by using repellent and wearing light-colored clothing that covers arms and legs. It is wise to avoid contact with certain wild animals, such as rabbits. Experts recommend that hunters wear rubber gloves when handling animals and that all meat be thoroughly cooked. Swimming in or drinking water that might be contaminated should be avoided.

See also

Bioterrorism

Meningitis

Osteomyelitis

Pneumonia

Tick-borne Infections

Zoonoses

Resources

Organizations

American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038. The American College of Emergency Physicians provides advice about avoiding tick bites in the article Tick BitesTheyre Not Just About Lyme Disease posted at its website.

Telephone 800-798-1822 http://www.acep.org

U.S. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333. The CDC is the U.S. government authority for information about infectious and other diseases. It has a web page explaining tularemia and how it can be used as a biochemical weapon.

Telephone 800-311-3435 http://www.cdc.gov

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Tularemia

Tularemia

Tularemia is a plague like disease caused by the Gram-negative bacterium Francisella tularensis. The organism is transferred to humans from animals (i.e., a zoonosis) such as rodents, voles, mice, squirrels, and rabbits. Reflecting the natural origin of the disease, tularemia is also known as rabbit fever. Indeed, the rabbit is the most common source of the disease. Transfer of the bacterium via contaminated water and vegetation is possible as well.

The disease can easily spread from the environmental source to humans (although direct person-to-person contact has not been documented). This contagiousness and the potential high death rate among those who contract the disease made the bacterium an attractive bioweapon. Both the Japanese and Western armies experimented with Francisella tularensis during World War II. Experiments during and after that war established the devastating effect that aerial dispersion of the bacteria could exact on a population.

Tularemia naturally occurs over much of North America and Europe. In the United States, the disease is predominant in south-central and western states such as Missouri, Arkansas, Oklahoma, South Dakota, and Montana. The disease almost always occurs in rural regions. The animal reservoirs of the bacterium become infected typically by a bite from a blood-feeding tick, fly, or mosquito.

Francisella tularensis does not form a spore. Nevertheless, it can survive for protracted periods of time in environments such as cold water, moist hay, soil, and decomposing carcasses.

The number of cases of tularemia in the world is not known, since accurate statistics have not been kept and illnesses attributable to the bacterium go unreported. In the United States, the number of cases used to be high. In the 1950s thousands of people were infected each year. This number has dropped considerably, to less than 200 each year. Those who are infected now tend to be those who are exposed to the organism in its rural habitat (e.g., hunters, trappers, farmers, and butchers).

Humans can acquire the infection through breaks in the skin and mucous membranes, by ingesting contaminated water, or by inhaling the organism. An obligatory step in the establishment of an infection is the invasion of host cells. A prime target of invasion is the immune cell known as a macrophage. Infections can initially become established in the lymph nodes,

lungs, spleen, liver, and kidney. As these infections become more established, the microbe can spread to tissues throughout the body.

Symptoms of tularemia vary depending on the route of entry. Handling an infected animal or carcass can produce a slow-growing ulcer at the point of initial contact and swollen lymph nodes. When inhaled, the symptoms include the sudden development of a headache with accompanying high fever, chills, body aches (particularly in the lower back), and fatigue. Ingestion of the organism produces a sore throat, abdominal pain, diarrhea, and vomiting. Other symptoms can include eye infection and the formation of skin ulcers. Some people also develop pneumonia like chest pain. An especially severe pneumonia develops from the inhalation of one type of the organism, which is designated as Francisella tularensis biovar tularensis (type A). The pneumonia can progress to respiratory failure and death. The symptoms typically tend to appear three to five days after entry of the microbe into the body.

The infection responds to antibiotic treatment and recovery can be complete within a few weeks. Recovery produces a long-term immunity to re-infection. Some people experience a lingering impairment in the ability to perform physical tasks. If left untreated, tularemia can persist for weeks, even months, and can be fatal. The severe form of tularemia can kill up to 60% of those who are infected if treatment is not given.

A vaccine consisting of a living, but weakened form of the bacterium is available for tularemia. To date it has been administered only to those who are routinely exposed to the bacterium (e.g., researchers). This is because the potential risks of the vaccine are statistically greater than the risk of acquiring the infection.

See also Bacteria; Disease; Zoonoses.

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Tularemia

Tularemia

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

BIBLIOGRAPHY

Introduction

Tularemia, also known as rabbit fever, deerfly fever, and lemming fever, is a highly infectious bacterial zoonotic (acquired from animals) disease that is endemic (occurs naturally) throughout the United States. The highly infectious nature of the bacterium poses a significant threat to humans and Francisella tularensis, the bacteria that causes tularemia, has also been considered a potential bioterrorism agent.

