Biological Weapons Defense

I n f e c t i o u s . D i s e a s eSERIES EDITOR: Vassil St. GeorgievNational Institute of Allergy and Infectious Diseases

National Institutes of Health

Biological Weapons Defense: Infectious Diseases and Counterbioterrorism, editedby Luther E. Lindler, PhD, Frank J. Lebeda, PhD, and George W. Korch, PhD,2005

Microbial Genomes, edited by Claire M. Fraser, PhD, Timothy D. Read, PhD, andKaren E. Nelson, PhD, 2004

Management of Multiple Drug-Resistant Infections, edited by Stephen H.Gillespie, MD, 2004

Aging, Immunity, and Infection, by Joseph F. Albright, PhD, and Julia W.Albright, PhD, 2003

Handbook of Cytokines and Chemokines in Infectious Diseases, edited by MalakKotb, PhD, and Thierry Calandra, MD, PhD, 2003

Opportunistic Infections: Treatment and Prophylaxis, by Vassil St. Georgiev, PhD,2003

Innate Immunity, edited by R. Alan B. Ezekowitz, MBChB, DPhil, FAAP, and Jules A.Hoffmann, PhD, 2003

Pathogen Genomics: Impact on Human Health, edited by Karen Joy Shaw, PhD,2002

Immunotherapy for Infectious Diseases, edited by Jeffrey M. Jacobson, MD, 2002Retroviral Immunology: Immune Response and Restoration, edited by Giuseppe

Pantaleo, MD, and Bruce D. Walker, MD, 2001Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New

Directions in Drug Discovery, edited by Philip J. Rosenthal, MD, 2001Drug Interactions in Infectious Diseases, edited by Stephen C. Piscitelli, PharmD,

and Keith A. Rodvold, PharmD, 2001Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic

Resistance, edited by Arch G. Mainous III, PhD, and Claire Pomeroy, MD,2001

Infectious Disease in the Aging: A Clinical Handbook, edited by Thomas T.Yoshikawa, MD, and Dean C. Norman, MD, 2001

Infectious Causes of Cancer: Targets for Intervention, edited by James J. Goedert,MD, 2000

Biological Weapons DefenseInfectious Diseases and Counterbioterrorism

Edited by

Luther E. Lindler, PhDNational Biodefense Analysis and Countermeasures Center, Fort Detrick, MD,and Department of Bacterial Diseases, Walter Reed Army Institute of Research,

Silver Spring, MD

Frank J. Lebeda, PhDDepartment of Cell Biology and Biochemistry,

US Army Medical Research Institute of Infectious Diseases,Fort Detrick, MD

George W. Korch, PhDDirector, National Biodefense Analysis and Countermeasures Center

Fort Detrick, MD

Forewords byDavid R. Franz, COL (RET.), DVM, PhDFlorida Division, Midwest Research Institute,

Palm Bay, FL

Matthew Meselson, PhDBelfer Center for Science and International Affairs,

Department of Molecular and Cellular Biology, Harvard University,Boston, MA

I n f e c t i o u s . D i s e a s eI n f e c t i o u s . D i s e a s e

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2004004125

Foreword

In 2003, the Presidents budget for bioterrorism defense totalled more than $5billion. Today, the nations top academic scientists are scrambling to begin work tounderstand Bacillus anthracis and develop new vaccines and drugs. However, just fiveyears ago, only the US Department of Defense (DOD) seemed concerned about theseexotic agents. In 1997, the DOD spent approximately $137 million on biodefense toprotect the deployed force, while academe, industry, local governments, and most ofour federal leadership was oblivious to, and in some cases doubtful of, the seriousnessof the threat.

The National Institutes of Health (NIH) received the largest budget increase in theorganizations history. Fortunately, during this time of national urgency, a sound baseexists on which to build our defenses against this new threat. A relatively small cadreof dedicated scientists within the US Army Medical Research and Materiel Command(USAMRMC) laid this foundation over the past 20 years.

While the nation as a whole slept, bacteriologists, virologists, immunologists, andcliniciansboth military and civilianwere busy studying the pathogenesis ofexotic organisms; developed vaccines, drugs, and diagnostics; educating health careproviders; supporting state and federal law enforcement in the development ofbioforensics; and contributing technical expertise to international arms control andnational defense policy. During the 1990s, as the nations military forces were beingdownsized, the US Army Medical Research Institute of Infectious Diseases, the DODslead laboratory for medical biodefense, lost approximately 30% of its personnelauthorizations. Yet, the scientists within the command developed new vaccinecandidates and recombinant delivery systems for anthrax, smallpox, plague,brucellosis, the botulium neurotoxins, and staphylococcal toxins along with the viralencephalitides. They established the nations finest biological forensic diagnosticscapability, demonstrated the efficacy of an antiviral drug against smallpox, and led thenation in medical biodefense education.

The dedicated scientists of the USAMRMC and the several other outstandingcontributors from the Centers for Disease Control and Prevention, academia, andinternational organizations to this volume are recognized worldwide as experts inbiological weapons defense. They were hard at work in the laboratory before the publiceven realized there was such a threat, and they stood in the gap for all of us afterOctober 4, 2001, when the United States experienced its first biological terrorismattack in modern history. It was an honor for me to serve with them.

David R. Franz, COL (RET.), DVM, PhD

Florida DivisionMidwest Research Institute

Palm Bay, FL

v

Foreword

vii

Biological Weapons Defense: Infectious Disease and Counterbioterrorism focuseson measures for dealing with the possible deliberate causation of disease and on theunderlying science. The fundamental advances in molecular biology of the last severaldecades are only beginning to find relevant application in the development of effectivesensors, rapid early diagnostics, vaccines, antimicrobials, antitoxins, and other relevantprophylactic, therapeutic, and supportive measures. Advances will also come with theincreased understanding of pathogenesis and of the mechanisms by which contagiousdiseases spread from person to person, leading to improved practical measures to limitoutbreaks, including measures that can be taken by an informed public.

Such advances will certainly be useful against naturally occurring diseases,including those that are newly emerging or re-emerging and, in the eventuality, againstdeliberately caused disease as well. Still, experience suggests that practical applica-tions available to the public, although sure to come, will most likely come at a slowerpace and at greater cost than legislators and the general public may expect. Unlike theconquest of certain naturally occurring communicable diseases, effective protectionagainst deliberately caused disease will remain problematic.

All of the agents or groups of agents to which specific chapters in BiologicalWeapons Defense: Infectious Disease and Counterbioterrorism are devoted wereselected as candidate biological weapons in the old offensive biological warfare (BW)programs of the United Kingdom, the United States, and the Soviet Union. Some ofthese agents were brought to the stage of mass production, were field-tested, and thenstockpiled in bulk and in munitions. It is remarkable how much of the technical basewas foreseen even before the big BW programs got underway, as exemplified, forexample, in the 1942 report of Theodor Rosebury and Elvin Kabat, declassified in1947 and published that year in the Journal of Immunology (1). By 1960, much of thetechnology of selecting, producing, and disseminating disease agents as weapons couldbe found in the open literature. Aside from the novel and modified agents that can beimagined, all of the select agents (except for smallpox) designated by the Centers forDisease Control and Prevention remain accessible from clinics or natural foci. Evenso, despite the industrial-scale preparations that have come and gone and the hundredsof wars and bitter insurgencies that have transpired in the past half-century, there hasbeen no BW, and only a few small-scale acts of bioterrorism or, more accurately,biocrime.

Prudent measures to prepare for a major biological attack and to limit its conse-quences are certainly in order. However, undisciplined speculation that a major bio-logical attack is inevitable risks distracting us from measures intended to keepbiological weapons from coming into use in the first place. Inadequate attention isbeing given to measures to sustain and reinforce the constraints that protect our speciesfrom exploiting biotechnology for hostile purposes, as it has exploited other major

technologies (2). Whatever the underlying reasons that have averted BW andbioterrorism, and whatever the factors that might disrupt this desirable state of affairs,they deserve closer and more disinterested study and attention than they have receivedso far.

As the old Western and Soviet programs recede into the past, the number of personswith the specific knowledge and skills required to create devastating biologicalweapons was rapidly declining. But some biodefense activities, especially secret ones,have begun to reverse this trend by causing a new generation of scientists, engineers,and others to turn their attention to vulnerabilities and conceivable future threat agents,and hence to technologies with offensive potential. The expanded number of facilitiesand individuals working with dangerous pathogens also makes access to these agentseasier, and the number of individuals who may become motivated to make hostile useof them greater.

