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Education and Training

Tularemia


a. Overview
b. Epidemiology
c. Potential as a Biological Weapon/Events that Might Take Place
d. Recognition/Diagnosis
e. Treatment/Environmental Decontamination and Protection

a. Overview:
Tularemia is a bacterial zoonosis1 resulting from infection with Francisella tularensis . Of note is the fact that Francisella tularensis is considered to be one of the most infectious bacterial agents known, requiring only a few organisms2 to cause disease. Humans can be exposed to the disease from a number of environmental sources.

Tularemia was first described as a disease of rodents in the early 20 th century. Soon thereafter, the human form of the disease and the potential for epidemic outbreaks3 resulted in growing concern among the medical and public health community.

Symptoms of tularemia include such non-specific symptoms as: fever, chills, headache, diarrhea, muscle and joint pain, non-productive cough and weakness. Depending upon the nature of exposure other symptoms can include: pneumonia, chest pain, ulcers of the skin or mouth, swollen lymph nodes and painful eyes and sore throat.

b. Epidemiology:
Tularemia has been reported in every state except for Hawaii . Most cases are reported in the south-central and western states4. Tularemia is almost exclusively a rural disease.

The organism can be found in soil, water and vegetation. Natural reservoirs of the infection include a number of small mammals such as mice, rats, squirrels and rabbits. Humans can be infected5 in a number of ways including: bites from arthropods, handling infective animal tissues, ingestion of contaminated food or water, and inhalation of aerosols.

Most cases of tularemia occur in spring and summer when infectious arthropods are active. Over the period of 1985 – 1992 there were an average of 171 cases per year with a fatality rate of less than 1.5%. Airborne cases6 in the US are uncommon.

Although it is highly infective, there have been no reports of the transmission of tularemia from person to person7.

c. Potential as a Biological Weapon/Events that Might Take Place:
The Working Group on Civilian Biodefense considers F tularensis to be a potential biological weapon for three reasons: high level of infectivity, ease of dissemination and capacity to cause a severe disease. It is considered to be a Category A agent (CDC).

Historically the organism has long been considered to have biological weapons potential8 since WWII.

F. Tularensis could be used as a biological weapon in a number of ways including contamination of food and water supplies. However, the Working Group on Civilian Biodefense considers that aerosol release would be the most probable. Such a release would result in the onset of large numbers of cases of acute febrile illness 3 – 5 days after release9.

In cases of exposure to F tularensis aerosols, illness would be expected to persist for several weeks with the potential for relapse. Immunization would only confer partial protection from infection. The impact10 in terms of morbidity and mortality and economic impact would be substantial.

d. Recognition/Diagnosis:
Inhalation tularemia11 would be associated with the sudden onset of febrile illness progressing in some cases to acute respiratory illness including pharyngitis, bronchiolitis, and pneumonitis (Figure 1). If untreated, the patient may become septic. Exposure to aerosols may also present result in eye contamination (ocular tularemia); skin penetration (glandular disease) or oropharylgeal disease with lympheadenitis) (Figure 2).

Recognition by health care workers would most likely come from observing.

a sudden unexplained increase in the number of cases of the disease as well as cases in areas where the disease is not endemic, during times of the year when the incidence is generally low or in populations not generally considered to be at risk.

Any health care worker exposed to acutely ill patients may be the first to recognize the potential threat. This would include medical technologists, radiologic technologists, respiratory therapists, nurses and physicians. Early recognition is important to ensure that patients receive appropriate antibiotic therapy to minimize the deleterious effects of the disease12.

Definitive laboratory diagnosis is essential; therefore, physicians who suspect tularemia should collect the appropriate laboratory specimens and alert the laboratory to the need for special diagnostic procedures13 and safety precautions14. For information on reporting and specimen submission refer to the Ohio Department of Health Laboratories site. (See References below)

e. Treatment/Environmental Decontamination and Protection:
The vaccine is an investigational drug currently under review by the FDA15.

Patients infected with tularemia are treated with antibiotics. Streptomycin is the drug of choice. Other antibiotics used to treat tularemia include: gentamicin, tetracyclines and chloramphenicol. Ciprofloxacin has been used off-label and has demonstrated promise in both children and adults.

Post-exposure treatment with antibiotics continued for 14 days may be protective.

