# Multiservice Tactics, Techniques, And Procedures For Treatment Of Biological Warfare Agent Casualties

March 2013
DISTRIBUTION RESTRICTION:  Approved for public release; distribution is unlimited.

FOREWORD
This publication has been prepared under our direction for use by our respective commands and other commands as appropriate.

This publication is available through the United States Army Knowledge Online Web site at:
https://armypubs.us.army.mil/doctrine/index.html (Common Access Card [CAC] required). To receive publishing updates, please subscribe at:

http://www.apd.army.mil/AdminPubs/new_subscribe.asp.;
this publication is available through the U.S. Marine Corps
Doctrine Web site at https://www.doctrine.usmc.mil/ (CAC
      required); through the U.S. Navy Web site at

http://www.med.navy.mil/directives/pages/default.aspx and

https://ndls.nwdc.navy.mil (CAC required); and through the U.S.
       Air Force at the Air Force Publishing Web site at

http://www.e-publishing.af.mil/.


This publication contains copyrighted material.

No endorsement by the Government is expressed or implied with any URL associated with a non- Government web site.

# *Atp 4-02.84 (Fm 8-284) *Mcrp 4-11.1C (Mcrp 4-11.1C) *Ntrp 4-02.23 (Ntrp 4-02.23 [Navmed P-5042]) *Afman 44-156_Ip (Afman [I] 44-156)

 Army Techniques Publication (ATP) No. 4-02.84
Headquarters Department of the Army Washington, District of Columbia Marine Corps Reference Publication (MCRP) No. 4-11.1C
Marine Corps Combat Development Command Quantico, Virginia Navy Technical Reference Publication (NTRP) 4-02.23
Navy Warfare Development Command Norfolk, Virginia Air Force Manual (AFMAN) 44-156_IP
Headquarters Air Force Doctrine Center Maxwell Air Force Base, Alabama

25 March 2013

## Multiservice Tactics, Techniques, And Procedures For Treatment Of Biological Warfare Agent Casualties Contents

|                                             | PREFACE iv                    |
|---------------------------------------------|-------------------------------|
|                                             |                               |
|                                             | INTRODUCTION ix               |
|                                             |                               |
| Chapter 1                                   | BIOLOGICAL WARFARE AGENTS 1-1 |
|                                             |                               |
| Background 1-1                              |                               |
|                                             |                               |
| Threat 1-1                                  |                               |
|                                             |                               |
| Employment of Biological Warfare Agents 1-2 |                               |
|                                             |                               |
| Novel Threat Agents 1-3                     |                               |
|                                             |                               |
| Classification 1-3                          |                               |
|                                             |                               |
| Dissemination 1-7                           |                               |
|                                             |                               |
| Routes of Entry 1-8                         |                               |
|                                             |                               |
| Prevention 1-9                              |                               |
|                                             |                               |
| Medical Countermeasures 1-9                 |                               |
|                                             |                               |
| Physical Protection 1-10                    |                               |
|                                             |                               |
| Hazard Management 1-12                      |                               |
|                                             |                               |

Distribution Restriction:  Approved for public release; distribution is unlimited.

*This publication supersedes FM 8-284/NTRP 4-02.23 (NAVMED P-5042)/AFMAN (I) 44-156/MCRP
4-11.1C, 17 July 2000 (Change 1 dated 8 July 2002).

Table 3-2.  Inhalational anthrax cases systematic review ........ 3-3 Table 3-3.  Gastropharyngeal anthrax cases systematic review ........ 3-4 Table 3-4.  Gastrointestinal anthrax cases systematic review ........ 3-4
Table 3-5.  Collection and transport of laboratory specimens for the diagnosis of
anthrax ........ 3-5
Table 3-5.  Collection and transport of laboratory specimens for the diagnosis of
anthrax (continued) ........ 3-6
Table 3-6.  Anthrax case-fatality rate ........ 3-7 Table 4-1.  Taxonomy of hemorrhagic fever viruses ........ 4-8
Table 4-2.  Viral hemorrhagic fever agents and disease characteristics (not all
inclusive) ........ 4-11
Table 4-3.  Ribavirin therapy recommendations* ........ 4-13 Table 4-4.  Viral hemorrhagic fever case-fatality rate and complications ........ 4-14
Table 4-4.  Viral hemorrhagic fever case-fatality rate and complications (continued) ........ 4-15 Table 6-1.  Associated medical applications/tasks ........ 6-6 Table A-1.  Characteristics of biological warfare agents ........ A-2 Table A-1.  Characteristics of biological warfare agents (continued) ........ A-3 Table A-2.  Specimen collection for suspect biological warfare agents ........ A-5 Table A-2.  Specimen collection for suspect biological warfare agents (continued) ........ A-6 Table A-3.  Examples of infectious substances, Category A ........ A-8
Table C-1.  Medical management precautions for select biological warfare agent
diseases ........ C-2

## Preface Purpose

This multiservice publication serves as a guide and a reference for trained members of the Armed Forces Medical Services and other medically qualified personnel on the recognition and treatment of biological warfare
(BW) agent casualties.  Its purpose is to provide an overview of potential BW agents directed against human beings, the problems that might be created during an attack in which a BW agent is utilized, and the current methods available to medical personnel for recognizing, preventing, and managing these problems.  Information contained in this publication may also be relevant for the diagnosis and treatment of patients with naturally acquired diseases or illnesses due to pathogens with BW potential.

## Scope

This publication classifies and describes BW agents associated with military operations.  Further, this publication


Provides procedures for collecting, handling and labeling, shipping, and identifying potential BW agents.

Describes procedures for medical diagnosis, treatment, and management of BW casualties.

Describes medical management and treatment in BW operations.
The material in this publication is applicable to the full range of military operations to include major operations and campaigns (including combating terrorism, homeland defense, and consequence management). The treatment modalities contained in this manual differ from standard textbooks in that they apply to BW agent exposures.  The method of exposure for most BW agents is by inhalation; whereas, some endemic exposures (if applicable) are by other means.  Some are by ingestion, some by arthropod bites, and others by dermal contact with the agent.  This does not preclude Service members from becoming BW casualties by these means. This publication contains copyrighted material. The term "sample" refers to "environmental" or "clinical."  The term "environmental sample" refers to nonhuman and nonanimal origin (for example, air, soil, water).  The term "clinical specimen" refers to human and animal origin (for example, serum, blood, and other body fluids). For the purpose of this publication, the following terms are defined:


Biological agents are capable of spreading disease through humans and agriculture and are
microorganisms categorized as either pathogens or toxins. Pathogens are microorganisms (for example, bacteria, viruses, rickettsia, prions) that directly attack human, plant, or animal tissue and biological processes.  Toxins are poisonous substances produced or derived from living plants, animals, or microorganisms; some toxins may be produced or altered by chemical means. Compared with microorganisms, toxins have a relatively simple biochemical composition and are not able to reproduce themselves.  For more information, refer to Joint Publication (JP) 3-11 and Allied Medical Publication (AMedP-6[C]).  This publication is primarily concerned with
BW agents that have effects on humans.

Biological warfare is the employment of BW agents to produce casualties in personnel or animals, or damage to plants or materiel; or defense against such employment.


Refer to the Centers for Disease Control and Prevention (CDC) 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings for information on isolation precautions. The following are guidelines for isolation precautions:


Universal precautions apply to blood, other body fluids containing visible blood, semen, and
vaginal secretions.  Universal precautions also apply to tissues and to the following fluids: cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids.  Universal precautions do not apply to feces, nasal secretions, sputum, sweat, tears, urine, and vomitus unless they contain visible blood.  Universal precautions do not apply to saliva except when visibly contaminated with blood or, in the dental setting, where blood contamination of saliva is predictable.  Universal precautions involve the use of protective barriers such as gloves, gowns, aprons, masks, or protective eyewear which can reduce the risk of exposure of the health care
worker's skin or mucous membranes to potentially infective materials.  In addition, under universal precautions, it is recommended that all health care workers take precautions to prevent injuries caused by needles, scalpels, and other sharp instruments or devices.

Standard precautions combine the major features of universal precautions and body substance
isolation and are based on the principle that all blood, body fluids, secretions, excretions except sweat, nonintact skin, and mucous membranes may contain transmissible infectious agents. Standard precautions include a group of infection prevention practices that apply to all patients,
regardless of suspected or confirmed infection status, in any setting in which health care is delivered.  These include hand hygiene; use of gloves, gown, mask, eye protection, or face shield, depending on the anticipated exposure; and safe injection practices.  Also, equipment or items in the patient environment likely to have been contaminated with infectious body fluids must be handled in a manner to prevent transmission of infectious agents (for example, wear gloves for direct contact, contain heavily soiled equipment, and/or properly clean and disinfect
or sterilize reusable equipment before use on another patient).

Transmission-based (contact, droplet, and airborne) precautions are used when the route of transmission is not completely interrupted using standard precautions alone.  For some diseases that have multiple routes of transmission (for example, severe acute respiratory syndrome), more
than one transmission-based precautions category may be used.  When used either singly or in combination, they are always used in addition to standard precautions.  The three categories of
transmission-based precautions are

Contact precautions which are intended to prevent transmission of infectious agents,
including epidemiologically important microorganisms, which are spread by direct or indirect contact with the patient or the patient's environment.  The application of contact precautions for patients infected or colonized with multidrug-resistant organisms is described in the CDC Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006.  Contact precautions also apply where the presence of excessive wound drainage, fecal incontinence, or other discharges from the body suggest an increased potential for extensive environmental contamination and risk of transmission.

Droplet precautions which are intended to prevent transmission of pathogens spread
through close respiratory or mucous membrane contact with respiratory secretions.  Because
these pathogens do not remain infectious over long distances in a health care facility, special air handling and ventilation are not required to prevent droplet transmission.

Airborne precautions which prevent transmission of infectious agents that remain infectious
over long distances when suspended in the air (for example, anthrax and possibly severe acute respiratory syndrome-associated coronavirus).

## Applicability

The audience for this publication is the members of the Armed Forces Medical Services and other medically qualified personnel. This publication implements North Atlantic Treaty Organization (NATO) multinational force compatibility agreement (Standardization Agreement [STANAG] 2879), Principles of Medical Policy in the Management of a Mass Casualty Situation.  It is also in consonance with the following NATO STANAGs:

|                                                                                 | TITLE    |      |   NATO STANAG  |
|---------------------------------------------------------------------------------|----------|------|----------------|
| National Military Strategies for Vaccination of NATO ForcesAMedP-23            | 2037     |      |                |
| Chemical Methods of Insect and Rodent ControlAMedP-3(B)                        |          | 2048 |                |
| Emergency War Surgery                                                           |          |      |          2068  |
| Emergency War Burial Procedures                                                 |          |      |          2070  |
| First-Aid Dressings, First Aid Kits and Emergency Medical Care Kits             |          | 2126 |                |
| Minimum Standards of Water Potability During Field OperationsAMedP-18          | 2136     |      |                |
| Policy for the Chemoprophylaxis and Immunotherapy of NATO Personnel             |          |      |                |
| against Biological Warfare Agents                                               |          |      |          2242  |
| NATO Handbook on the Medical Aspects of NBC Defensive Operations                |          |      |                |
| (Biological)AMedP-6(C) Volume II                                               |          |      |          2462  |
| Medical Support Planning for Nuclear, Biological and Chemical Environments      | 2478     |      |                |
| Rapidly Deployable Outbreak Investigation Team (RDOIT) for Suspected            |          |      |                |
| Use of Biological Warfare Agents                                                |          |      |          2529  |
| NATO Planning Guide for the Estimation of CBRN CasualtiesAMedP-8(C)            | 2553     |      |                |
| Materials Handling in the Field                                                 |          |      |          2827  |
| Concept of Operations of Medical Support in Chemical, Biological, Radiological, |          |      |                |
| and Nuclear EnvironmentsAMedP-7(D)                                             |          |      |          2873  |
| Principles of Medical Policy in the Management of a Mass Casualty Situation     | 2879     |      |                |
| Training of Medical Personnel for NBC Defence Operations                        |          |      |          2954  |
| Deployable NBC Analytical Laboratory                                            |          |      |          4632  |

The use of trade names or trademarks in this publication is for illustrative purposes only.  Their use does not constitute endorsement by the Department of Defense (DOD). The proponent of this publication is the United States (U.S.) Army Medical Department Center and School (USAMEDDC&S).  Send comments and recommendations directly to Commander, USAMEDDC&S, ATTN: MCCS-FCD-L, 2377 Greeley Rd, Suite D, Fort Sam Houston, Texas 78234-7731.

## Implementation Plan

Participating Service command offices of primary responsibility will review this publication, validate the information and, where appropriate, reference and incorporate it in Service manuals, regulations, and curricula.

## United States Army The U.S. Army Will Incorporate This Publication In U.S. Army Training And Doctrinal Publications As Directed By The Commander, U.S. Army Training And Doctrine Command.  Distribution Is According To Initial Distribution Number 115795 Requirements For Field Manual (Fm) 8-284. United States Marine Corps*

The United States Marine Corps (USMC) will incorporate the procedures in this publication in USMC training and doctrinal publications as directed by the Commanding General, U.S. Marine Corps Combat Development Command.  Distribution is according to USMC publication distribution.

*Marine Corps PCN:  144 000080 00

## United States Navy

The United States Navy (USN) will incorporate these procedures in USN training and doctrinal publications as approved by the U.S. Navy Surgeon General and directed by the Commander, Navy Warfare Development Command.  Distribution is according to Military Standard Requisitioning and Issue Procedures Desk Guide, Navy Supplement Publication (NAVSUP P-) 409.

## United States Air Force

The United States Air Force (USAF) will validate and incorporate appropriate procedures according to applicable governing directives.  Distribution is according to Air Force Instruction 33-360.

## User Information The U.S. Army Medical Department Center And School

The USAMEDDC&S developed this publication with the joint participation of the approving Service commands.

## Service And Joint Doctrine

This publication reflects current Service and joint doctrine on prevention, protection, and medical management of BW agent casualties.

## Recommended Changes

We encourage recommended changes for improving this publication.  Key your comments to the specific page and paragraph and provide a rationale for each comment or recommendation.  Send comments and recommendations directly to

Army. Commander United States Army Medical Department Center and School ATTN:  MCCS-FCD-L Building 4011 2377 Greeley Road, Suite D Fort Sam Houston, TX 78234-7731 DSN 471-9411/9524 COMM (210) 221-9411/9524
Email:  usarmy.jbsa.medcom-ameddcs.mbx.ameddcs-medical-doctrine@mail.mil


***Marine Corps**.
Deputy Commandant for Combat Development and Integration ATTN:  MCCDC CDD MID DCB C116 3300 Russell Road Suite 204 Quantico, VA 22134-5021 DSN 278-6233; COMM (703) 784-6233
Web site: https://www.doctrine.usmc.mil/
*Marine Corps.  Readers of this publication are encouraged to submit suggestions and changes through the Universal Need Statement process.  The Universal Need Statement submission process is delineated in Marine Corps Order (MCO) 3900.15B which can be obtained from the Marine Corps Publications Electronic Library Online (universal reference locator at:  http://www.marines.mil/news/publications/Pages/default.aspx).  The Universal Need Statement recommendation should include the following information:  (1)  Location of change (publication number and title; current page number; paragraph number (if applicable); line number; and figure or table number [if applicable].  (2)  Nature of change (addition/deletion of text; proposed new text).


Navy. Commander Navy Warfare Development Command 1528 Piersey Avenue, Bldg O-27
Norfolk, VA 23511-2699 DSN 341-4203; COMM (757) 341-4203
Web site:  https://ndls.nwdc.navy.mil


Air Force. Commander Air Force Doctrine Center ATTN:  DR 155 North Twining Street Maxwell AFB, AL 36112-6112 DSN 493-7442; COMM (334) 953-7442
Email:  afdc.dr2@maxwell.af.mil

## Acknowledgments

The copyright owners listed here have granted permission to reproduce material from their works.  Other sources of quotations are listed in the source notes. Center for Infectious Disease Research and Policy (CIDRAP), Copyright Regents of the University of Minnesota (http://www.cidrap.umn.edu).

No endorsement by the Government is expressed or implied with any URL associated with a non-Government web site.

## Introduction Biological Warfare Agents

Chapter 1 provides information on the threat of BW agents against the U.S. Armed Forces and civilian population.  It also discusses its employment; novel threat agents policies and guidelines; classification of BW agents; and enemy's most effective modes of delivery (aerosol, foodborne, waterborne, vectorborne, or injection).  It discusses how BW agents enter the body via the portals of entry and how its effects are preventable through a number of protective measures.

