Tularemia --- Missouri, 2000--2007

Tularemia --- Missouri, 2000--2007

Tularemia is an uncommon but potentially fatal zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis. Approximately 40% of all tularemia cases reported to CDC each year occur in Arkansas, Oklahoma, and Missouri (1). To define the epidemiologic and clinical features of tularemia in Missouri, the Missouri Department of Health and Senior Services (MDHSS) analyzed surveillance data and conducted a retrospective clinical chart review of cases that occurred during 2000--2007. This report describes the results of that analysis, which identified 190 cases (87 confirmed and 103 probable), for an average annual incidence of 0.4 cases per 100,000 population statewide. Most cases occurred during the summer months (78%) and among males (66%). Analysis of 121 clinical charts revealed that children were more likely than adults to be diagnosed with glandular tularemia, whereas adults were more likely to be diagnosed with pneumonic tularemia. Sixty-three (52%) patients were hospitalized; one patient died. Among 78 cases with a documented exposure source, 72% were associated with tick bite. In 33 (85%) of 39 culture-confirmed cases, the laboratory received specimens without any indication of suspicion of a tularemia diagnosis. Clinicians should 1) be aware of the range of tularemia symptoms, 2) consider the diagnosis in patients reporting fever and tick or animal exposure, and 3) initiate empiric antimicrobial therapy while awaiting laboratory confirmation. Laboratory staff should take appropriate precautions when processing culture specimens from tularemia-endemic regions, even if suspicion of tularemia is not noted when the specimen is submitted.

Tularemia is a nationally notifiable disease. Although tularemia was removed from the list of nationally notifiable diseases in 1994, it was reinstated in 2000 because of increased concern about potential use of F. tularensis as a biologic weapon (1,2). In Missouri, since 2000, clinicians and laboratories have been required to report to MDHSS cases of illness that are clinically compatible with tularemia and have presumptive or confirmed laboratory evidence of infection. The clinical presentation of tularemia ranges from cutaneous ulcers to pneumonia and depends on the mode of transmission and site of inoculation (3). Routes of F. tularensis transmission to humans include arthropod bites, contact with infected animal tissues, ingestion of contaminated food or water, and inhalation of contaminated aerosols (e.g., aerosols generated by mowing over infected animal carcasses and through improper handling of laboratory cultures).

To define the epidemiologic and clinical features of tularemia in Missouri, MDHSS analyzed 190 tularemia case reports from the period 2000--2007 and conducted an independent review of 121 available clinical records (including clinician notes, laboratory results, and drug administration records) using an abstraction form modified from the CDC case report form.* Reports were included in this analysis if the diagnosis of tularemia met the National Notifiable Disease Surveillance System case definition.† The primary clinical form of the disease was classified according to health-care provider diagnosis and documented clinical features. For the purpose of this analysis, patients with tularemia who presented with undifferentiated febrile illness or sepsis without localizing signs (often referred to as typhoidal tularemia) were categorized as pneumonic tularemia, because these cases frequently have evidence of respiratory disease (3). Data on exposures occurring within 3 weeks of illness onset were abstracted from clinical notes; aerosol exposure was defined as exposure through inhalation of agricultural grains or dusts, or aerosols created by mowing over animal carcasses. MDHSS reviewed clinical notes of all culture-confirmed cases to determine whether the provider had documented suspicion of tularemia by the time specimens were submitted to the laboratory. Appropriate antibiotic therapy was defined as treatment with an aminoglycoside or a fluoroquinolone for at least 10 days or a tetracycline for at least 15 days (4). The county of residence and 2000 census data were used for county incidence calculations. Continuous variables were analyzed by Student's t-tests, and categorical variables were analyzed using chi-square or Fischer's exact tests, as appropriate.