Isolation is not recommended for patients with tularemia.

Laboratory specimens should be handled using BSL-3 precautions16.

F tularensis may survive for extended period in cold, moist environments17.

References:
Tularemia--- United States , 1990 – 2000. CDC, MMWR, 51(09):182-84, March 8, 2002. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5109a1.htm

Emergency preparedness and response: key facts about tularemia, CDC, http://www.bt.cdc.gov/agent/tularemia/facts.asp

Infectious disease control manual, Ohio Department of Health, http://www.odh.ohio.gov/healthresources/infectiousdiseasemanual.aspx

Recognition of illness associated with the intentional release of a biologic agent. CDC, MMWR, 50(41):893-97, October 19, 2001. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5041a2.htm

The Ohio State University Medical Center, Epidemiology Department, Annual Infection Control Education 2004.

Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon. JAMA 285(21):2763 – 73, June 6, 2001, http://jama.ama-assn.org/cgi/content/full/285/21/2763

Carroll K, Held M, Stombler R, Bryan J. Laboratory preparedness for bioterrorism: from the phlebotomist to the pathologist. Laboratory Medicine 24(3):169-182, March 2003.

Overview of Anthrax:

Incubation Period (days) Clinical Features
1. Early signs
2. Highly suggestive signs
Infection Control
Inhalation: 2 – 10 days
 
1. Fever, fatigue, chills, cough, malaise, body ache, headache, chest pain, GI symptoms
2. ARDS, plural effusion, hemoptysis, sepsis
Standard precautions. No person to person spread by air.

Laboratory: BSL-3 environment

Laboratory Samples Adult Treatment Prophylaxis
Blood, sputum, gastric aspirate, ulcer swab, lymph node aspirate Antibiotic therapy. Streptomycin is drug of choice.

Duration: 10 – 14 days
Doxycycline or cyprofloxicin

Duration: 14 days

Notes:
1Zoonosis
: a disease that can be acquired by humans from an animal source.

2As few as 10 organisms can cause serious, potentially fatal disease.

3Waterborne outbreaks of tularensis occurred in Europe during the 1930's and 40's.

4The highest number of reported cases in Missouri, Arkansas, Oklahoma, South Dakota and Montana.

5 Laboratory workers are at particular risk for tularemia infection due to potential exposure to aerosols and open culture plates and the potential for needle injuries.

6 There was an airborne epidemic in Sweden in 1966 – 67 due to exposure to contaminated aerosols while farming.

7 NOTE: Since there is no know cases of person-to-person transmission, confirmed cases of tularemia do NOT require isolation. Isolation is an appropriate precaution until there is laboratory confirmation of the disease.

8Japanese germ warfare units studied the organism in the 1930's and 40's. In the 1950's the US developed weapons that would disseminate F. tularensis aerosols. In the 1070's development of biological weapons was terminated in the US and stockpiles were destroyed.

9The incubation period for the disease is 1 – 14 days.

10A WHO expert estimated that an aerosol of 50 kg of F tularensis over a metropolitan area of 5 million persons would result in 250, 000 serious illnesses and 19,000 deaths. One estimate of the economic impact was $5.4 billion dollars per 100,00 exposed individuals.

11Note: Tularemia has a number of forms, which differ based on the virulence of the organism, the dose and the site of the innoculum. The disease may present with ocular symptoms, skin lesions, lymphadenitis and GI symptoms.

Figure 1

Chest Radiograph of Patient with Pulmonary Tularemia (http://jama.ama-assn.org/cgi/content/full/285/21/2763)

Figure 2

Lymphadenitis (http://jama.ama-assn.org/cgi/content/full/285/21/2763)

12Untreated pneumonic and systemic forms of the disease have reported mortality rates of 30 - 60%.

13The organism will not be successfully isolated using routine laboratory procedures.

14Laboratory workers are at high risk of infection and Biosafety Level 3 precautions must be used.

15Research indicates that the vaccine is only partially protective against inhalation infection. Vaccine is not recommended for post-exposure protection.

16Information on BSL precautions can be found on the following site: (http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s2.htm)

17Details on environmental decontamination and infection control can be found at the following site:(http://jama.ama-assn.org/cgi/content/full/285/21/2763)