Clinical Recognition and Management of Tularemia in Missouri: A Retrospective Records Review of 121 Cases

Ingrid B. Weber () 1 2 3 George Turabelidze 0 2 Sarah Patrick 0 2 Kevin S. Griffith 1 2 Kiersten J. Kugeler 1 2 Paul S. Mead 1 2 0 Missouri Department of Health and Senior Services , Jefferson City 1 Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention , Fort Collins, Colorado 2 Received 16 February 2012; accepted 10 August 2012; electronically published 21 August 2012. and Prevention, Division of Vector-Borne Diseases , 3150 Rampart Rd, Fort Collins, CO 80521 3 Epidemic Intelligence Service, Centers for Disease Control and Prevention , Atlanta, Georgia Background. Clinical recognition of tularemia is essential for prompt initiation of appropriate antibiotic treatment. Although fluoroquinolones have desirable attributes as a treatment option, limited data on efficacy in the US setting exist. Methods. To define the epidemiology of tularemia in Missouri, and to evaluate practices and outcomes of tularemia management in general, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state from 2000 to 2007. Results. We reviewed records of 121 of 190 patients (64%) reported with tularemia; 79 (65%) were males; the median age was 37 years. Most patients presented with ulceroglandular (37%) and glandular (25%) forms of tularemia, followed by pneumonic (12%), typhoidal (10%), oculoglandular (3%), and oropharyngeal (2%) forms. Most cases (69%) were attributed to tick bites. Median incubation period was 3 days (range, 1-9 days), and patients sought care after a median of 3 days of illness (range, 0-44 days). Systemic disease occurred more commonly in older patients. Patients were prescribed tetracyclines (49%), aminoglycosides (47%), and fluoroquinolones (41%). Nine of 10 patients treated with ciprofloxacin for 10 days recovered uneventfully, without accompanying aminoglycosides or tetracyclines. Conclusions. Tularemia is frequently initially misdiagnosed. A thorough exposure history, particularly for tick bites, and awareness of clinical features may prompt clinicians to consider tularemia and facilitate appropriate testing. Promising success with oral fluoroquinolones could provide an acceptable alternative to intravenous aminoglycosides or long courses of tetracyclines where clinically appropriate. Tularemia is an uncommon but potentially severe zoonosis caused by the gram-negative coccobacillus Francisella tularensis [1]. In North America, human illness is caused by 2 subspecies: F. tularensis subsp tularensis (type A), and F. tularensis subsp holarctica (type B). The organism is highly infectious [2] and can be transmitted to humans through arthropod bites, contact with infected animal tissues, ingestion of contaminated food or water, and inhalation of contaminated aerosols Epidemiology and Treatment of Tularemia in Missouri - generated through agricultural, laboratory, or landscaping activities [3]. Disease typically manifests as regional lymphadenopathy with or without skin or mucosal ulceration following percutaneous inoculation, or as pneumonia or systemic disease following inhalational exposure. Hematogenous dissemination can result in infection of distant anatomical sites, and the clinical course may be influenced by underlying medical conditions [4]. Prior to the advent of antibiotics, overall case fatality rates for tularemia caused by type A strains was 5% to 15%; current mortality is <2% among reported cases in the United States [5]. In addition to its role as the cause of naturally occurring tularemia, F. tularensis has been designated a Category A select agent with potential for use as an agent of bioterrorism [6, 7]. Concern regarding bioterrorism has driven heightened disease surveillance efforts and raised important questions regarding antimicrobials for prophylaxis and treatment in mass casualty settings. At present only aminoglycosides, tetracyclines, and chloramphenicol have been approved for treatment of tularemia by the US Food and Drug Administration (FDA). Use of these drugs is complicated by the need for intravenous administration of aminoglycosides, treatment regimens of at least 2 weeks with tetracyclines, or serious side effects [8, 9]. Although not FDAapproved for the treatment of tularemia, fluoroquinolones are highly effective against F. tularensis in vitro [10] and have been used successfully to treat a small number of patients in Europe [11]. This clinical experience may not be fully applicable to North America, however, as only type B strains occur in Europe. [12]. Missouri is a long-standing focus of tularemia in North America [13]. Brosius documented illness consistent with tularemia in Missouri as early as 1909 [1]. From 2000 through 2007, the average annual incidence in the state was 4 cases per 1 000 000 population, accounting for approximately one-fifth of all cases reported nationally [14]. To better define current clinical and epidemiological features of tularemia in Missouri, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state during 2000 2007. This assessment also provided an opportunity to evaluate outcomes of US patients who, for various reasons, received treatment with fluoroquinolones. Cases were ascertained through review of reports to the Missouri Department of Health and Senior Services (MDHSS) through the Missouri Health Surveillance Information System, the statewide reporting system for notifiable conditions. All cases categorized as confirmed or probable tularemia were included. Consistent with national surveillance case definitions, a confirmed case of tularemia was defined as clinically compatible illness in a patient from whom F. tularensis has been isolated in a clinical specimen or there was a 4-fold change in serum antibody titer to F. tularensis antigen. A probable case was defined as clinically compatible illness in a patient with an elevated serum antibody titer (without documented 4-fold or greater change) or detection of F. tularensis in a clinical specimen by fluorescent assay. We contacted the reporting provider associated with each of the cases by mail, telephone, or fax and requested access to medical records from at least 2 months before to at least 2 months after the reported date of diagnosis. Medical records included clinical notes, special investigations, prescription charts, and results of special investigations. We reviewed all available paper-based and electronic clinical records pertaining to these cases from facilities throughout Missouri using a standard data collection form. We collected information on exposure history, demographic features, clinical presentation, treatment, and outcome. When large portions of data were missing from facility records, we contacted other physicians listed as care providers in the records to provide supplementary documentation. We categorized tularemia clinical forms as ulceroglandular, glandular (...truncated)