Beyond that, the impression of extensive secret work risks motivating other states toinitiate or expand secret programs of their own, further multiplying the pool ofpotential security risks and perhaps verging into offensively oriented activities. Closerto home, a further risk of secrecy in biodefense work is that it risks losing theconfidence of the public, essential to the actual implementation of protective measures.The practice of public health traditionally rests on open discussion and public under-standing in order to gain the acceptance and trust of those it is intended to benefit.

Considering the great and growing pervasiveness of biotechnology, the key elementin averting bioterrorism and biowarfare is not access but intent, whether on the part ofindividuals, groups, or national governments. At the level of the individual scientistand through our institutions and professional societies there is a modest but easilypracticed way in which we can address the element of intent. That is the customaryopenness and professional amicability to which scientists are traditionally accustomed.Scientific visits, exchanges, joint projects, studies abroad, development of personalfriendships across cultures and across national frontiers are intellectually andprofessionally beneficial, as well as personally rewarding. Beyond that, the moreopenness within a society as a whole, the more likely it is that improper activitieswithin it will come to light or, better, be discouraged in the first place.

Matthew Meselson, PhDBelfer Center for Science and International Affairs

Department of Molecular and Cellular BiologyHarvard University

Boston, MA

REFERENCES

1. Rosebury, T. and Kabat, E. A. (1947) Bacterial Warfare. J. Immunol. 56, 796.2. Meselson, M. (2002) Bioterror: What Can Be Done? In: Striking Terror. (Silvers, R. and

Epstein, B., eds.) New York Review Books, New York, NY, pp. 259276.

Foreword viii

ix

Preface

The attacks on the World Trade Center (WTC) and the Pentagon and the first major useof bioterrorism that coincided in the fall of 2001 are now infamous. The Al Qaedaperpetrators of the horrible attacks on the WTC and Pentagon were clear in their intent.However, to date we have not achieved a similar clear understanding regarding thedistribution of anthrax spores in the US postal system. We know neither exactly whoperpetrated this crime, nor the perpetrators exact intent. What is known is that the anthraxletter attacks cost billions of dollars to clean up, caused major disruptions in the everydaylives of countless citizens, undermined the trust and confidence that citizens have long heldin this bastion of everyday life, and resulted in the deaths of innocent citizens. The impactwas felt not only in the United States but also in countries around the world, as panic wasprecipitated by the possibility of innocuous white powder being an infectious agent.

The scientists and leadership within the US Department of Defense (DOD) played aunique role in mitigating this event by performing the initial identification of the infectiousmaterial (anthrax) as well as advising and participating in the decontamination process inthe Hart Senate office building. Indeed, it can be argued that the DOD was the only federalagency capable of fully responding to this threat at that time because of its long-standingmission to provide the means to defend against a biological weapons attack. This criticalmission has now transitioned into the newly established Department of Homeland Security(DHS).

The DOD biological defense program and similar defense programs in other countrieshave long involved research aimed at countering the use of biological and chemicalweapons. The United States also had an active offensive biological program from the 1950suntil 1969, when it was terminated by President Nixon.

Given the experience and history of the defense-associated programs in the developmentof countermeasures and in planning for future research in this area, Biological WeaponsDefense: Infectious Disease and Counterbioterrorism is heavily represented by researcherswho work within the biological defense community. However, we have also includedcontributors from other communities, including academia, the Centers for Disease Controland Prevention, the Department of Energy (DOE), and the Department of Healthand Human Services (DHHS). Most of these groups have been working with variousaspects of bioterrorism for the past four years. The intensity and urgency of those effortshave increased since the 2001 attacks. Also, within the DHHS, funding has been greatlyincreased for bioterrorism research and for the development of medical countermeasures. Itis anticipated that this increase in funding will yield further discoveries that will enhancenational defense.

Even with the warnings of experts and the years of funding and preparation for an actof bioterrorism, the United States was not fully prepared for the anthrax attacks. Becauseof the decades of research and development that DOD scientists and physicians hadaccomplished in the treatment, prevention, and diagnosis of these rare diseases, manyindividuals and research centers within the DOD were asked to step up in that time

of national crisis. This is an indication of the professionalism and capabilities of thisrelatively small group of people. It was against this backdrop that Biological WeaponsDefense: Infectious Disease and Counterbioterrorism was written. The purpose of thisvolume is to cover many aspects of the defense against biological agents that we, as mem-bers of the human community, must address on a continuing basis. We have divided thisvolume into four parts that concentrate on the major areas of interest and research.

Part I, Preparation and Military Support for a Possible Bioterrorism Incident, providesthe reader with a view into the behind-the-scenes efforts that many people might not beaware of because they are outside the government network. This includes the policy andlaws that govern the DOD and its programs. We have also included aspects of eventmodeling as well as a general description of the diseases of greatest concern.

Part II, Medical Countermeasures and Decontamination, gives an accountof general knowledge of these particular diseases including pathogenesis, treatment, andthe unique aspect of studying the aerosol route of infection.

Part III, Emerging Threats and Future Preparation, could have easily been titledfuture directions. The number of nefarious manipulations or discovery of previouslyunknown threats that might be developed into biological weapons is almost unlimited. Thissection informs readers of these threats and describes some of the ongoing research thatattempts to counter these unknown agents. This section includes genomic efforts, whichdescribe the current rapid pace of information that is gleaned from analysis of the genomesand proteomes of these agents. Following the anthrax letters, there has been a continuingeffort by the National Institutes of Health, DOD, and DOE in the area of biodefensegenomics. This research has the potential to accelerate many aspects of preparation againstthe use of biological weapons, including future threats, diagnostics, therapeutics,vaccinations, pathogenesis, genotyping, and forensics.

Finally, Part IV, Diagnostic Development for Biowarfare Agents, discusses the manyaspects of the development and use of our current technology to identify and characterizethese infectious organisms.

Although it was not possible to cover every aspect of biodefense in this volume, we hopereaders will gain a greater understanding of the diseases caused by these organisms anddevelop a sense of the scope of issues that must be overcome to develop necessary medicalcountermeasures to bioterrorism. Readers should also understand the status of currentprograms and future plans regarding specific diseases as well as future technology or futurethreats.

A quote from retired US Army Major General Phillip K. Russell could be considered atheme for this book: Deficiencies in our scientific knowledge and a paucity of experts willultimately limit our capability to rapidly and precisely identify agents and respondeffectively in a crisis (1). Biological Weapons Defense: Infectious Disease andCounterbioterrorism is intended to give readers a sense of where we are on this issue andwhere we are moving in the future. We hope that you will find our book informative.

Luther E. Lindler, PhDFrank J. Lebeda, PhD

George W. Korch, PhD

REFERENCESRussell, P. K. (1997) Biologic terrorismresponding to the threat. Emerg Infect. Dis. 3, 203204.

x Preface

Disclaimer for US Department of Defense Authors

The opinions, interpretations, conclusions, and recommendations are those of theauthors and are not necessarily endorsed by the US Army. All research was conductedin compliance with the Animal Welfare Act and other federal statutes and regulationsrelating to animals and experiments involving animals and adheres to principles statedin the Guide for the Care and Use of Laboratory Animals, National Research Council,1996. The facility where this research was conducted is fully accredited by theAssociation for Assessment and Accreditation of Laboratory Animal CareInternational. The research by these authors was funded either entirely or partially bythe Medical Biological Defense Research Program, US Army Medical Research andMateriel Command.

xi

xiii

Contents

Foreword by David R. Franz, COL (RET.), DVM, PhD .................................................vForeword by Matthew Meselson, PhD .................................................................. viiPreface .......................................................................................................................... ixDisclaimer .................................................................................................................. xii

Contributors ............................................................................................................ xvii

I. PREPARATION AND MILITARY SUPPORT FOR A POSSIBLE BIOTERRORISM INCIDENT1 Department of Defense Capabilities Supporting

Bioterrorism ResponseAnna Johnson-Winegar, Karl Semancik, Robert S. Borowski,

Keith R. Vesely, Brenda Wyler, Matt Eussen, and John V. Wade .............................................................................................. 3

2 Modeling for Bioterrorism IncidentsZygmunt F. Dembek .......................................................................................... 23

3 Biological Weapons Defense: Effect LevelsRoss D. LeClaire and M. Louise M. Pitt ............................................................. 41

II. MEDICAL COUNTERMEASURES AND DECONTAMINATION4 Pathogenesis by Aerosol

M. Louise M. Pitt and Ross D. LeClaire ....................................................... 65

5 Bacillus anthracis and the Pathogenesis of AnthraxDominique M. Missiakas and Olaf Schneewind......................................... 79