## Recognition

Chapter 2 discusses epidemiology; warning and detection; surveillance; sample collection; medical reporting; and also discusses the U.S. Public Health Biological Warfare Monitoring and Assessment.

## Bacterial Agents

Chapter 3 describes bacterial agents including cells and spores which comprise the greatest number of pathogens in the list of potential BW agents.  This list includes anthrax, brucellosis, melioidosis and glanders, plague, Q fever, tularemia, and cholera.  Discussion of each agent includes etiology; reservoir; mode of transmission; endemic disease; delivery method; environmental detection; prevention; clinical presentation; diagnosis; treatment; control of patients, contacts, and treatment areas; and medical evacuation.

## Viral Agents

Chapter 4 discusses potential viral BW agents which include smallpox; Venezuelan equine encephalitis;
Western equine encephalitis (WEE); Eastern equine encephalitis (EEE); and viral hemorrhagic fevers (VHFs). Discussion of each agent includes etiology; reservoir; mode of transmission; endemic disease; delivery method;
environmental detection; prevention; clinical presentation; diagnosis; treatment; control of patients, contacts, and treatment areas; and medical evacuation.

## Toxins

Chapter 5 describes toxins which include Clostridium (C.) botulinum; *C. perfringens*; ricin; saxitoxin;
staphylococcal enterotoxin B (SEB); and trichothecene mycotoxins.  Discussion of each agent includes etiology; reservoir; mode of transmission; endemic disease; delivery method; environmental detection;
prevention; clinical presentation; diagnosis; treatment; control of patients, contacts, and treatment areas; and medical evacuation.

## Identification Technologies

Chapter 6 provides information on different methods for identifying BW agents.  It discusses the advantages and disadvantages of using orthogonal testing; lateral flow immunoassays; enzyme-linked immunosorbent assays; electrochemiluminescence (ECL); and polymerase chain reaction.  This chapter also discusses the confidence levels of laboratory analysis.



## Introduction Program Participants

The following commands and agencies participated in the development of this publication:


Joint

Joint Requirements Office, Chemical, Biological, Radiological and Nuclear Defense, 8000
Joint Staff Pentagon, Rm 1D958, Washington, D.C. 20318-8000

Joint Program Executive Office, Chemical/Biological Defense, 5203 Leesburg Pike, Ste
1609, Falls Church, VA 22041-3203


Air Force

Headquarters Air Force Doctrine Center, ATTN:  DR, 155 North Twining Street, Maxwell AFB, AL  36112-6112


Army

United States Army Office of The Surgeon General, 5111 Leesburg Pike, Ste. 401, Falls Church, VA 22041-3258

United States Army Public Health Command, 5158 Blackhawk Road, Aberdeen Proving Ground, MD 21010-5403

United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702-5011

United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400

United States Army Chemical, Biological, Radiological, and Nuclear School, 484
MANSCEN Loop, Ste 2617,  Fort Leonard Wood, MO 65473-8926


Marine Corps

United States Marine Corps Combat Development Command, ATTN:  C42 (Director),
3300 Russell Road, Quantico, VA  22134-5001


Navy

United States Navy Warfare Development Command, 1528 Piersey St, Bldg 0-27, Norfolk, VA 23511-2699

United States Navy Medical Research Center, 503 Robert Grant Avenue, Silver Spring, Maryland 20910

Bureau of Medicine and Surgery, Bldg 7, Room 7105, 2300 E St, NW, Washington, DC
20372-5300


Other Government Agencies

National Biosurveillance Integration Center, 3801 Nebraska Avenue NW, Building 20, Room 01-106, Washington, DC 20016

Centers for Disease Control & Prevention, 1600 Clifton Road, NE, MS E-97, Atlanta, GA
30329

## Chapter 1 Biological Warfare Agents Background

1-1. Biological weapons are unique in their potential ability to inflict large numbers of casualties over a wide area with minimal logistical requirements and by means that can be virtually untraceable.  Although wide area delivery of a BW agent may be technically challenging, the cost of producing an agent; the difficulty in detecting its presence and protecting (and treating) its intended victims; and the possibility to selectively target humans, animals, or plants conspire to make defense against this class of weapon particularly difficult.

1-2. The U.S. remains highly vulnerable to the strategic, tactical, and terrorist use of biological weapons.
As the military and economic gaps between nations grow and as some less advantaged nations seek a balance of power, there may be a tendency by these nations to overcome their disadvantage by choosing weapons of mass destruction that can be produced easily and cheaply.  Biological warfare agents are relatively easy and inexpensive to produce compared to chemical agents or radiological and nuclear material.
1-3. In contrast to all other weapon systems, the full impact of a BW attack may take several days or even weeks to develop and is difficult to predict during the early stages.  A BW attack using an agent transmissible from man-to-man may spread to susceptible personnel requiring implementation of strict control measures such as restriction of movement and quarantine.

## Threat

1-4. Biological warfare agents are unconventional weapons and can be delivered by unconventional means.  Conventional explosive munitions are inefficient delivery systems for BW; the heat generated by the explosion will destroy most of the BW agent.  In addition, an explosion will generate a wide range of particle sizes with only a fraction of the BW agent being aerosolized in particles of a size suitable for deposition in the lower respiratory tract.  The efficiency of explosive munitions delivering a viable BW agent is in the range of 1 to 2 percent.  Aerosol generators capable of generating particles of optimal size are easily constructed by adapting available agricultural and industrial sprayers.  Aerosols may be delivered via point source (stationary release point, bomblets, or other devices equipped with sprayers) or from a line source (such as a moving vehicle or cruise missile releasing agent).
1-5.  In 1969, the U.S. adopted a policy to cease offensive BW research and never again to produce, stockpile, weaponize, or use BW agents.  By 1970 all offensive BW research was terminated.  The U.S.

biological arsenal was destroyed by the end of 1972.  In addition, the U.S. is a party of the Biological Weapons Convention which was entered into force in 1975, which prohibits offensive BW agent research, stockpiling, weaponization, and use.  However, several foreign governments and terrorist organizations have continued to develop offensive BW programs.  The U.S. conducts research to develop vaccines, chemoprophylaxes, diagnostic tests, and therapies to minimize the potential impact of a BW attack.
1-6. The 1990s saw a well-placed increasing concern over the possibility of the terrorist use of BW agents to threaten either military or civilian populations.  First responders (public health and medical personnel and law enforcement agencies) have dealt with the exponential increase in biological weapons hoaxes around the country over the past decade.  The events of September 11, 2001, and subsequent anthrax mail attacks brought immediacy to planning for the terrorist use of weapons of mass destruction in the U.S.

1-7. Since 2001, the U.S. Government has significantly expanded its efforts to improve the Nation's ability to recognize and respond to acts of bioterrorism or other significant outbreaks of infectious disease;
however, efforts targeted to prevent such threats have received comparatively limited policy focus or substantive guidance at the National level.  Although it is entirely feasible to mitigate the impact of even a large-scale biological attack upon a city's population, doing so incurs a significant cost and effort.
1-8. The National Strategy for Countering Biological Threats provides guidance to our efforts to prevent such incidents by reducing the risk that misuse of the life sciences or derivative materials, techniques, or expertise will result in the use or intent to use BW agents to cause harm.  It also complements existing policies, plans, and preparations to advance our ability to respond to public health crises of natural, accidental, or deliberate origin.

1-9. The National Defense Strategy defines the strategic environment as a global struggle against extremist ideology that seeks to overturn the international nation-state system.  It outlines how DOD will support the objectives outlined in the National Security Strategy, including the need to strengthen alliances and build new partnerships to defeat global terrorism.  It also outlines the need to prevent attacks from our enemies and to prevent them from threatening the U.S. and our allies with chemical, biological, and nuclear weapons.
1-10. The National Strategy for Homeland Security and the Homeland Security Act of 2002 were developed in response to the terrorist attacks.  The 2006 Pandemic and All-Hazards Preparedness Act requires the Secretary of Health and Human Services to lead all federal public health and medical response to public health emergencies and incidents covered by the National Response Framework.

1-11. Biological warfare has interested several foreign governments and terrorist organizations for a number of reasons


Biological warfare agents are relatively easy to obtain and produce.  Naturally occurring viruses
and bacteria, which cause disease, are obtainable from soil, water, animal reservoirs, clinical specimens, and clinical and research laboratories.  Also, the development of recombinant genetic engineering has introduced the potential to genetically modify viruses and bacteria to enhance their ability to cause disease.  Such modifications may include antibiotic resistance, enhanced invasiveness or toxin production, or enhanced ability to evade host immune defenses.

It is possible that in addition to the traditional BW agents, other pathogens could be used to create terror or disruption of commerce.  The effects might appear to be a natural epidemic when
in fact the results are due to covert actions of foreign government or terrorist organization.
1-12. The threat of the use of biological weapons against U.S. military forces and civilians is more acute than at any time in U.S. history, due to the widespread availability of agents, widespread knowledge of production methodologies, and potential dissemination devices.  Therefore awareness of and preparation for this threat will require the education of our government officials, health care providers, public health officials, and law enforcement personnel, as well as the public.

1-13. Intrinsic features of BW agents, which influence their potential for use as weapons, include
infectivity, virulence, toxicity (toxins), pathogenicity, incubation period, transmissibility, lethality, and stability.  Infectious organisms have to multiply within the body in order to cause disease, in contrast to toxins where the effect is dependent upon the dose received.  Refer to Appendix A for more information on characteristics of BW agents.

## Employment Of Biological Warfare Agents

1-14. Chemical, biological, radiological, and nuclear (CBRN) weapons are classified as weapons of mass destruction.  Aerosols of BW agents may deliver incapacitating or lethal doses over large geographic areas and produce mass casualties.  The epidemic produced by the BW agent can quickly overwhelm the supporting military health system or public health capabilities; thus reducing the ability of emergency response teams and emergency medical providers to respond.
1-15. Livestock and other animals of economic importance may be targeted by animal pathogens.  The BW
agents may be plant pathogens used to destroy crops, devastate the food chain, and cause famine. Contamination of water systems/supplies and the food chain with potential human pathogens is another mode of delivery to a targeted population.

1-16. The threatened use of BW agents can result in fear and panic in a population (whether under attack or being threatened to gain political advantage in political activities).  The potential psychological impact of BW agents adds to an adversary's strategic threat.

1-17. Most BW agents are probably poor tactical weapons on the modern battlefield.  Given that most BW
agents have incubation periods of several days to weeks duration, the outcome of a rapidly developing battle will be determined before the effects of a BW attack are realized.  However, rapid-acting toxins (such as saxitoxin) may have tactical utility.  Potential targets for delayed-onset BW agents may include areas with relatively fixed positions (for example, logistics support facilities, aerial ports of debarkation, and sea ports of debarkation).

1-18. Biological warfare agents are adaptable for terrorist operations.  A BW agent with its delivery system can be easily concealed and transported.  Given the difficulties in identifying a BW agent attack and the incubation periods for most BW agents, the perpetrators could escape before the BW release is detected.
The employment of BW agents is not limited to war; the potential for BW agent use exists and can occur at anytime, anyplace, and by anyone with an intent to cause injury, disturbance, or create political discord.
The employment of BW agents during political events (especially during multinational events) is a major threat.

## Novel Threat Agents

1-19. When Brent Scowcroft was the U.S. national security adviser, he issued a memorandum in 1975
providing policy guidelines for U.S. implementation of the Biological Weapons Convention.  The Scowcroft Memorandum states that biodefense activities permitted under the convention were limited to "activities concerned with the protection of human beings, animals, plants, and materiel from the effects of exposure to microbial or other BW agents or toxins, including vulnerability studies and research, development and testing of equipment and devices such as protective masks and clothing, air and water filtration systems, detection, warning and identification devices, and decontamination systems."  The Scowcroft Memorandum authorized vulnerability studies but not the creation of novel pathogens or weaponization techniques for purposes of threat assessment.

1-20. The efforts for medical countermeasure development and acquisition have been focused on those threat agents known to have the potential to cause catastrophic effects on our nation and its citizens.

Government agencies are investing efforts to address threat agents that the U.S. might face in the future, including novel threats (for example, genetically modified antibiotic-resistant anthrax).   Current changes in science and technology and adversary behavior will produce new threats that must be assessed by DOD in the future.  Adversaries will always think of ways to employ irregular, disruptive, and potentially catastrophic strategiesincluding the use of terror and weapons of mass destruction to challenge not only the U.S. power but our allies as well.

1-21. Nontraditional potential BW agents such as severe acute respiratory syndrome and influenza are appearing with increasing frequency and are a threat with many medical and legal implications.  Emerging disease outbreaks such as severe acute respiratory syndrome and hantavirus pulmonary syndrome may be difficult to distinguish from the intentional introduction of infectious diseases by terrorist groups.  Other pathogens such as prions that can cause fatal diseases to humans and animals could be used to create panic and terror within the DOD and the civilian populace.  Performing health risk assessments using the operational risk model described in FM 5-19 documenting and disseminating information using appropriate risk communication techniques and archiving available data will be beneficial should issues arise later.

## Classification

1-22. Biological warfare agents may be classified as medical or operational.  The classification of BW
agents is important to the


Medical services in terms of identification, prophylaxis, and treatment.  Biological agents may be genetically modified in order to evade standard detection and identification.

Combatant/theater commanders in order to provide guidance to tactical commanders on their impact on operations.  Operational considerations should incorporate all recognized variables likely to impact on effectiveness, to include lethality, transmissibility, and persistence.
1-23. Refer to Table 1-1 for more information on pathogens and toxins.  Also, refer to Table 1-2 for disease threats from BW agents and Table 1-3 for the BW threat agents that will be covered in this publication.  Although not discussed in this manual, a number of emerging threats (severe acute respiratory syndrome and hantavirus pulmonary syndrome) are potential BW agents.


