Tularemia

Francisella tularensis, the organism that causes tularemia, is one of the most infectious pathogenic bacteria known, requiring inoculation with or inhalation of as few as 10 organisms to cause disease. It is considered to be a dangerous potential biological weapon because of its extreme infectivity, ease of dissemination and substantial capacity to cause illness and death.

During World War II, the potential of F. tularensis as a biological weapon was studied by the Japanese as well as by the U.S and its allies.

Tularemia was one of several biological weapons stockpiled by the U.S. military in the late 1960s, all of which were destroyed by 1973. The Soviet Union continued weapons production of antibiotic- and vaccine-resistant strains into the early 1990s.

F. tularensis is a hardy non-spore-forming organism capable of surviving for weeks at low temperatures in water, moist soil, hay, straw or decaying animal carcasses.

F. tularensis is divided into two subspecies: F. tularensis biovar tularensis (type A), which is the most common biovar isolated in North America and may be highly virulent in humans and animals; and F. tularensis biovar palaearctica (type B), which is relatively avirulent and thought to be the cause of all human tularemia in Europe and Asia.

Tularemia is a zoonosis. Natural reservoirs include small mammals such as voles, mice, water rats, squirrels, rabbits and hares. Naturally acquired human infection occurs through a variety of mechanisms such as:

• bites of infected arthropods
• handling infectious animal tissues or fluids
• direct contact or ingestion of contaminated water, food or soil
• inhalation of infective aerosols

F. tularensis is so infective that examining an open culture plate can cause infection. Human-to-human transmission has not been documented.

In the natural setting, tularemia is noted to be a predominately rural disease with clinical presentations including ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, typhoidal and septic forms.

The Working Group on Civilian Biodefense at the School believes that of the various possible ways that F. tularensis could be used as a weapon, an aerosol release would cause the greatest adverse medical and public health consequences.

A World Health Organization (WHO) expert committee reported in 1970 that if 50 kg of virulent F. tularensis were dispersed as an aerosol over a metropolitan area with a population of 5 million, there would be an estimated 250,000 incapacitating casualties, including 19,000 deaths.

Aerosol dissemination of F. tularensis in a populated area would be expected to result in the abrupt onset of large numbers of cases of acute, non-specific, febrile illness beginning 3 to 5 days later (incubation range, 1-14 days), with pleuropneumonitis developing in a significant proportion of cases over the ensuing days and weeks. Without antibiotic treatment, the clinical course could progress to respiratory failure, shock and death.

The overall mortality rate for severe Type A strains has been 5–15 percent, but in pulmonic or septicemic cases of tularemia without antibiotic treatment the mortality rate has been as high as 30–60 percent. With treatment, the most recent mortality rates in the U.S. have been 2 percent. Aminoglycosides, macrolides, chloramphenicol and fluoroquinolones have each been used with success in the treatment of tularemia.

In the U.S. a live-attenuated vaccine derived from the avirulent live vaccine strain (LVS) has been used to protect laboratory personnel who routinely work with F. tularensis. Given the short incubation period of tularemia and the incomplete protection of current vaccines against inhalational tularemia, vaccination is not recommended for post-exposure prophylaxis.

Given the lack of human-to-human transmission, isolation is not recommended for tularemia patients.

The Working Group lacks information on survival of intentionally dispersed particles, but would expect a short half-life due to dessication, solar radiation, oxidation and other environmental factors, and a very limited risk from secondary dispersal.

Simple, rapid and reliable diagnostic tests that could be used to identify persons infected with F. tularensis in the mass-exposure setting need to be developed. Research is also needed to develop accurate and reliable procedures to rapidly detect F. tularensis in environmental samples.

Copyright © 2001 The Johns Hopkins University on behalf of its Center for Civilian Biodefense Studies. All rights reserved.