6 Virologic and Pathogenic Aspects of the Variola Virus (Smallpox)as a Bioweapon

Robert G. Darling, Timothy H. Burgess, James V. Lawler,and Timothy P. Endy ................................................................................... 99

7 Plague Vaccines: Retrospective Analysis and Future DevelopmentsJeffrey J. Adamovicz and Gerard P. Andrews............................................ 121

8 Medical Protection Against BrucellosisDavid L. Hoover and Richard H. Borschel ................................................. 155

9 Pathogenesis of and Immunity to Coxiella burnetiiDavid M. Waag and Herbert A. Thompson ................................................ 185

10 Glanders: New Insights Into an Old DiseaseDavid M. Waag and David DeShazer ......................................................... 209

11 Medical Countermeasures for Filoviruses and Other Viral AgentsAlan Schmaljohn and Michael Hevey ............................................................. 239

xiv Contents

12 Medical Defense Against Protein Toxin Weapons: Reviewand Perspective

Charles B. Millard .............................................................................................. 255

13 Antimicrobials for Biological Warfare AgentsJon B. Woods ........................................................................................................ 285

14 Nonspecific Immunomodulator Therapy: CpGD. G. Cerys Rees, Arthur M. Krieg, and Richard W. Titball .................... 317

15 DecontaminationRobert J. Hawley and Joseph P. Kozlovac ................................................. 333

III. EMERGING THREATS AND FUTURE PREPARATION16 Definition and Overview of Emerging Threats

Luther E. Lindler, Eileen Choffnes, and George W. Korch ...................... 351

17 Department of Defense Global Emerging Infections SystemPrograms in Biodefense

Julie A. Pavlin and Patrick W. Kelley ............................................................ 361

18 Information Resources and Database Development for DefenseAgainst Biological Weapons

Frank J. Lebeda, Murray Wolinsky, and Elliot J. Lefkowitz ..................... 387

19 Genomic Efforts With Biodefense PathogensRekha Seshadri, Timothy D. Read, William C. Nierman,

and Ian T. Paulsen .......................................................................................... 417

20 Genomics for Biodefense: Exploiting the Francisella tularensisGenome Sequence

Siv G. E. Andersson, Mats Forsman, Petra C. F. Oyston,and Richard W. Titball ................................................................................. 435

21 Genetic Fingerprinting of Biodefense Pathogens for Epidemiologyand Forensic Investigation

Luther E. Lindler, Xiao-Zhe Huang, May Chu, Ted L. Hadfield,and Michael Dobson ...................................................................................... 453

22 Yersinia pestis as an Emerged Pathogen: What Lessons CanBe Learned?

Luther E. Lindler ................................................................................................. 481

IV. DIAGNOSTIC DEVELOPMENT FOR BIOWARFARE AGENTS23 Requirements for Biological Threat Identification Systems

Erik A. Henchal and George V. Ludwig ...................................................... 509

24 DNA-Based Diagnostic Tests for Detection and Identificationof Biological Weapons

Luther E. Lindler, David Norwood, Michael Dobson,and Ted L. Hadfield ........................................................................................ 525

25 Concepts for the Development of Immunodiagnostic Assaysfor Detection and Diagnosis of Biothreat Agents

George V. Ludwig, Cynthia A. Rossi, and Robert L. Bull ........................... 551

Index .......................................................................................................................... 581

Contents xv

xvii

Contributors

JEFFREY J. ADAMOVICZ, PhD, LTC, USA Bacteriology Division, US Army MedicalResearch Institute of Infectious Diseases, Fort Detrick, MD

SIV G. E. ANDERSSON, PhD Department of Molecular Evolution, University ofUppsala, Sweden

GERARD P. ANDREWS, PhD, LTC, USA Bacteriology Division, US Army MedicalResearch Institute of Infectious Diseases, Fort Detrick, MD

ROBERT S. BOROWSKI, PhD Homeland Security Institute-ANSER Corporation,Arlington, VA

RICHARD H. BORSCHEL, PhD Department of Bacterial Diseases, Walter Reed ArmyInstitute of Research, Silver Spring, MD

ROBERT L. BULL, PhD Navy Biological Defense Research Directorate, NavalMedical Research Center, Silver Spring, MD

TIMOTHY H. BURGESS, MD, MPH, LCDR, MC, USNR Immunology Section, ViralDiseases Department, Naval Medical Research Center, and Assistant Professor,Department of Medicine, Uniformed Services University of the Health Sciences,Bethesda, MD

EILEEN CHOFFNES, PhD Policy and Global Affairs Division, The NationalAcademies, Washington, DC

MAY CHU, PhD Division of Vector-Borne Infectious Diseases, National Center forInfectious Diseases, Centers for Disease Control and Prevention, Ft. Collins, CO

ROBERT G. DARLING, MD, CAPT, MC, USN Navy Medicine Office of HomelandSecurity, Bureau of Medicine and Surgery, Washington, DC, and US ArmyMedical Research Institute of Infectious Diseases, Fort Detrick, MD, andDepartment of Military and Emergency Medicine, Uniformed ServicesUniversity of the Health Sciences, Bethesda, MD

ZYGMUNT F. DEMBEK, PhD, LTC, MS, USAR Epidemiology Program, ConnecticutDepartment of Public Health, Hartford, CT and Assistant Clinical Professor,Department of Community Medicine and Health Care, Graduate Program inPublic Health, University of Connecticut Health Center, Farmington, CT

DAVID DESHAZER, PhD Bacteriology Division, US Army Medical ResearchInstitute of Infectious Diseases, Fort Detrick, MD

MICHAEL DOBSON, PhD Department of Infectious and Parasitic Diseases, ArmedForces Institute of Pathology, Washington, DC

TIMOTHY P. ENDY, MD, MPH, COL, MC, USA Division of Communicable Diseases andImmunology, Walter Reed Army Institute of Research, Silver Spring, MD, andDepartment of Medicine Uniformed Services University of the Health Sciences,Bethesda, MD

MATT EUSSEN, MD Field Office, US Foreign Service, Katmandu, NepalMATS FORSMAN, PhD National Defence Research Establishment, Ume, Sweden

xviii Contributors

DAVID R. FRANZ, COL (RET.), DVM, PhD Frederick Division, Midwest ResearchInstitute, Frederick, MD

TED L. HADFIELD, PhD Chief BioScience Advisor, Florida Division, MidwestResearch Institute, Palm Bay, FL

ROBERT J. HAWLEY, PhD, CBSP Safety and Radiation Protection, US Army MedicalResearch Institute of Infectious Diseases, Fort Detrick, MD

ERIK A. HENCHAL, PhD Diagnostic Systems Division, US Army MedicalResearch Institute of Infectious Diseases, Fort Detrick, MD

MICHAEL HEVEY, PhD Virology Division, US Army Medical Research Instituteof Infectious Diseases, Fort Detrick, MD

DAVID L. HOOVER, MD Department of Bacterial Diseases, Walter Reed ArmyInstitute of Research, Silver Spring, MD

XIAO-ZHE HUANG, PhD Department of Bacterial Diseases, Walter Reed ArmyInstitute of Research, Silver Spring, MD

ANNA JOHNSON-WINEGAR, PhD Office of the Secretary of Defense, DeputyAssistant Secretary for Chemical and Biological Defense, Washington, DC

PATRICK W. KELLEY, MD, DrPH, COL (RET.), MC, USA Director, Board of Public Health,Institute of Medicine at the National Academies of Science, Washington, DC

GEORGE W. KORCH, PhD Deputy Director, National Biodefense Analysis andCountermeasures Center, Fort Detrick, MD

JOSEPH P. KOZLOVAC, MS, CBSP Environment, Health, and Safety, SAIC-Frederick,National Cancer Institute at Frederick, Fort Detrick, MD

ARTHUR M. KRIEG, MD Department of Internal Medicine, University of IowaCollege of Medicine, Iowa City, IA, and Coley Pharmaceutical Group,Wellesley, MA

JAMES V. LAWLER, MD, LCDR, MC, UCDR Infectious Diseases Service, NationalNaval Medical Center, Bethesda, MD

FRANK J. LEBEDA, PhD Department of Cell Biology and Biochemistry, US ArmyMedical Research Institute of Infectious Diseases, Fort Detrick, MD

ROSS D. LECLAIRE, DVM, PhD Chief, Toxinology and Aerobiology Division, USArmy Medical Research Institute of Infectious Diseases, Frederick, MD, and USArmy Center for Health Promotion and Preventive Medicine, Camp Zama, Japan

ELLIOT J. LEFKOWITZ, PhD Molecular and Genetic Bioinformatics Facility,University of Alabama at Birmingham, Birmingham, AL