| Group                                        | Description        | Classes       | Description    |
|----------------------------------------------|--------------------|---------------|----------------|
| Bacteria                                     |                    |               |                |
|                                              |                    |               |                |
| Pathogens                                    |                    |               |                |
| Bacteria                                     | are                | single-celled | micro-         |
| organisms whose deoxyribonucleic acid        |                    |               |                |
| is not enclosed in a nuclear membrane.       |                    |               |                |
| Bacteria are small free-living organisms,    |                    |               |                |
| most of which may be grown on solid or       |                    |               |                |
| liquid culture media.  The organisms         |                    |               |                |
| have a structure consisting of nuclear       |                    |               |                |
| material, cytoplasm, and cell membrane.      |                    |               |                |
| They reproduce by simple division.           |                    |               |                |
| Some bacteria such as rickettsiae and        |                    |               |                |
| chlamydia can only grow inside host cells    |                    |               |                |
| and therefore cannot be grown readily on     |                    |               |                |
| artificial media.  Other bacteria (for       |                    |               |                |
| example,                                     | Bacillus anthracis | ) can form    |                |
| spores that enable them to survive for       |                    |               |                |
| long                                         | periods            | in            | the            |
| Diseases produced by bacteria often          |                    |               |                |
| respond                                      | to                 | specific      | therapy        |
| antibacterial drugs such as antibiotics.     |                    |               |                |
|                                              |                    |               |                |
| Rickettsiae                                  |                    |               |                |
|                                              |                    |               |                |
| Rickettsiae are bacteria, but like viruses,  |                    |               |                |
| are unable to multiply unless inside a       |                    |               |                |
| living cell.  Most spread via insect vector. |                    |               |                |
| Pathogens                                    | are                | also          | referred       |
| infectious agents.  The primary BW           |                    |               |                |
| pathogens are disease-causing bacteria,      |                    |               |                |
| viruses, and rickettsiae.  These broad       |                    |               |                |
| categories/classes include a variety of      |                    |               |                |
| microorganisms which may be free-living      |                    |               |                |
| or require host cells to replicate and       |                    |               |                |
| persist.  They enter the body through the    |                    |               |                |
| lungs, digestive tract, skin, or the mucous  |                    |               |                |
| membranes of body openings.  Once they       |                    |               |                |
| enter the body, they multiply, overcoming    |                    |               |                |
| the body's natural defenses.  Pathogens      |                    |               |                |
| are naturally occurring, and outbreaks of    |                    |               |                |
| disease may occur spontaneously in           |                    |               |                |
| specific regions of the world.  Certain, but |                    |               |                |
| not all, pathogens may spread from           |                    |               |                |
| person-to-person.                            |                    |               |                |
| Virus                                        |                    |               |                |
|                                              |                    |               |                |
| Viruses are organisms that require living    |                    |               |                |
| cells in which to replicate. They are        |                    |               |                |
| therefore intimately dependent upon the      |                    |               |                |
| cells of the host, which they infect.  They  |                    |               |                |
| produce diseases which do not respond        |                    |               |                |
| to                                           | antibiotics        | but           | which          |
| responsive                                   | to                 | antiviral     | compounds;     |
| however, few antivirals are available and    |                    |               |                |
| those that are available are of limited      |                    |               |                |
| use.                                         |                    |               |                |
|                                              |                    |               |                |
| Neurotoxins                                  |                    |               |                |
|                                              |                    |               |                |
| Neurotoxins disrupt nerve impulses.  Like    |                    |               |                |
| nerve agents, neurotoxins may cause          |                    |               |                |
| paralysis or convulsive seizures leading     |                    |               |                |
| to coma and death.                           |                    |               |                |
| Toxins                                       |                    |               |                |
| Toxins                                       | are                | poisonous     | substances     |
| produced                                     | and                | derived       | from           |
| organisms. Toxins may be countered by        |                    |               |                |
| specific antisera, but only a limited range  |                    |               |                |
| of antisera are available.                   |                    |               |                |
| Cytotoxins                                   |                    |               |                |
| Cytotoxins destroy cells by disrupting cell  |                    |               |                |
| respiration and metabolism.  They may        |                    |               |                |
| cause                                        | vomiting,          | diarrhea,     | choking,       |
| blistering,                                  | or                 | even          | radiation-like |
| symptoms, as well as marked weakness,        |                    |               |                |
| coma, and death.                             |                    |               |                |
| Class                                    | Agent    |
|------------------------------------------|----------|
| Bacterial                                |          |
|                                          |          |
| Anthrax                                  |          |
| Brucellosis                              |          |
| Cholera                                  |          |
| Shiga toxemia                            |          |
| Epidemic typhus                          |          |
| Glanders                                 |          |
| Melioidosis                              |          |
| Plague                                   |          |
| Q fever                                  |          |
| Rocky Mountain spotted fever             |          |
| Salmonellosis                            |          |
| Scrub typhus                             |          |
| Shigellosis                              |          |
| Tularemia                                |          |
| Typhoid fever                            |          |
| Bacillus anthracis                       |          |
| Brucella spp                             |          |
| Vibrio cholerae                          |          |
| Escherichia coli                         |          |
| Rickettsia typhi                         |          |
| Burkholderia mallei                      |          |
| Burkholderia pseudomallei                |          |
| Yersinia pestis                          |          |
| Coxiella burnetii                        |          |
| Rickettsia rickettsii                    |          |
| Salmonella spp                           |          |
| Orientia tsutsugamushi                   |          |
| Shigella dysenteriae                     |          |
| Francisella tularensis                   |          |
| Salmonella Typhi                         |          |
| Viral                                    |          |
| Junin virus                              |          |
| Machupo virus                            |          |
| Chikungunya virus                        |          |
| Crimean-Congo hemorrhagic fever virus    |          |
| Ebolavirus                               |          |
| Eastern equine encephalomyelitis virus   |          |
| European tickborne encephalitis virus    |          |
| Influenza virus                          |          |
| Hantaviruses                             |          |
| Lassa virus                              |          |
| Marburg virus                            |          |
| Monkeypox virus                          |          |
| Omsk hemorrhagic fever virus             |          |
| Rift Valley fever virus                  |          |
| Flaviviruses                             |          |
| Variola virus                            |          |
| Venezuelan equine encephalitis virus     |          |
| Western equine encephalitis virus        |          |
| Yellow fever virus                       |          |
| Argentine hemorrhagic fever              |          |
| Bolivian hemorrhagic fever               |          |
| Chikungunya fever                        |          |
| Crimean-Congo hemorrhagic fever          |          |
| Ebola                                    |          |
| Eastern equine encephalitis              |          |
| European tickborne encephalitis          |          |
| Influenza                                |          |
| Korean hemorrhagic fever (Hantaan)       |          |
| Lassa                                    |          |
| Marburg                                  |          |
| Monkeypox                                |          |
| Omsk hemorrhagic fever                   |          |
| Rift Valley fever                        |          |
| Russian spring-summer encephalitis group |          |
| Smallpox                                 |          |
| Venezuelan equine encephalitis           |          |
| Western equine encephalitis              |          |
| Yellow fever                             |          |
| Toxins                                   |          |
| Aspergillus flavus                       |          |
| Clostridium botulinum                    |          |
| Clostridium perfringens enterotoxin      |          |
| Palytoxin                                |          |
| Ricins                                   |          |
| Saxitoxins                               |          |
| Staphylococcus aureus                    |          |
| Trichothecene mycotoxins                 |          |
| Aflatoxicosis                            |          |
| Botulism                                 |          |
| Clostridium perfringens enteritis        |          |
| Palytoxin                                |          |
| Ricin                                    |          |
| Saxitoxin                                |          |
| Staphylococcal enterotoxin               |          |
| Mycotoxin                                |          |
Bacterial agents
Viral agents
Toxins
Smallpox Venezuelan equine encephalitis
Viral hemorrhagic fever
Clostridium botulinum Clostridium perfringens
Ricin Saxitoxin Staphyloccocal enterotoxin B Tricothecene mycotoxins
Anthrax Brucellosis
Cholera Glanders Melioidosis Plague Q fever Tularemia

## Dissemination Method Of Delivery

1-24. Biological warfare agents are most effectively delivered as an aerosol.  Aerosol delivery systems aim to generate invisible clouds with particles or droplets between 0.5 and 10 micrometers in diameter, which can remain suspended for long periods.  The aerosol release of respirable particles in that size range results in a predominantly inhalation hazard since the particles can settle deep in the lungs.

1-25. Biological warfare agents may be used to contaminate food or water systems/supplies.  Heat destroys most pathogens and toxins; thus, to be effective most agents would have to be used on food that will be served raw or added after the food is prepared and presented for serving.  Standard water purification methods (chlorination and filtration) may well inactivate many pathogens and some toxins.  However,
chlorination will not inactivate many spores and commercial filtration will be largely ineffective against spores, cysts, viruses, and many bacteria.  Filtration will be all but useless against toxins unless something like activated charcoal is used.

1-26. Biological warfare agents have been delivered by covert injection.  Some agents (for example, ricin)
are lethal when injected.

## Mode Of Attack

1-27.  The possible modes of BW attack in any operational environment will vary significantly with location, depending on the nature of the delivery system employed, the time of day, the weather conditions, and the local geography.

## On-Target Attack

1-28. In this attack, the point of release of the BW agent occurs within the target location.  These attacks are much less likely to be covert, enabling personnel to assume protective measures in a more timely manner (respiratory protection and postexposure prophylaxis).  Service members will have to take the following hazards into consideration:


Primary aerosol.  Large concentrations of aerosolized agent may be generated very quickly by an on-target attack, whether from spraying or bursting munitions, exposing personnel to high levels of inhaled agent.  Protection against such exposure levels may require the combined employment of medical prophylaxis and full respiratory protection (individual or collective). The primary aerosol may persist in the same location (until dispersed, diluted, or possibly decayed), this may
take several hours, particularly in atmospherically stable conditions.  There may be a significant downwind hazard for many kilometers, the exact area depending on wind speed, direction, and size of release, as well as environmental conditions.  Significant differences in the effect of
weapons are seen with different atmospheric conditions including humidity, ultraviolet light
(sunlight), temperature, and time of day as well as the condition of the agent.  Bacterial spores are especially persistent and may germinate a long time after delivery.  In addition, pockets of aerosolized BW agent may persist for longer periods of time within confined spaces (for
example, buildings, shelters, and vehicles), even after the primary aerosol has dispersed or moved on.


Residual contamination.  While data on the significance of residual contamination following a BW agent aerosol attack is incomplete, it is anticipated that any on-target delivery system will
produce a degree of surface contamination close to the point of release.  Relative to the primary
aerosol, the immediate hazard associated with contamination will be considerably less than that
of the primary aerosol, unless there is a risk of percutaneous exposure (for example, through wounds sustained during the attack). The persistence of residual contamination is uncertain, but
will be substantially longer than the BW agent in aerosol form.  Once the primary aerosol has moved from the location, residual contamination may continue to represent a significant hazard depending on the environmental stability of the BW agent.  Even relatively low levels of residual contamination may be viewed as significant if personnel remain contaminated or are required to continue operating in the contaminated area.  Protection against inhaled and percutaneous hazards may be afforded by the use of medical prophylaxis, the continuous use of appropriate physical protection (with associated operational degradation), and high standards of personal and unit hygiene.

Reaerosolization.  Residual contamination may be reaerosolized by the movement of vehicles
and personnel.  At this time the operational impact of reaerosolized BW agent cannot be
measured therefore a worst-case scenario should be assumed.

## Off-Target Attack

1-29. In this attack, the point of release of the BW agent is outside the target location.  The BW agent used in such an attack must be sufficiently stable to reach the target location in a viable form.  Off-target attacks are more likely to be covert, denying exposed personnel the opportunity to take timely defensive measures. A similar state will exist downwind of an on-target attack.  Service members will have to take the following hazards into consideration:


Primary aerosol. The behavior of aerosolized BW agent entering a location after release offtarget will be the same as for an on-target attack, although at a generally reduced level of concentration for the same amount of BW agent released.  Furthermore, dispersion of the aerosol cloud prior to arrival may result in large variations of concentration within specific areas of the location.

Residual contamination. Off-target attacks are least likely to result in a reduced contamination hazard compare to the primary aerosol.  A significant contamination hazard may exist from use of an environmentally stable agent (for example, spores).  Contamination of unprotected supplies
of food and water, in which deposited BW agent may multiply or resist degradation may exist.

Reaerosolization. Off-target attacks have a lower likelihood of producing significant
reaerosolization of BW agent compared to on-target attacks due to lower levels of residual contamination.  However, consideration should be given to the possibility of reaerosolization
where an off-target attack is detected sufficiently early to take defensive action.

## Routes Of Entry

1-30. Biological warfare agents enter the body through the same routes of entry pertinent to natural spread of disease; that is, through inhalation, ingestion, or percutaneous inoculation.  Other routes of entry are thought to be less important than inhalation but are nonetheless potentially significant.  The routes of entry are as follows:


In respiratory exposure (inhalation), the natural process of breathing causes a continuing influx of BW agent into the respiratory tract.  Infection by the respiratory route may induce disease at doses lower than those generally associated with naturally acquired infections by the oral route. The subsequent illness may differ from the natural pattern and the incubation period may be shorter.

In alimentary exposure (ingestion), consumption of contaminated food and water could result in disease.  There is also the possibility of the inadvertent swallowing of an agent delivered as an aerosol.

In dermal exposure (percutaneous), intact skin provides an effective barrier against most BW
agents, except mycotoxins.  However, mucous membranes including the conjunctiva and
damaged skin constitute breaches in this normal barrier through which BW agents may readily pass, causing local or systemic infection.  Traumatic wounds and superficial abrasions and cuts
can provide routes of entry.  The protective barrier of the skin can also be bypassed by injection (a technique which has been used in covert assassination).  Biological agents can be introduced through the skin via vectors.
1-31. Though the disease produced by a BW attack may mimic the naturally occurring infectious disease caused by the same pathogen or toxin, in many instances the disease produced by a BW attack will present with an uncharacteristic epidemiology pattern.  For example, predominantly SEB is ingested in food leading to acute gastrointestinal (GI) illness; however, when delivered via aerosol to the respiratory tract, it produces respiratory disease.

1-32. Following exposure to a BW agent there could be a time delay of hours to weeks before symptomatic cases of the disease occur consistent with the incubation period of the microorganism and the dose received by the individual.   For toxins, the time delay may be hours to days consistent with latent period.  The number of casualties in any exposed population may be difficult to predict.  Primary cases may occur over several days amongst those in the hazard area from the original attack.  If the disease spreads directly from person-to-person, personnel in close contact with the initial cases may become infected.  This secondary spread may be controlled by medical prophylaxis and strict infection control measures including restriction of movement.

## Prevention

1-33. The effects of many BW threat agents are preventable or can be mitigated with proper precautions.

Immunizations, preexposure and postexposure prophylaxes, therapeutics, and protective clothing are available to provide protection.  Personnel must have all required immunizations administered prior to entering an area of operations where BW agent employment is a threat.  If an attack is felt to be imminent, or is known to have occurred, command-directed chemoprophylaxis would be appropriate for all personnel in the area.  However, it is impractical and wasteful to place everyone located in a potential target area on prolonged, routine antimicrobial prophylaxis in the absence of such a threat condition.

1-34. All immunizations should be administered in sufficient time to provide the initial protection to take effect before troops are deployed to the area of operations; when administration prior to deployment is impossible, troops must receive the immunizations as soon as the mission permits in the area of operations. Some immunizations are used in conjunction with preexposure chemoprophylaxes or postexposure chemoprophylaxes to provide protection.  The supporting public health/preventive medicine (PVNTMED) units/staffs can assist commanders in determining which specific immunizations, therapeutics, and chemoprophylaxes are required for the area of operations.  For those BW agents for which a specific immunization is not available, the use of protective equipment combined with chemoprophylaxis may be employed to provide protection.

## Medical Countermeasures

1-35. Vaccination is an important practical means of providing continuous protection against BW threats prior to, as well as during, hostile actions.  Vaccines against a number of potential BW agents are available. Many of these vaccines were developed for the protection of laboratory workers or individuals working where the target diseases are endemic.  Some of the considerations to take when planning for medical countermeasures are as follows:


In a BW agent attack the number of infectious or toxin units to which an individual is exposed may be greater than in the case of natural exposure.  Exposure by inhalation may represent an unnatural route of infection with many BW agents.  The efficacy of  protection afforded by most
vaccines is based on natural route of exposure and presentation of disease.  Available vaccines
against naturally occurring BW agents may not provide a similar degree of protection to individuals exposed to aerosolized or genetically altered agents.

An appropriate immunization policy is essential.  Vaccines are BW agent-specific and do not provide immediate protection.  Not all vaccines can be administered simultaneously; therefore,
to prevent the logistic problems caused by in-theater vaccination, prior immunization is essential.

If a vaccination program is required in theater, the possibility of adverse reactions from
vaccination and the accompanying degradation of operational efficiency must be taken into account.  Vaccines are currently available in the U.S. for the following potential BW agent
threats:

Anthrax.

*Argentine hemorrhagic fever.

*Botulinum toxin.

*Plague.

*Rift Valley fever.

Smallpox.

*Venezuelan equine encephalitis (VEE).

Yellow fever.

*Investigational new drug (IND) is available only under Food and Drug Administration (FDA)-
approved protocol with informed consent.

1-36. Chemoprophylaxis using appropriate drugs (such as antibacterials, antivirals, and antitoxins) offers additional protection in the setting of a BW threat.  For bacterial agents, antibiotics should be administered as soon as possible following exposure.  Initiation of chemoprophylaxis during the incubation period is always worthwhile, however, the earlier the antibiotic is given the greater is the chance of preventing disease.  In some cases, for example, inhalational anthrax, postexposure vaccination should be given in addition to antibiotics to personnel previously unvaccinated in order to prevent late onset of disease when antibiotics are withdrawn.  Postexposure chemoprophylaxis considerations are as follows:


Consideration should be given to the possibility of the interaction between drugs in multidrug regimens that address the multiple elements of force protection.

Postexposure chemoprophylaxes are available for anthrax, plague, Q fever, and tularemia.  See Chapters 3 through 5 for details on vaccines and chemoprophylaxes for specific BW agents.

Along with the initiation of chemoprophylaxis, many patients may require intensive supportive
care such as respiratory support.
1-37. For some BW agents, the only available medical countermeasure might be specific antiserum.  Under certain conditions, passive immunoprophylaxis with immunoglobulin products might be considered.  Use may be limited by lack of adequate sources and quantities of material, limited duration of protection, and the risk of serum sickness associated with antisera of animal origin.  However, recent scientific advances in products for immunoprophylaxis (for example, human monoclonal antibodies, despeciated equine, or ovine antisera) are making this option technically more attractive.

## Physical Protection

1-38. Contaminated patients potentially create increased hazard to first responders, medical evacuation teams, medical personnel, and medical facilities.  Therefore standard precautions and the wear of individual protective equipment (IPE)/personal protective equipment (PPE) while taking care of personnel that have been exposed to BW agents have to be followed.  The three key purposes of adhering to standard precautions and conducting patient decontamination are to


Protect the medical treatment facility (MTF) staff and equipment/materiel within.

Protect evacuation team and equipment along the evacuation route.

