Tularemia is a highly infectious, potentially fatal illness caused by Francisella tularensis, a gram-negative bacterium. The terms “rabbit fever” and “deer fly fever” reflect two common routes of transmission (as well as the rabbit’s role as a major reservoir), but tularemia may not persist in nature without its tick vectors, Dermacentor species (spp) (dog and wood ticks) and the Lone Star tick Amblyomma americanum (deer ticks have not been demonstrated to be a vector). While clearly tick-borne, tularemia may also be transmitted by blood-sucking arthropods such as deer flies (greenheads), by direct mechanical contact via handling infected animals, or by inhalation of infectious organisms.

Considered a rare disease in humans, there are fewer than 150 cases reported each year in the entire U.S., mainly in Kansas, Missouri, and Oklahoma. Tularemia cases have been diagnosed every year since 2000 on Martha’s Vineyard, and more than half of the 50 cases reported from 2000-2005 presented as community-acquired pneumonia, the remainder having been tick-transmitted. CDC investigators identified landscapers as the major occupational risk group, via skin exposure or by inhalation of as yet unidentified material during blowing or mowing activities. Researchers from the Harvard School of Public Health and Imugen tested stored samples from residents of coastal Massachusetts, and found serologic evidence that 3% of patients with fevers of unknown origin had had exposure to F. tularensis. Infection thus appears to be more common than believed in those occupationally exposed (e.g. landscapers, hunters, wildlife biologists, and veterinarians treating cats and dogs with self-limiting, non-specific symptoms).

The clinical onset of tularemia is typically abrupt, with fever greater than 101°F, headache, myalgias, fatigue, chills, vomiting, sore throat, and abdominal pain. The incubation period – as short as one day, as long as 3 weeks, depending on inoculum and portal of entry – and the signs and symptoms are highly variable, as is their duration (days to weeks), creating a diagnostic challenge.

Six classical clinical presentations are recognized:

  • Ulcero-glandular
  • Glandular
  • Oculo-glandular
  • Oropharyngeal
  • Typhoidal
  • Pneumonic

The ulcero-glandular form, with ulceration at the arthropod bite site or other portal of entry, and regional lymphadenopathy is most common (70-80% of all cases). The typhoidal presentation, next most common, has an acute onset with enteric symptoms, sore throat, high fevers, and chills. No ulcer or portal of entry is evident, nor is there lymphadenopathy.

Laboratory findings in suspected cases are relatively non-specific. Sterile pyuria may be observed. White blood cell counts and erythrocyte sedimentation rate may be normal or slightly elevated. Serum transaminases are not elevated, although serum CPK may be increased in typhoidal tularemia. Blood, lymph node aspirates, or pleural fluid may be cultured, although this organism does not grow well on routine culture media. It is possible to identify F. tularensis by polymerase chain reaction PCR, but detection of the agent or its DNA is rare, even in acutely ill patients.

Definitive diagnosis requires serologic testing of paired acute and convalescent specimens,as antibody is not detectable during the first week of infection. Titers, by tube or slide agglutination testing, peak at 4-6 weeks; a single titer of 1:128 is diagnostic, as is a four-fold increase in paired testing. Cross-reactivity with Brucella or Yersinia species (spp) may be observed, confounding test interpretation.

In sites where dog or wood ticks are common, tularemia should be part of the differential diagnosis for patients with extensive exposure to wildlife or their habitat (landscapers and others) who present for medical care with an acute febrile disease, with or without respiratory involvement. Due to the time required for sero-diagnosis, initial diagnosis is presumptive, based on clinical features, as is treatment with appropriate antibiotic therapy. Tularemia is usually treatable when diagnosed quickly, but the case fatality rate in untreated patients approaches 5% and may be even greater in those who develop pneumonia. Even with treatment, convalescence may be prolonged.

Indications for Testing

  • Sudden onset of high fever with shaking chills, particularly in presence of skin ulcer and lymphadenopathy; history of exposure to rabbits, to dead or dying animals, or to ticks.
  • Septicemia with severe sore throat, nausea, vomiting, loose watery diarrhea, headache, high fever, chills; history of outdoor activity such as landscaping or contact with animals.
  • Mild upper respiratory infection or bronchopneumonia, abrupt onset of fever greater than 101°F, dyspnea, nonproductive cough, pleuritic chest pain, sweating; history of outdoor activity such as landscaping.
  • Fever of unknown origin with fatigue or cachexia in a patient who had recently traveled to Martha’s Vineyard, or rural Kansas, Missouri, or Oklahoma during the spring and summer.

Imugen offers F. tularensis antibody testing by microagglutination assay.

The staff at Imugen is highly trained in performing and interpreting these assays, has experience in analyzing these test results in the context of various clinical situations, and is available to assist healthcare providers in interpreting tests and answering questions about the detection of tick-borne infections.

Suggested additional reading
1. Cunha BA. Tick-borne Infectious Diseases, Diagnosis and Management. Tularemia. Marcel Dekker, Inc. 2000; 251-268
2. Pullen, RL, Stuart BM. Tularemia: Analysis of 225 cases. JAMA 1945; 129: 495-498
3. Shapiro DM, Mark E. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. A 60 year old farm worker with bilateral pneumonia. NEJM 2000; 342: 1430-1438
4. Feldman KA, Enscore RE, Lathrop SL, Matyas BT, McGuill M, Schriefer ME, et al. An outbreak of primary pneumonic tularemia on Martha’s Vineyard. N Engl J Med 2001; 345: 1601-1606