LUTHER E. LINDLER, PhD Science and Technology Directorate, National BiodefenseAnalysis and Countermeasures Center, Department of Homeland Security, FortDetrick, MD, and Department of Bacterial Diseases, Walter Reed ArmyInstitute of Research, Silver Spring, MD

GEORGE V. LUDWIG, PhD Diagnostic Systems Division, US Army MedicalResearch Institute of Infectious Diseases, Fort Detrick, MD

MATTHEW MESELSON, PhD Belfer Center for Science and International Affairs,Department of Molecular and Cellular Biology, Harvard University, Boston, MA

CHARLES B. MILLARD, PhD, LTC, USA Chief of Toxinology and Aerobiology Division,US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD

Contributors xix

DOMINIQUE M. MISSIAKAS, PhD Committee on Microbiology, Universityof Chicago, Chicago, IL

WILLIAM C. NIERMAN, PhD The Institute for Genomic Research, Rockville, MDDAVID NORWOOD, PhD Diagnostic Systems Division, US Army Medical

Research Institute of Infectious Diseases, Fort Detrick, MDPETRA C. F. OYSTON, PhD Defence Science and Technology Laboratory, CBS

Porton Down, Salisbury, Wilts, UKIAN T. PAULSEN, PhD The Institute for Genomic Research, Rockville, MDJULIE PAVLIN, MD, MPH, LTC, MC, USA Department of Field Studies, Walter Reed

Army Institute of Research, Silver Spring, MDM. LOUISE M. PITT, PhD Department of Aerobiology and Product Evaluation,

Toxinology and Aerobiology Division, US Army Medical Research Instituteof Infectious Diseases, Fort Detrick, MD

TIMOTHY D. READ, PhD The Institute for Genomic Research, Rockville, MDD. G. CERYS REES, PhD Biomedical Sciences, Defence Science and Technology

Laboratory, CBS Porton Down, Salisbury, Wilts, UKCYNTHIA A. ROSSI, MS Diagnostic Systems Division, US Army Medical Research

Institute of Infectious Diseases, Fort Detrick, MDALAN SCHMALJOHN, PhD Virology Division, US Army Medical Research

Institute of Infectious Diseases, Fort Detrick, MDOLAF SCHNEEWIND, MD, PhD Committee on Microbiology, University of Chicago,

Chicago, ILKARL SEMANCIK, COL (RET.) BS, MBA Raytheon, Arlington, VAREKHA SESHADRI, PhD The Institute for Genomic Research, Rockville, MDHERBERT A. THOMPSON, PhD Rickettsial Section, Viral and Rickettsial Zoonoses

Branch, Division of Viral and Rickettsial Diseases, National Center forRickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA

RICHARD W. TITBALL, PhD Defence Science and Technology Laboratory, CBSPorton Down, Salisbury, Wilts, UK, and Department of Infectious and TropicalDiseases, London School of Hygiene and Tropical Medicine, London, UK

KEITH R. VESELY, PhD Chemical and Biological Defense Directorate, DefenseThreat Reduction Agency, Alexandria, VA

DAVID M. WAAG, PhD Bacteriology Division, US Army Medical ResearchInstitute of Infectious Diseases, Fort Detrick, MD

JOHN V. WADE, DVM, PhD Battelle Memorial Institute, Biodefense MedicalSystems, Columbus, OH

MURRAY WOLINSKY, PhD Bioscience Division, Los Alamos National Laboratory,Los Alamos, NM

JON WOODS, MD Operational Medicine Division, US Army Medical ResearchInstitute of Infectious Diseases, Fort Detrick, MD

BRENDA WYLER, BS, MBA Headquarters, Department of the Army, Washington, DC

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DOD Capabilities 1

PART IPREPARATION AND MILITARY SUPPORT FOR A POSSIBLE

BIOTERRORISM INCIDENT

DOD Capabilities 3

3

From: Infectious Diseases: Biological Weapons Defense: Infectious Diseases and CounterterrorismEdited by: L. E. Lindler, F. J. Lebeda, and G. W. Korch Humana Press Inc., Totowa, NJ

1Department of Defense Capabilities Supporting

Bioterrorism Response

Anna Johnson-Winegar, Karl Semancik, Robert S. Borowski,Keith R. Vesely, Brenda Wyler, Matt Eussen, and John V. Wade

1. INTRODUCTION

As the 20th century drew to a close, most biological defense professionals, bothmilitary and civilian, were in agreement that the probability of a bioterrorist eventoccurring in the United States was not a matter of if, but when. However, few expectedto be engaged in countering the effects of a bioterrorist attack in October 2001.Although it is still unclear whether the anthrax letters were directly related to the moredramatic terrorist events of September 11 or merely took advantage of the opportu-nity they presented, the line has been crossed and there is no turning back. If is nowbehind us, and we are left with the burning issues of who, where, when next, andwhy (personal observation).

Fall 2001 pointed out both the possibilities and vulnerabilities of bioterrorism in amanner that virtually no one had predicted. Until that point a majority of the specula-tion, discussion, planning, training, and preparation for a bioterrorism event hadfocused on the use of a biological agent as a weapon of mass destruction (WMD).Whereas Department of Defense (DOD) personnel participated, and continue to con-tribute extensively in such discussions, other departments of the government have takenthe lead for both planning and responding to a bioterrorist attack. Most working defi-nitions of a biological WMD event were based on at least 1000 casualties; if an agentdidnt meet that minimum criterion, it was often deemed inconsequential for planningpurposes. The emphasis was focused more on the biological consequences ofbioterrorism rather than on an act of terrorism using a biological agent. This is not atrivial distinctionfour envelopes containing a highly virulent and extremely potentformulation of anthrax spores resulted in enormous fear, panic, disruption of the mailservice, distrust in the US governments ability to protect its citizens, and hundreds ofmillions of dollars in remediation expenses by producing fewer than 22 cases of clini-cal anthrax and only 5 deaths.

The DOD Chemical and Biological Defense Research Program (CBDP) wasdesigned to counter the threat of biological warfare (BW) agents employed against ourmilitary forces in a battlefield environment. Although many of the biological agentsavailable for use by a terrorist are the same as those our potential adversaries have

4 Johnson-Winegar et al.

perfected for the battlefield, the circumstances surrounding their use renders many ofthe military approaches to the problem impractical, inappropriate, or impossible toimplement in a widespread manner in a civilian scenario. However, many of the tech-nologies are readily applicable, as we have seen during this, our first major bioterrorismevent.

2. THE BIOLOGICAL TIMELINE

Intentional dissemination of a biological agent (bacteria, virus, or toxin) for the pur-pose of producing casualties follows the same sequence of events whether it is BW orbioterrorism. In many instances, it is a matter of scale, depending on the quantity ofmaterial prepared and disseminated, the area affected, and thus, the number of poten-tial casualties expected. There are seven phases common to both (see Fig. 1). The ear-lier in this timeline that one intervenes, the greater the likelihood of minimizing thetotal number of casualties and reducing further spread of the agent. A comprehensivebiological defense strategy, whether to counter BW or bioterrorism, must address mul-tiple points along this continuum. The response measures for bioterrorism differ fromthose currently employed for BW defense primarily in terms of their applicability andrelative emphasis along this timeline.

3. BW DEFENSE

The battlefield BW threat has been well-characterized based on the ability of spe-cific agents to be mass produced and weaponized. From a military perspective, theemphasis remains on countering BW agents delivered as an aerosol to produce masscasualties as a result of inhalation exposure. The Chairman of the Joint Chiefs of Staff(CJCS) validates a consolidated BW threat list annually. This list, with input from theRegional Combatant Commanders, prioritizes the BW threat based on the presence andmaturity of a potential adversarys offensive BW capability within a given theater ofoperations. DODs current biological defense strategy relies primarily on individualprotection, starting with immunization against specific BW agents using US Food andDrug Administration (FDA) licensed vaccines and early, rapid biodetection. Immuni-zation provides the greatest degree of protection in the event that an attack goesundetected. Rapid detection provides individuals with the necessary warning to donprotective equipment and commanders with the information necessary to avoid con-tamination, anticipate and treat casualties, and initiate decontamination procedures.Currently, fielded chemical defense protective equipment (e.g., masks, suits, andgloves) provides adequate protection against all known BW agents delivered by anaerosol route; therefore, fielding a combination of immunization plus biodetectionassures the greatest certainty of maintaining an effective fighting force in the face of aBW attack. Unfortunately FDA-licensed vaccines are not yet available for every BWthreat agent and biodetection technology is limited to point-source biodetectors. Withcurrent biodetectors, both personnel and the detector must breathe the same BWagent cloud for some interval (seconds to minutes) before a positive alarm and sub-sequent agent identification (1015 min). Recognizing this, the DOD also emphasizesR&D on rapid diagnostics, effective postexposure therapeutics, and efficient decon-tamination countermeasures. A fully integrated biological defense doctrine, supportedby approved training, ties all of these countermeasures together. The collective goal of

DOD Capabilities 5

these countermeasures is to maintain a fighting force capable of accomplishing itsassigned mission while minimizing casualties to the greatest extent possible.

