TULAREMIA

by Shelley Peebles

DISEASE NAME: Tularemia (1); Also known as "Rabbit Fever" (2), "Deer Fly Fever" (Utah) (1), "Glandular Tick Feve" (Idaho & Montana) (1), and "O'Hara's Disease' (Japan) (1)

MEANS OF TRANSMISSION

• Zoonotic disease spread by arthropods (i.e. ticks, deerflies) (2)
• Can also be contracted by contact with infected animals, such as rabbits (4)
• Can be transmitted by handling or ingesting contaminated soil, food, or water. (8)
• Inhalation of infected aerosols can infect a person as well. (4)
• Person-to-person transmission has not been documented. (3)
• Adult men are most likely to be exposed by activities such as hunting, butchering, & trapping. (3)

USUAL RESERVOIRS: Mammals such as rabbits (8), squirrels, ticks, and rats acquire the infection through bites from ticks and mosquitoes, and/or contact with a contaminated environment. (3)

ETIOLOGIC AGENT: Francisella tularensis (1) Divided into two subspecies:

• Francisella tularensis biovar tularensis (Type A) (3), Considered the more virulent form (5);
• Francisella tularensis biovar palaearctica (Type B) (5), Relatively avirulent (3)
• Other synonyms include Bacillus tularensis & Pasteurella tularensis (4)

GENERAL CHARACTERISTICS

• Small, nonmotile, aerobic bacteria (8)
• Non-spore forming (3)
• Poorly staining, Gram negative bacteria (6)
• Survives for weeks at low temperatures (8) in water, soil, hay, and decaying animal carcasses. (3)
• Fastidious with Cysteine required for vigorous growth (1)

KEY TESTS FOR IDENTIFICATION

• Culture of F. tularensis by isolation from a clinical specimen (11); is very difficult to isolate from blood (3)
• Grows poorly on Sheep Blood Agar (6)
• Grows very well in Enriched Chocolate Agar (1)
• After incubating for 48 hours at 35ƒC, colonies appear as grey-white, opaque circles (6)
• Gram Stain shows poorly staining, very small, Gram-negative coccobacilli (1)
• Differential Diagnosis should be done in order to rule out other agents (such as Chlamydia pneumoniae, in the case of Pneumonic Tularemia) (5)
• A definitive diagnosis can be made by serological tests: a fourfold increase in titer using microagglutination or tube agglutination of Tularemia ñ the titer usually reaches a maximum in 4-8 weeks (5) but can detect serum antibodies 10 days after illness onset. (3)
• Agglutination tests are done on patient serum to see if it reacts with specific antigens to form visible clumps. (7)
• Direct fluorescent antibody stain is the most rapid method of identification (3)
• The Polymerase Chain Reaction (PCR) procedure is another rapid method of identification. (3)
• Oxidase test will be negative (3) and helps differentiate between Tularemia and other microbes with a weak Gram stain, such as Brucella sp. (6)
• Other tests that can be performed include gel electrophoresis and immunoblotting (3)<o:p</o:p

HISTORICAL INFORMATION

• First seen in Japan in early 1800s. (9)
• Appeared in the US around 1911 (10), when healthcare workers began investigating an epidemic in squirrels and rodents (3) that they first believed was bubonic plague. (9)
• First named Bacterium tularense, after Tulare County, where it was first documented in California. (10)
• Later, Dr. Edward Francis isolated the bacterium and discovered the causes of infection, so the microbe was renamed Francella (for Dr. Francis) tularensis (for Tulare County, California). (4)
• Large waterborne outbreaks of F. tularensis occurred in the Soviet Union & in Europe during the 1930s and 1940s. (3)
• Military studies in the 1950s and 1960s (10) developed biological weapons using Tularemia in its aerosol form. (3)
• Thought to be the cause of the Biblical passage, "the hare...their flesh shall ye not eat, and their carcass shall ye not touch" (4)

SIGNS & SYMPTOMS OF THE DISEASE

• Incubation period of 1-21 days, with an average of 3-5 days. (1)
• Duration of illness is approximately 2 weeks. (1)
• Can infect humans by way of mucous membranes, skin, lungs, ang GI tract. (3)
• There are six different forms of Tularemia: Typhoidal, Pneumonic, Oculoglandular, Oropharyngeal, Ulceroglandular, and Glandular. (5)
  • The Ulceroglandular form usually arises from handling infected carcasses or from an infective arthropod bite (3)
  • Oropharyngeal tularemia is acquired from drinking contaminated water (3)
  • Pneumonic Tularemia occurs as a result of inhaling contaminated aerosols. (5)
• All forms produce similar signs and symptoms, such as fever, chills, & malaise. (8)
• Lymph nodes may become swollen and tender. (8)
• Lesions or ulcers may appear on the skin or in the eyes. (4)
• Other signs and symptoms include nausea, vomiting, abdominal pain, and diarrhea. (5)
• Unless treated, septic shock, coma, organ failure, and death can occur (5)

