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Tularemia --- Oklahoma, 2000

In June 2000, seven cases of tularemia were reported to the Oklahoma State Department of Health (OSDH) over an 18-day period. Enhanced tularemia surveillance by OSDH during July--September 2000 detected four additional cases. During 1995--1999, an average of six cases were reported each year. This report summarizes clinical and epidemiologic information from the investigation of the 11 cases, presents three case reports to illustrate different risk factors for tularemia, and underscores the danger of delayed diagnosis of tularemia and the risk for acquiring tularemia in laboratory settings. Physicians should consider tularemia in ill persons with fever who reside in or visit areas where the disease is endemic and who have been exposed to ticks or carcasses or tissue from rabbits or other animals.

Cases were classified as either probable (i.e., compatible illness with laboratory findings indicative of presumptive infection [1]) or confirmed (i.e., compatible illness with confirmatory laboratory results). The median age of the 11 patients was 50 years (range: 3--77 years); six were female. All 11 resided in central or eastern Oklahoma. Symptoms included fever (11), cutaneous ulcer (seven), painful adenopathy (six), cough (five), and diarrhea (two). For surveillance purposes, OSDH staff categorized the clinical presentations as ulceroglandular (nine), typhoidal (one), and pneumonic (one) (1). Eight patients were hospitalized and two died. The median duration from onset of symptoms to tularemia diagnosis was 18 days (range: 3--57 days) for the nonfatal cases and 45 days for one fatal case; the date of onset was unknown for the second fatal case.

Eight cases, including both fatal cases, were confirmed either by culture (four patients) or four-fold rises in serum agglutination titer (four patients). Of the three probable cases, two patients had a single high titer (1:640 and 1:1280) and one was positive for IgM, IgA, and IgG antibody to Francisella tularensis by ELISA. Of the four culture-confirmed cases, F. tularensis was isolated from the blood of three patients and from the wound of the fourth patient. On the basis of testing at CDC, all three blood isolates were F. tularensis biovar tularensis (type A). Molecular typing by multiple-locus variable-number tandem repeat analysis at the Laboratory of Paul Keim, Northern Arizona University, indicated that the isolates were similar to seven other F. tularensis strains isolated in Oklahoma during 1992--1996.

Possible F. tularensis exposures for nonfatal cases included known tick attachment within 14 days of illness onset (three patients), possible environmental tick exposure (three patients), skinning rabbits (two patients), and laboratory exposure (one patient). One person who died had possible tick exposure; the exposure for the other fatal case was undetermined.

Case Reports

Case 1. On June 16, 2000, a 64-year-old man was found comatose in his home and taken to a local emergency department (ED). In the ED, he had evidence of acute renal failure, and pulmonary infiltrates were seen on his chest radiograph. He had a history of fever of unknown duration, generalized muscle weakness, cough, hemoptysis, anorexia, and fatigue. Laboratory findings included marked elevation of creatine phosphokinase (>23,000 U/L) (normal=24--195 U/L), elevated blood urea nitrogen (120 mg/dL) (normal=8--18 mg/dL) and creatine (7.5 mg/dL) (normal=0.2--0.5 mg/dL), white blood cell (WBC) count of 10.5x103/cumm (normal=4.5--11x103/cumm), elevated aspartate aminotransferase (AST) (720 U/L) (normal=0--35 U/L), alanine aminotransferase (ALT) (86 U/L) (normal=7--35 U/L), total bilirubin (1.7 mg/dL) (normal=0.1--1.1 mg/dL), myoglobin (10,928 ng/mL) (normal=<116 ng/mL), and proteinuria. The patient was treated for acute renal failure and given intravenous ceftriaxone. Blood cultures performed on June 16 and 17 grew an organism that was identified as Actinobacillus actinomycemcomitans. The patient's condition deteriorated and, because he had a history of training dogs, intravenous doxycycline was started for a possible tickborne illness. The patient died on June 29. On July 14, F. tularensis was isolated from blood culture at the OSDH laboratory.

Case 2. On July 3, 2000, a 51-year-old female microbiologist presented to an ED with a 10-day history of fever, headache, myalgia, loss of appetite, abdominal tenderness, painful respiration, and sharp pain in the upper right quadrant of her back. Physical findings included fever (103 F [39.4 C]), cervical adenopathy, and a right lower lobe pulmonary infiltrate on chest radiograph. Laboratory findings included leukocytosis (WBC count of 14.8x103/cumm), lymphocytosis (12.5x103/cumm), elevated AST (61 U/L), ALT (121 U/L), and alkaline phosphatase (272 U/L) (normal=39--117 U/L). She was diagnosed with possible food poisoning and given a 10-day course of oral levofloxicin. Approximately 14 days before becoming symptomatic, she had worked with the blood culture bottles and plates obtained from case 1 in the hospital laboratory. When F. tularensis was isolated in case 1 specimens, case 2 was notified about a potential exposure to the organism. An agglutination titer performed on a blood specimen collected during ED examination was negative (<1:80), but a sample obtained 11 days later had a titer of 1:320. The patient recovered completely. None of the three other laboratory workers who had contact with case 1 specimens reported illness.