Remove contamination from the patient to reduce further agent exposure.
1-39. Respiratory protection is essential in the presence of any BW inhalation hazard.  Currently fielded military respirators (CBRN protective mask which includes MCU-2A/P, M40 series, and the M50 series) equipped with standard CBRN filter canisters will provide a high degree of protection against particles greater than 0.3 micrometers in size.  Standard issue military filters combine the protective mechanisms of a charcoal filter (for chemical-agent vapors) and a high-efficiency particulate air filter against BW agent particles.

1-40. When worn alone, military protective masks utilizing a high-efficiency particulate air filter will provide a high level of protection against inhalation of BW agents.  Standard issue military protective masks are negative-pressure air purifying respirators as a vacuum is created in the mask during the wearer's respiration cycle.  While high-efficiency particulate air filters provide a high degree of protection, the compromise of the seal interface between the mask and the wearer's face is the most likely point of entry with a negative pressure respirator/mask.  Protective masks used in conjunction with a powered airpurifying respirator or self-contained breathing apparatus that maintains positive pressure inside the mask provides a greatly increased protection factor compared to a negative pressure respirator.  Maintenance of the protective mask is essential to provide maximum protection as is periodic replacement of the filter elements.

1-41. Commercially available respirators, certified against CBRN contaminants by the National Institute for Occupational Safety and Health such as full facepiece powered air purifying respirators, will provide comparable protection as do military masks.  The National Institute for Occupational Safety and Health commercial air supplied respirators (for example, self-contained breathing apparatus and supplied air devices) may also be appropriate, but selection should be made by a competent authority and used only by properly trained individuals.  The N95 rated particulate masks (also called dust masks), that may provide some protection against naturally occurring pathogens transmitted via aerosolized droplets of infected sputum, should NOT be considered for protection against BW agents because they do not provide an airtight seal against the face.

1-42. Intact skin provides an excellent barrier against BW agents, however, any skin abrasions or exudative inflammation must be covered with a bandage or any covering that provides a seal against the skin.  In some instances it may be necessary to protect the mucous membranes of the eye.  Individual protective equipment or PPE clothing employed against BW agents will protect against skin contamination with BW agents, although standard uniform clothing affords a certain degree of protection against dermal exposure to the surfaces covered.  Refer to FM 3-11.4/MCWP 3-37.2/NTTP 3-11.27/AFTTP(I) 3-2.46 for additional information on protective measures.

1-43. Casualties unable to continue wearing IPE/PPE in a BW agent contaminated area, should be held and/or transported using containment measures (such as patient protective wrap) to protect the casualty against further BW agent exposure.  Barrier measures should be used for contagious patients in holding areas and/or being transported to prevent secondary infections and to prevent environmental contamination.

1-44. A collective protection shelter is a dedicated hardened or unhardened shelter equipped with a CBRN
air filtration unit.  This shelter provides an overpressure environment to allow medical treatment personnel to work inside with minimal IPE/PPE or without the need of additional IPE/PPE.  Contaminated patients, staff, and equipment/materials must be decontaminated prior to entering a collective protection shelter in order to maintain its integrity.

1-45. Collective protection is the most effective method for protecting clean patients, medical personnel, and the MTF during the primary BW attack.  Patients whose illness is thought to be the result of a BW
attack, or those who are thought to have a transmissible disease, will necessarily be cared for using barrier protection techniques.  The environment within collective protection may promote cross-infection between casualties and staff and it may be appropriate to care for these patients outside collective protection.  For more information on individual, patient, and caregiver protection, refer to FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3.

Instruction (DODI) 3020.52/6055.1 for more information.

## Hazard Management

1-46. The importance of effective hygiene and sanitation in a biological operations environment cannot be overemphasized.  One of the primary responsibilities of all personnel is to ensure that standards of hygiene are maintained even in the most difficult circumstances.  Personal hygiene measures such as frequent and adequate washing with soap and water, regular changes with laundered clothing, use of clean toilets and field latrines with handwashing devices should be emphasized.  Refer to STANAGs 2048 and 2136 for additional information on provision of environmental health measures.

1-47. High standards of food preparation and water purification are essential, as is the protection of food and water supplies from incidental airborne contamination or sabotage.

1-48. Standard methods of disinfection and waste disposal are effective in the context of BW.  Particular care and attention should be paid to handling and disposal of clinical waste.

1-49. Since BW agents may be spread by mechanical means or natural vectors, rodents and arthropods must be effectively controlled.

## Infection Control

1-50. Infection control procedures should be reinforced for mass casualty situations with undifferentiated febrile illness following a suspected BW attack.  Isolate patients and use respiratory droplet precautions, in addition to standard precautions, until the BW agent is identified.  Infection control practices can then be modified based on the identified agent.  Specific precautions are discussed for each agent in the following chapters and in Appendix C, Table C-1.
1-51. Patient isolation of suspected or confirmed cases of transmissible disease should be in designated shelters, tents, or fixed facilities if available.  The use of surgical masks on patients is appropriate when designated areas are not available or practical.

## Casualty Management

1-52. Precise diagnosis of BW casualties in a CBRN environment is likely to be difficult. Biological warfare casualties may coexist with conventional, nuclear, radiological, and/or chemical warfare casualties. In that case, both casualties and medical personnel may be in full IPE.  Signs and symptoms of BW agent infection (agent produces the disease) or intoxication (agent has debilitating effect on patient) are common to many diseases.  Adequate or appropriate laboratory facilities may not be available.  The treatment required for BW casualties will not differ in basic principle from that in patients suffering from the same disease incurred by natural means, but the approach to casualty management will need to consider additional factors related to operating in the context of a BW agent attack.  One of these additional factors may be implementing restriction of movement through isolation, quarantine, social distancing, or shelterin-place.

1-53. Social distancing measure is an exclusion of a person with an infectious disease from the unit.
Shelter-in-place measure is to take immediate shelter wherever the person is at the time of the BW attack or event.  This may also mean sealing the room to prevent contaminated air from coming in.  For more information regarding isolation and quarantine, refer to paragraph 1-91.

1-54. Casualties arising after a BW agent attack may be contagious or noncontagious and present with


Physical injury only.

Physical injury and who are contaminated or have agent residue on their person.

Illness (caused by BW agent) that may or may not be contagious.

Psychological effects.
1-55.  In addition, casualties may be contaminated with radiological or chemical warfare agent.
Management of all these casualties must minimize the risk of cross-contamination without significantly compromising the effective treatment of their traumatic wounds or effects from CBRN agents.

1-56. Triage of arriving casualties is extremely important.  A decision must be made as to whether emergency medical treatment or decontamination of the casualty requires priority.  Airway management and/or control of hemorrhage will usually be more urgent than any decontamination procedures. Emergency medical treatment measures may have to be performed in rapid sequence to include
decontamination.

## Emergency Medical Treatment

1-57. When a contaminated casualty has respiratory difficulty, hemorrhage, or shock, the order of priority for emergency action is as follows:


Control respiratory failure (provide assisted ventilation) and/or control bleeding.

Decontaminate the casualty as necessary.

Administer additional emergency medical treatment for shock, wounds, and illnesses so severe that delay may be life- or limb-threatening.

Evacuate the casualty as appropriate.
1-58. For most BW agent casualties, first aid consists of basic procedures to protect against further exposure as described below.  When specific first aid procedures exist for a specific BW agent, the procedures will be discussed within the text for that agent.

## Self-Aid

1-59. Takes preexposure and postexposure chemoprophylaxes as directed by the commander/command surgeon.  Seeks medical evaluation for fever and other signs of illness.

## Buddy Aid

1-60. Assists any Service member who develops fever and is not able to move on his own, as the mission permits.  A buddy should request medical assistance in all cases.

## First Responder Aid (Combat Lifesaver/Combat Medics/Corpsmen/Air Force Medics)

1-61. Provides airway support, fluid hemorrhaging management, and patient transport support.

## Patient Decontamination And Hazard Reduction

1-62. The purpose of decontamination is hazard reduction.  However, given the inherent incubation periods of BW agents, significant time may have elapsed between the BW attack and when patients present with illness due to the attack.  During this time, it is quite probable that external decontamination of any residual agent may have already occurred.  Thus, it is only in rare circumstances that patients presenting with illness due to BW attack will require external decontamination.

1-63. External decontamination will be important in instances such as


Intentional release (for example, use of a crop duster) of persistent aerosolized BW agent.

Presence of unidentified powders found in clothing or on skin.

Other events or attacks that raise a high degree of suspicion that a BW agent may have been
dispersed.

## Primary Contamination

1-64. Skin exposure from a suspected attack should be managed by external decontamination at the earliest opportunity.  Potentially contaminated clothing should be removed immediately and disposed of in the designated area.  For more information on removal and disposal of contaminated clothing, refer to FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3.  As soon as it is practical, external decontamination should be implemented by protected personnel (that is, appropriate level of IPE/PPE) in an area isolated from clean patients.  In the absence of agent-specific guidance, exposed areas should be cleansed using copious quantities of liquid soap and water.  In the absence of liquid soap, use copious amount of water, and in the absence of water, use soft towel to remove contaminants.  The FDA has cleared Reactive Skin Decontamination Lotion (RSDL) for use by the U.S. military intended to remove or neutralize T-2 fungal toxin from the skin.  It is a liquid decontaminant dispensed on a sponge.  The RSDL can be used for the decontamination of intact skin around wounds, but is not approved for the decontamination of wounds.  See Appendix B for a complete description of decontamination procedures and appropriate decontaminants.
Note.  The use of 0.5 percent hypochlorite solution is not recommended for skin decontamination.  Soap and water is the preferred method.

## Secondary Contamination

1-65. Secondary contamination is particularly worrisome from casualties recently exposed near the dissemination source where high levels of contamination may occur.  Since it will be difficult to distinguish those personnel exposed near the source from those contaminated some distance away, proper physical protection of health care providers or other persons handling exposed personnel should be maintained until decontamination is complete.

1-66. All casualties should be decontaminated at their unit; however, some may require immediate lifesaving care or may become contaminated en route to an MTF.  Potentially contaminated patients arriving at an MTF must be decontaminated before they are admitted into the clean treatment area. Medical personnel perform triage and provide emergency medical treatment in the patient decontamination area/site while supervising the decontamination personnel.  See FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3 and Air Force Medical Service in-place patient decontamination concept of operations for patient decontamination procedures.

Note 1.  Performing external decontamination does not necessarily mean the patient or casualty is noninfectious (not a carrier) and may still require isolation/quarantine. Note 2.  According to CDC guidelines, clothing should be handled as little as possible to avoid agitation and reaerosolization when conducting decontamination of persons exposed to anthrax.

## Treatment Principles

1-67. General supportive measures should be taken to lower body temperature, relieve pain, maintain spontaneous respiration, and secure intravenous (IV) access for the administration of drugs and fluids. Symptomatic treatment and treatment of coexisting injuries should follow established principles.

1-68. In the context of BW casualties, adherence to principles of patient isolation (such as barrier protection) is essential to preventing cross-infection with transmissible BW agent.  Separation of nonaffected individuals from contaminated victims of BW agent attack (such as cohorting, reverse isolation) and implementation of barrier protection procedures should be initiated as soon as practicable after a BW incident.  Cohorting is the imposed grouping of personnel (such as medical staff) potentially exposed to designated diseases while reverse isolation is where uninfected Service members are isolated from the infected population.

1-69.  All suspected BW casualties should be treated with medical countermeasures appropriate for the suspected BW agent-related disease. Empiric antibiotic therapy with at least one broad-spectrum antibiotic given parenterally in full therapeutic doses may be indicated depending on clinical presentations, differential diagnoses, specific threat or threats, and evidence or suspicion of antibiotic resistance.

1-70. The only broad-spectrum antiviral drug currently available for operational use is Ribavirin.  This compound has been a useful adjunct to the treatment of some potential viral threats when they have occurred under natural conditions (Lassa fever, Crimean-Congo hemorrhagic fever, and viral hemorrhagic fever with renal syndrome [HFRS]).  In addition, there is evidence of antiviral activity in vitro and in vivo against certain other viruses (influenza, Junin virus, Rift Valley fever virus), but little or no activity is seen with other (filoviruses, flaviviruses) agents. Ribavirin is available under an IND protocol for the treatment of arenavirus and bunyavirus hemorrhagic fevers.  Patients may be enrolled by contacting U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).  Other antiviral drugs, such as amantadine, acyclovir, and azidothymidine, are restricted in their therapeutic spectrum to single virus families and, thus, have little application as nonspecific antivirals.  Cidofovir and its oral derivatives are now IND for postexposure prophylaxis and treatment of some viruses (for example, smallpox).

1-71.  There is no current FDA-approved preexposure prophylaxis for botulinum at this time.  Through a CDC-sponsored FDA IND protocol, a new heptavalent botulinum antitoxin is available.  Heptavalent botulinum antitoxin contains equine-derived antibody and is the only botulinum antitoxin available in the U.S. for naturally occurring noninfant botulism.  Botulism immune globulin is an orphan drug that consists of human-derived botulism antitoxin and is approved by FDA for the treatment of infant botulism (types A and B).  This botulism antitoxin remains available through California Infant Botulism Treatment and Prevention Program.

## Investigational New Drugs And Emergency Use Authorizations

1-72. Personnel carrying out military operations shall be provided the best possible medical countermeasures to chemical, biological, radiological, or nuclear warfare or terrorism and other health threats.  Refer to DODI 6200.2 for more information.

1-73. The DOD components shall make preferential use of products approved by the FDA for general commercial marketing, when available, to provide the needed medical countermeasure.

1-74. Under emergency conditions, the heads of DOD components may request approval by the Assistant Secretary of Defense for Health Affairs to use an unapproved product under an emergency use authorization, or under an IND application if no satisfactory FDA-approved, cleared, or licensed medical product is available.  Such requests must be justified based on the available evidence of the safety and efficacy of the drug and the nature and degree of the threat to personnel.

## Mass Casualty Management This Paragraph Implements Stanag 2879

1-75. Biological warfare attacks have the potential to create mass casualty situations; that is, any large number of casualties produced in a relatively short period of time that exceeds the local medical support capabilities for their care.  There may be significant differences in the methods of providing basic medical care in mass casualty situations.
1-76. If physical facilities have been destroyed by other means of warfare, most civilian casualties will be cared for in the home, an area shelter, or a local medical facility; military casualties may well be treated by unit medical personnel rather than being moved to a hospital.  Unlike a typical mass casualty situation, few of these patients will require surgery.  However, the restriction of movement of contagious casualties by necessity would impact the medical estimate.  This would have a major influence on the required medical resources in theater.

1-77. There is likely to be great demand for intensive care facilities including both equipment and qualified personnel but the vast majority of patients will not require surgical procedures.  This is especially true of biological toxins where dramatic, acute signs such as respiratory paralysis would necessitate various types of advanced equipment (for instance, mechanical ventilators).

1-78. If the BW agent causes an illness that results in relatively few deaths (for example, VEE or Q fever), medical care can be effectively provided at the local level.  If the disease is one for which specific therapy such as antibiotics is indicated (for example, Tularemia), instructions for obtaining and administering the drug should be disseminated.  With a disease like yellow fever, with high mortality and for which no specific therapy is available, instructions for general supportive care that might be provided by nonmedical personnel should be disseminated.  The level of medical care required can only be precisely defined and planned for once the BW agent has been definitively identified.

1-79. Although many individuals becoming ill from an attack with a BW agent would likely present for medical evaluation over a short time span, all would not become casualties simultaneously, as they would for example, following saturation bombing or a massive surprise attack with nerve gas.  An exception to this pattern might be seen following an attack with a biological toxin.

1-80. Personnel potentially exposed to a BW agent can safely remain operationally active during the incubation period until the initial appearance of clinical signs.  However, if the agent is transmissible from human to human, they should be placed in quarantine during this period.

1-81. It may be necessary for one physician, with a small number of ancillary personnel, to care for several hundred patients.  Information could be disseminated about the normal course of the disease, the specific signs or symptoms of adverse prognostic significance, the situations requiring individual medical attention or advice, and the procedures for obtaining essential medical supplies.  This arrangement would allow a limited number of professional personnel to care for the maximum number of patients.  For more information regarding management and treatment of biologically contaminated casualties, refer to Appendix C.

## Psychological Effects

1-82. During a CBRN incident, many people are fearful of having been exposed to a BW agent, even though they are either at very low risk or have tested negative for exposure. The common term used to describe people in this situation is psychological effects or *worried well*. This term generally refers to people who are worried (or convinced) that they have been exposed to a BW agent, even though they are physically well and do not actually display the signs and symptoms of being exposed to a BW agent.
1-83. The actual cause is usually psychological, rather than medical, among psychological effects people.

Psychological problems commonly associated with personnel having psychological effects include


Clinical depression.

Severe anxiety disorders.

Phobias.

Obsessive-compulsive disorder.