MICROBIAL VIRULENCE MECHANISMS

• Has a thin envelope containing lipopolysaccharides (3)
• The microbe can grow & is able to survive in monocytes, making it able to withstand humoral antibodies and complement. (4)
• For the most part, the virulence mechanisms of F. tularensis are poorly understood (3)<o:p</o:p

TREATMENT OF DISEASE

• Not contagious (1)
• Infective dose = approximately 10-50 organisms (1)
• Streptomycin dose of 30mg per kg of body weight, every day (via intramuscular injection) for 10-14 days. (5)
• Gentamicin dose of 3-5 mg/kg every day via intravenous injection for 10-14 days (5) ñ is more widely available. (3)
• Tetracycline dose of 500mg, four times a day for 14 days (via intravenous injection) ñ Chloramphenicol may be substituted. (8)
• Other drug choices include Ciproflaxin and Doxycycline (3)

PREVENTION

• A live attenuated vaccine (5) is recommended only for people with a high risk of contracting Tularemia (10), such as health care workers or lab personnel routinely exposed to the bacterium. (3)
• Doxycycline or Tetracycline can be taken orally as a method of prevention in case of an epidemic (5)
• Wear impenetrable gloves while handling animals or tissues. (8)
• Protect skin from insect bites with repellant of some sort. (3)
• Avoid bathing in, swimming in, or drinking of stagnant or untreated water. (8)

CURRENT RESEARCH

• Plasmids have been engineered to express chloramphenicol and Tetracycline resistance in F.tularensis (3)
• Streptomycin-resistant strains are being examined for possible use in biowarfare in the US and Soviet Union (2)
• The live, attenuated vaccine is currently under review by the FDA, and may be available to the general public in the next several years. (3)

OTHER MEANS OF CONTROL

• Organisms can be rendered harmless by mild heat, about 55ƒC for 10 minutes (5)
• Can use standard disinfectants such as one part bleach to nine parts water (5)

REFERENCES:

1. Chu, May. "Agents of Bioterrorism". URL:http://www.bt.cdc.gov/Documents/PPTResponse/BTSRCIPT1edits.pdf accessed on 4/24/02.

2. Anonymous. "Tularemia-United States, 1990-2000". 03/08/02. URL:http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5109al.htm accessed on 4/22/02.

3. The Working Group on Civilian Biodefense. "Tularemia As A Biological Weapon". 6/06/01. URL: http://www.bt.cdc.gov/Agent/Tularemia/TularemiaConsensus.pdf accessed on 4/22/02.

4. Anonymous. "Francisella tularensis". 12/14/98. URL: http://www.medinfo.ufl.edu/year2/mmid/bms5300/bugs/frantula.html accessed on 4/24/02.

5. Anonymous. "Francisella tularensis As A Bioterrorist Agent". 10/26/01. URL: http://www.tdh.state.tx.us/bioterrorism/facts/tularemia.html accessed on 5/01/02.

6. Anonymous. "Protocol For Level A Labs to Rule Out Tularemia". 10/08/01. URL: http://www.tdh.state.tx.us/bioterrorism/facts/lab/template%5Fprotocol.html accessed on 5/01/02.

7. Anonymous. "Agglutination Tests". 11/09/99. URL: http://www.tdh.state.tx.us/lab/serology%5Fagg.htm accessed on 5/01/02.

8. Rand, Michael S. "Tularemia". (No date). URL: http://www.research.ucsb.edu/connect/pro/disease.html accessed on 5/01/02.

9. Cassani, Margaret-Erminia. "Bioterrorism Experiment in Marthaís Vineyard?". 10/01/00. URL: http://www.moonbowmedia.com/ei/biot.htm accessed on 5/01/02.

10. Anonymous. "Tularemia". (No date). URL: http://beaglesunlimited.com/rabbithunting_tularemia.htm accessed on 5/01/02.

11. Anonymous. "Tularemia - 1999 Case Definition". 5/01/99. URL: http://www.cdc.gov/epo/dphsi/casedef/tularemia_current.htm accessed on 5/06/02.