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Tularemia As a Biological Weapon Medical and Public Health Management

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Tularemia As a Biological Weapon Medical and Public Health Management CONSENSUS STATEMENT Tularemia as a Biological Weapon Medical and Public Health Management David T. Dennis, MD, MPH Objective The Working Group on Civilian Biodefense has developed consensus- Thomas V. Inglesby, MD based recommendations for measures to be taken by medical and public health pro- fessionals if tularemia is used as a biological weapon against a civilian population. Donald A. Henderson, MD, MPH Participants The working group included 25 representatives from academic medi- John G. Bartlett, MD cal centers, civilian and military governmental agencies, and other public health and Michael S. Ascher, MD emergency management institutions and agencies. Edward Eitzen, MD, MPH Evidence MEDLINE databases were searched from January 1966 to October 2000, using the Medical Subject Headings Francisella tularensis, Pasteurella tularensis, bio- Anne D. Fine, MD logical weapon, biological terrorism, bioterrorism, biological warfare, and biowar- Arthur M. Friedlander, MD fare. Review of these references led to identification of relevant materials published prior to 1966. In addition, participants identified other references and sources. Jerome Hauer, MHS Consensus Process Three formal drafts of the statement that synthesized infor- Marcelle Layton, MD mation obtained in the formal evidence-gathering process were reviewed by mem- Scott R. Lillibridge, MD bers of the working group. Consensus was achieved on the final draft. Joseph E. McDade, PhD Conclusions A weapon using airborne tularemia would likely result 3 to 5 days later in an outbreak of acute, undifferentiated febrile illness with incipient pneumonia, pleu- Michael T. Osterholm, PhD, MPH ritis, and hilar lymphadenopathy. Specific epidemiological, clinical, and microbiologi- Tara O’Toole, MD, MPH cal findings should lead to early suspicion of intentional tularemia in an alert health system; laboratory confirmation of agent could be delayed. Without treatment, the Gerald Parker, PhD, DVM clinical course could progress to respiratory failure, shock, and death. Prompt treat- Trish M. Perl, MD, MSc ment with streptomycin, gentamicin, doxycycline, or ciprofloxacin is recommended. Prophylactic use of doxycycline or ciprofloxacin may be useful in the early postexpo- Philip K. Russell, MD sure period. Kevin Tonat, DrPH, MPH JAMA. 2001;285:2763-2773 www.jama.com for the Working Group on Civilian Biodefense infected through diverse environmen- CONSENSUS METHODS tal exposures and can develop severe and The working group comprised 25 rep- I know of no other infection of animals com- municable to man that can be acquired from sometimes fatal illness but do not trans- resentatives from academic medical sources so numerous and so diverse. In short, mit infection to others. The Working centers, civilian and military govern- one can but feel that the status of tularemia, Group on Civilian Biodefense consid- mental agencies, and other public health both as a disease in nature and of man, is one ers F tularensis to be a dangerous poten- and emergency management institu- of potentiality. R. R. Parker1 tial biological weapon because of its ex- tions. This group followed a specified treme infectivity, ease of dissemination, process in developing a consensus state- ULAREMIA, A BACTERIAL ZOONO- and substantial capacity to cause illness ment. MEDLINE databases from Janu- sis, is the subject of this fifth ar- and death.8-11 ary 1966 to October 2000 were searched ticle in a series providing rec- ommendations for medical and Author Affiliations: National Center for Infectious Dis- (Drs Fine and Layton), and Kroll Associates (Mr Hauer), Tpublic health management following use eases, Centers for Disease Control and Prevention, New York, NY; ican Inc, Eden Prairie, Minn (Dr Oster- of various agents as biological weapons Atlanta, Ga (Drs Dennis, Lillibridge, and McDade); Cen- holm); and Office of Emergency Preparedness, Depart- 2-5 ter for Civilian Biodefense Studies, Johns Hopkins Uni- ment of Health and Human Services, Rockville, Md (Dr of terrorism. The causative agent of tu- versity Schools of Medicine (Drs Inglesby, Bartlett, and Tonat). laremia, Francisella tularensis, is one of Perl) and Public Health (Drs Henderson, O’Toole, and Ex Officio Participants in the Working Group on Ci- Russell), Baltimore, Md; Viral and Rickettsial Diseases vilian Biodefense are listed at the end of this article. the most infectious pathogenic bacteria Laboratory, California Department of Health Services, Corresponding Author and Reprints: David T. Den- known, requiring inoculation or inha- Berkeley (Dr Ascher); US Army Medical Research Insti- nis, MD, MPH, Division of Vector-Borne Infectious Dis- tute of Infectious