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Studying Tularemia in an Endemic US Locale

By Amesh A. Adalja, MD, FACP, September 21, 2012

Francisella tularensis is a highly contagious bacterium that is endemic in parts of the United States and is classified as a category A biological agent. Francisella tularensis is an agent of concern because it has an extremely low infectious dose, survives aerosolization, and causes severe symptoms. Without benefit of modern therapies, the case fatality rate of all forms of tularemia (ulceroglandular, oropharyngeal, glandular, oculoglandular, typhoidal, and pneumonic) combined can be as high as 15%.

Francisella tularensis is endemic in some parts of the United States, including Missouri, where 121 cases (20% of the US total) were documented from 2000 to 2007. These cases offer an important opportunity to understand the pathophysiology, epidemiology, and clinical course of the disease. To this end, a team from the CDC and the Missouri Department of Health and Senior Services recently published a retrospective review of the Missouri cases.

Ulceroglandular Tularemia Most Common

As expected, of the 121 cases of tularemia reviewed, the ulceroglandular form was the most common (37%); less common (10% of cases) was pneumonic tularemia. Most cases occurred between the months of May and September, and more men than women were infected. Most infections occurred as a result of bites from infected ticks and cats, handling infected animal tissue, mowing grass, and being exposed to agricultural aerosols.

Difficult Diagnoses

Patients presented to healthcare providers after a median 3 days of illness. Hospital admission occurred in 58%, with a median length of stay of 4 days. More than 75% of those with more severe forms of tularemia (pneumonic, typhoidal, and oculoglandular) were hospitalized.

In 68% of patients who had ulceroglandular, glandular, and oropharyngeal tularemia, the initial diagnoses were incorrect (ie, cat-scratch disease, EBV, gram positive lymphadenitis, or cellulitis). Every case of pneumonic tularemia was misdiagnosed as ordinary community-acquired pneumonia.

In approximately 66% of patients, the correct diagnosis was made by positive cultures; in another third, serology led to the correct diagnosis. Of the culture positive patients, only 10% were suspected of having tularemia at the time the culture results were reported.

Suboptimal Antibiotic Therapy

The median time from onset of symptoms to effective antibiotic therapy (aminoglycosides, tetracylines, fluoroquinolones, or chloramphenicol) was 13 days, with a range that stretched to 82 days. Aminoglycosides were administered to 47% of patients, tetracyclines to 49%, and fluoroquinolones to 41%. Combinations of these antimicrobials classes were also used. All but one of the 121 Missouri cases survived.

Room for Diagnostic Improvement

This retrospective study underscores the need for both increased clinical astuteness in tularemia endemic areas and better diagnostic tests. In 90% of patients, tularemia was not suspected until positive cultures were reported. While these cultures were pending, it is likely that many patients received ineffective (or no) antimicrobial therapy because of a misdiagnosis of cellulitis, community acquired pneumonia, EBV, or the like. Anything that shortens the time to effective therapy or decreases the time to definitive diagnosis would likely improve outcomes, such as decreased length of hospitalization.

It is worrying that misdiagnosis and delays in diagnosis prevailed in a state in which Francisella tularensis has been known to be endemic since 1909 and which accounts for a major proportion of US cases. Faster, more reliable diagnosis will be essential if there is an intentional tularemia outbreak. The best possible result of this study may be to prompt development of better clinical and laboratory diagnostics for this pathogen.

References

Weber IB, Turabelidze, Patrick S, et al. Clinical recognition and management of tularemia in Missouri: a retrospective records review of 121 cases. Clin Infect Dis 2012. First published online August 21, 2012 doi:10.1093/cid/cis706. http://cid.oxfordjournals.org/content/early/2012/08/23/cid.cis706.short?rss=1. Accessed September 18, 2012.