Francisella tularensis, is a highly infectious bacterium that naturally colonizes (lives at population levels below that which cause disease) many species of small animals. Transmission of the disease to humans is via vectors such as ticks and mosquitoes, contact with infected animals, or ingestion of contaminated soil, water, or food. Symptoms present after a short incubation and may include fever, nausea, headache, diarrhea, and joint and muscle pain. The infection can spread to the lungs, liver, and lymphatic system. In around two percent of cases, tularemia is fatal.

Treatment with antibiotics is usually effective and readily available. Prevention may be achieved through the use of insect repellents, avoidance of contact with infected animals, and the maintenance of uncontaminated food and water sources.

WORDS TO KNOW

AEROSOL: Particles of liquid or solid dispersed as a suspension in gas.

ARTHROPOD: A member of the largest single animal phylum, consisting of organisms with segmented bodies, jointed legs or wings, and exoskeletons.

COLONIZE: Colonize refers to the process where a microorganism is able to persist and grow at a given location.

ENDEMIC: Present in a particular area or among a particular group of people.

FULMINATE: In medicine, a disease that appears suddenly and follows a severe, intense course is said to fulminate. In chemistry, a fulminate is fulminic acid, HONC, or any other compound containing the -ONC group.

HOST: Organism that serves as the habitat for a parasite, or possibly for a symbiont. A host may provide nutrition to the parasite or symbiont, or simply a place in which to live.

INOCULUM: An inoculum is a substance such as virus, bacterial toxin, or a viral or bacterial component that is added to the body to stimulate the immune system, which provides protection from an infection by the particular microorganism.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

VECTOR: Any agent, living or otherwise, that carries and transmits parasites and diseases. Also, an organism or chemical used to transport a gene into a new host cell.

VIRULENCE: Virulence is the ability of a disease organism to cause disease: a more virulent organism is more infective and liable to produce more serious disease.

ZOONOSES: Zoonoses are diseases of microbiological origin that can be transmitted from animals to people. The causes of the diseases can be bacteria, viruses, parasites, and fungi.

Disease History, Characteristics, and Transmission

Tularemia was first described in Japan in 1837, but gained its name from Tulare County, California, where a plague-like illness arose among squirrels in 1911. The causative agent, Francisella tularensis, is considered to be among the most infectious bacteria known, and, if left untreated, infection may prove fatal.

Symptoms of tularemia usually appear within three to five days of exposure, but can take up to 14 days in some cases. Presentation includes a sudden fever, chills, headache, diarrhea, muscle aches, joint pain, dry cough, and progressive weakness. Disease caused by tularemia can vary in severity and presentation according to virulence (pathogenicity, or the ability to cause disease) of the infecting organism, dose, and site of inoculums (where the bacteria enters the body). Symptoms can include ulcers on the skin or mouth, swollen painful lymph glands, and a sore throat. Some persons with tularemia also become susceptible to pneumonia and develop chest pain, bloody sputum (mucus from the lungs), and have breathing complications.

Only a small number of the bacteria are required for tularemia disease to fulminate (appear suddenly and intensely); the infection is established when particles invade white blood cells and subsequently attack the immune system following multiplication. The major target organs are the lymph nodes, lungs, spleen, liver, and kidneys. While the inoculation may be focal, the disease will often become disseminated and cause problems throughout the body. The disease is fatal in around two percent of cases, with the most common cause of death being failure of the respiratory system or multiple organs.

Many small animals, including rodents, rabbits, and hares, provide natural reservoirs for the bacteria. Transmission of the infection to humans may occur through vectors such as ticks, biting flies, and mosquitoes. Humans may also contract the disease by handling infected animals or by ingesting contaminated water, soil, or food. Inhalation is also a significant form of transmission, but person-to-person transmission has not been established.

Scope and Distribution

The F. tularenisis bacterium is endemic throughout North America and in parts of Europe and Asia. Cases of tularemia have been reported in every state of America except Hawaii, with the majority occurring in southcentral and western states. The widely present nature of the bacteria may be attributed to the fact that F. tularensis is found in diverse hosts and habitats, and it can survive for weeks at low temperatures in water, moist soil, hay, straw, and decaying animal carcasses.

People at a higher risk of contracting tularemia include hunters and trappers engaging in the skinning of potentially infected animals. Activities that lead to the aerosolization (dispersion into the air) of the bacteria can also increase the likelihood of infection, with lawn mowing the most common example of such an activity.

Currently in the United States, cases of tularemia occur most commonly between May and August when they are largely attributed to transmission by arthropod (a group of invertebrate animals including insects) vectors. This is in contrast to the historical incidence of tularemia, which was previously considered a winter disease contracted mostly from infected rabbits.

The incidence of tularemia has dropped significantly in the United States, from several thousand cases per year in the 1950s to around 200 per year in the 1990s. The fatality rate in the United States has also declined and is relatively low, at 1.4%. This is most likely due to the current availability of antimicrobial therapies. The exact prevalence of tularemia, however, is unknown, as it is assumed that the disease is greatly under-recognized and therefore, underreported. Tularemia occurs more often among males than females; it is also more prevalent among children between the ages of five and nine and adults between the ages of 75–84.

