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Plague As a Biological Weapon Medical and Public Health Management

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Plague As a Biological Weapon Medical and Public Health Management CONSENSUS STATEMENT Plague as a Biological Weapon Medical and Public Health Management Thomas V. Inglesby, MD Objective The Working Group on Civilian Biodefense has developed consensus- David T. Dennis, MD, MPH based recommendations for measures to be taken by medical and public health profes- Donald A. Henderson, MD, MPH sionals following the use of plague as a biological weapon against a civilian population. Participants The working group included 25 representatives from major academic John G. Bartlett, MD medical centers and research, government, military, public health, and emergency man- Michael S. Ascher, MD agement institutions and agencies. Edward Eitzen, MD, MPH Evidence MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological ter- Anne D. Fine, MD rorism, biological warfare, and biowarfare. Review of the bibliographies of the refer- Arthur M. Friedlander, MD ences identified by this search led to subsequent identification of relevant references pub- Jerome Hauer, MPH lished prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. John F. Koerner, MPH, CIH Consensus Process The first draft of the consensus statement was a synthesis of in- Marcelle Layton, MD formation obtained in the formal evidence-gathering process. The working group was Joseph McDade, PhD convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunc- Michael T. Osterholm, PhD, MPH tion with final consensus recommendations supported by all working group members. Tara O’Toole, MD, MPH Conclusions An aerosolized plague weapon could cause fever, cough, chest pain, Gerald Parker, PhD, DVM and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after expo- sure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset Trish M. Perl, MD, MSc and would lead to septic shock with high mortality without early treatment. Early treat- Philip K. Russell, MD ment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoro- quinolone classes of antimicrobials would be advised. Monica Schoch-Spana, PhD JAMA. 2000;283:2281-2290 www.jama.com Kevin Tonat, DrPH, MPH the availability of Y pestis around the biological terrorism, biological warfare, for the Working Group on Civilian Biodefense world, capacity for its mass produc- and biowarfare. Review of the bibliog- tion and aerosol dissemination, diffi- raphies of the references identified by HIS IS THE THIRD ARTICLE IN A culty in preventing such activities, high series entitled Medical and Pub- fatality rate of pneumonic plague, and Author Affiliations: Center for Civilian Biodefense Studies, Johns Hopkins University Schools of Medi- lic Health Management Follow- potential for secondary spread of cases cine (Drs Inglesby, Bartlett, and Perl) and Public Health ing the Use of a Biological during an epidemic, the potential use (Drs Henderson, O’Toole, Russell, and Schoch- Spana and Mr Koerner), Baltimore, Md; National Cen- TWeapon: Consensus Statements of the of plague as a biological weapon is of ter for Infectious Diseases, Centers for Disease Con- Working Group on Civilian Biode- great concern. trol and Prevention, Fort Collins, Colo (Dr Dennis), and Atlanta, Ga (Dr McDade); Viral and Rickettsial 1,2 fense. The working group has iden- Diseases Laboratory, California Department of Health tified a limited number of agents that, CONSENSUS METHODS Services, Berkeley (Dr Ascher); United States Army Medical Research Institute of Infectious Diseases, Fred- if used as weapons, could cause dis- The working group comprised 25 rep- erick, Md (Drs Eitzen, Friedlander, and Parker); Sci- ease and death in sufficient numbers to resentatives from major academic medi- ence Application International Corporation, McLean, Va (Mr Hauer); Office of Communicable Disease, New cripple a city or region. These agents cal centers and research, government, York City Health Department, New York, NY (Drs Fine and Layton); Office of Emergency Preparedness, De- also comprise the top of the list of military, public health, and emergency partment of Health and Human Services, Rockville, Md “Critical Biological Agents” recently de- management institutions and agencies. (Dr Tonat); and Infection Control Advisory Network Inc, Eden Prairie, Minn (Dr Osterholm). veloped by the Centers for Disease Con- MEDLINE databases were searched Corresponding Author and Reprints: Thomas V. trol and Prevention (CDC).3 Yersinia from January 1966 to June 1998 using Inglesby, MD, Johns Hopkins Center for Civilian Bio- defense Studies, Johns Hopkins University, Candler Bldg, pestis, the causative