Tularemia

Background and potential as a bioweapon

Tularemia was first described as a plaguelike disease of rodents in 1911. The bacterium that causes tularemia is highly infectious and can enter the human body through the skin, eyes, mouth, or lungs. Symptoms of infection vary depending on the route of entry (CDC 2021).

Tularemia has since been weaponized. Before signing the Biological Convention, the U.S. military stockpiled 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. Although urban and suburban exposures occasionally occur, tularemia is almost entirely a rural disease. 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 increased awareness among hunters of the risks of 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 from ticks, flies, mosquitoes, and 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 ingesting contaminated water, food, or soil, and inhaling 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. The clinical course could lead to respiratory failure, shock, and death without treatment. 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 present as 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.