4. THE BIOTERRORISM EVENT

The Department of Health and Human Services (DHHS) and Centers for DiseaseControl and Prevention (CDC) have developed a list of high priority biological agentsthat is similar to the DOD threat list. Most of the biological agents are zoonotic animaldiseases that can also affect humans, particularly by the inhalation route (such asanthrax, plague, tularemia, brucellosis, and so on), rather than by typical human patho-gensthe smallpox virus being a notable exception. The potential number ofbioterrorism scenarios may only be limited by ones imagination; a bioterrorist is notconstrained by the requirement to predictably produce a significant number of casu-alties at a specific time and place to achieve an operational goal. This expands thepotential number of biological agents to choose from, as well as the route or means ofdissemination. The location of the attack does not have to correlate with any largerconcept of operations, and the bioterrorist is free to act on their own terms and timeline.Following the terrorist nerve agent attack in the Tokyo subway by Aum Shinrikio, itwas learned that they had also attempted to release anthrax spores on at least threeseparate occasions. These events went undetected because no one was suspecting them,and no anthrax casualties occurred. The same could be said about any futurebioterrorism event occurring in the United States. Unless the Homeland Security Advi-sory System alert status is high and biodetectors are set up around obvious high-valuetargets (e.g., government buildings) or high-profile events (e.g., the Olympics), theattack will likely go unnoticed unless it produces a significant number of recogniz-able casualties.

Most biological agent casualties following inhalation of an aerosol will initiallypresent with nonspecific flu-like symptoms such as fever, malaise, muscle aches, andrespiratory distress. These indications might easily be dismissed, particularly if anattack occurs during the season for their natural occurrence. The greatest tool to thecivilian sector will be a robust and vigilant public health system that facilitates earlyrecognition that a disease outbreak is abnormal and provides for a rapid, definitivediagnosis of the specific agent. Thus, the primary goal in countering bioterrorism isidentifying and treating those individuals suspected of or known to be exposed to theagent to minimize casualties. Aside from a return to normalcy, there is no mission toaccomplish. However, what may represent the greatest challenge as demonstrated bythe anthrax letters, is to assure individuals that they have not been infected and can

Fig. 1. Seven phases of a biological attack.

6 Johnson-Winegar et al.

return to reside or work in a previously contaminated area. With these differences inmind, the following sections examine how biological defense countermeasures devel-oped by the DOD for the battlefield can be applied to a bioterrorism event.

5. DOD BW COUNTERMEASURES

5.1. Biological Defense Vaccines

Preexposure immunization with FDA-approved vaccines remains the cornerstone ofthe DODs medical force protection strategy; yet even within a military population,further analysis of when to immunize against which agent(s) is ongoing. TheDODs current BW defense vaccine acquisition strategy acknowledges the need todevelop and license effective vaccines against all known BW threats, with stockpilessufficient to support service members deployed in support of between half and twomilitary theaters of war.

If one examines the current Anthrax Vaccine Immunization Program, the Secretaryof Defenses decision to immunize the total force was based on three factors: the BWthreat of anthrax warranted immunization of personnel at high risk (e.g., assigned ordeployed to Southwest Asia or Korea); there was an available stockpile of FDA-licensed anthrax vaccine; and the label use of that product required six doses ofvaccine given over 18 mo. Given the rapid turnover of personnel assigned to South-west Asia or Korea, the short tour lengths, and the time necessary to receive the fullimmunization series, it was clear that the entire force would ultimately have to be im-munized to provide adequate protection from anthrax. These conditions might not ubiq-uitously apply to all of the BW vaccines currently under development. It may beinappropriate to simply consider total force immunization as each new BW vaccinebecomes licensed and available for use, depending on the nature of the threat and theimmunization schedule required for each specific vaccine. Table 1 is a notional riskassessment matrix that might serve as one basis for a flexible immunization policy. It isbased on the assumption that the decision of who needs to be immunized and at whattime could be based on the magnitude of risk versus the time necessary to achieveprotective immunity. It intentionally does not address specific BW agents by name sothat it may focus attention on the operational use of the vaccines based upon thesecharacteristics of both the agent and vaccine (see Table 1). In this example, if a BWagent was usually nonfatal, responded to available therapeutics (e.g., antibiotics), and avaccine was available that afforded protection within 30 d after receiving two doses(14 d apart), then the decision might be to only stockpile that vaccine in limited quan-tities (Category D).

Althought this is only one way of addressing the issues of whom to immunize andwhen (which, at the time of this writing, have not been approved or formally adoptedby the DOD), it demonstrates the difficulties in identifying who is at risk and whoshould be vaccinated in a civilian population in anticipation of a bioterrorism event.

Vaccines have a long history of being safe and effective in preventing disease inindividuals and being capable of eliminating disease in a population. However, whengiven to large numbers of people even the safest vaccine product has a likelihood ofproducing unwanted or unexpected side effects or adverse event in a small percentageof that population. The decision to vaccinate is always based on a benefit-to-risk (or arisk-reduction) analysisdoes the benefit derived from immunization outweigh any

DOD Capabilities 7

potential untoward effects of the vaccine? The use of BW defense vaccines by themilitary relies on an intelligence estimate of the probability and the consequence ofBW agent use as the risk part of this equation, with the desire to maintain an effectivefighting force as the benefit. If one knew when and where a civilian bioterrorist attackwas to occur, the benefit of immunization against the agent used would be clear. Unfor-tunately, the uncertainty of this risk for any given group of citizens in the United Statesmakes the benefit-to-risk analysis very difficult.

Civilian use of vaccines as a means of countering bioterrorism falls into three pos-sible categories: pre-exposure immunization of individuals suspected of being at highrisk; immunization immediately following exposure (or suspected exposure), given inaddition to therapy; and immunization of a larger segment of the population followingbioterrorist use of a highly contagious agent to prevent epidemic spread. This analysislimits civilian BW defense vaccine use to three agents: anthrax, smallpox, and (per-haps, when an effective vaccine is licensed) plague. These three BW agents, discussedbriefly here, will be covered in more depth in other chapters.

5.2. Biodetection

Rapid detection of biological agent aerosols remains a considerable challenge.Unlike volatile toxic chemicals or chemical warfare agents, biological agents exist as aparticulate aerosol rather than as a vapor. A biological agent cloud behaves more likesmoke than fog and biological agent concentrations are expressed in terms of par-ticle counts rather than conventional measures of vapor, such as parts per million ormilligrams per cubic meter. Because spores or bacteria or virus particles are rarelymonodispersed but occur clumped together or adhering to dust particles, the unit ofmeasure agent-containing particle per liter of air (ACPLA) has been adopted. It is thisdifference in physical characteristics that presents the greatest difficulty in biodetection.Given the potency of the agents in question, we are concerned with aerosols containingas few as 110 ACPLA.

Because these particles do not exert any vapor pressure, they are not amenable to thesame types of detection technology used for volatile chemicals. The first step in aero-sol biodetection involves actively drawing a fairly sizeable air sample through a collec-

Table 1Notional Risk Assessment Matrix for DevelopingImmunization Schedules and Vaccine Stockpile Strategies

Time to immunity Fatal Fatal Nonfatal Nonfatalno therapy treatable no therapy treatable

>90 d A* A B B

8 Johnson-Winegar et al.

torconcentrator to trap the particles, which are usually then suspended in a bufferedfluid sample. This sample is then applied to an identifier to determine the presence of abiological agent and its presumptive identity. For field detection, this is usuallyachieved using specific antibody binding in an enzyme-linked immunosorbant anti-body (ELISA) assay or polymerase chain reaction (PCR) technology. Therefore, spe-cific identification is limited to those agents for which there are handheld antibodyassays or the necessary DNA probes and primers for PCR in field devices. Handheldassays are very similar in operation to a home pregnancy test kit: the liquid sample isapplied, allowed to react for a set interval of time, and a positive test results in avisible color change on the antibody test strip that is detectible by the naked eye or anoptical reader (usually with a laser). The PCR devices also result in a color change thatis detected by the device. With proper sampling procedures, both handheld assays andPCR devices can also be used to presumptively identify biological agents from con-taminated surfaces.

