Tularemia: A threat to animals and humans

In mid-July 2009, several domestic cats and dogs in South Dakota’s Sioux Falls neighborhood were found infected by tularemia. Reportedly, one animal died of the disease and pet owners were advised to protect their animals by using tick repellant or checking pets for ticks. No human infection was recorded during the event.

Tularemia was also recently discovered among the prairie dog population of South Dakota’s Badlands National Park, according to the National Parks Traveler’s website. Experts with the United States National Park Service said the pathogen could sicken and kill prairie dogs; they warned tularemia may have the potential to decimate the park’s prairie dog population and perhaps undo much of the effort that’s been invested in reestablishing black-footed ferrets there.

Tularemia — also known as rabbit fever, deerfly fever, Pahvant valley plague, Ohara’s disease and Francis disease — was described in Europe as early as 1653 (as lemming fever). It was first described in the United States between 1908 and 1911 as a plague-like disease of ground squirrels that prevailed in Tulare county, California, where McCoy and Chapin demonstrated the etiologic agent and named it Bacterium tularense. Since then, the disease has been reported in all U.S. states except Hawaii.

Tularemia was removed from the list of nationally notifiable diseases in 1994, but increased concern about potential use of its causative agent, Francisella tularensis, as a biological weapon, led to its reinstatement in 2000. The disease is also included in the OIE list of notifiable animal diseases, within the group of “multi species” diseases.

Francisella tularensis

Francisella tularensis (formerly known as Pasteurella tularensis) is a Gram negative, non–motile coccobacillus. Two subspecies exist: F. tularensis tularensis (also known as Jellison type A) and F. tularensis holarctica (Jellison type B). F. tularensis tularensis is found in lagomorphs (hares and rabbits) in North America and is highly virulent for humans and domestic rabbits; F. tularensis holarctica is less virulent and occurs in beaver, muskrats and voles in North America and in hares and small rodents in Eurasia (continental Europe, Russia, China and Japan).

F. tularensis can be transmitted by ingestion, inhalation, arthropod–borne transfer or direct contact through the skin and mucous membranes. Organisms are found in the blood and tissues of infected animals and can survive for long periods on fomites including food and water. Aquatic animals may develop tularemia after being immersed in contaminated water. Carnivores sometimes become infected after ingesting a contaminated carcass. Vectors for F. tularensis tularensis include ticks (including Dermacentor andersoni, D. variabilis and Amblyomma americanum) and biting flies (particularly deerflies). F. tularensis holarctica is also transmitted by mosquitoes in Russia. Rarely the organism is spread by animal bites.

F. tularensis can survive for long periods in arthropod vectors and in the environment. Individual flies may carry the organism for two weeks and ticks throughout their lifetimes. Viable bacteria can also be found for weeks to months in the carcasses and hides of infected animals and in fomites including grain dust, straw, water, soil and bedbugs. This organism is highly resistant to freezing; live organisms have been found after three years in rabbit meat stored at –15° C.

Infections in animals

More than 100 species of animals can be infected with F. tularensis. The natural hosts include cottontail and jack rabbits, hares, voles, vole rats, squirrels, muskrat, beaver and lemmings. Among domestic animals, sheep seem to be particularly susceptible to clinical disease. Tularemia has also been seen in dogs, cats, pigs and horses; cattle seem to be resistant. Infections in birds, reptiles and fish have been reported.

In sensitive animals, clinical signs of severe depression are followed by a fatal septicemia. The course of the disease is approximately two to 10 days in susceptible species; animals are usually dead when presented for diagnosis. Most domestic species do not usually manifest signs of tularemia infection, but they do develop specific antibodies to the organism following infection.

Cats have been reported to be able to act as a carrier of the bacterium and the disease is occasionally spread from cats to humans.

At necropsy, animals that have died from acute tularemia are usually in good body condition. There are signs of septicemia characterized by whitish foci of necrosis randomly distributed in the liver, bone marrow and spleen. Foci of caseous necrosis are often present in one or more lymph node(s). In less sensitive species, the histological picture can resemble that of tuberculosis with chronic granulomas in liver, spleen, lungs and kidneys.

There is a high risk of human infection from F. tularensis, as the infective dose is extremely low and infected animals excrete bacteria in urine and feces. Infection can occur by simple contact. Suitable precautions, such as the wearing of gloves, masks and eyeshields during any manipulation of pathological specimens or cultures, must be taken to avoid human infection. The veterinary microbiological laboratory and animal facilities should meet at least the requirements for Containment Group 3 pathogens. Experimentally-inoculated animals and their excreta are especially hazardous to humans

Infections in humans

According to CDC statistics, there were 873 cases of human tularemia reported in the United States between 2000 and 2006.

The incubation period in humans is three to 15 days; clinical signs usually appear after three to five days.

Six forms of tularemia are seen in humans: typhoidal, ulceroglandular, glandular, oculoglandular, oropharyngeal and pneumonic. The form of the disease depends on the inoculation site.

Tularemia can affect all ages. Infections occur most often in hunters, butchers, farmers, fur handlers and laboratory workers. In natural infections, ulceroglandular tularemia is the most common form; it occurs in 75 to 85% of cases. The typhoidal form is seen in 5% to 15%; the glandular form in 5% to 10% and the oculoglandular form in 1% to 2%. Typhoidal tularemia would be expected to be the predominant form after an attack by aerosolized F. tularensis in a biological weapon.

The mortality rate is approximately 30% to 35% for untreated F. tularensis tularensis infections and 5% to 15% for F. tularensis holarctica infections. Typhoidal tularemia is the most dangerous form; if untreated, the case fatality rate is approximately 35%. In contrast, the case fatality rate for the untreated ulceroglandular form is 5%. Naturally–acquired cases are rarely fatal if treated; case fatality rates up to 1% to 3% are cited by some authorities. Higher fatality rates would be expected after a biological attack. Permanent immunity usually develops after a single episode of tularemia.

Person-to-person transmission has not been seen; however, infectious organisms can be found in the blood and other tissues.

Diagnostic tests

Tularemia is often diagnosed by immunofluorescent staining of F. tularensis antigens in tissue samples or blood, and by serology. Commonly used serologic tests include tube agglutination, microagglutination and enzyme–linked immunosorbent assays (ELISA). A rising titer is diagnostic. Significant titers begin to appear during the second week of infection, although some specific antibodies are seen within the first seven days. Cross–reactions occur with Brucella species, Proteus OX19, and Yersinia.

Tularemia can also be diagnosed by isolating F. tularensis from blood, sputum, pharyngeal or conjunctival exudates, ulcers, lymph nodes and gastric washings. F. tularensis does not grow well on standard media but may be isolated on media containing cysteine or sulfhydryl compounds.

Treatment and vaccination

F. tularensis is susceptible to a variety of antibiotics. Relapses are not common but can occur if treatment is stopped before all bacteria are eliminated.

Vaccines have been produced with the aim of protecting humans, but as all vaccine development involves testing in animals, it is clear that some of the vaccines could be used to protect animals. However, in most countries, there is no vaccine licensed for use in animals.

Live-attenuated vaccines have been used in mass vaccinations of people in the former Soviet Union since 1946, either as monocultures or as a mixture of strains.

An attenuated live vaccine strain of F. tularensis biovar palaearctica is available and can be used for restricted vaccination of individuals at high risk.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.

For more information:

• Chapter 2. 1.18 - TULAREMIA, OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2009.
• http://oie.int/eng/normes/mmanual/2008/pdf/2.01.18_TULAREMIA.pdf