148 Tularemia

Tularemia is primarily a specific, infectious disease of rodents and Iagomorphs. The causative organism, however, has been isolated from over 100 species of mammals, 9 species of domestic animals, 25 species of birds, 70 species of insects, and several species of fish and amphibians.

Etiology and Epidemiology

Two variants (biovars) of the causative organism are recognized. F. tularensis biovar tularensis (type A) has been isolated in nature only in North America and is the most virulent in human beings. The sec­ond is designated F. tularensis biovar palaearctica (type B) and is found in all areas where tularemia is endemic in the Northern Hemisphere.

Tularemia is unique in the number of ways in which humans can become infected, and the clinical picture of the disease depends upon the infection route. The most common route is via the skin, either by insect bite or by direct passage through intact skin by contact with infected carcasses or a scratch from an infected animal. Of the numerous insects that transmit the disease, the tick is the most impor­tant. The wood tick (Dermacentor andersoni) and three species of rabbit tick are especially important in the United States. Biting insects such as the deer fly (Chrysops discalis) and the stable fly (Stomoxys calcitrans) also carry the disease to humans.

Susceptibility to tularemia is independent of age, sex, race, and health status. That men are more often infected is related to their intrusion into the transmission cycle through hunting and handling of infected, fur-bearing animals. Human-to-human transmission is extremely rare, and the disease is largely confined to rural areas. The disease may occur in any season but is least prevalent in winter when insect vectors are least abundant and small animals are not much hunted.

The fatality rate in North America, prior to the widespread use of streptomycin in the late 1940s, ranged from 5 to 9 percent. Today that figure has been reduced to less than 1 percent. In Europe, the mortality rate has always been much lower, in the realm of 1 percent owing, probably, to the lower virulence of F. tularensis strain. An attack confers relatively solid lifelong immunity. A live attenuated vaccine is now available that reduces the severity of the Ulceroglandular infection and reduces the inci­dence of typhoid-type tularemia. However, the vac­cine is still being investigated and used primarily for laboratory workers who are always at high risk in working with the tularemia organism.

Distribution and Incidence

Tularemia, in humans, is confined to the Northern Hemisphere with three main areas of epidemicity: North America, Europe, especially eastern Europe and Russia, and to a lesser extent Japan. It is not found in nature in the British Isles. Tularemia has been reported everywhere in the United States ex­cept Hawaii. In Canada, the disease is endemic in the central and western provinces, as well as the Northwest Territories, but seldom is reported from the eastern provinces.

In the United States, tularemia became a report­able disease in 1927 and rose to a peak incidence in 1939 with 2,291 cases reported (17.5 per million population). Since the 1950s, the disease has under­gone a dramatic decline. In 1984 in the United States only 291 cases were reported (1.2 per mil­lion). Since 1931 in Canada nearly 400 cases have been reported but with a steady decline over the years. In Russia a similar decrease has been ob­served. In the mid-1940s, 100,000 cases per year were reported; yet these were reduced to a few hun­dred cases per year by the mid-1960s. The reasons for this worldwide decline are controversial. The reasons advanced range from ecologically induced selection against the more virulent strains of F. tularensis and reduction of the organism circulating in wild reservoirs, to an increased awareness of the disease through mass education, to a failure to de­tect and report cases.

Clinical Manifestations and Pathology

Tularemia may manifest an extremely variable clini­cal picture depending upon the site of inoculation and the extent of-its spread. In general, the incuba­tion period averages about 3 days, varying from 1 to 9. The disease begins with headache, chills, vomit­ing, fever, with generalized aches and pains. An ulcer develops at the site of initial entry, while associ­ated lymph nodes become enlarged and tender. The disease lasts 3 to 4 weeks, with sweating, weight loss, and general debility. Convalescence requires 2 to 3 months.

Several clinical types of the disease have been described:

1. The cutaneous (ulceroglandular) type in which an inflamed papule develops at the site of inocula­tion, which soon breaks down, leaving a punched- out ulcer.

2. The ophthalmic (Oculoglandular) type, which oc­curs when the bacterium enters via the conjunc­tival sac. Local inflammation occurs with enlarge­ment of the lymph nodes of the neck. Permanent impairment of vision may occur.

3. The pleuropulmonary type, which develops secon­dary to the other forms. Milder forms resemble atypical pneumonia and may include shortness of breath, malaise, chills, and pleuritic pain.

4. The gastrointestinal (oropharyngeal) form that is contracted from the ingestion of contaminated food and water and may be accompanied by acute abdominal symptoms such as pain, vomiting, and diarrhea with ulcerative lesions in the intestinal mucosa.