The sensitivity of handheld assays is a function of the purity and affinity of theantibodies used, but in any case, it will require a minimum number of organisms toregister as positive. Use of automated ticket readers, rather than visual inspection for acolor change, enhances sensitivity and reproducibility; however, the technology stillhas its limitations. PCR amplifies the agents DNA, greatly enhancing sensitivity with-out loss of agent specificity. Field-portable devices are now available (see Subheading5.3.). In addition to field identification, a confirmatory sample is usually collected andsent to a reference laboratory for definitive identification (which also answers the ques-tion of whether the biological agent is viable).

The first biodetector system was fielded in 1992, following Operation Desert Storm.The Biological Integrated Detection System (BIDS) was manned by two personnelwho had to manually transfer suspected samples from the collectorconcentrator tohandheld assays and visually look for this color change. The Navy had a similar ship-board device called the Interim Biological Agent Detector (IBAD). Both BIDS andIBAD relied heavily on available commercial off-the-shelf technology.

Since fielding of the BIDS and IBAD, the process has been significantly automated,first in a device developed through the Advanced Concept Technology Demonstrationprocess for Air Base/Port Biological Detection (known as Portal Shield) and morerecently in the Joint Biological Point Detection System (JBPDS). Portal Shield wasdeveloped for fixed-site installation and achieved significant reductions in false-posi-tive alarm rates by being arrayed as a sensor network in which more than one devicehad to give a positive reading for an alarm to be sounded. JBPDS can be configured foreither fixed or mobile applications and is programmed to replace the BIDS and IBADsystems.

Both the Portal Shield device and JBPDS have a trigger associated with the collec-torconcentrator that senses an increase in the number of aerosol particles above thenormal background levels, automatically sending a sample to the identifier only whenthere is a suspicious increase in particle count. This has two advantages: it takes humansout of the loop as far as sample collection, preparation, and transfer; and it reduces theenormous cost and logistics burden of consumables (buffer solutions and antibody tick-ets) that would be associated with continuous real-time monitoring if samples wereanalyzed simply at fixed intervals. The JBPDS is capable of identifying multiple agents

DOD Capabilities 9

in less than 15 min, unattended for missions up to 12 h between consumable replenish-ment. This tiered approach also allows quick, generic detection, followed by slightlylonger, specific identification.

Both handheld assays and field-potable PCR were used to determine anthrax con-tamination of environmental surfaces as a result of the anthrax letters. The limitingfactor in their utility for this purpose was not the devices themselves, but the heretoforeuntested swabbing and sampling techniques and procedures and their correlation withreference laboratory results. It should be noted that these devices, as described, weredeveloped for environmental samples, not clinical specimens, and given the paucity ofinformation regarding re-aerosolization or spread of anthrax spores under these cir-cumstances, interpretation of results should be limited to presence/absence of spores orrelative contamination.

Automated biodetectors developed for BW defense use, such as Portal Shield andJBPDS, have been deployed in support of high-visibility events (e.g., the PresidentialInauguration, G7-Summit, and the Olympics). However, their current cost ($300$500K per device, depending on the numbers required and thus the size of the produc-tion base) limits their routine application in the civilian community. Many of theirinherent technologies, particularly given the improvements in sensitivity, specificity,and decreased consumable burdens achieved in recent years, might one day find theirway into simpler monitoring devices. Routine use of biodetectors in public areas (suchas the ubiquitous smoke detector) is probably unrealistic until a significant technologi-cal breakthrough results in a solid-state (nonfluidic) identifier mechanism.

Broad-based employment of biodetectors in a civilian community may be limitedmore by questions of policy than technology. By their design and nature, they provideinformation that is far more applicable to a population than to any given individual, andin a civilian bioterrorism scenario, the response to an alarm might be quite differentthan on the battlefield. As previously stated, in a battlefield BW defense scenario,biodetection is just one part of an integrated biodefense system. Their deployment willbe predicated on an intelligence assessment of the threat (thus dictating which agentsthe device must be capable of identifying and how the agent might be offensivelydeployed), where possible service members will be immunized against those threatagents. In either case, they will be equipped with (and most likely will carry with them)effective individual protective measures (e.g., protective masks) and/or medical coun-termeasures (such as packets of the antibiotic ciprofloxacin for anthrax postexposuretreatment). Further, they have been trained as to the appropriate immediate response totake when an alarm is sounded.

The appropriate civilian response to an automated biodetectors alarm is less clear.Unlike a smoke detector, which sounds an alarm long before most individuals canactually smell the smoke and causes the unquestionable response to leave the buildingor be burned, the nature of the biological agent threat makes the response less clear.Depending on the biodetectors sensitivity and the interval of time required for it toalarm and/or identify the agent, individuals in the vicinity may have already breathedin a casualty-producing dose. Whereas limiting further exposure to those individuals isdesirable, their dispersal as a group may be contraindicated from an epidemiologicalperspective. A single point-source device is insufficient to identify the extent of theattack or area of agent contamination; however, if deployed in the right place at the

10 Johnson-Winegar et al.

right time, it would provide information that a bioterrorism event has occurred andcould identify which biological agent was used. Such early warning information wouldallow execution of plans to rapidly conduct active environmental sampling and, per-haps more importantly, to implement the diagnostic methods described here.

5.3. Diagnostics

The DOD has a very aggressive program to develop an FDA-approved diagnosticdevice capable of identifying at least eight specific BW agents of operational signifi-cance in numerous types of clinical samples and specimens. This program is in theprocess of downselecting from several of competing PCR-based technologies todevelop and field a device known as the Joint Biological Agent Identification andDiagnosis System (JBAIDS). It will develop, validate, and field 810 gene probes andprimers for PCR diagnosis of biological threat agents. JBAIDS will provide US forceswith a reusable, portable, and modifiable diagnostic device capable of simultaneous,reliable identification of multiple biological organisms from appropriate clinicalsamples. JBAIDS will be operated by DOD medical laboratory personnel who are quali-fied in compliance with the Clinical Laboratory Improvement Act. FDA approval iscritical, because the results of JBAIDS will be used to make diagnostic and therapeuticdecisions about individual patients.

One enormous challenge facing clinicians trying to manage those individuals whoeither came in contact with, or were in the vicinity of, the anthrax letters was rapid andreliable identification of those who had in fact, been exposed. There were no validatedfield methods for such things as identifying anthrax spores in nasal swabs. It is unclearwhether the techniques implemented would have yielded as comparable results withlive bacteria or viruses. For a device such as JBAIDS to be effective, it will need to bevalidated with numerous types of clinical specimens (using research animals as surro-gates for humans) to establish the timecourse of the agents appearance in, or disap-pearance from, those various clinical specimens following an inhalation exposure.There are likely to be significant differences from one agent to another, based on thepathophysiology of the disease following exposure by inhalation.

This is an area that represents both the greatest opportunity for collaborationbetween the DOD and civilian medical research communities and the most signifi-cant potential return on investment. In an unanticipated, unannounced bioterrorismevent, with a large number of exposed civilians, the first indication may be an increasein patients presenting with nonspecific respiratory illness accompanied by fever andmalaise. Suspicions that it is not a naturally occurring disease outbreak will most likelybe triggered by either the unexpected numbers of cases, the rapidity with which thesymptoms progress, or the lack of responsiveness to conventional therapy. The readyavailability of specific diagnostic devices such as JBAIDS, particularly if there is aparallel effort to develop diagnostic gene probes and primers for more common ail-ments, will significantly increase the likelihood of early definitive diagnosis of the firstindex case. As was seen with the first gentleman from Florida, once a diagnosis ofinhalation anthrax had been made (and some degree of consensus was achieved that itwas not a natural occurrence) the medical community at large became far more vigi-lant. Readily available, validated diagnostic methods also serve a secondary (but per-haps nearly as important) function: the ability to determine that a suspected casualty

DOD Capabilities 11

has not been exposed, thus allaying fear and concern in the individual and conservingprecious, limited medical care facilities and services for those who actually need them.

