Tularemia as Terror
Abstract & Commentary
Synopsis: Tularemia is a bacterial zoonosis caused by one of the most infectious pathogenic bacteria currently known, Francisella tularensis. Inhalation or inoculation of as few as 10 organisms can cause disease. F tularensis has previously been considered a potent agent for bioterrorism. Given recent bioterrorist events, this review highlights known disease manifestations, as well as unusual patterns of disease occurrence and summarizes reports of known cases occurring in the United States between 1990 to 2000.
Source: Tularemia—United States, 1990-2000. Morb Mortal Wkly Rep MMWR. 2002;51:181-184.
In 1911, tularemia was first described as a plague-like disease of rodents, but it was soon recognized as a serious and sometimes fatal illness of humans, who are infected through various unique environmental exposures. Large waterborne outbreaks occurred in Europe and the Soviet Union in the 1930s and 1940s, which demonstrated the organisms’ epidemic potential. The highest incidence of human cases in the United States occurred in 1939 and through the 1940s—mostly as a result of infective arthropod bites, or from hunters handling animal tissues, such as rabbit skins.
F tularensis can be found in widely diverse animal hosts and habitats where natural reservoirs of infection persist in small mammals such as voles, mice, water rats, squirrels, and rabbits, which acquire their infections through bites by ticks, flies, and mosquitoes or by contact with contaminated water soil or vegetation. Lawn mowing or brush cutting has also been associated with outbreaks of tularemia in the United States. Persons of all ages and both sexes appear to be equally susceptible, although activities such as hunting, trapping, butchering and farming have been traditionally most likely to cause exposures in adult men. The organism represents a truly virulent laboratory hazard as workers can accidentally inoculate themselves or inhale aerosolized organisms. Though highly infectious, person-to-person transmission has not been documented.
The incidence of tularemia in the United States has declined substantially since the first half of the 1900s. The number of cases has continued to decline since the 1950s. Recent cases are clustered, as seen in the Figure, within Arkansas, Missouri, South Dakota, and Oklahoma accounting for the majority of reported cases. From 1990 to 2000, a total of 1368 cases of tularemia were reported to the CDC. Fifty-nine percent were reported as confirmed and 6% were reported as probable. The disease was not classified as a notifiable disease from 1995 to 1999 but an increase in reporting occurred during 2000 when notifiable status was restored. Annual incidence was highest in persons aged 5-9 years and in persons older than 75 years. Males had a higher incidence in all age categories. Incidence was highest among American Indians/Alaska Natives, compared with whites, blacks, and Asian/Pacific Islanders. Date of onset was available in 936 cases—of which 70% reported onset during May through August, although cases were reported during all months of the year.
Tularemia characteristically presents as an acute febrile illness typically associated with fatigue, chills, headache, body aches, and malaise. F tularensis is a facultative intracellular bacterium that multiplies within macrophages. The major target organs are lymph nodes, lungs and pleura, spleen, liver, and kidneys. Depending upon route of infection, various clinical manifestations can include granulomatous ulceration at the site of cutaneous or mucous membrane inoculation, pharyngitis, ocular lesions, regional lymphadenopathy, and pneumonia. (See Table 1.) During the largest recorded airborne tularemia outbreak in 1966, which occurred in a farming area of Sweden, 10% of confirmed patients had symptoms of pneumonia such as dyspnea and chest pains.
Any form of tularemia may be complicated by hematogenous spread resulting in secondary pleuropneumonia, sepsis, and rarely meningitis.
Typhoidal tularemia is a term used to describe illness in persons with fever and constitutional signs without cutaneous or mucosal involvement. Sometimes these patients present with prominent gastrointestinal manifestations, such as diarrhea and pain. Tularemia sepsis is potentially severe and fatal, and presents with an initial nonspecific intestinal syndrome followed soon after by a toxic appearance, confusion, coma, shock, DIC, ARDS, and multiorgan failure.
In ulceroglandular tularemia, the form that typically arises from handling a contaminated carcass or following an infective bite, a local cutaneous papule appears at the inoculation site at about the time of onset of generalized symptoms. It becomes pustular and ulcerates within a few days of its first appearance. The ulcer is tender, indolent and may be covered by an eschar. Typically, one or more regional lymph nodes may become enlarged and tender within days, and may rupture even with antibiotic treatment. Oculoglandular tularemia follows direct contamination of the eye with ulceration of the conjunctiva as well as chemosis, vasculitis, and regional lymphadenitis. The glandular form is characterized by lymphadenopathy without an ulcer. Oropharyngeal tularemia is acquired by drinking contaminated water ingesting contaminated food, or by inhaling contaminated droplets or aerosols. Stomatitis, exudative pharyngitis or tonsillitis with ulceration can occur. Pronounced cervical or retropharyngeal lymphadenopathy can occur.
Presumptive diagnosis of tularemia can be made by direct fluorescent antibody or immunohistochemical stains of secretions, exudates, or biopsy specimens. By light microscopy the organism is characterized by its small size (0.2 um × 0.2-0.7 um) pleomorphism and faint staining. It is easily distinguished from the plague organism (Yersinia pestis), which shows bipolar staining, and from anthrax (Bacillus anthracis), which is a large gram-positive rod. Definitive diagnosis is by culture of the organism or by a fourfold titer change of serum antibodies against F tularensis.
Comment by Maria D. Mileno, MD
The incidence of tularemia in the United States remains low following a dramatic decline in the second half of the 20th century. A weapon using airborne tularemia would likely result in pulmonary presentations 3-5 days later, such as an outbreak of an acute febrile illness with ensuing pneumonia, pleuritis, and hilar adenopathy. Unusual clustering of such cases should lead to early suspicion of intentional tularemia. Until an etiology is clearly established, clinicians would need to work closely with epidemiologists and diagnostic laboratories to differentiate the illness from various community-acquired pneumonias and to exclude other bioterrorist weapons such as those causing plague, anthrax, or Q fever. Prompt treatment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended while awaiting laboratory confirmation. Without treatment the clinical course could progress rapidly to respiratory failure, shock, and death. Treatment with aminoglycosides should be continued for 10 days. Exposed persons should be prophylactically treated with 14 days of oral doxycycline or ciprofloxacin.
Dr. Mileno, Director of Travel Medicine, The Miriam Hospital, and Assistant Professor of Medicine, Brown University, Providence, RI, is Associate Editor of Travel Medicine Alert.
Reference
1. Dennis DT, et al. Tularemia as a biological weapon. JAMA. 2001;2285:2763-2773.
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