Other psychological disorders.
1-84. A primary care or emergency medical care provider trained to manage BW cases should


Determine if a patient does or does not have a potential BW disorder/illness or psychological effects.

Use standardized triage and case definition protocols.

Follow established risk communication guidelines.
1-85. During the sarin gas release in the Tokyo subway system in 1995, the hospitals were presented with over 5,500 possible casualties.  Only 1,000 were casualties related to the attack and only 12 deaths were related to this catastrophe.  The total number of those who presented themselves to the hospital with complaints of postexposure symptoms exceeded the number who did require medical treatment caused by exposure.

1-86. The importance of the appropriate response to the psychological effects during a CBRN incident has to be considered.  Medical personnel and behavioral health treatment providers must be prepared to provide some level of treatment for individuals showing acute or transient emotional and behavioral signs and symptoms.  While the acutely ill patients have priority of treatment, attention must also be paid to the personnel with psychological effects. If these personnel are not cared for immediately, the command or community will experience behavioral health consequences, even long after the CBRN crisis is over.

## Handling Of Contaminated Human Remains

1-87. The handling of biologically contaminated remains within the medical system is a medical responsibility.  The handling, transport, and disposition of biologically contaminated remains on the battlefield or after removal from the medical system are not a medical responsibility, but a logistics function; however, medical expertise should be sought.  Considerations when handling contaminated human remains are as follows:


When dealing with contaminated human remains in the MTF, remains must be placed in leakproof and/or specific human remains pouches intended for containing contaminated body
parts and body fluid to include blood (for example, some remains pouches have absorbent pads
capable of neutralizing several types of microorganisms).  Once placed inside the remains pouch, the external areas should be cleaned with appropriate disinfectants according to the MTF standing operating procedures.  Moreover, contaminated human remains pouches should be clearly labeled/marked with a tag noting the type of biological hazard present (if known) and placed in a designated holding area.  In the event of leakage of bodily fluids, the remains should not be removed but placed in a second human remains pouch.  Then the outer pouch should be labeled/marked in the same manner as the initial human remains pouch.


General principles governing medical disposition of contaminated human remains at a patient decontamination site or casualty collection point include

Contaminated human remains are segregated from other casualties.

A temporary morgue area may be set up for holding remains while awaiting transportation
to a mortuary affairs contaminated remains mitigation system.

The human remains, as determined by the senior medical authority, are not evacuated with
other casualties, nor are they routinely evacuated on medical vehicles.

Department of Defense (DD) Form 1380, U.S. Field Medical Card, should be initiated and
securely attached to the remains, if possible.  The "OTHER" block should be checked and the type of BW agent present (if known) annotated in block 3.
1-88. Those charged with the responsibility for handling, transporting, and determining disposition of biologically contaminated remains must be cognizant of and utilize all means to minimize the risk of potential secondary transmission hazards.  Mortuary affairs personnel using proper IPE/PPE, search remains for personal effects and identification media (for example, identification tags, identification cards, wallet, credit cards, or supporting items) during remains processing.  The detailed mortuary affairs process for handling biologically contaminated remains is identified in JP 4-06.  As part of the mortuary affairs process, the Armed Forces Medical Examiner can direct that a deoxyribonucleic acid (DNA) specimen be harvested using an approved scientific method.  For more information, refer to Department of Defense Directive (DODD) 5154.24.  If the geographic combatant commander authorizes temporary interment, remains must be interred according to current procedures found in JP 4-06 until a determination is made regarding further disposition of the remains.  To minimize risk of transmission hazard, the following considerations should be taken:


Although the process has not been tested or approved, current evidence indicates that remains contaminated with spore-forming bacteria can be reliably sterilized only by gamma-ray irradiation or by electron beam.  However, alternative decontamination schemes may be employed which could reduce spore burdens to levels acceptable with regard to later transmission risk.

When transporting contaminated remains, an appropriate container that minimizes the risk of
onward transmission of BW agent or environmental contamination should be used.
1-89. In 2003, the Armed Forces Epidemiological Board conducted a systematic review of the medical and scientific literature pertaining to BW agent contaminated human remains.  Due to high risks involved, the board recommended not to autopsy or embalm BW agent-contaminated human remains with CDC Category A pathogens.  Tularemia, VHFs, smallpox, glanders, Ebola, and Q fever have been transmitted to persons performing autopsies; certain infections have been fatal.  All autopsies involve exposure to blood, a risk of being splashed or splattered, and a risk of percutaneous injury.  All autopsies generate fine aerosols which can create airborne particles that contain infectious pathogens not normally transmitted by the airborne route.  Refer to Technical Guide 195, Safety and Health Guidance for Mortuary Affairs Operations: Infectious Materials and CBRN Handling  for more information or go to http://phc.amedd.army.mil/topics/workplacehealth/ih/Pages/IHTechnicalGuides.aspx.

1-90. For index cases or in instances where the BW agent etiology is unknown, autopsy may be conducted using optimal containment, appropriate protective equipment, and disinfectant techniques.

## Restriction Of Movement, Isolation, And Quarantine

1-91. To prevent the spread of an infectious disease or contagious illness, public health authorities use different strategies.  Three of these strategies are:  restriction of movement, isolation, and quarantine.
These are common practices in public health and aim to prevent and control exposure to potentially infected or infectious persons.  The following measures may be voluntarily implemented or be a directive by public health authorities or by military commanders:


Restriction of movement refers to potentially infected persons and the restriction of their
movement to stop the spread of that illness.  Restrictions of movement may be implemented to prevent the spread of communicable diseases.  In the case of military personnel, restrictions of movement, including isolation or quarantine, or any other measure necessary to prevent or limit transmitting a communicable disease may be implemented.  In the case of persons other than military personnel, restrictions of movement may include limiting ingress and egress to, from, or on a military installation.

Isolation refers to the separation of persons who have a specific infectious illness from a healthy
population.  Isolation allows for the target delivery of specialized medical care to people who are
ill, while protecting healthy people from getting sick.  Infected people in isolation may be cared for in their homes, in hospitals, or in designated MTFs.

Isolation is a standard procedure used in hospitals for patients with tuberculosis and certain
other infectious diseases.  Although in most cases, isolation is voluntary; however, many levels
of government (federal, state, and local) and especially the DOD have basic authority to compel
isolation of sick people to protect the public.

Protective sequestration is a form of reverse isolation where uninfected Service members
are isolated from the infected population or contaminated environment as a tactical or strategic
reserve.  Protective sequestration is a measure or option that commanders may use after a CBRN incident.
Note.  Until diagnosis has been made, medical personnel must establish respiratory precautions.
Patients are infectious until proven otherwise.


Quarantine refers to the separation and restriction of movement of persons who, while not yet ill and have not shown signs and symptoms of the disease, have been exposed to an infectious agent and therefore may become infectious.  Quarantine involves the confinement and active,
continued health surveillance of an individual who is suspected of having been exposed to an infectious agent until determined that they are free of infection.  Quarantine is medically very
effective in protecting the public from disease.  For more information, refer to AR 40-12.
1-92. During a declared public health emergency, a commander, in consultation with the public health emergency officer, may exercise special powers relating to persons necessary to prevent the spread of communicable diseases.  To the extent necessary for protecting or securing military property or places and associated military personnel, such special powers may also include persons other than military personnel who are present on a DOD installation or other area under DOD control.  For more information, refer to DODD 6200.3, DODI 5200.8 and DODI 6200.3.

## Medical Evacuation

1-93. When preparing casualties for medical evacuation, attempts should be made to identify the agent in order to provide medical and casualty evacuation personnel additional information to protect themselves and patients from possible exposure to contagious diseases.  If available, analytical analysis of environmental samples and or attempts to perform early diagnosis based on clinical manifestations and rapid laboratory diagnostic tests (such as an enzyme-linked immunosorbent assays [ELISA] and/or polymerase chain reaction [PCR] tests) should be performed.  However, patient evacuation is dependent on patient acuity and should not be delayed pending field confirmatory results.

1-94. Potentially contaminated casualties should be decontaminated prior to evacuation; however, patients may have to be evacuated that have not been completely decontaminated.  Measures must be taken to prevent contamination of ground and air evacuation assets when evacuating potentially contaminated casualties.  Ground ambulances should be used first in a contaminated environment because they are easier to decontaminate than are air evacuation assets.  This does not preclude the use of air evacuation assets in a contaminated environment.  Commanders must evaluate the situation and make a determination as to which assets they will commit in the contaminated environment.  Already contaminated ground and air evacuation assets should be used first.  Only commit clean assets if they are required to meet the medical evacuation needs of the command.

1-95. Normally, patients that are air evacuated by USAF aircraft must be externally decontaminated prior to loading onto the aircraft.  In rare situations where decontamination is not possible due to the tactical situation, and such transport is deemed essential to preserve life or continue critical missions, the theater and U.S. Transportation Command commanders will determine whether USAF aircraft will be used for patient aeromedical evacuation.  Issues regarding the decontamination/quarantine of potentially contaminated USAF aircraft will also be determined at geographic combatant command levels.  Planners will ensure procedures are in place to assure patients, aircrew, and aircraft are appropriately protected.
Refer to FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3 and FM 4-02.2 for information regarding procedures on patient evacuation by USAF aircraft.

1-96. Once patients are externally decontaminated, further aeromedical evacuation decisions should be based on the actual or suspected clinical diagnosis as well as the patient's condition.  Since BW agent incubation times are variable, all patients should be considered potentially infectious during transport.  As a minimum, standard precautions as outlined in the CDC 2007 Guideline for Isolation Precautions:
Preventing Transmission of Infectious Agents in Healthcare Settings, will be followed.

1-97. Biological warfare attacks may occur with multiple agents with short and prolonged incubation times
(botulinum toxin, 12 to 36 hours and smallpox, 7 to 17 days).  Multiple agents can lead to the presence of an acute coinfection illness with short incubation period while incubating a disease with a longer incubation time like smallpox (which may declare itself after patients have been evacuated for evaluation/treatment of the short incubating disease).  Therefore, consideration should be given to quarantine patients for 17 days after aeromedical evacuation from the BW area if plague, VHF, or smallpox cannot be excluded. Reevaluate patients carefully for recurrent fever or other changes in clinical status.  If clinical or laboratory findings suggest prodromal or syndromic smallpox, plague, or VHFs, institute appropriate isolation until the diagnosis is clarified.

1-98. According to Presidential Executive Order 13375 and Section 361 of the Public Health Service Act, the Secretary of Health and Human Services in consultation with the Surgeon General, makes and enforces regulations necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the United States, or from one state or possession into any other State or possession. Diseases for which individuals may be quarantined, apprehended, detained, or released conditionally to prevent the introduction, transmission, or spread of communicable diseases are specified as follows:


Cholera; Diphtheria; infectious Tuberculosis; Plague; Smallpox; Yellow fever; and VHFs (Lassa, Marburg, Ebola, Crimean-Congo, South American, and others not yet isolated or named).

Severe acute respiratory syndrome which is a disease associated with fever and signs and
symptoms of pneumonia or other respiratory illness, is transmitted from person-to-person predominantly by the aerosolized or droplet route, and, if spread in the population, would have severe public health consequences.

Influenza caused by novel or reemergent influenza viruses that are causing, or have the potential to cause, a pandemic.
1-99. Many BW agent casualties may be safely evacuated using basic infection control guidelines.  Plague, smallpox, and the hemorrhagic fevers pose significant challenges.  These patient movements will require approval of the destination country, overflight privileges, and approval of any country where the aircraft will land for servicing or where patients will remain overnight.  Countries from which approval is sought are bound by Article 37 of the Geneva Convention (I) for the Amelioration of the Condition of the Wounded and Sick in Armed Forces in the Field of 12 August 1949 to ensure humanitarian treatment to wounded and sick.  That should include approval under most circumstances of transit of those injured by exposure to BW agents.  Additionally, some countries, notably Germany, have already developed procedures for expedited approval of transit of dangerous/hazardous goods in their air space.  That information is contained in DODD 4500.54E.  Coordination between the theater or U.S. Transportation Command commander/surgeon and the Department of State is required for such movements.

## Patient Isolation Unit

1-100. The patient isolation unit (PIU) provides a capability to move a small number of highly contagious patients through the aeromedical evacuation system.  In most situations, it is recommended that the necessary medical resources be moved to the event location (treat in place) rather than moving the contagious patient.  The PIU will enhance force protection by providing medical personnel the capability to transport contagious patients without fear of contamination to caregivers, other patients, passengers, and transport vehicles.  The PIU will be light enough for use in the field and rugged enough to support movement through the DOD patient movement system.  Evacuation of potentially contagious patients requires close coordination with multiple agencies both military and civilian (such as the Department of State and CDC).  The PIU will be strategically placed at locations based on risk vulnerability to a pathological event and is not intended to be included in the patient movement items inventory.  The USAF Critical Care Air Transport Team is now responsible for the transport of a highly contagious patient that has been exposed to a biological contaminant and to prevent further contamination to the medical staff and the environment.

1-101. The procurement of more PIUs does not mean that more biologically contaminated/contagious patients can or will be transported to MTFs.  Factors such as the theater CBRN evacuation policy, the aeromedical evacuation crew's PIU level of training, and most importantly, the ability of a destination facility to accept them have to be considered.  For more information on PIU, refer to FM 4-02.7/MCRP
4-11.1F/NTTP 4-02.7/AFTTP 3-42.3.

## Chapter 2 Recognition Epidemiology

2-1. With current technology, it is likely that a BW attack will be completed before the local commander, or his medical advisor, is aware that it has taken place.  The medical officer must attempt to distinguish between an epidemic of natural origin and a BW attack.  Specific considerations include


Biological warfare agents may be delivered overtly.

Sick individuals may be the initial indication that an attack has occurred.  Distinguishing a BW attack from background endemic disease may be difficult under some circumstances.  Mixed infections, more than one BW agent used concurrently, or intoxications may occur, thereby complicating or delaying diagnosis.

A large number of casualties may occur during a short period of time.

In a given geographic area, both military and civilian casualties will occur; effects on animals
may be the first sign of an attack.

Targets may be large geographical areas or smaller tactically important objectives.  The size of
an area in which casualties occur can help narrow the list of likely agents.  For example, certain BW agents, like toxins, can be used most effectively on smaller targets, while others can be disseminated effectively over extremely large areas (for example, anthrax spores).

Rapid detection and definitive identification of suspected BW agents are essential for tactical, political, and forensic, as well as medical purposes.

In the operational environment, atmospheric conditions are critical to the effective use of BW agents.  In general, the optimal time for use of BW weapons is during late night and early morning.  It is during these hours that inactivation of BW aerosols by ultraviolet radiation is
minimal.  In addition, neutral or inversion meteorological conditions are most likely to be present at these times.  The phenomenon of atmospheric inversion best allows an agent cloud to travel along the land surface.

Environmental conditions within buildings can impact the effectiveness of a BW agent release.
Examples includeairflow, climate control system, and activity of exposed personnel.
2-2. Determining who is at risk and making appropriate decisions regarding prophylaxis, as well as other response measures after a biological weapon attack, will require the tools of epidemiology.  With a covert attack, the most likely first indicator of an event will be an increased number of patients presenting to individual care providers or MTF with clinical features caused by the disseminated disease agent.  The possibility exists that the recognizing authority for something unusual may be other medical professionals. For example, pharmacists or laboratory personnel may receive more than the usual numbers of prescriptions or requests for laboratory tests from a number of different care providers.  Since animals may be sentinels of disease in humans and many of the high-threat BW agents discussed in this book are zoonoses, it is possible that veterinarians might recognize an event in animals before it is recognized in humans.

Note.  Veterinary/PVNTMED/public health personnel may collect samples from suspect contaminated food and perform field clinical and postmortem examinations
(autopsies/necropsies) on suspect animals for specimen collection and laboratory analysis.

2-3. An understanding of disease ecology and epidemiology can be extremely useful in distinguishing natural outbreaks from those induced by BW agent weapons.  For example, diseases that are naturally vectorborne will have environmental parameters that predispose to naturally occurring outbreaks.
Appearance of disease in the absence of these parameters would be highly suggestive of a BW attack.  For more information regarding recognition of BW agent casualties, refer to Appendix D.