During 2000--2007, a total of 190 cases of tularemia (87 confirmed and 103 probable) were reported to MDHSS, yielding a statewide average annual incidence of 0.4 cases per 100,000 population. No increase or decrease was observed in annual trend (range: 13--32 cases per year). The majority of cases were reported from central and southwestern Missouri. The total number of cases by county for the 8-year period ranged from zero to 14, yielding average annual incidence rates that ranged up to 5.25 cases per 100,000 population. Males accounted for 125 (66%) patients; median patient age was 37 years (range: 6 months--93 years), with a distinct bimodal distribution among males (Figure 1).

Clinical records were available for 121 (64%) patients, including 59 (49%) with confirmed and 62 (51%) with probable tularemia. For the 107 (88%) cases with data on primary clinical form, ulceroglandular tularemia was the most common overall (42%). The distribution of clinical form differed significantly between children and adults (p<0.01). Children were diagnosed with glandular tularemia more than twice as often as adults, whereas adults were diagnosed with the pneumonic form 10 times as often as children (Table).

For the 26 cases categorized as pneumonic tularemia based on clinical features, 12 (46%) had recorded exposures, of which six were inhalational (four patients worked with grain or hay; two mowed over dead animals) and six were tick exposures (without lesions or lymphadenopathy). Ten (38%) patients had cough, and seven (27%) had shortness of breath or chest pain. The mean initial temperature documented in clinical record was 100.7°F (38.2°C) (range: 98.0--105.0°F [36.7--40.6°C]). Among the 16 patients for whom initial chest radiograph reports were available, six (38%) reports were normal, six (38%) noted unilateral pulmonary infiltrates, and four (25%) noted pleural effusions. Two (13%) patients developed empyema, and two (13%) developed generalized sepsis.

Eighty (66%) of the 121 patients had an uneventful clinical course with full recovery, 40 (33%) patients had a complicated clinical course, and one patient died of sepsis (Table). Sixty-three (52%) of the 121 patients were hospitalized (median duration: 4 days [range: 1--27 days]). Three patients with pneumonic and one patient with ulceroglandular tularemia were admitted to an intensive-care unit. Six patients with glandular and two with pneumonic tularemia were rehospitalized because of relapse or other complications. Among 17 (14%) patients who required surgical intervention, 15 had suppurated lymph nodes requiring incision and drainage, and two developed a loculated empyema requiring thoracotomy and decortication.

Information on antimicrobial treatment was available for 109 patients; 97 (89%) received at least one appropriate antibiotic to treat tularemia (4) (Table), and the remaining 12 (11%) were treated with combinations of antibiotics that are considered ineffective against tularemia. Among 14 patients initially treated with 10 days of ciprofloxacin monotherapy, 12 (86%) recovered completely, whereas two (14%) experienced persistence of symptoms. Of 73 patients for whom sufficient data were available, the median interval between onset of symptoms and commencement of an effective antimicrobial was 14 days (range: 0--82 days). The incidence of complications was not related to age, sex, or the timing of effective therapy.

The total number of specimens submitted for culture and serology could not be determined; however, of the 57 confirmed cases, 39 (68%) had positive cultures, most commonly from blood, lymph nodes, or lesions, and 18 (32%) had a fourfold or greater difference in paired serum antibody titers. All probable cases were diagnosed based on a single elevated serum antibody titer to F. tularensis. Among the 39 culture-confirmed cases, 33 (85%) laboratory results were available before the health-care provider documented a suspicion of tularemia in the clinical record.

Among 78 cases for which exposure was known, tick bites were the most commonly noted exposures (72%) (Table), and 80% of tick bite exposures occurred during May--September. Cases associated with other exposures did not show a distinct seasonal trend (Figure 2). Animal and aerosol exposures accounted for 16% of cases, with aerosol exposures reported only for adults.

Reported by: G Turabelidze, MD, PhD, S Patrick, PhD, Missouri Dept of Health and Senior Svcs. PS Mead, MD, KS Griffith, MD, Div of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; IB Weber, MBChB, MMed, EIS Officer, CDC.

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Tularemia --- Missouri, 2000--2007