Tularemia

Tularemia is a zoonotic disease caused by Francisella tularensis, a fastidious, gram-negative coccobacillus that infects vertebrates, especially rabbits and rodents. In humans, tularemia is classified into six major syndromes: ulcero-glandular (the most common form), glandular, typhoidal, oculoglandular, oropharyngeal, and pneumonic. The case-fatality rate among humans can reach 30%-60% in untreated typhoidal cases (1). Although bites from ticks and handling infected animals are considered the most common modes of tularemia transmission in the United States (2-4), the disease also is spread through ingestion of contaminated food or water, inhalation, and insect bites (1-5). During 2001-2003, Wyoming experienced an increase in reported human cases of tularemia. This report describes the subsequent investigation by the Wyoming Department of Health (WDH), which indicated that 1) insect bites (particularly from deerflies and other horseflies) were the most commonly reported likely mode of transmission, and 2) the increase in cases was geographically and temporally associated with an outbreak of tularemia among rabbits in southwestern Wyoming. To obtain a timely diagnosis and provide information on appropriate preventive measures, health-care providers and public health officials should have knowledge of the local epidemiology of tularemia, particularly regarding modes of transmission and resultant clinical syndromes.

Tularemia is a reportable disease in Wyoming and is designated as a nationally notifiable disease. In this investigation, a case was defined as a confirmed or probable case of tularemia reported to WDH during 1990-2003. A confirmed case was defined as a clinically compatible case with confirmatory laboratory results, which might include either isolation of F. tularensis in a clinical specimen or a fourfold or greater change in antibody titer. A probable case was defined as a clinically compatible case with laboratory results indicative of infection, which might include either a single elevated antibody titer or detection of F. tularensis in a clinical specimen by immunohistochemistry or immunofluorescence (6). A case of insect-borne tularemia was defined as tularemia that occurred within 14 days of a fly, flea, or other insect bite in a patient with no other known exposures, including tick bites and handling of infected animal tissues. Patient interviews, medical record reviews, or reviews of archived follow-up forms were conducted for each case. In this report, location refers to the geographic location of exposure, except where a definite exposure location was not reported (four cases); in those instances, location refers to place of residence (Table; Figure 1).

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During 2001-2003, a total of 11 cases (six confirmed; five probable) of tularemia were reported in Wyoming, for an average of 3.7 cases per year. In contrast, 10 cases (seven confirmed; three probable) were reported during 1990-2000, for an average of 0.9 cases per year (Figure 2).

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Of the 11 cases reported during 2001-2003 (Table), nine (82%) were in male patients. Six (55%) of the tularemia cases were the ulceroglandular type, and all included insect bites as the likely mode of transmission. Two cases (18%) were the typhoidal type, and the remaining three cases were the glandular, oculoglandular, and pneumonic types (9% each). No deaths were reported.

In seven (64%) cases, insect bites (from deerflies or other horseflies in six cases; flies and/or fleas in one case) were determined to be the most likely mode of transmission. Six of these patients had ulceroglandular tularemia; one patient had typhoidal tularemia. Median age of persons for whom insect bites were the likely mode of transmission was 40 years (range: 18 months-68 years). Median age of those with other modes of transmission was 53 years (range: 40-70 years). Likely modes of transmission in the other four cases were infected rabbit exposure (one), infected sheep exposure (one), and unknown (two). In contrast, during 1990-2000, no cases were linked to insect bites. The likely modes of transmission in cases during 1990-2000 were ticks (four), rabbits (three), sheep (one), and unknown (two). Eight (73%) of the 11 cases reported during 2001-2003 were reported from counties in southwestern Wyoming (Sweetwater [five], Lincoln [two], and Uinta [one]); the remaining three (27%) were distributed among counties elsewhere in the state (one case each in Fremont, Park, and Teton counties) (Figure 1). The F. tularensis isolates from the six confirmed cases that occurred during 2001-2003 were further classified into types A or B. Five of these typed isolates were from cases in the southwestern region of the state, where an epizootic among rabbits was thought to have occurred; all five were classified as type A. One isolate from the northwestern region was classified as type B.