2-4. A sound epidemiologic investigation of a disease outbreak, whether natural or human-engineered, will assist medical personnel in identifying the pathogen and lead to the institution of appropriate medical interventions.  Identifying the affected population, possible routes of exposure, signs and symptoms of disease, along with rapid laboratory identification of the causative agents, will greatly increase the ability to institute an appropriate medical and public health response.  Good epidemiologic information can guide the appropriate follow-up of those potentially exposed, as well as assist in risk communication and responses to the media.  Many diseases caused by BW agents present with nonspecific clinical features that may be difficult to diagnose and recognize as a biological attack.  Features of the epidemic may be important in differentiating between a natural and a terrorist or warfare attack.  Epidemiologic clues that may indicate an intentional attack are listed in Table 2-1.  While a helpful guide, it is important to remember that naturally occurring epidemics may have one or more of these characteristics and a BW attack may have none. However, if many of the listed clues are recognized, one's index of suspicion for an intentionally spread outbreak should increase.

-
The presence of a large outbreak with a similar disease or syndrome, especially in a discrete

population.
-
Many cases of unexplained diseases or deaths.
-
More severe disease than is usually expected for a specific pathogen or failure to respond to

standard therapy.
-
Unusual routes of exposure for a pathogen, such as the inhalational route for diseases that normally

occur through other exposures.
-
A disease that is unusual for a given geographic area or transmission season.
-
Disease normally transmitted by a vector that is not present in the local area.
-
Multiple simultaneous or serial outbreaks of different diseases in the same population.
-
A single case of disease by an uncommon agent (for example, smallpox, some viral hemorrhagic

fevers, inhalational anthrax, or pneumonic plague).
-
A disease that is unusual for an age group.
-
Unusual strains or variants of organisms or antimicrobial resistance patterns different from those

known to be circulating.
-
A similar or exact genetic type among agents isolated from distinct sources at different times and or

locations.
-
Higher attack rates among those exposed in certain areas, such as inside a building if released

indoors, or lower rates in those inside a sealed building if released outside.
-
Disease outbreaks of the same illness occurring in noncontiguous areas.
-
A disease outbreak with zoonotic impact.
-
Intelligence of potential attack claims by a terrorist, aggressor, nonstate entities, or individual actors

of a release and discovery of munitions, tampering, or other potential vehicle of spread (for

example, spray device or contaminated letter).
2-5. Once a BW agent attack or any outbreak of disease is suspected, the epidemiologic investigation should begin.  There is also a requirement to report occurrence through higher channels, especially to public health channels.  For more information, refer to medical reporting section in this chapter.  Although the conduct of the investigation will not differ significantly whether the outbreak is intentional or not, there are some important differences.  Because the use of a biological weapon is a criminal act, it will be very important for the evidence gathered to be able to stand up to scrutiny in court.  Therefore, samples must be handled through a strict chain of custody and there must be good communication and information sharing between public health, the Federal Bureau of Investigation, and other law enforcement authorities.

In addition, if the attack is intentional, one must be prepared for the unexpectedthere is the possibility of multiple outbreaks at different locations, as well as the use of multiple different agents, including mixed chemical and BW agents or multiple BW agents depending upon the intentions of the perpetrator.

2-6. The first step in the investigation is to confirm that a disease outbreak has occurred.  An outbreak generally means there is a higher rate of an illness than is normally seen in a specific population.  It is helpful to have background surveillance data to determine whether what is being seen constitutes a deviation from the norm.  For example, in midwinter thousands of cases of influenza may not be considered an outbreak, whereas in the summer, it might be highly unusual.  In addition, even a single case of a very unusual illness, such as inhalation anthrax, might constitute an outbreak and should be viewed with suspicion.  The clinical features seen in the initial cases can be used to construct a case definition to determine the number of cases and the attack rate (the population that is ill or meets the case definition divided by the population at risk).  The case definition allows investigators who are separated geographically to use the same criteria when evaluating the outbreak.  The use of objective criteria in the case definition is critical to determining an accurate case number, as additional cases may be found and some cases may be excluded, especially as the potential exists for hysteria and subjective complaints to be confused with actual disease.

2-7. Once the attack rate has been determined, the outbreak can be described by time, place, and person.
These data will provide crucial information in determining the potential source of the outbreak.  The epidemic curve is calculated based upon cases over time.  An epidemic curve is a graphical depiction of the number of cases of illness by the date of onset of an illness.  See Figure 2-1 for an example of an epidemic curve.  It can provide the following information of an outbreak


Pattern of cases over time.

Magnitude.

Time.

Incubation periods.
2-8. In a point-source outbreak, which is most likely in a biological attack or terrorism situation, individuals are exposed to the disease agent in a fairly short time frame.  The early parts of the epidemic curve may be compressed compared to a natural disease outbreak.  In addition, the incubation period could be shorter than what is seen with a natural outbreak if individuals are exposed to higher inoculums of the agent than would occur in the natural setting.  The peak may occur in days or even hours.  Later phases of the curve may also help determine if the disease is able to spread from person-to-person.  Determining whether the disease is contagious will be extremely important for determining effective disease control measures.

2-9. Once the disease is recognized, appropriate prophylaxis, treatment, and other measures to decrease disease spread, such as isolation (if needed for a contagious illness) would be instituted.  The ultimate test of whether control measures are effective is whether they reduce ongoing illness or spread of disease.

2-10. The recognition of and preparation for a biological attack will be similar to that for any infectious disease outbreak, but the surveillance, response, and other demands on resources will likely be of an unparalleled intensity.  Public anxiety will be greater after an intentionally caused event; therefore, a sound risk-communication plan that involves public health authorities will be vital to an effective response and to allay the fears of the public.  A strong public health infrastructure with an effective epidemiologic investigating capability, practical training programs, and preparedness plans are essential to prevent and control disease outbreaks, whether they are naturally occurring or intentional.

## Warning And Detection

2-11. Adequate, accurate, and timely intelligence is required in order to develop an effective defense against BW.  Biological warfare agent aerosol detectors can be configured to detect general hazards or specific agents.  The positioning of detectors and their sensitivity critically affects their performance.  They should be deployed as a network and may be described as located relative to personnel in two ways


Upwind of personnel in order to give prior warning of an attack before exposure occurs.

Collocated with personnel to confirm that exposure has occurred and ensuring to provide a detect-to-warn capability.
Note.  It should be noted that a single detector may act in both ways simultaneously in a near real-time basis for personnel in different locations.

2-12. Human beings are sensitive, and in some cases, the only biodetector after an undetected BW agent.
The first sign of an event may be the appearance of casualties (military or civilian, human or animal).  The earlier that patterns of an emerging outbreak of a disease are recognized, the greater is the chance of protecting Service members who have not yet developed symptoms.  Advanced medical surveillance and epidemiological reporting systems with collation and analysis of data can be used to identify spikes of disease on a real-time basis.  The background level of naturally occurring BW diseases is a critical information requirement for epidemiological reporting.  These systems also play an important part in the subsequent assessment and management of a recognized attack.  In this context, medical surveillance of unusual outbreaks of diseases in the theater of operations is important.

2-13. Medical requirements resulting from attacks with BW agents may be substantially different from those resulting from conventional, nuclear, or chemical combat.  In most tactical situations, there would be no indication of the presence of BW agents.  The ability to estimate possible casualties and contingency requirements and treatments would assist in the determination of the magnitude of a BW attack.  Planning considerations for casualty estimation guides and models are as follows:


Exposure guidelines, casualty estimation guides (refer to AMedP-8), and computer models based on the guides fielded by some nations, integrate current available information (operational scenario, agent type, delivery type, attack intensity, and atmospheric conditions) and predict the possible effects of future BW agent attacks on specific populations at risk.

The primary purpose of these estimations and models is to predict the appropriate level of
medical management (triage, treatment, and supportive care) of the BW casualties and the
contingency requirements for medical personnel, medical materiel, stockpiles, patient transport or evacuation capabilities, and facilities needed to perform treatment and supportive care.  Refer to Appendix C for more information on medical management.

Since there are an unlimited number of attack variables, only a few scenarios can be modeled to provide useful estimates.  For the cases not modeled, only provisional guidance for estimates can be provided.  The command surgeon or medical planners may need to amplify or modify
estimations to meet emergent requirements as a result from combined attack (such as biological and conventional).

## Surveillance

2-14. In order to recognize any unusual changes in disease occurrence, surveillance of background disease activity must be ongoing and any worrisome variation should be promptly investigated.  Additionally, analytical methods must achieve the best balance between sensitivity and specificity, with the balance leaning toward sensitivity in order to avoid missing any serious events.  The downside of an overly sensitive surveillance system is false positive alerts.  To counterbalance this problem, the ability to quickly, and accurately, determine the validity of the outbreak, its extent, and its cause, is essential.
2-15. The DOD has its own syndromic surveillance system, called Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE).  This system collects data from health encounter recordssuch as the International Classification of Diseases codes; orders for laboratory and radiology tests; and medications dispensed through pharmacies.  The application then groups the data into defined syndromes, such as influenza-like illness, fever, and GI illness.  These syndromes are broad-based and capture events with similar signs and symptoms, for example, influenza-like illness consists of events where fever, sore throat, and/or cough were prominent, the same constitution of symptoms produced by many BW agents.  These data travel daily from the DOD's MTFs to a central collection site.

2-16. Though syndromic surveillance can provide early evidence of outbreaks, it is most effective at characterizing an event and providing ongoing medical situational awareness.  Syndromic surveillance cannot definitively identify the source or specific pathogen involved in an event.  This can be especially challenging if genetically tailored and/or multiple BW agents are used simultaneously, or chemical and BW agents are combined in a single attack.  Rapid coordination with clinical and public health laboratories is essential to validating that an outbreak is *real* and characterizing it sufficiently to allow for a meaningful response.
2-17. No single surveillance system fits every situation.  For instance, many BW agents also cause disease in animal populations.  Examples of complementary DOD health surveillance systems, and their parent organizations, include:  medical intelligence (National Center for Medical Intelligence); sentinel mortality surveillance (Office of the Armed Forces Medical Examiner); and laboratory-based surveillance to identify emerging, re-emerging, or changing pathogens, such as the DOD Global Influenza Surveillance program (part of the Global Emerging Infections Surveillance and Response System within the Armed Forces Health Surveillance Center [AFHSC]).  For additional information about health surveillance in the DOD, both in garrison and deployed settings, the reader is referred to DODD 6490.02E, DODI 6490.03, and Memorandum for the Chairman (MCM) 0028-07.

## Sample Collection Diagnosis

2-18. General policies for collecting samples in order to facilitate identification of BW agents are essential.
The accurate clinical findings may be critical in alerting other units to both the probability and nature of a BW attack.  Unfortunately, attempts to reach a firm diagnosis on clinical grounds alone may not be productive.  However, rapid isolation and differential identification of the BW agent is of prime importance for patients and risk management.  Emerging technology will likely provide provisional diagnostic capabilities locally.  However, establishing a definitive diagnosis will often require specialized laboratory facilities.

## Medical Sampling Principles

2-19. Medical responsibilities normally are limited to collection and submission of diagnostic materials from patients.  When specialized diagnostic systems are available, specimens of blood and other body fluids can be taken to allow rapid agent identification.  Swabs of contaminated areas such as the nose or throat can also be employed.  The type of sample taken depends on the deployed laboratory equipment. General principles of the collection and processing of medical specimen can be found in Appendix A.

## Environmental Sampling

2-20. The collection of environmental samples is an important element in corroborating the occurrence of a BW attack and involves other agencies.  Rapid sampling and analysis is preferred.  Close coordination and cooperation between CBRN and medical personnel will be vital to optimize sampling.

## Accredited Laboratories

2-21. Samples must be identified at laboratories using an accredited testing method.  The Laboratory Response Network was established by the Department of Health and Human Services, CDC, according to Presidential Decision Directive 39.

2-22. For more information on identification, diagnostic and detection systems, refer to Chapter 6 and Appendix D.

## Medical Reporting Reporting Of Notifiable Medical Conditions

2-23. Health officials of the U.S. Armed Forces medical departments are required to centrally report all occurrences of conditions with urgent or significant public health and/or military operational implications. Conditions considered notifiable are specified in the Tri-Service consensus list of reportable medical events.  Surveillance of notifiable events is an important part of the health surveillance programs of the Service medical departments.  Each of the medical departments uses a different system for reporting and tracking reportable conditions at their supported installations.  For more information on the Tri-Service consensus list of reportable medical events, go to: http://afhsc.army.mil/reportableEvents.

2-24. It is imperative that clinicians report cases of suspected BW-related illnesses to the appropriate line and medical chains of command.  Prompt epidemiological investigations must begin and preventive measures implemented to control the disease or reduce the number of cases.

2-25. Since 2010, the U.S. Army Medical Department has conducted reporting of notifiable medical conditions through the Web-based Disease Reportable System internet.  In 1998, the USN and USAF
medical departments began automated reporting of notifiable medical conditions through the Navy Disease Reporting System and Air Force Reportable Events Surveillance System, respectively.  Notifiable event case reports from all of the Services are forwarded to the AFHSC for incorporation in the centralized Defense Medical Surveillance System (DMSS).  Theater reporting procedures should also be in accordance with combatant commander's guidance and International Health Regulations.

## Reporting Medical Events And Epidemiological Assessment

2-26. Reportable medical events should be collected, reported, distributed, and archived according to DOD
and Service-specific policies.  The DOD health surveillance requirements should be met for reporting and archiving of health surveillance data and reports (disease and injury, reportable medical events, occupational and environmental health surveillance data, and so forth).  Additionally, the CBRN warning and reporting network should be employed to keep combatant commanders and the Services informed. Documentation in the individual medical records of all individual health treatment should be provided at all roles of care and any significant occupational and environmental exposures should also be documented.
2-27. According to MCM 0028-07, a reportable medical event is an event that meets the following criteria and may be defined by the supported combatant command or subordinate organization


There must be a clear case definition and a single standard code (from the International
Classification of Diseases, 10th revision, http://www.cdc.gov/nchs/icd/icd10cm.htm).

An intervention must be available and/or a public health response indicated.

The condition/event must also meet one of the following criteria

It represents an inherent, significant threat to public health by having the potential to affect
large numbers of people, to be widely transmitted within a population, or to have severe/life threatening clinical manifestations.

It represents a significant military operational threat by having the potential to disrupt
military training, deployment, or operations.

It is commonly reportable by state or federal laws, regulations, or guidelines.

See MCM 0028-07 and go to: http://afhsc.army.mil/reportableEvents for the current Tri-Service
Reportable Medical Event List.  Also for more information, refer to MCM 0026-02, DODI 6490.03, and DODI 6200.03.
2-28. Exposures to occupational and environmental health hazards that may result in some clinically relevant adverse health outcomes to exposed individuals as determined by an appropriate medical/health professional should be reported.  These include situations where specific occupational and environmental health hazards are determined to


Present a moderate or higher level of operational risk based on quantified occupational and environmental health data that indicate acute effects are anticipated.

Be plausibly and causally associated with actual observed (acute) clinical health outcomes that
are reported and/or treated even in the absence of quantitative exposure data and/or an actual occupational and environmental health risk assessment being performed.

Present a low risk because onset of associated health outcomes would occur postdeployment but where the confidence is high that such a latent long-term (chronic) health impact has been strongly associated with exposures of similar magnitude and duration.  For example, the use of facilities with substantial friable asbestos as the official (1-year) living/working quarters for a
deployed unit may be a low risk relative to the acute impacts to the mission.  However, the asbestos exposure could be deemed significant if toxicological and or epidemiological scientific evidence supports high confidence exposures of similar magnitude and duration are strongly associated with the development of disease (for example, asbestosis or mesothelioma).  Most low risk exposures associated with potential long-term chronic health effects will not be considered significant because available scientific data does not support extrapolation of the dose-response curve to low exposures with any degree of confidence in the predictive value.
2-29. Combatant commands will forward copies of the reports to the Defense Occupational and Environmental Health Surveillance data portal at oehs@apg.amedd.army.mil or the portal Web site at https://doehsportal.apgea.army.mil for archiving.

## Vaccine Adverse Event Reporting System

2-30. The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety surveillance program cosponsored by the CDC and the FDA.  The VAERS is a safety surveillance program, collecting information about adverse events (possible side effects) that occur after the administration of vaccines licensed for use in the U.S.

2-31. A Form VAERS-1 must be completed and submitted using Service reporting procedures for those events resulting in a hospital admission or time lost from duty for greater than 24 hours or for those events suspected to have resulted from contamination of a vaccine lot.  Health care providers are encouraged to report other adverse events that in the provider's professional judgment, appear to be unexpected in nature or severity.  In addition, the patient or a health care provider may submit a Form VAERS-1 directly to the FDA for any possible adverse event.  The VAERS report forms may be accessed at the MILVAX Web site at www.vaers.hhs.gov or by calling VAERS at 1-800-822-7967.