IN CONTEXT: TERRORISM AND BIOLOGICAL WARFARE

The Division of Vector-Borne Infectious Diseases at Centers for Disease Control and Prevention (CDC) states that “Francisella tularensis is very infectious. A small number (10-50 or so organisms) can cause disease. If F. tularensis were used as a weapon, the bacteria would likely be made airborne for exposure by inhalation. People who inhale an infectious aerosol would generally experience severe respiratory illness, including life-threatening pneumonia and systemic infection, if they are not treated. The bacteria that cause tularemia occur widely in nature and could be isolated and grown in quantity in a laboratory, although manufacturing an effective aerosol weapon would require considerable sophistication.”

A part of the CDC program for bioterrorism preparedness and response the CDC states that as part of its preparations the CDC (or partners in the preparedness program) is:

  • Stockpiling antibiotics to treat infected people
  • Coordinating a nation-wide program where states share information about tularemia
  • Creating new education tools and programs for health professionals, the public, and the media.

SOURCE: Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Vector-Borne Infectious Diseases

Treatment and Prevention

Treatment of tularemia is generally effective with anti-biotics, usually streptomycin or gentamicin. Due to the nature of the infection, treatment should be continued for at least 10 days to ensure complete recovery. Longterm immunity will usually follow recovery from tularemia, but re-infection is possible, and repeated cases have been reported.

Although not yet available to the market, a vaccine was developed using a live attenuated strain of the disease. As of 2007, the vaccine is under review by the Food and Drug Administration. Post-exposure vaccination is not considered a viable public health strategy due to the three-to-five day incubation period of the disease, as well as the time necessary for immunity to develop.

Preventative measures should be adopted by people working in endemic areas. These should include the use of insect repellent on skin and clothing to minimize chance of insect bites and effective handwashing using antibacterial soap for people handling animal carcasses. The general public can also minimize infection by thoroughly cooking animal meat and ensuring the safety of water sources.

Impacts and Issues

Tularemia is identified as a Category A agent by the Centers for Disease Control (CDC), meaning that it is considered a high risk to society poses a potential threat to national security. The extremely low infectious dose required by the F. tularensis bacteria, in addition to the possible aerosol nature of transmission, makes tularemia potentially hazardous in large populations.

It is for these reasons that tularemia has been previously considered a viable option as a biological warfare agent. During World War II (1939–1945), Japanese researchers investigated this avenue. In the 1950s and 1960s, the United States developed weapons to deliver aerosolized F. tularensis organisms. These were destroyed in 1973. The World Health Organization (WHO) released a statement in 1969 that estimated that the successful release of 50 kilograms of the virulent bacteria over a metropolitan area housing five million people in a developed country would result in 250,000 cases of illness, including 19,000 fatalities. Although it was removed from the list of nationally notifiable diseases in 1994, it was reinstated in 2000 due to its potential for use as a biological weapon. As of 2007, this impact is still recognized and the CDC acts to ensure the rapid availability of substantial amounts of available antibiotics effective against the bacteria that causes tularemia.

See AlsoAntibacterial Drugs; Bacterial Disease; Bioterrorism; CDC (Centers for Disease Control and Prevention); Vaccines and Vaccine Development; World Health Organization (WHO); Zoonoses.

BIBLIOGRAPHY

Books

Mandell, G.L., J.E. Bennett, and R. Dolin. Principles and Practice of Infectious Diseases, Vol. 2. Philadelphia, PA: Elsevier, 2005.

Fong, I.W., and K. Alibek. Bioterrorism and Infectious Agents: A New Dilemma for the 21st Century. New York: Springer Science, 2005.

Mims, C., H. Dockrell, R. Goering, I. Roitt, D. Wakelin, and M. Zuckerman. Medical Microbiology. St. Louis, MO: Mosby, 2004.

Web Sites

Centers for Disease Control (CDC). “Consensus Statement: Tularemia as a Biological Weapon: Medical and Public Health Management.” June 6, 2001. <http://www.bt.cdc.gov/agent/tularemia/tularemia-biological-weapon-abstract.asp#2> (accessed April 5, 2007).

Centers for Disease Control (CDC). “Tularemia.” February 21, 2005. <http://www.cdc.gov/ncidod/dvbid/tularemia.htm> (accessed April 5, 2007).

Infectious Diseases Society of America. “Tularemia: Current, Comprehensive Information on Pathogenesis, Microbiology, Epidemiology, Diagnosis, Treatment, and Prophylaxis.” March 5, 2007. <http://www.cidrap.umn.edu/idsa/bt/tularemia/biofacts/tularemiafactsheet.html#_Agent> (accessed April 5, 2007).

Tony Hawas

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