5.4. Therapeutics

The DOD strategy of BW immunization, detection, individual protection, and diag-nosis, although not ignoring therapeutics, has historically given it a lower priority.From the perspective of mission accomplishment, it is far preferable to prevent casual-ties than it is to treat them. By the time an individual is exhibiting symptoms followinginhalation exposure with most BW agents, therapy is extremely difficult. For the bacte-rial agents, numerous broad-spectrum antibiotics (ciprofloxacin, doxycycline, penicil-lin, and derivatives or penicillin) have been shown to be effective in vitro. Mostmicrobiology or pharmacology texts list suggested drugs or drug combinations shownto be effective in treating the naturally occurring disease, but their efficacy against aninhalation challenge can only be inferred from animal studies. For example, over halfof the inhalational anthrax cases observed following exposure to the anthrax lettersdied in spite of very aggressive multidrug treatment regimens. Anthrax therapy repre-sents the most challenging of the bacterial agents because of the uncertainty as to howlong ungerminated spores can remain viable in the pulmonary lymph nodes followinginhalation. Given the limited number of FDA-licensed antiviral agents, postexposuretherapy for viral BW reagents remains primarily supportive in nature. Scientists at theUS Army Medical Research Institute of Infectious Diseases (USAMRIID) continue totest the efficacy of these and other compounds being developed by various pharmaceu-tical manufacturers against the viral BW threat agents. Many of the toxin agents couldbe treated therapeutically with antitoxins; however, the only clinically available prod-uct at this time is for botulinum toxin, and it is in limited supply and for use only underan investigational new drug protocol.

The administration of hyperimmune globulin or antibodies against specific proteinsis a therapeutic concept that has been known for many years. It has been used in thetreatment and prevention of various diverse infections such as diphtheria, tetanus, botu-lism, and snake venom intoxication. The pathophysiology of many bacterial illnessesinvolves production and/or release of various of protein toxins. In theory, specifichyperimmune globulin could be used to circumvent or block these toxin activities. Thiscould represent a final or prophylactic line of defense for patients potentially infectedwith drug- or vaccine-resistant strains of the pathogen. The use of hyperimmune globu-lin as an adjunct to antibiotics or vaccines in the treatment of anthrax in experimentalanimals has been demonstrated. These studies also serve to demonstrate that theseantibodies might be used as an effective postexposure treatment for anthrax.

5.5. Individual and Collective Protection

DOD has fielded a diverse array of individual and collective protection counter-measuresfrom the individual service members protective suit, gloves, and mask tocombat vehicles or shelters equipped with high-efficiency filtration and providing anoverpressure environment to prevent entry of contamination. Few of these items orsystems have widespread, direct applicability to a civilian setting. None of the biologi-cal agents poses a percutaneous hazard; in most instances, the intact skin provides uswith the first barrier to infection. Protective suits are limited in their applicability to

12 Johnson-Winegar et al.

those involved in sampling or clean-up of a biologically contaminated area and arealready commercially available. In the absence of an indication to put them on (e.g.,alarm by a Biodetector) protective masks for civilians are simply not practical. Once itis specifically known that a bioterrorist attack has occurred, the civilian responder com-munity is already equipped with masks that are more appropriate to the threat than themilitary protective mask which is designed to protect against specific chemical as wellas biological agents and is not suitable or approved for indiscriminant entry into anunknown noxious environment. Integration of biological filtration or pressure gradi-ents into existing buildings (or new construction) is costly and maximally effective ineither keeping contamination in or out of the structure, not necessarily both.

5.6. Decontamination

The goal of decontamination is to provide a capability for force restoration after aWMD attack. In the traditional sense, the DOD has pursued this area through develop-ment of systems that rely on the physical application and rinse of decontaminants oncontaminated systems. Current systems are effective against a wide array of threatagents, including biologicals, but are logistical burdens with regard to time, labor, andmaterial resources. Additionally, decontamination techniques and procedures present asignificant safety burden.

The DOD has expended considerable developmental resources to improve our abil-ity to decontaminate. However, there are significant technical challenges in this area.The first challenge is the development of decontaminants that are reactive, nonaque-ous, noncorrosive, safe for use on sensitive equipment, environmentally safe, able todecontaminate a broad spectrum of biological agents, and that pose no unacceptablehealth hazards. The second challenge is the development of systems that effectivelyclean all surfaces while reducing the manpower and logistics burden.

The DOD has programs in place to develop systems and technologies to address thesechallenges. These programs include advances in sorbents, coatings, catalysis, and physicalremoval. This area has the potential for significant impact on restoration operations withinthe civilian community after a biological attack. Since September 11, the DOD has beeninstrumental in the application of technologies to restore entire buildings contaminatedwith biological spores and to ensure safe maintenance of the nations postal system.

5.7. Modeling and Simulation

The understanding of the effects of biological agents is critical to an appropriateresponse that will protect the individual members of the nations armed forces. Thisunderstanding is facilitated by the utilization of effective models and simulations thatportray the physical effects and dispersion of biological agents after a release or attack.The DOD has expanded its efforts in this area through the establishment of a ChemicalBiological Modeling and Simulation Advisory Council to examine and validate allmodels of chemical biological effects within the department.

The three models currently in use or under development within the DOD (Vapor,Liquid, Solid Tracking; Hazard Prediction and Assessment Capability, and SecondOrder Closure Integrated Puff) include advanced dispersion models that take intoaccount real-time weather and complex terrain effects. Efforts are currently underwayto integrate a functional combination of the best of the best capabilities from these

DOD Capabilities 13

three models into an interoperable architecture and a user-friendly interface resultingin the development of a Joint Effects Model (JEM). These advanced models will pro-vide near instantaneous predictions of the effects of a biological release on the environ-ment and the military force. JEM will be capable of modeling hazards in variousscenarios including counterforce; passive defense; accidents and/or incidents; high al-titude releases; urban nuclear, biological, and chemical (NBC) environments; buildinginteriors; and human performance degradation.

Many of the algorithms used by the DOD, and in fact the models themselves, arebeing transferred for use in the civilian community by the DODs consequence man-agement forces and state and local first responders. The major challenge faced by thecivilian community in using these models will continue to be the estimation of thesource term usedthe actual amount of biological agent releasedwhich may differsubstantially from DOD estimates based on weaponization.

6. DOD SUPPORT

The DOD is not a lead federal agency for response to terrorist incidents, but it pro-vides significant and unique capabilities to support other agencies in conducting theirresponsibilities. Military support is provided to civil authorities under the auspices ofthe Federal Response Plan (FRP) and is governed by policies that distinguish betweennatural disasters and acts of terrorism. Requests for military support to natural disastersand accidents are approved by the Secretary of the Army (as DOD Executive Agent)and coordinated in advance with the Chairman of the Joint Chiefs of Staff. Requests formilitary support to civil authorities for terrorist incidents must be approved by the Sec-retary of Defense. On a case-by-case basis, the Secretary will decide whether to assignresponsibility for the requested support to the DOD Executive Agent for Civil Supportor to the Combatant Commander of the US Joint Forces Command (JFCOM). Missionsassigned to JFCOM may be executed by its standing Joint Task Force for Civil Support(JTF-CS) or by the Response Task Force (RTF). When deployed for domestic opera-tions, the JTF-CS and RTF report to the Secretary of Defense through their respectivechains of command. In all cases, legal constraints bind military response. Doctrinally,military commanders are never in charge at a crisis response, but, rather, are supportingmembers of the Federal team.

6.1. Military Support Units

The DOD encompasses a wide range of special rapidly deployable organizationsstaffed by trained personnel and equipped with unique hardware. The Secretary ofDefense has tasked JFCOM to establish a standing JTF-CS to lead DODs responseefforts. The JTF-CS is commanded by a general/flag officer and includes an 8-personadvance survey party and an 80-person headquarters staff (30 permanent personnel and50 augmentees). Depending on the nature of the event, the JTF-CS is augmented byvarious agencies and operational units (medical, transportation, supply, and so on) thatmay be required in the crisis area. The RTF was established to maintain a militaryWMD consequence management response capability for the Atlanta Olympic Games.US Forces Command assigns missions east and west of the Mississippi River to theFirst and Fifth US Armies, respectively.