## United States Public Health Biological Warfare Monitoring And Assessment National Biosurveillance Integration System

2-32.  The National Biosurveillance Group provides decisionmakers early recognition of biological events of potential national significance, to include natural disease outbreaks, accidental or intentional use of BW
agents, and emergent biohazards through the acquisition, integration, analysis, and dissemination of information from existing human disease, food, agriculture, water, meteorological, and environmental surveillance systems and relevant threat and intelligence information.  The resulting improved information sharing and enhanced situational awareness facilitates national decisionmaking to enable timely response.

2-33. The 9/11 Commission recommended the creation of a National Biosurveillance Integration Center
(NBIC), which was included in the Implementing Recommendations of the 9/11 Commission Act of 2007. This Act requires that Department of Homeland Security ensures NBIC has the ability to rapidly identify, characterize, localize, and track a biological event of national concern with the goal being real time or near real time. The bioterrorism threat presents a risk to the population, economy, or infrastructure of the U.S.
Section 1101 of the Act requires NBIC to operate by integrating and analyzing data relating to human health, animal, plant, food, and environmental monitoring systems and must be fully operational by September 30, 2008.  According to NBIC, their strategy to ensure that national biosurveillance information is integrated, the following agencies were considered critical and should be represented:  Department of Homeland Security; Department of Commerce; DOD; Environmental Protection Agency; Department of Health and Human Services; Department of the Interior; Department of Justice; Department of State; Department of Transportation; U.S. Postal Service; Department of Veterans Affairs; as well as state, local, private sector, and international partners.

## Biowatch

2-34. In response to the 2007 law, the Department of Homeland Security is developing two initiatives to enhance national preparednessNBIC and the BioWatch program.  The NBIC is intended to be a center where information on biological events can be integrated and coordinated.  BioWatch will operate systems and detectors nationwide, which will be used to test the air for BW agents.  BioWatch continues to  work towards developing and acquiring technologies that can provide real-time or near real-time information about a biological release.

## Biophusion

2-35. BioPHusion's mission is to provide a CDC-wide resource that facilitates the exchange, integration, and visualization of relevant information from a variety of sources to enhance agency and programmatic situational awareness for decisionmaking and early-event detection.

2-36. BioPHusion is not a data generator.  The integration or *fusion* of public health information is derived from existing CDC programs, external partners, or other sources to


Increase situation awareness.

Improve early event detection.

Support decision-making to protect the public's health.

## Biosense

2-37. As mandated in the Public Health Security and Bioterrorism Preparedness and Response Act of
2002, the CDC BioSense program was launched in 2003 to establish an integrated national public health surveillance system for early detection and rapid assessment of potential bioterrorism-related illness.
2-38. In fiscal year 2010, CDC started redesigning the BioSense program based on input and guidance from local, state, and federal partners.  The goal of the redesign is to create a new BioSense, which coordinates and links existing health monitoring surveillance systems to enable rapid and enhanced interchange of information and improvement of BioSense's utility through a user-centered approach.  The key components of the BioSense program redesign are


Assist in building health monitoring infrastructure and workforce capacity where needed at the
state, local, tribal, and territorial levels.

Facilitate the interchange of information that can be used to coordinate responses and monitor health-related outcomes routinely and during an event.

Retain the original purpose of BioSense to detect and characterize events (or health-related
threats) early by building on state and local health departments systems and programs.

Expand the utility of BioSense data to multiuse [and all-hazard] beyond early event detection.

Improve the ability to detect emergency health-related threats by supporting the enhancement of systems to signal alerts for potential problems.

Increase local and state jurisdictions participation in BioSense.

## Department Of Defense Chemical/Biological Defense Program

2-39. The DOD Chemical Biological Defense Program provides oversight authority for all aspects of Chemical Biological Defense.  Working with the Services and combatant commanders, the Joint Staff 8/
Joint Requirements Office for CBRN Defense identifies and documents the needed CBRN capabilities for DOD.  The Joint Program Executive Office for CBRN Defense is the advanced developer and acquisition source for the Chemical Biological Defense Program.  Several program offices within the Joint Program Executive Office oversee programs providing biological defense capabilities.

2-40. The Joint Project Manager for Biological Defense provides defensive equipment and technology to detect and identify biological threats in near real time, and collect and assimilate data for commanders who require an understanding of the biological threat situation in their area of operation. The biological defensive systems are critical to the areas of *Sense, Shape, Shield, and Sustain*, and meet the needs of U.S.

forces to warn personnel of imminent hazards (preattack) and aid in the treatment of personnel exposed to a biological hazard (postattack).  The following are BW agents programs of records


The Joint Biological Standoff Detection System provides commanders the first joint early warning system to detect BW agents in near real time. The system offers standoff detection, ranging, tracking, and discrimination (agents of biological versus nonbiological origin) of aerosol clouds.  The system will be configured for both mobile and fixed site platforms to meet the needs of the Joint Services.

The Dry Filter Unit is a commercial ambient air sampler that is used in and around critical facilities.  The Dry Filter Unit is housed in a rugged container and is available in multiple
configurations.  Depending upon configuration, it is portable by one or two persons and is simple to set up, use, maintain, and train.

The Biological Integrated Detection System integrates detection, communication, power, and environmental control equipment into a mobile suite.  The M31-series generations of the Biological Integrated Detection System offer either manual, semiautomatic and fully automatic detection and identification capabilities, respectively, for CBRN units across the world.

The Joint Biological Point Detection System is a modular suite of equipment that provides commanders detection and presumptive identification of BW agents in near real time.  The suite fully automates the biological detection and warning, sample collection, and identification functions.  The system is available in various configurations and is compatible with the requirements of each of the four Services.
2-41. The Joint Program Manager for Chemical Biological Medical Systems is the advanced developer and acquisition source for CBRN medical countermeasures, such as vaccines, prophylaxes, and therapeutic treatments for BW agents.  Chemical Biological Medical Systems also developed and manages the Joint Biological Agent Identification and Diagnostic System program of record and is now completing advanced development of the Next Generation Diagnostic System.

2-42. The Joint Program Manager for Consequence Management, in concert with Joint Program Manager for Chemical Biological Medical Systems and Joint Project Manager for Biological Defense, is developing

## Chapter 2

the Common Analytical Laboratory System program of record.  The Common Analytical Laboratory System will provide a common, integrated mobile modular laboratory to Service units which currently perform CBRN field analytics in a variety of field laboratories.


## Chapter 3 Bacterial Agents Bacterial Organisms

3-1. Bacterial organisms comprise the greatest number of pathogens in the list of potential BW agents.
They include the etiologic agents of anthrax, brucellosis, cholera, glanders, melioidosis, plague, Q fever, and tularemia.  Of these, anthrax is the most likely BW threat that troops will encounter in an area of operations.  See Appendix C for guidance on medical management of BW agent casualties.

Note.  Many of the pathogens may be produced in a laboratory for BW purposes, using a single cell, or a small amount of the organism from a natural source.

## Anthrax Etiologic Agent

3-2. The spores of *Bacillus anthracis* is an encapsulated gram-positive bacillus.  Sporulation occurs under adverse environmental conditions. The spores are extremely hardy and can survive extremes of temperature, dryness, and flooding.  When conditions improve, the spores germinate to produce vegetative bacteria.

## Reservoir

3-3. The soil; with worldwide distribution.

## Transmission

3-4. The stage in the bacterial life cycle which poses a health hazard is the spore.  Grazing animals contract spores from the vegetation.  Humans contract spores via contact with infected animals, their hides, wool, or other products; from ingesting contaminated meat; or from inhaling spores during the processing of wool for textiles.  Biting flies in sub-Saharan Africa may also transmit anthrax to humans.  Humans usually do not contract anthrax directly from the soil, unless they work with fertilizers (bonemeal) prepared from infected animals.  Humans can contract anthrax from inhalation of aerosolized spores released during a BW attack.

## Endemic Disease

3-5.  Endemic infectious disease is contracted by cutaneous exposure, ingestion, and inhalation.  The three routes by which infection anthrax can be contracted are discussed below:


Cutaneous anthrax accounts for more than 90 percent of all anthrax cases worldwide.  Disease results when *Bacillus anthracis* spores are introduced into the skin via inoculation of small cuts/abrasions or inapparent skin lesions.  It may possibly be introduced by biting flies. Cutaneous anthrax features a painless necrotic ulcer with a black eschar and local edema.  The case-fatality rate for untreated cutaneous anthrax is up to 20 percent, but with early effective
therapy is reduced to less than 5 percent.

Oropharyngeal and GI diseases occur following the ingestion of anthrax spores, usually from consuming meat from infected animals.

Inhalation anthrax occurs when individuals working with animal hides, wool, or bonemeal inhale the spores.  Also, inhalation anthrax may occur from inhalation of aerosolized spores released during a BW attack.

## Biological Warfare Agent Delivery

3-6. Aerosolized spores may be delivered by missiles, bomblets, artillery fires, point release, or airborne line release.  Contamination of food and water may also be used.  In the fall of 2001, anthrax spores were delivered in the U.S. mail by sending letters with powder containing anthrax spores, resulting in 22 cases of confirmed or suspected anthrax disease (including five deaths).

## Environmental Detection

3-7. The CBRN reconnaissance teams collect aerosol and surface samples; medical personnel collect medical specimens; PVNTMED/veterinary/public health personnel collect suspect or contaminated food samples; and PVNTMED/public health/bioenvironmental engineering personnel collect suspect or contaminated water samples for supporting laboratory analyses and confirmations.  Veterinary personnel may collect specimens from animals for laboratory analysis and confirmation.

## Prevention Preexposure Prophylaxis

3-8. Prevention may be accomplished by immunization plus chemoprophylaxis.  Anthrax vaccine is given in five doses at 0 and 4 weeks and 6, 12, and 18 months, with annual boosting.  Currently, there are no FDA-approved preexposure protocols for chemoprophylaxis.

## Postexposure Prophylaxis

3-9. Use immunization with chemoprophylaxis to prevent the clinical manifestation of the disease.
Information regarding postexposure prophylaxis is discussed below:


There are no FDA-approved vaccine protocols for postexposure prophylaxis.
Note: For personnel who have not received the anthrax immunizations as part of their profile, begin five-dose series.  Personnel who have received at least three initial doses within 6 months prior to exposure, no additional doses are indicated, except to complete the series.


Chemoprophylaxis is recommended as an adjunct to immunization for postexposure prophylaxis.  Ciprofloxacin hydrochloride tablets (500 milligram [mg]) should be taken orally every 12 hours for at least 60 days.  When ciprofloxacin hydrochloride tablets are not available,
doxycycline hyclate tablets (100 mg) should be taken orally every 12 hours for at least 60 days. The duration of chemoprophylaxis administration for individuals without receipt of any vaccine should be extended until they receive at least three doses of vaccine.  Chemoprophylaxis should be withdrawn under careful observation and with access to an MTF with intensive care and
consultative assets.  If fever develops following the withdrawal of chemoprophylaxis, empiric therapy for anthrax is indicated pending etiologic diagnosis.

## Biological Warfare Clinical Presentation Incubation Period

3-10. The average incubation period for inhalational anthrax is 7 days (range 1 to 43 days).

## Signs And Symptoms

3-11. Inhalation anthrax begins with nonspecific sign/symptoms of fever, malaise, and fatigue (Table 3-1).

A nonproductive cough and vague chest discomfort may be present. These initial sign/symptoms may be followed by a prodromal phase usually 2 to 4 days in duration. Table 3-2 shows inhalation anthrax cases systematic review.  The acute phase is complicated by bacteremia, toxemia, septic shock, and metastatic infection such as meningitis.  Death usually occurs within 24 to 36 hours in most untreated patients from the onset of the acute phase.  In the 2001 U.S. anthrax attack, in the treated patients, the mortality rate was
45 percent.

*Symptoms for 10 patients with inhalational anthrax identified during the 2001 U.S.
outbreak:
Fever, chills (100%) (7 were febrile on initial presentation)

Sweats, often drenching (70%)

Fatigue, malaise, lethargy (100%)

Cough (minimally or nonproductive) (90%)

Nausea or vomiting (90%)

Dyspnea (80%)

Chest discomfort or pleuritic pain (70%)

Myalgia (50%)

Headache (50%)

Confusion (40%)

Abdominal pain (30%)

Sore throat (20%)

Rhinorrhea (10%)

*Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.

*A systematic review of 82 inhalational anthrax cases reported between 1900 and 2005
found that most common symptoms or findings on admission included the following:
Abnormal lung findings (80%)

Fever or chills (67%)

Tachycardia (66%)

Fatigue or malaise (64%)

Cough (62%)

Dyspnea (52%)
All 26 patients who had chest radiography had abnormal findings, including pleural effusion (69%) or widened mediastinum (54%)

*Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.


3-12. Oropharyngeal or GI anthrax can occur following ingestion of food contaminated with anthrax spores.  Signs and symptoms of oropharyngeal anthrax are discussed below:


Oropharyngeal anthrax will present with initial symptoms of fever, sore throat, and difficulty swallowing.  The disease may progress to an acute phase with symptoms including a necrotic ulcer or eschar involving the hard palate, tonsils, or posterior oropharyngeal wall, edema of cervical tissues (possibly resulting in upper airway obstruction), and cervical lymphadenopathy.
Most acute cases progress to septic shock and death.  Refer to Table 3-3 for a gastropharyngeal anthrax cases systematic review in Thailand.

*One outbreak of oropharyngeal anthrax in Thailand demonstrated the following findings for 24 patients:
Neck swelling (100%)

Fever (96%)

Sore throat, dysphagia (63%)

Mouth or pharyngeal ulcerative or necrotic lesions (100%) (pseudomembranes

also were noted in some patients)

Respiratory distress (25%)

Hoarseness (8%)

Sensation of a "lump in throat" (8%)

Diarrhea (4%)

Bleeding from the mouth (4%)

*Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.



Gastrointestinal anthrax begins with vague initial symptoms featuring fever, anorexia, nausea, and vomiting.  Abdominal pain, bloody vomiting, bloody diarrhea, and possibly massive abdominal swelling (ascites) may follow these symptoms.  Also, septic shock and death may follow these symptoms.  Refer to Table 3-4 for a GI anthrax case systematic review in Uganda.


*One outbreak in Uganda demonstrated the following findings in 143 patients:
Fever (may be low-grade) (70%)

Abdominal tenderness (85%)

Diarrhea (80%; bloody in only 5%)

Vomiting (may be coffee-ground or blood-tinged) (90%)

Headache (100%)

Pharyngeal edema (10%)


Ascites may develop 2 to 4 days after onset (fluid may be clear or purulent)


Ulcerations can occur anywhere along the gastrointestinal tract and may
                    cause hemorrhage, obstruction, or perforation

Symptoms last about 2 weeks

*Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.



## Diagnosis

3-13. During the incubation period, nasal swabs and specimens of respiratory secretions sent for PCR are the most important screening specimens.  During the early disease, blood and respiratory secretions may be sent for rapid identification by genetic typing (PCR).  A rapid diagnostic test is available that detects toxin antigens in the blood during the acute phase.  Chest x-ray may be normal or may show a widened mediastinum and pleural effusions during the acute phase.  Table 3-5 outlines the collection of laboratory specimens for diagnosis of anthrax.


Type of illness
Specimen collection** and transport
Comments
Cutaneous
anthrax

- Swabs:  moisten with sterile saline or
water; transport in sterile tube at 2o to 8o centigrade (C).  Transport swabs for PCR only at -70oC.  Do not use transport medium.
- Tissue, fresh:  5 millimeter3; store and
transport at 2o to 8oC (2 hour [hr]) or frozen at -70oC (>2 hr).
- Tissue, preserved in 10% buffered
formalin:  1.0 centimeter3; store and
transport at room temperature.
- Biopsy of lesions for histopathology,
preserved in 10% buffered formalin: 0.3
millimeter
diameter;
store
and
transport at room temperature.
- Freeze serum after separation at -20oC
or colder, ship on dry ice.  Ship part of sample (>1.0 mL) and retain part in case of shipping problems.
- All stages:  Collect 2 swabs, 1 for Gram stain and culture and 1 for PCR.
- Vesicular stage:  Perform Gram stain, culture, and PCR of fluids from unroofed vesicle (soak 2 dry sterile swabs in vesicular fluid).  (Note:  Gram stain is most sensitive during vesicular stage.) - Eschar stage:  Perform Gram stain, culture, and PCR of ulcer base or edge of eschar without removing it. - Ulcer (no vesicle or eschar present): swab base of ulcer with premoistened sterile saline. - A punch biopsy for immunohistochemistry testing and a second biopsy for culture, Gram
stain,
PCR,
and
frozen
tissue
immunohistochemistry if patient has not received antibiotics should be obtained on all patients with suspected cutaneous anthrax. Include skin adjacent to papule or vesicle.  If vesicles and eschars are both present, separate biopsies should be obtained. - Serum:  collect acute serum within first 7
days of symptom onset, and convalescent serum 14 to 35 days after symptom onset. - Collect blood for culture and PCR with evidence of systemic involvement.
- Obtain blood for culture per local
protocol.  Collect blood for PCR in ethylenediaminetetra-acetic acid (purple top) tube.  Ship at room temperature (2 hr transport) or 2o to 8oC (>2 hr transport).