agent of plague, is the Medical Subject Headings (MeSH) Suite 850, 111 Market Place, Baltimore, MD 21202 one of the most serious of these. Given plague, Yersinia pestis, biological weapon, (e-mail: [email protected]). ©2000 American Medical Association. All rights reserved. JAMA, May 3, 2000—Vol 283, No. 17 2281 MANAGEMENT OF PLAGUE USED AS A BIOLOGICAL WEAPON this search led to subsequent identifi- rats and humans or more quickly from a microbiologist with suspect motives cation of relevant references published country to country by ships. The pan- was arrested after fraudulently acquir- prior to 1966. In addition, participants demic lasted more than 130 years and ing Y pestis by mail.10 New antiterrorism identified other unpublished refer- had major political, cultural, and reli- legislation was introduced in reaction. ences and sources in their fields of ex- gious ramifications. The third pan- pertise. Additional MEDLINE searches demic began in China in 1855, spread EPIDEMIOLOGY were conducted through January 2000 to all inhabited continents, and ulti- Naturally Occurring Plague during the review and revisions of the mately killed more than 12 million Human plague most commonly occurs statement. people in India and China alone.4 Small when plague-infected fleas bite hu- The first draft of the consensus state- outbreaks of plague continue to occur mans who then develop bubonic plague. ment was a synthesis of information ob- throughout the world.4,5 As a prelude to human epidemics, rats tained in the initial formal evidence- Advances in living conditions, pub- frequently die in large numbers, precipi- gathering process. Members of the lic health, and antibiotic therapy make tating the movement of the flea popula- working group were asked to make for- future pandemics improbable. How- tion from its natural rat reservoir to hu- mal written comments on this first draft ever, plague outbreaks following use of mans. Although most persons infected of the document in September 1998. The a biological weapon are a plausible threat. by this route develop bubonic plague, a document was revised incorporating In World War II, a secret branch of the small minority will develop sepsis with changes suggested by members of the Japanese army, Unit 731, is reported to no bubo, a form of plague termed pri- working group, which was convened to have dropped plague-infected fleas over mary septicemic plague. Neither bu- review the second draft of the docu- populated areas of China, thereby caus- bonic nor septicemic plague spreads di- ment on October 30, 1998. Following ing outbreaks of plague.6 In the ensu- rectly from person to person. A small this meeting and a second meeting of the ing years, the biological weapons pro- percentage of patients with bubonic or working group on May 24, 1999, a third grams of the United States and the Soviet septicemic plague develop secondary draft of the document was completed, Union developed techniques to aerosol- pneumonic plague and can then spread reviewed, and revised. Working group ize plague directly, eliminating depen- the disease by respiratory droplet. Per- members had a final opportunity to re- dence on the unpredictable flea vector. sons contracting the disease by this route view the document and suggest revi- In 1970, the World Health Organiza- develop primary pneumonic plague.11 sions. The final document incorpo- tion (WHO) reported that, in a worst- Plague remains an enzootic infection rates all relevant evidence obtained by case scenario, if 50 kg of Y pestis were re- of rats, ground squirrels, prairie dogs, and the literature search in conjunction with leased as an aerosol over a city of 5 other rodents on every populated con- consensus recommendations sup- million, pneumonic plague could oc- tinent except Australia.4 Worldwide, on ported by all working group members. cur in as many as 150000 persons, 36000 average in the last 50 years, 1700 cases The assessment and recommenda- of whom would be expected to die.7 The have been reported annually.4 In the tions provided herein represent the best plague bacilli would remain viable as an United States, 390 cases of plague were professional judgment of the working aerosol for 1 hour for a distance of up reported from 1947 to 1996, 84% of group based on data and expertise cur- to 10 km. Significant numbers of city in- which were bubonic, 13% septicemic, rently available. The conclusions and habitants might attempt to flee, further and 2% pneumonic. Concomitant case recommendations need to be regu- spreading the disease.7 fatality rates were 14%, 22%, and 57%, larly reassessed as new information be- While US scientists had not suc- respectively.12 Most
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