The US Army Soldier, Biological and Chemical Command (SBCCOM) Chemical-Biological Rapid Response Team (CB-RRT) is a Congressionally mandated, one-of-a-

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kind national asset that is capable of coordinating and synchronizing DODs technicalassistance support (medical and nonmedical) for crisis response and consequence man-agement operations involving WMD. Located at the Edgewood Area of Aberdeen Prov-ing Ground in Maryland, the CB-RRT provides a technical support package specificallytailored for WMD incident response. The CB-RRT is composed of members of theArmed Forces and employees of the DOD with specialized chemical, biological, medi-cal, and explosive ordnance disposal expertise who are capable of providing technicalassistance to aid federal, state, and local officials in the response to and mitigation ofincidents involving WMDs containing chemical or biological materials (or related haz-ardous materials). The CB-RRT can be under the operational control of a geographicCINC, JSOTF, or other designated JTF or can be in direct support of a lead FederalAgency. The unit is colocated with the SBCCOM 24-h operations center. The CB-RRTis designed to provide forward elements to assist the lead Federal Agencies (the Fed-eral Bureau of Investigation [FBI], Federal Emergency Management Agency [FEMA],Environmental Protection Agency [EPA], United States Secret Service, United StatesPublic Health Service, and others) with technical expertise and contingency develop-ment options during times of crisis. In addition, through the state-of-the-art SBCCOMoperations center, the CB-RRT brings together some of the nations leading chemicaland biological technical experts without the need for the experts to be deployed to anincident site. Technical elements that are managed and coordinated by the CB-RRTinclude, but are not limited to, the US Army Technical Escort Unit; the US ArmyEdgewood Chemical and Biological Center; the US Army Edgewood Chemical andBiological Center Forensic Analytical Center (FAC); the US Army MEDCOM SpecialMedical Augmentation Response Teams (SMART) and Regional Medical Commands(RMC); the US Army Medical Research Institute of Chemical Defense (USAMRICD);the USAMRIID; the US Army Center for Health Promotion and Preventative Medi-cine; the US Navy Medical Research Center; the US Navy Environmental Health Cen-ter; the US Navy Environmental and Preventive Medicine Units; and the US NavalResearch Laboratory.

USAMRIID plays a key role in national defense and in infectious disease researchas the only maximum containment biological laboratory in the DOD for the study ofhighly hazardous diseases. USAMRIID collaborates with the World Health Organ-ization in Geneva and the CDC in Atlanta in helping to diagnose and treat unusualdiseases wherever they occur. USAMRIID has the unique capability of deploying up totwo Aeromedical Isolation Teams (AITs), each composed of physicians, nurses, medi-cal assistants, and laboratory technicians. These personnel are specially trained to carefor and to transport patients with diseases caused by either BW agents or infectiousdiseases requiring high containment. The teams are deployable worldwide on a 12-hnotice using US Air Force airlift. The AIT uses specialized isolation that maintains acontained environment under negative pressure and HEPA filtration to safely transportpatients or to care for them in place for limited periods of time. This capability islimited to two patients at a time, based on the number of trained personnel and equip-ment on hand.

The US Marine Corps Chemical/Biological Incident Response Force (CBIRF) canrespond to biological or chemical incidents to assist the on-the-scene commander in

DOD Capabilities 15

providing initial postincident consequence management. The CBIRF provides a stand-ing, highly trained consequence management and force protection package tailored forshort-notice response to terrorist-initiated chemical, biological, and/or radiologicalincidents and for credible threats.

State National Guard units form key elements of each state governors emergencycapability. As such, their role is generally performed at the direction of state authori-ties. The National Guard Civil Support Team (CST) WMD requirement came from theprinciple that domestic disaster relief is fundamentally a state mission. The units aredeployed at the discretion of the state governor, unless they are federalized. The CSTfocus is on filling a void in the states initial assessment capability and initiatingrequests for additional state or federal response assets. Each CST unit consists of 22full-time National Guard personnel.

7. DOD CRISIS MANAGEMENT POLICY AND PRACTICE

In the event of a WMD incident, crisis and consequence management occur simulta-neously, but there is only one on-the-scene commander. Local law enforcement estab-lishes the perimeter, controls access to scene, and may begin interviews with witnesses;the FBI can take control of any WMD scene. The special agent in charge will call FBIassets to the scene, including the Hazardous Materials Response Unit and the HostageRescue Team. The special agent in charge may also request other federal assistancethrough the Attorney General. If the DOD is requested to provide assistance, JointSpecial Task Forces are established, tailored to the mission profile. Usually, but notalways, these units consist of explosive ordinance disposal technicians, DOD animalhandlers, and/or Special Forces personnel. National Guard personnel, acting under theauthority of the state governor, also are often utilized for area searches.

8. DOD CONSEQUENCE MANAGEMENT POLICY AND PRACTICE

The DOD is a signatory to the FRP. That plan, coordinated by the FEMA, takes anall-hazards approach to addressing actions to mitigate an incident. As with any emer-gency, the first line of response is the local first responder community, including po-lice, fire, and emergency medical services. They also employ any mutual aid compactsthey have with the surrounding area. When local resources are exhausted or over-whelmed or a critical capability is not available in the immediate area, the localauthorities request assistance from the state. This is usually done through emergencymanagement offices but can also flow through functional areas (i.e., local medicalofficials to state medical officials) or political channels (i.e., the mayor or countyofficials requesting help from the governor). The state can bring substantial resourcesto bear, including the National Guard. Many states are also members of emergencysupport compacts that permit one states resources to be used in support of anothermember state.

When state resources are exhausted or overwhelmed or there is a need for a capabil-ity that is not available, the state goes to the federal government. This is accompishedwhen the governor declares a state of emergency or designates a specific disaster area.The governor then requests a presidential emergency declaration or a presidential

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disaster declaration. Once there is a presidential declaration, FEMA coordinates thefederal response.

9. FEDERAL MEDICAL CONSEQUENCE MANAGEMENT POLICYAND PRACTICE

In accordance with the FRP, the DHHS is responsible for providing health and medi-cal services, including those incidents of bioterrorism. DHHS has established theNational Disaster Medical System (NDMS) to satisfy this responsibility. It must benoted that although DHHS exercises the consequence management responsibilities,the FBI continues to execute their crisis management responsibilities in parallel. Thepurpose of the NDMS is to supplement state and local medical resources during disas-ters or major emergencies and provide backup medical support to the DOD/DVA medi-cal care systems during an overseas conflict. To that end, the NDMS provides medicalresponse, patient evacuation, and definitive medical care. The NDMS, like the FRP, isan all-hazards response plan and addresses all aspects of consequence managementmedical care including:

Assessment of health and medical needs Health surveillance Medical care personnel Health/medical equipment and supplies Patient evacuation In-hospital care Food, drug, and medical device safety Worker health/safety Radiological, chemical, and biological hazards Mental health Public health information Vector control Potable water, wastewater, and solid waste disposal Victim identification and mortuary services Veterinary services

The DHHS, recognizing the need to provide additional training and support forWMD incidents, developed WMD-specific national medical response teams within itsdisaster medical assistance teams. These teams provide triage, austere medical care,and casualty clearing/staging at disaster sites and patient reception at the local disasterreception areas. Each team is composed of roughly 100 personnel drawn from volun-teers and in major metropolitan areas may be augmented by a Metropolitan MedicalResponse System grant and plan from DHHS, which provides additional resources forWMD incident planning, equipping, and training.

The DOD may be requested to assist at any stage of the NDMS and has some spe-cific responsibilities in conjunction with the Department of Veterans Affairs to providedefinitive medical care at existing facilities should an incident overwhelm hospital carefacilities. During the incidents occurring in Fall 2001, the DOD provided assistanceacross the full spectrum of response. It deployed hospital ships to New York harbor inthe aftermath of the September 11 attacks on the World Trade Center; it provided labo-ratory facilities and personnel to determine the nature and source of anthrax, the provi-

DOD Capabilities 17

sion of environmental sampling systems for the detection and characterization ofanthrax, and expertise on the decontamination of civilian facilities.

10. BIOLOGICAL EXERCISES AND LESSONS LEARNED

Preparations for terrorist incidents involving NBC/WMD have been ongoing sincethe Gulf War and the breakup of the Soviet Union. Early focus centered on fears thatterrorists could obtain nuclear weapons as a result of profiteering by the former Sovi-ets. However, the attacks on the Murrah Federal Building and the Tokyo subway sys-tem in 1995 added emphasis to the potential of high-yield explosives and chemicalattacks. In the wake of the September 11 attacks and the mailing of the anthrax-con-taminated letters, concern for bioterrorist incidents has caused officials at all levels ofgovernment to re-elevate both the threat and the governmental structures and resourcesto deal with such a threat. DOD support and cooperative efforts are vital to facilitatingfederal agency cooperation and resource sharing. Federal agencies have enhanced theirability to respond to terrorist incidents by conducting exercises that train key personneland test response plans. Presidential Decision Directive 39, issued in June 1995,requires key federal agencies to ensure that their counterterrorism capabilities are wellexercised.

Exercises fall into two general categories: tabletop and field exercises. Tabletopexercises are performed around a table, a classroom, or a simulated command post asthe players progress through a scenario or series of scenarios and discuss how theiragency or unit might react to different situations. Field exercises are performed in thefield under simulated operational conditions. Such exercises focus on performing tasksat the operational and tactical levels and typically include the tactics, techniques, andprocedures that would be used in a real incident. Field exercises test agency and inter-agency capabilities to actually deploy personnel and their equipment and c