5. The glandular form, which develops without a primary lesion but with enlargement of regional lymph nodes.

6. The typhoidal (septicemic) form that also devel­ops without a primary lesion and without enlarge­ment of the regional nodes. Infection arises via the respiratory route or is the late result of local infection.

7. The meningitic type, which is rare in North Amer­ica but not infrequent in Asia, under certain condi­tions of insect transmission.

In all these types, Subclinical infections may be more common than previously supposed. A recent study in Sweden showed that about 23 percent of the population had been infected, but 32 percent of these were Subclinical cases.

History and Geography

Tularemia enjoys a unique place in medical history as it is the first disease to be identified and entirely described by American investigators. In 1910 G. W. McCoy of the U.S. Public Health Service, while studying plague in California ground squirrels, re­ported a “plague-like disease of rodents” in these animals. The following year, he and C. W. Chapin, using a special nutrient medium, succeeded in cul­turing the causative organism and named it Bacte­rium tularense after Tulare County, California, where infected squirrels were first discovered.

Earlier, in 1911, R. A. Pearse had described sev­eral cases of deer-fly fever in humans from Utah and suggested that the disease was caused by the bite of Chrysops discalis, the common deer fly. It was left to Edward Francis, a surgeon with the U.S. Public Health Service, to piece together the complicated etiologic connection among deer-fly fever in hu­mans, the plaguelike disease of rodents in Califor­nia, and similar illnesses in small mammals of Utah and Indiana. Francis isolated the organism in 1921 and proved that it was indeed spread by the bite of the deer fly as well as by direct contact with infected meat. The role of the tick in the spread of tularemia was determined in 1924 by R. R. Parker, R. R. Spen­cer, and Francis. It was also Francis who coined the term “tularemia” after finding the organism in the blood of infected individuals. In the late 1950s the genus name of the organism was changed to Pas- teurella because of a supposed relationship to the causative organism of plague. In 1974, upon recom­mendation of microbiologists in the Soviet Union and the United States, the genus name was changed to Francisella to honor Francis who, through more than 30 years of investigation into tularemia, was the man most responsible for sorting out its com­plexities and many manifestations.

In 1925, Hachiro Ohara, a Japanese scientist, pub­lished a paper entitled “Concerning an Acute Febrile Disease Transmitted by Wild Rabbits,” followed shortly by a second paper describing how an illness that would become known as Ohara’s disease was successfully transmitted to humans. Other papers by Japanese scientists soon followed, but none made reference to American investigations of tularemia.

Francis and a colleague, recognizing that Ohara’s disease seemed similar to tularemia in every way, requested serums from convalescent Japanese pa­tients.

The first isolation of F. tularensis outside North America and Japan occurred in the Soviet Union in 1926, and by 1928 almost 800 cases were reported, rising to a peak incidence in 1941-2 of approxi­mately 100,000 cases, but, as in North America, there has subsequently been a dramatic delcine in cases.

Although tularemia is often described as a “new disease,” it is perhaps best to consider it new only in terms of its discovery. Medical historians believe there is good evidence that tularemia was endemic in the United States, Scandinavia, and the Soviet Union in the eighteenth and nineteenth centuries. Many travelers in Russia as early as 1741 noted a disease with all the characteristics of tularemia and termed “Siberian ulcer.”

In the United States at least three written records survive describing the disease, including one from California in 1904 and another from Arizona in 1907. In fact, the wide distribution of the disease and its adaptation to a wide variety of animals suggest that the disease is ancient in nature, perhaps dating to the latter end of the Miocene or early Pliocene periods.

Despite the dramatic decline in the incidence of tularemia since the 1950s, it would appear that tu­laremia will remain a hazard to humans for many years to come. In spite of the great amount of re­search over the past 70 years, numerous questions remain unanswered because of the very complex in­teractions among hosts, vectors, and varied environ­ments. Because of these complex ecological interac­tions, eradication of tularemia seems unlikely.

Patrick D. Home

Bibliography

Foshay, L. 1950. Tularemia. Annual Review of Microbiol­ogy 4: 313—30.

Francis, E. 1925. Tularemia. Journal of the American Medical Association 84: 1243-50.

Gelman, A. C. 1961. Tularemia. In Studies in disease ecology, ed. J. M. May, 89-108. New York.

Jellison, W. L. 1972. Tularemia: Dr. Edward Francis and his first 23 isolates of Francisella tularensis. Bulletin of the History ofMedicine 46: 477-85.

Olsen, P. F. 1975. Tularemia. In Diseases transmitted from animals to man, 6th edition, ed. W. T. H. Hubbert et al., 191-233. Springfield, Ill.

Pollitzer, R. 1967. History and incidence Oftularemia in the Soviet Union. New York.

Simpson, W. M. 1929. Tularemia: History, pathology, diag­nosis and treatment. New York.