Diseases, Ft Detrick, Md (Drs Eitzen, eases, National Center for Infectious Diseases, Cen- lation of as few as 10 organisms to cause Friedlander, and Parker); Bureau of Communicable ters for Disease Control and Prevention, PO Box 2087, disease.6,7 Humans become incidentally Disease, New York City Health Department Fort Collins, CO 80522 (e-mail: [email protected]). ©2001 American Medical Association. All rights reserved. (Reprinted) JAMA, June 6, 2001—Vol 285, No. 21 2763 Downloaded from jama.ama-assn.org by guest on April 25, 2012 MANAGEMENT OF TULAREMIA AS A BIOLOGICAL WEAPON using the Medical Subject Headings 1950s and 1960s, the US military devel- larensis and other potential biological Francisella tularensis, Pasteurella tu- oped weapons that would disseminate warfare agents to better protect the US larensis, biological weapon, biological ter- F tularensis aerosols10; concurrently, it military, including protocols on decon- rorism, bioterrorism, biological war- conducted research to better under- tamination, prophylaxis, clinical rec- fare, and biowarfare. Review of the stand the pathophysiology of tulare- ognition, laboratory diagnosis, and bibliographies of these references led mia and to develop vaccines and anti- medical management.29 The CDC op- to identification of relevant materials biotic prophylaxis and treatment erates a national program for bioter- published prior to 1966. In addition, regimens. In some studies, volunteers rorism preparedness and response that participants identified other pub- were infected with F tularensis by di- incorporates a broad range of public lished and unpublished references and rect aerosol delivery systems and by ex- health partnerships.30,31 sources for review. posures in an aerosol chamber.10 A live The first draft of the consensus state- attenuated vaccine was developed that EPIDEMIOLOGY ment was a synthesis of information ob- partially protected against respiratory Geographic Distribution tained in the formal evidence-gathering and intracutaneous challenges with the and Human Exposures process. Members of the working group virulent SCHU S-4 strain of F tularen- Tularemia occurs throughout much of were asked to make written comments sis,6,7 and various regimens of strepto- North America and Eurasia.15,21,22,32 In on this first draft in May 1999. Subse- mycin, tetracyclines, and chlorampheni- the United States, human cases have quent revised drafts were reviewed and col were found to be effective in been reported from every state except edited until full consensus of the work- prophylaxis and treatment.25-27 By the Hawaii; however, most cases occur in ing group was achieved. late 1960s, F tularensis was one of sev- south-central and western states (es- eral biological weapons stockpiled by the pecially Missouri, Arkansas, Okla- HISTORY AND POTENTIAL US military.10 According to Alibeck, a homa, South Dakota, and Montana).33-35 AS A BIOLOGICAL WEAPON large parallel effort by the Soviet Union In Eurasia, the disease is also widely en- Tularemia was first described as a plague- continued into the early 1990s and re- demic, although the greatest numbers like disease of rodents in 1911 and, sulted in weapons production of F tu- of human cases are reported from shortly thereafter, was recognized as a po- larensis strains engineered to be resis- northern and central Europe, espe- tentially severe and fatal illness in hu- tant to antibiotics and vaccines.24 cially Scandinavian countries and those mans.12 Tularemia’s epidemic potential In 1969, a World Health Organiza- of the former Soviet Union.36,37 Tula- became apparent in the 1930s and 1940s, tion expert committee estimated that an remia is almost entirely a rural dis- when large waterborne outbreaks oc- aerosol dispersal of 50 kg of virulent ease, although urban and suburban ex- curred in Europe and the Soviet F tularensis over a metropolitan area with posures occasionally do occur.38-41 Union13-15 and epizootic-associated cases 5 million inhabitants would result in Throughout its range, F tularensis is occurred in the United States.16,17 As well, 250000 incapacitating casualties, includ- found in widely diverse animal hosts F tularensis quickly gained notoriety as ing 19000 deaths.28 Illness would be and habitats and can be recovered from a virulent laboratory hazard.18,19 Public expected to persist for several weeks and contaminated water, soil, and vegeta- health concerns impelled substantial disease relapses to occur during the en- tion.15,20-22,32 A variety of small mam- early investigations into tularemia’s ecol- suing weeks or months. It was assumed mals, including voles, mice, water rats, ogy, microbiology, pathogenicity, and that vaccinated individuals would be squirrels, rabbits, and hares, are natu- prevention.19-22 only partially protected against an aero- ral reservoirs of infection. They ac- Francisella
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