Case 3. On September 1, 2000, an 11-year-old girl with a 2-day history of fever (103 F [39.4 C]), painful adenopathy, headache, and muscle aches was taken to a hospital. On physical examination, she had cellulitis of the forearm and an enlarged axillary lymph node. Her peripheral blood count was normal. She was treated for cellulitis of undetermined etiology with an oral cephalosporin. When she did not improve after 3 days, she was taken to her regular physician who suspected tularemia and ordered serologic tests. Paired serum titers for F. tularensis collected 15 days apart were 1:40 and 1:1024, respectively. After taking doxycycline 100 mg/BID for 10 days, she recovered. The girl had a hobby of sewing together tanned rabbit hides to make blankets, and a week before illness onset she had skinned and tanned a rabbit killed by the family dog.

Reported by: K Bradley, DVM, M Grubbs, M Lytle, M Crutcher, MD, State Epidemiologist, Oklahoma State Dept of Health. K Smith, DVM, P Keim, PhD, The Laboratory of Paul Keim, Northern Arizona Univ, Flagstaff, Arizona. State Br, Div of Applied Public Health Training, Epidemiology Program Office; and an EIS Officer, CDC.

Editorial Note:

F. tularensis is transmitted to humans by direct contact with or ingestion of infected animal tissues, through the bite of infected arthropods, by consumption of contaminated food or water, or from inhalation of aerosolized bacteria (2). It also is a potential bioterrorism agent (3). The occurrence of seven cases over a 2-week period in Oklahoma prompted an investigation of exposures, including the possibility of a bioterrorism event; however, the exposure history, clinical presentations, and geographic distribution of cases were compatible with natural transmission (3). In addition, the strains involved in this cluster were genetically similar to those previously acquired in the state.

Tularemia occurs throughout North America, but during 1985--1994, 55% of cases in the United States were reported from Arkansas, Missouri, and Oklahoma (4). The incidence of tularemia in the United States and in Oklahoma has declined markedly since the 1940s, and national incidence has remained between 0.05 and 0.15 cases per 100,000 population since 1965 (2). Reasons for the increase in cases in 2000 are unknown.

Tularemia has a broad clinical spectrum (2) and may be overlooked in the differential diagnosis of patients with suspected infectious diseases, particularly when the typical ulcer is absent. Delayed diagnosis and late administration of effective antibiotic therapy result in increased morbidity and mortality. Tularemia should be included in the differential diagnosis of any patient in an area where the disease is endemic who has unexplained febrile illness and exposure to ticks, biting flies, or animal tissue.

The acquisition of tularemia in a laboratory worker emphasizes the need to follow Biosafety Level 2 precautions when processing human specimens (5). Appropriate laboratory precautions include gloves, laboratory coats, face protection for manipulations outside a biosafety cabinet, use of a biosafety cabinet for procedures that may create aerosols, and decontamination of laboratory surfaces. Laboratory workers should wash their hands after removing gloves and before leaving the laboratory. Laboratory personnel should be informed of the possibility of tularemia as a differential diagnosis when samples are submitted for diagnostic tests. Work with cultures or contaminated materials should be performed at Biosafety Level 3 with all manipulations conducted in a biosafety cabinet, including preparations of materials for automated identification systems.

Information on the distribution of specific F. tularensis strains could provide a baseline reference for bioterrorism preparedness in the United States. For the public, education about risk factors for tularemia is the primary prevention measure.

References*

  1. CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(no. RR-10).
  2. Cross TJ, Penn RL. Francisella tularensis (tularemia). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 5th ed. Philadelphia, Pennsylvania: Churchill Livingston, 2000.
  3. Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: medical and public health management. JAMA 2001;285:2763--73.
  4. Dennis DT. Tularemia. In: Wallace RB, ed. Public Health and Preventive Medicine, 14th ed. Stamford, Connecticut: Appleton and Lang, 1998.
  5. Richmond JY, McKinney RW. Biosafety in microbiological and biomedical laboratories, 4th ed. Washington, DC: CDC, National Institutes of Health, 1999.

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