Using Francisella tularensis as a Bioweapon

Tularemia is a serious infectious disease caused by the bacterium Francisella tularensis. F. tularensis is a small gram-negative non-motile coccobacillus. The bacterium has several subspecies with varying degrees of virulence. The most important of those is F. tularensis tularensis (Type A), which is found in lagomorphs in North America and is highly virulent for humans and domestic rabbits. F. tularensis palaearctica (Type B) occurs mainly in aquatic rodents in North America and in hares and small rodents in northern Eurasia. It is less virulent for humans and rabbits. The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. The disease is named after Tulare County, California.  Read more about Biologics in Infectious Diseases: Stakeholder Opinions

Francisella tularensis was discovered in 1911 during an outburst of rabbit fever, when the disease killed a large number of ground squirrels in the area of Tulare Lake in California. Scientists determined that tularemia could be dangerous to humans; a human being may catch the infection after contacting an infected animal. The ailment soon became frequent with hunters, cooks and agricultural workers.

The disease is endemic in North America, and parts of Europe and Asia. The most common mode of transmission is via arthropod vectors. Rodents, rabbits, hares often serve as reservoir hosts, but waterborne infection accounts for 5 to 10% of all tularemia in the US. Tularemia can also be transmitted by biting flies, particularly the deer fly Chrysops discalis. Individual flies can remain infective for 14 days and ticks for over two years. Tularemia may also be spread by direct contact with contaminated animals or material, by ingestion of poorly cooked flesh of infected animals or contaminated water, or by inhalation. The most likely method for bioterrorist transmission is through an aerosol.

The incubation period for tularemia is 1 to 14 days; most human infections become apparent after 3 to five days. In most susceptible mammals, the clinical signs include fever, lethargy, anorexia, signs of septicemia, and possibly death. Animals rarely develop the skin lesions seen in people. Subclinical infections are common and animals often develop specific antibodies to the organism. Fever is moderate or very high and tularemia bacillus can be isolated from blood cultures at this stage. Face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may suppurate (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever. Death occurs in less than 1% if therapy is initiated promptly.

Francisella tularensis is an intracellular bacterium, meaning that it is able to live as a parasite within host cells. It primarily infects macrophages, a type of white blood cell. It is thus able to evade the immune system. The course of disease involves spread of the organism to multiple organ systems, including the lungs, liver, spleen, and lymphatic system. The course of disease is similar regardless of the route of exposure. Mortality in untreated (pre-antibiotic-era) patients has been as high as 50% in the pneumoniac and typhoidal forms of the disease, which however account for less than 10% of cases. Overall mortality was 7% for untreated cases, and the disease responds well to antibiotics with a fatality rate of about 1%. The exact cause of death is unclear, but it is thought to be a combination of multiple organ system failures.

The Centers for Disease Control and Prevention regard F. tularensis as a viable bioweapons agent, and it has been included in the biological warfare programs of the USA, USSR and Japan at various times. A former Soviet biological weapons scientist, Kenneth Alibek, has alleged that an outbreak of Tularemia among German soldiers shortly before the siege of Stalingrad was due to intentional release of F. tularensis by Soviet forces, but this claim is rejected by others who have studied the outbreak. In the USA, practical research into using Tularemia as a bioweapon took place at Camp Detrick in the 1950s. It was viewed as an attractive agent because:

• It is easy to aerosolize

• It is highly infective; 10-50 bacteria are required to infect

• It is non-persistent and easy to decontaminate (unlike anthrax)

• It is highly incapacitating to infected persons

• It has low lethality, which is useful where enemy soldiers are in proximity to non-combatants, e.g. civilians

Read more about Biologics in Infectious Diseases: Stakeholder Opinions