In October 2003, WDH was informed that two ill rabbits from the Seedskadee National Wildlife Refuge in southwestern Wyoming collected in the summer and early fall of 2003 tested positive for tularemia. Refuge personnel reported an increase in the number of dead or ill rabbits during the summers of 2002 and 2003.

Editorial Note: The organism that causes tularemia was isolated from humans in 1919 during an investigation of the cause of deerfly fever in Utah. Laboratory studies conducted at the time confirmed that deerflies (Chrysops discalis) can transmit the organism among animals. Despite this original association with biting flies, most cases in the United States are attributed to noninsect exposures, especially tick bites and contact with infected animal tissues (2,3). This report illustrates how the epidemiology of tularemia can be region-dependent and change over time. Because proper diagnosis and treatment of tularemia relies on a high index of suspicion and clinical presentation is related to the method of acquisition (e.g., development of ulceroglandular tularemia after an insect bite) (1,2), health-care providers should understand the local epidemiology of tularemia. On the basis of this knowledge, public health officials can recommend locally appropriate prevention and control measures, such as wearing gloves when handling dead animals (particularly rabbits and rodents); cooking game meat thoroughly; avoiding bites of ticks, flies, and mosquitoes by using insect repellent and wearing long clothing; and avoiding drinking untreated water. In addition, a local epizootic of tularemia might correlate with an increase in human cases and should heighten awareness that tularemia might be a possibility in clinically compatible cases.

In this outbreak, insect bites accounted for 64% of recent human cases. These cases were geographically and temporally associated with an epizootic among rabbits in southwestern Wyoming. Subtyping data revealed that all isolates from humans in this area were type A, the subtype most commonly associated with rabbits (7), thereby supporting a likely connection between these events. Deerflies have been implicated in two previous outbreaks of tularemia; in both instances, a concomitant epizootic among rabbits was observed (5). Whereas enzootic cycles of tularemia might not be apparent, epizootics with die-off of animal hosts might correlate with increases of tularemia in humans (5).

The findings in this report are subject to at least two limitations. First, the likely modes of transmission in the recent Wyoming cases were determined from the histories reported by patients and therefore might be limited by recall bias. Second, other unrecognized modes of transmission might have coincided with the exposures that were reported.

As with many other diseases, proper diagnosis and treatment of tularemia relies on a high index of suspicion. Laboratory diagnosis of F. tularensis depends on the laboratory being notified that tularemia is a clinical possibility. Identification of the organism is important because it is often resistant to antibiotics commonly used empirically for skin and systemic infections (1,8).

Acknowledgments

This report is based, in part, on contributions by D Damberg, Seedskadee National Wildlife Refuge, Green River; F Hall, A Heryford, MS, K Roich, Wyoming Dept of Health.

References

(1.) Chin J, ed. Control of communicable diseases manual. 17th ed. Washington, DC: American Public Health Association; 2000.

(2.) CDC. Tularemia--United States, 1990-2000. MMWR 2002;51:182-4.

(3.) Evans ME, Gregory DW, Schaffner W, et al. Tularemia: a thirty year experience with 88 cases. Medicine 1985;64:251-69.

(4.) Finley CR, Hamilton BW, Hamilton TR. Tularemia, a review. Mo Med 1986;83:741-3.

(5.) Klock LE, Olsen PF, Fukushima T. Tularemia epidemic associated with the deerfly. JAMA 1973;226:149-52.

(6.) CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(No. RR-10).

(7.) Acha PN, Szyfres B. Zoonoses and communicable diseases common to man and animals. 3rd ed. Washington, DC: Pan American Health Organization; 2001.

(8.) Jacobs RF. Tularemia. Adv Pediatr Infect Dis 1996;12:55-69.

Reported by: S Seys, MPH, K Musgrave, DVM, Wyoming Dept of Health. J Cassady, PhD, Drew Univ, Madison, New Jersey. J Hunt, Univ of Utah School of Medicine, Salt Lake City, Utah. T Murphy, MD, EIS Officer, CDC.

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