Francisella tularensis

Francisella tularensis is the pathogen of tularemia. Its 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

Organism

F. tularensis is a small, nonmotile, aerobic, Gram-negative coccobacillus. It has a thin lipopolysaccharide-containing envelope and is a hardy non–spore-forming organism that survives for weeks at low temperatures in water, moist soil, hay, straw, and decaying animal carcasses. By light microscopy, the organism is characterized by its small size (0.2 µm x 0.2-0.7 µm), pleomorphism, and faint staining. It does not show the bipolar staining characteristics of Yersinia pestis, the agent of plague, and is easily distinguished from the large Gram-positive rods characteristic of vegetative forms of Bacillus anthracis.

The organism has two major substrains (biovars), which can be differentiated by virulence testing, biochemical reactions, and epidemiological features. 'Francisella tularensis biovar tularensis (type A) may be highly virulent in humans and animals, produces acid from glycerol, demonstrates citrulline ureidase activity, and is the most common biovar isolated in North America.

Francisella tularensis biovar palaearctica (type B) is relatively avirulent, does not produce acid from glycerol, and does not demonstrate citrulline ureidase activity. In Europe and Asia, all human tularemia is thought to be caused by the milder type B strains, although recent studies there have identified naturally occurring F. tularensis related to F. tularensis biovar tularensis.

Epidemiology and risk

Francisella tularensis is among the most infectious pathogens known. An exceptionally small number (10-50 or so organisms) can cause disease. Routine laboratory handling, such as centrifuging, can produce a dangerous aerosol.

If F. tularensis were used as a weapon, the bacteria would likely be made airborne for exposure by inhalation. People who inhale an infectious aerosol would generally experience severe respiratory illness, including life-threatening pneumonia and systemic infection, if they are not treated. The bacteria that cause tularemia occur widely in nature and could be isolated and grown in quantity in a laboratory, although manufacturing an effective aerosol weapn would require considerable sophistication.

Epidemiology

It is widely distributed in nature through North America and Eurasia. In the U.S., it is most common in the south-central and western states, where in Eurasia, it is most common in Scandinavia and Russia. F. tularensis has a wide range of animal hosts, but also can be acquired by inhalation, or from contaminated water, soil, or vegetation.

A variety of small mammals, including voles, mice, water rats, 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. Although enzootic cycles of F tularensis typically occur without notice, epizootics with sometimes extensive die-offs of animal hosts may herald outbreaks of tularemia in humans.

Laboratory presentation

Physicians who suspect inhalational tularemia should promptly collect specimens of respiratory secretions and blood and alert the laboratory to the need for special diagnostic and safety procedures. Still, it is more a diagnosis of clinical suspicion, with the key laboratory role being one of differential diagnosis. Since it will only grow on media containing cysteine, routine blood cultures are negative, and it usually will not appear in Gram-stained sputum.

It may be identified by direct examination of secretions, exudates, or biopsy specimens using direct fluorescent antibody or immunohistochemical stains.

Growth of F tularensis in culture is one definitive means of confirming the diagnosis of tularemia; blood samples are unlikely to be positive, but pharyngeal washings, sputum specimens, and even fasting gastric aspirates may demonstrate the organism in inhalational cases.

A faster definitive diagnosis uses fluorescent-labeled antibodies, and is a rapid diagnostic procedure performed in designated reference laboratories in the National Public Health Laboratory Network; test results can be made available within several hours of receiving the appropriate specimens if the laboratory is alerted and prepared. ref name=AMA-FT-BW />

Antibiotic sensitivity

Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexposure period...Transformed plasmids have been engineered to express chloramphenicol and tetracycline resistance in F tularensis. Virulent, streptomycin-resistant F. tularensis strains have been examined in biowarfare agent studies both in the United States and the Soviet Union.