Tularemia

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This article is about the disease. See Francisella tularensis for a separate article about the organism. The two should be read together. Tularemia is a acute illness, endemic in animal populations but with high biological warfare potential, caused by Francisella tularensis. Untreated, it can be 15% or more lethal, but mortality drops to 1% when appropriate antibiotics are given promptly.

Formal characterization is based on the 1911 work by Edward Francis, on the prevalence of a plaguelike illness in ground squirrels in Tulare County, California; the origin of the tularensis part of the organism name. Francis' 1928 description of over 800 cases led to Franciscella. [1] Nevertheless, there are indications that there was much earlier recognition. A reading, in the Old Testament (Leviticus 11:6–7) warns against touching or eating wild hares may suggest very early awareness,[2] and a Japanese journal referred to a first report in 1837. [3]

The organism is found worldwide, in over 100 different animal populations, with two major strains. There is geographic differentiation in the distribution of the strains, which differ in virulence. tularensis is the most virulent and is most common in North America. "Rabbit fever" is a common name for the disease.

While it is not transmissible between humans, its infectivity and epidemic potential caused it to be listed as a human threat in the Select Agent Program. The inhalation hazard is so high that suspected inhalational tularemia must immediately be reported to public health authorities. It was stockpiled as a biological weapon by, at least, the Soviet Union and United States and is in CDC Bioterrorism Agents-Disease list Category A.

I know of no other infection of animals communicable to man that can be acquired from sources so numerous and so diverse. In short, one can but feel that the status of tularemia, both as a disease in nature and of man, is one of potentiality. — R. R. Parker[4]

Prevention

Naturally occurring tularemia is most likely to be contracted from tick bites outdoors, so tick repellent, covering one's skin in endemic area, and careful skin examination for ticks after being outside are basic protective measures.

It can also be contracted through ingestion of contaminated food and water, and handling infected animal carcasses. This calls for caution in people who eat wild game, as well as veterinarians, butchers and others who might handle susceptible wild animals. Observe domestic animals, especially rodents and rabbits, for changes in behavior and get prompt veterinary evaluation. [5]

A biological attack, using airborne organisms, would present, 3 to 5 days after the exposure, to a large number of cases of patients with an acute fever without clearly specific symptoms. As the disease progressed, pneumonia and pleuritis, as well as enlargement of lymph nodes in the chest would appear. The epidemiological pattern, in the opinion of a consensus panel, as well as preliminary laboratory tests, "should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed."[6]

General measures

A vaccine, using live, attenuated organisms, was first introduced in the Soviet Union in the 1930s. A different live, attenuated vaccine is being evaluated in the U.S., and was in use at a biological warfare research center. Not all personnel there were protected by the vaccine, and it is not recommended for post-exposure prophylaxis, but only for laboratory personnel who will work with the organism.

Chemoprophylaxis

If an attack were confirmed during the incubation period, exposed persons should receive a 14 day course of doxycycline or ciprofloxacin. If the attack became obvious only with the presentation of numerous patients, people that may have been exposed should be told to get medical attention if they demonstrate unexplained fever or flu-like symptoms. This population should be treated as if they have the illness, following the contained versus epidemic treatment recommendations below.

In the laboratory, persons who have had potentially infective exposures to F tularensis should be administered oral postexposure antibiotic prophylaxis if the risk of infection is high (eg, spill, centrifuge accident, or needlestick). If the risk is low, exposed persons can be placed on a fever watch and treated if they develop symptoms.

Clinical Presentation

Forms of the disease

  • Ulceroglandular forms have skin ulcers at the site of infection. If acquired from handling rabbits or other animals, these will be on the hands; in tick-acquired cases, common sites include the groin, armpits, and trunk. Lymph glands in the relevant region will be swollen and painful.[1]
  • Glandular form; similar to ulceroglandular in distribution and lymphadenopathy; the lack of ulcers suggests entry through small abrasions or possibly through unbroken skin.
  • Oculoglandular tularemia presents with a painful, red eye, often with pus. Lymph glands in the head and neck may be swollen.
  • Oropharyngeal form comes from eating infected meat, and includes both sore throat and gastrointestinal symptoms, sometimes including gastrointestinal bleeding.
  • Pneumonic would be the form presented by a biological attack, but has been reported from outdoor landscaping, or handling infected organisms. It shows dry cough, pleuritic chest pain, or may present as relatively asymptomatic pneumonia detected with a stethoscope or X-ray. (Note: Considering tularemia in patients presenting with atypical pneumonia, especially with the epidemiologic profile as below, is important.
  • Typhoidal (septicemic) form is rare and difficult to diagnose. Symptoms include fatigue, chills and fever, muscle pain and weight loss.

Differential diagnosis

Other diseases to be ruled out include:

Laboratory presentation

When inhalational tularemia is suspected, the clinician should collect respiratory secretion and blood samples, and send them to the laboratory for analysis. The samples should include a prominent warning about handling precautions, which should be at Biological Safety Level 2 (BSL-2). Specific tests, such as fluorescent antibody detection, should be requested.

See detailed discussion in Francisella tularensis#Laboratory presentation. Gram-negative pleomorphic bacterium,

Treatment and prognosis

In a contained outbreak, the preferred drugs are parenteral streptomycin or [[gentamicin], with doxycycline, chloramphenicol, or ciprofloxacin as alternatives. There are additional recommendations for children and pregnant women.

For postexposure prophylaxis or an epidemic situation, the logistical difficulty of mass parenteral treatment will require oral therapy for most cases, using doxycycline or ciprofloxacin. The Working Group believes that the benefit justify the risk of a tetracycline in children.

With appropriate and timely antibiotic therapy, the mortality will be in the 1% range.[1]

Significant outbreaks

As a result of natural infection, the largest outbreak took placed in 1966-1967 in an extensive farming area of Sweden. It involved the milder European substrain, and seems to have been acquired while doing farm work that created aerosols. In the United States, there have been only small clusters, but primarily single cases. [6]

Biological warfare

Japan, the Soviet Union, and the U.S. all weaponized tularemia. Ken Alibek, who was a senior scientist in the Soviet program, indicated that tularemia outbreaks on the Russian front during World War II may have been the result of the use of a weapon.[7]

References

  1. 1.0 1.1 1.2 Edlow, Jonathan A, "Tick-Borne Diseases, Tularemia", eMedicine
  2. Weinberg, Arnold N. (2004), "CENTENNIAL PERSPECTIVE COMMENTARY: Wherry WB, Lamb BH. Infection of man with Bacterium tularense. J Infect Dis 1914; 15:331–40.", J Infect Dis 189: 1317–1331
  3. Ohara S. (1954), "Studies on Yato-Byo (Ohara's disease, tularemia in Japan)", Jap J Exp Med 24: 69–79
  4. Parker RR (1934), "Recent studies of tick-borne diseases made at the United States Public Health Service Laboratory at Hamilton, Montana", Proceedings of the Fifth Pacific Congress: 3367-3374
  5. "Key Facts About Tularemia", Centers for Disease Control
  6. 6.0 6.1 Working Group on Civilian Biodefense (2001), "Tularemia as a Biological Weapon: Medical and Public Health Management", Journal of the American Medical Association 285 (21): 2763-2773
  7. Alibek, K. (1999), Biohazard, at 29-38