Tularemia

Background and potential as a bioweapon

Tularemia was first described as a plaguelike disease of rodents in 1911. Tularemia has since been weaponized. Prior to signing the Biological Convention the U.S. military did stockpile it for use as a biological weapon. According to a former Soviet Union biological weapons scientist, the Soviet Union continued to develop stocks of the organism that causes tularemia into the 1990’s, including developing strains of the organism engineered to be resistant to antibiotics and vaccines. The WHO has estimated that an aerosol dispersal of 50 kg of Fransicella tularensis, the organism that causes tularemia, over an urban area of 5 million people would cause 250,000 casualties and approximately 19,000 deaths. Illness would persist for several weeks and disease relapses would occur for weeks to months. The CDC estimates that the economic impact of an F. tularensis attack would be $5.4 billion for every 100,000 persons exposed.

Epidemiology

Francisella tularensis, a small gram-negative coccobacillus, can infect humans through the skin, mucous membranes, gastrointestinal tract, and the lungs. The major target organs for the resulting tularemia infection are the lymph nodes, lungs and pleura, spleen, liver, and kidney. Tularemia occurs in nature throughout much of North America, Europe, and Asia. In the U.S., human cases have been reported from every state except Hawaii. Most cases in the continental U.S. occur in south-central and western states, especially Missouri, Arkansas, Oklahoma, South Dakota, and Montana. Tularemia is almost entirely a rural disease, although urban and suburban exposures occasionally occur. There has been a decline in naturally occurring tularemia in the U.S., potentially related to the fact that wild rabbits are no longer sold in markets and to an increased awareness among hunters of the risks posed by sick rabbits.
F. Tularensis is found in widely diverse animal hosts and habitats and can be found in contaminated water, soil, and vegetation. A variety of small animals, including mice, squirrels, rabbits, and hares are natural reservoirs of infection. They acquire infection through bites by ticks, flies, and mosquitoes, and by contact with contaminated environments. Humans become infected with F. tularensis from bites by infected animals, handling infectious animal tissues or fluids, direct contact with or ingestion of contaminated water, food, or soil, and inhalation of infective aerosols. Although tularemia is highly infectious and pathogenic, its transmission from person to person had not been documented. Most naturally occurring cases are seen in June through September, when disease transmission is most common. The largest recorded airborne tularemia outbreak occurred in 1966-7 in an extensive farming area of Sweden. Most individuals acquired the infection while doing farm work that created contaminated aerosols.

Although F. tularensis could be used as a weapon in a number of ways, it is believed that an aerosol release would have the greatest adverse medical and public health consequences. A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with developing symptoms of pneumonia. Without treatment, the clinical course could lead to respiratory failure, shock, and death. Tularemia in humans occurs infrequently, resulting in a low index of diagnostic suspicion among clinicians and laboratories. Since rapid diagnostic testing for tularemia is not widely available, the first indication of intentional tularemia might follow recognition by public health authorities of a clustering of acute, severe respiratory illness with unusual epidemiological features. Public health authorities would most likely become aware of an outbreak of an unusual respiratory disease in its early stages, but this could be difficult to distinguish from a natural outbreak of community acquired infection, especially influenza or various atypical pneumonias. The abrupt onset of large numbers of acutely ill persons, rapid progression in a relatively high proportion of cases from upper respiratory symptoms and bronchitis to life-threatening pleuropneumonitis and systemic infection affecting, among others, young previously healthy adults and children, should quickly alert medical professionals. At the same time, public health authorities would be alerted to a critical and unexpected public health event and to bioterroism as a possible cause.

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Tularemia is not transmitted directly from person to person.

Clinical course

The onset of tularemia is usually abrupt, with fever, headache, chills, generalized body aches, and sore throat. A dry or slightly productive cough and substernal pain or chest tightness often occur with or without objective signs of pneumonia, such as purulent sputum, dyspnea, tachypnea, pleuritic pain, or hemoptysis. Sweats, fever and chills, progressive weakness, malaise, anorexia, and weight loss characterize the continuing illness. In general, tularemia would be expected to have a slower progression of illness and a lower case-fatality rate than either inhalation plague or anthrax. Humans with inhalation exposures may develop hemorrhagic inflammation of the airways early in the course of illness, which may progress to bronchopneumonia.

Disease Management

Prompt treatment with streptomycin, gentamicin, doxycyline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early post exposure period. In a contained casualty situation, in which patients can be individually managed, parenteral antibiotic therapy is recommended. Streptomycin is the drug of choice, although gentamicin may also be given intramuscularly or intravenously as an acceptable alternative. Ciprofloxacin, which is not labeled for use in tularemia, has been shown to be active against F. tularensis in vitro and in animals. In a mass casualty situation with hundreds of persons infected, doxycycline and ciprofloxacin, given orally, are the preferred choices for treating both adults and children.
In the U.S., a live attenuated vaccine has been used to protect lab personnel routinely working with F. tularensis. The use of tularemia vaccine is currently under review by the U.S. Food and Drug Administration. Given the short incubation period of tularemia and incomplete protection of current vaccines against inhalation tularemia, vaccination is not recommended for post exposure prophylaxis. As human-to-human transmission of tularemia does not occur, isolation of patients is not required. Standard universal precautions should be used for hospitalized patients. However, autopsy procedures that are likely to cause the release of aerosols, such as bone sawing, should be avoided.

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