Inhalational
anthrax
- If sputum is being produced, collect sputum specimen for Gram stain and culture (Note:  inhalational anthrax does not usually result in sputum production).
- Obtain blood for smear, culture, and PCR.
- Sputum:  transport at room temperature in sterile, screw-capped container (1 hr
transport time) or at 2o to 8oC (>1 hr transport time).
- Blood cultures:  Obtain appropriate blood volume, number, and timing of sets per laboratory protocol; transport at room temperature. - Blood
for
PCR:

10
mL
in
ethylenediaminetetra-acetic acid (for pediatric patients collect volumes allowable). Transport directly to laboratory at room temperature (2o to 8oC if transport 2 hr).

## Diagnosis Of Anthrax (Continued)

Type of illness
Specimen collection** and transport
Comments
- Pleural fluid:  Collect >1 mL in sterile container.  Store and transport at 2o to 8oC.
- If a pleural effusion is present, collect a specimen for culture, Gram stain, and PCR.
Inhalation
anthrax
(continued)
- CSF:  Transport directly to laboratory at
room temperature or 2o to 8oC if transport 2
hr.

- Collect cerebrospinal fluid (CSF) if meningeal signs are present or meningitis is suspected for culture, Gram stain, and PCR.
- Serum:  collect acute serum within first seven days of symptom onset and convalescent serum 14 to 35 days after symptom onset.
- Transport
serum
or
citrated
plasma
(separated and removed from clot) at 2o to 8oC (transport <2 hr) or freeze at -20oC or colder (transport 2 hr), ship on dry ice.  Ship part of sample (>1.0 mL) and retain part in case of shipping problems.

- Preserve
biopsies
in
10%
buffered
formalin, and transport at room temperature.
- Biopsy material:  bronchial or pleural biopsy material can be evaluated if available.
Gastrointestinal
anthrax
- Obtain
stool
specimen
for
culture
(>5.0 gm).
- Stool:  Transport in sterile container
unpreserved (1 hr transport time) or at 2o to
8oC in Cary-Blair medium or equivalent (>1 hr transport time); specimen >5.0 gm.

- Obtain rectal swab from patients unable to produce stool (insert swab 1 inch beyond anal sphincter).
- Blood:  Transport at room temperature.
- Obtain blood for smear and culture (and possibly PCR testing). - Blood cultures most likely to yield B anthracis if taken 2 to 8 days postexposure and prior to administration of antibiotics. - If ascites is present, obtain a specimen for Gram stain and culture (and possibly PCR testing).
Anthrax
meningitis
- Obtain cerebrospinal fluid specimen  for Gram stain.
- See comments above for collection and
transport of blood and CSF for Gram stain, culture, and PCR.
- Obtain blood for Gram stain, culture, and PCR.

**Serologic testing may be useful in certain situations for retrospective diagnosis, since antibodies take several weeks to develop.  Serum should be collected during the acute illness and 14, 28, 42, and 60 days after onset.

Consult with testing laboratory for specific instructions. Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.



3-14. When the diagnosis of anthrax is being considered, the hospital clinical laboratory should be alerted because some laboratories will not further identify bacillus species unless specifically requested.

## Treatment

3-15. Medical management is a follows:


Supportive care includes maintaining the airway, providing resuscitative fluids, and providing vasopressors as indicated for shock.

Specific therapy includes the administration of ciprofloxacin (500 mg IV every 12 hours) or doxycycline (200 mg IV loading dose, followed by 100 mg IV every 12 hours).  A second antibiotic (for example, penicillin, ampicillin, meropenem, rifampin, or vancomycin for meningitis) must also be administered if a drug that penetrates the meninges is needed.

A tracheostomy may be indicated for upper airway obstruction due to oropharyngeal anthrax. Surgical debridement of cutaneous lesions is contraindicated.  Surgical drainage of the
mediastinum for inhalation anthrax is not recommended.

## Prognosis

3-16. The number of cases of inhalation anthrax occurring during the antibiotic era is too small to establish case-fatality rates and efficacy of treatment.  Almost all inhalation anthrax cases in which treatment was begun after onset of significantly severe symptoms have been fatal, regardless of treatment.  Despite medical therapy, most patients with inhalation anthrax die within 24 hours of the onset of the acute phase of the illness.  However, in nonhuman primate trials, animals have responded to aggressive therapy.  The case-fatality rate in the U.S. outbreak is lower (45 percent) and was likely due to early diagnosis and aggressive therapy.  The prognosis for oropharyngeal and GI anthrax is poor, with case-fatality rates 25 to 60 percent, even with aggressive therapy.  For more information on case-fatality rate, refer to Table 3-6.

| Feature                                                                             |
|-------------------------------------------------------------------------------------|
| Inhalational anthrax                                                                |
| case-fatality rate                                                                  |
| -                                                                                   |
| Sverdiovsk outbreak:  86%.                                                          |
| - U.S. outbreak:  45% (lower observed case-fatality rate in the U.S. outbreak       |
| likely was due to early diagnosis and aggressive therapy).                          |
| - In a systematic review of 82 cases of inhalational anthrax, the overall case-     |
| fatality rate was 85%; however, patients in the U.S. 2001 outbreak who              |
| received early antibiotic therapy (such as during the prodromal phase [<4.7         |
| days after illness onset]) had a case-fatality rate of 40% and those who            |
| received antibiotics >4.7 days after illness onset had a case-fatality rate of 75%. |
| - A literature review of pediatric anthrax cases identified between 1900 and        |
| 2005 demonstrated an overall mortality rate for inhalational disease of 60%         |
| (3 of 5 cases).  Not all cases in this report received antimicrobial therapy.       |
|                                                                                     |
| Gastrointestinal and                                                                |
| oropharyngeal case-                                                                 |
| fatality rate                                                                       |
| -                                                                                   |
| Rate for GI anthrax is between 25% and 60%.  In outbreaks where patients            |
| received antibiotic therapy, rates have ranged from 0% to 29%.                      |
| - A literature review of pediatric anthrax cases identified between 1900 and        |
| 2005 demonstrated an overall mortality rate for GI disease of 65% (13 of 20         |
| cases).  Not all cases in this report received antimicrobial therapy.               |
| - In the Thailand outbreak of oropharyngeal disease, rate was 13%.  In              |
| another report of 6 cases of pharyngeal anthrax, rate was 50%.                      |
|                                                                                     |

Source:  Center for Infectious Disease Research and Policy, Copyright Regents of the University of Minnesota.



## Control Of Patients, Contacts, And Treatment Areas

3-17. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.

Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.

Employ standard precautions for handling, treating, and moving all active cases.

Use sporicidal agents, such as disinfectant strength iodophors, in MTFs for general area
disinfection.  Antiseptic strength iodophors are not sporicidal.  Hypochlorite solutions may be
attenuated by organic matter, but will provide a disinfectant capability when used in a 5 percent
solution.  The hypochlorite solution should be replaced frequently.  Autoclaving or steam
sterilizing is required for complete eradication of spores.
Note:  Five percent hypochlorite (full strength household liquid hypochlorite) solution is highly reactive and oxidative.  It should never be used on patient's skin.  It can damage sensitive electrical equipment.  Equipment decontaminated with hypochlorite solution must be thoroughly rinsed with clean water before use.

## Medical Evacuation

3-18. Patients with anthrax may be evacuated with other categories of patients.  Anthrax is not transmissible person to person.  Standard precautions should be observed during evacuation.

## Brucellosis Etiologic Agent

3-19. The genus *Brucella* is encapsulated nonmotile bacteria consisting of short, gram-negative coccoid bacillus.  There are four members of the genus *Brucella* that are human pathogens.  These are Brucella melitensis, Brucella abortus, *Brucella suis*, and *Brucella canis*.

## Reservoir

3-20. The following are reservoirs in nature for the disease:


Brucella melitensis.  Primarily sheep, goats, and camels.  It may also be found in bison, elk,
caribou, and some species of deer.

Brucella abortus.  Cattle.

Brucella suis.  Swine.

Brucella canis.  Dogs and coyotes.

## Transmission

3-21. The disease is transmitted to humans by


Inhalation of aerosols or dusts that contain organisms.

Ingestion of unpasteurized dairy products and contaminated meat or meat not properly prepared/cooked.

Inoculation of abraded skin or mucosal surfaces.

## Endemic Disease Pathogenesis

3-22. Following introduction into the body, *Brucella* organisms are phagocytized by polymorphonuclear or mononuclear cells and are transported to regional lymph nodes.  However, *Brucella* organisms can survive intracellularly.  This results in the release of bacteria from lysed cells, resulting in hematogenous metastasis to other organs, particularly organs high in reticuloendothelial content (notably the liver, spleen, bone marrow, and possibly, the lungs).

## Acute Disease

3-23. Onset may be sudden or insidious (in approximately one-half of all cases) with nonspecific symptoms of fever, malaise, fatigue, anorexia, weight loss, and depression.  Illness persists as a systemic illness, with or without localizing signs and symptoms.  Fever can be intermittent.  Physical examinations may be unrevealing or may disclose fever, mild lymphadenopathy, and hepatosplenomegaly.  Disease localization occurs usually in tissues high in reticuloendothelial content.  Complications in patients with brucellosis are discussed below:


Osteoarticular.  Bone and joint disease is the most common localizing complication, occurring in
up to 40 percent of cases.  These include bursitis, sacroilitis, spondylitis, peripheral joint arthritis, and osteomyelitis.  Vertebral osteomyelitis can result in epidural abscess resulting in spinal cord compression and psoas abscess.  In addition to developing pyogenic septic osteoarticular infection, patients may also develop reactive arthropathies.  Imaging studies
should include magnetic resonance imaging, computed tomography, or technetium bone scans; plain radiographs may be insensitive early in disease.

Pulmonary infection.  Although the respiratory tract is a portal of entry for brucellosis,
pulmonary disease is rare, usually under 15 percent.  Complications may include hilar and paratracheal adenopathy, interstitial pneumonia, pulmonary nodules, pleural effusions, and empyema.

Genitourinary tract infection.  Acute orchitis or epididymo-orchitis are the most common genitourinary complications, usually in the absence of systemic symptoms or signs.  Intrapartum infection is rare, but can result in abortion although there is no convincing evidence that the risk is higher than that of other bacteremic infections.  Early diagnosis and therapy will prevent an
adverse outcome.  Chronic pyelonephritis has been reported as a rare complication.

Cardiovascular.  Endocarditis occurs in less than 2 percent of the cases, but accounts for most of
the deaths from brucellosis.  Other cardiovascular complications may include pericarditis, myocarditis, and mycotic aneurysms.

Neurologic.  Acute or chronic meningitis occurs in less than 2 percent of the cases.  Depression,
fatigue, and headache occurring in most cases represent nonspecific features of systemic disease.

## Biological Warfare Agent Delivery

3-24.  The primary threat is by aerosol release.  A foodborne brucellosis attack is unlikely, but could be executed.

## Environmental Detection

3-25.  Currently, detection is primarily by laboratory analysis of specimens from patients presenting with the illness or by laboratory testing of foods for the organism.  Veterinary/PVNTMED/public health/bioenvironmental engineering personnel should collect samples from dairy products and other food items suspected of being contaminated with the organism. Teams trained in field environmental CBRN surveillance may collect and presumptively identify the agent or transport to the supporting laboratory for analysis and confirmation.

## Prevention Preexposure Prophylaxis

3-26. Vaccines are not currently available for human use; attenuated vaccines for veterinary use have caused brucellosis following accidental percutaneous or mucous membrane exposures.  Chemoprophylaxis has not been proven to be effective and may delay or mask the onset of the disease.

## Postexposure Prophylaxis

3-27. The CDC has published an interim recommendation for a 3-week course of dual therapy
(doxycycline twice daily and rifampin once daily).  This is advised following high-risk exposures to

## Chapter 3

attenuated vaccines for veterinary use, which have been associated with human disease.  Accordingly, this course of therapy is advised for exposed personnel following a proven brucellosis BW attack.  Clinical diagnosis of brucellosis requires a 6-week course of therapy.  Postexposure chemoprophylaxis is generally not advised following possible natural exposures to endemic disease.

## Biological Warfare Clinical Presentation Incubation Period

3-28. Incubation varies from one week to many months.  Many patients are symptomatic within 3 to 4
weeks.

## Signs And Symptoms

3-29. For signs and symptoms, see endemic disease above.

## Diagnosis

3-30. A definitive diagnosis is made by culturing the organism from blood, bone marrow, or other clinical specimens.  The laboratory should be advised to maintain cultures for at least 4 weeks, as *Brucella* species grow slowly in vitro.  The sensitivity of cultures varies with clinical specimens; 15 to 70 percent for blood, greater than 90 percent for bone marrow.  Isolates may be misidentified as Moraxella or Haemophilus species in automated bacterial identification systems that lack specific profiles for *Brucella* species. Submit specimens for immunoassay testing and PCR.  Serologic tests are valuable for diagnosis.  Most patients with brucellosis will have serum-agglutinating titers of 1:160 or greater; lower titers must be analyzed within the patient's clinical context.  The serum-agglutinating titers will not detect antibodies to Brucella canis; a specific test is required.  False negative tests may occur because of blocking antibodies; dilution to 1:320 or a *Brucella* Coomb's test is indicated for suspected cases with negative titers.

## Treatment

3-31. Medical management is as follows:


Undifferentiated febrile illness.  Antibiotic therapy requires a combination of two medications as
follows:

Doxycycline, 200 mg, daily for 6 weeks and rifampin, 600 mg, daily for 6 weeks.

Doxycycline, 200 mg, daily for 6 weeks and streptomycin, 1 gram (gm) intramuscular,
daily for 2 to 3 weeks.

Doxycycline, 200 mg, daily for 6 weeks and gentamicin, 1 mg/kilogram (kg)/day for 7
days.

Osteoarticular disease.  Treat as indicated above, but extend therapy to 12 weeks.

Endocarditis.  Administer antibiotic therapy as indicated above.  Optimal duration of therapy is
undefined; however, treatment is often continued for 6 to 9 months.  Surgical heart valve replacement is usually necessary for total cure and should be strongly considered.

Central nervous system disease.  Administer antibiotic therapy as indicated above, but extend therapy for 6 to 9 months.

Abscesses.  In addition to treatment as indicated above, drainage of abscesses should be done as
surgically indicated.

## Prognosis

3-32. The case-fatality rate for untreated brucellosis has historically been less than 2 percent.  Most fatalities in untreated cases result from endocarditis due to *Brucella melitensis*.  Untreated brucellosis may result in severe morbidity for months, and occasionally years.

## Control Of Patients, Contacts, And Treatment Areas

3-33. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions for disease control.  The disease is not communicable from person to person.

## Medical Evacuation

3-34. Patients with brucellosis are evacuated with other patients.  Apply standard precautions for disease control.

## Melioidosis And Glanders Etiologic Agent

3-35. Melioidosis is caused by the agent *Burkholderia* (B.) *pseudomallei* (formerly Pseudomonas pseudomallei), a small, gram-negative aerobic bacillus.  Glanders is caused by *B. mallei*, a gram-negative bacillus that is close relative of *B. pseudomallei*.

## Reservoir

3-36. For melioidosis, soil and water throughout the world between 20 degrees north and south latitudes serve as reservoirs.  For glanders, several animals, including sheep, goats, horses, swine, monkeys, and rodents, serve as reservoirs.  However, there is no evidence that animals are important reservoirs, except that they spread the agent to new foci (soil and water).

## Transmission

3-37. It is transmitted by the organism invading the nasal, oral, and conjunctival mucous membranes, by inhalation into the lungs, and by invading abraded or lacerated skin.

## Endemic Disease

3-38. These diseases are not widespread.  The cases of glanders have been among veterinarians, horse and donkey caretakers, abattoir workers, and laboratory personnel.  For melioidosis as a tropical bacterial disease, it is most prevalent during the rainy season in people who have direct contact with wet soils and who have predisposing medical conditions (for example, diabetes mellitus).

## Biological Warfare Agent Delivery

3-39. The primary threat is aerosol release.

## Environmental Detection

3-40. Refer to paragraph 3-7 for information on environmental detection.
Note.  Conduct health risk assessments of food supplies and/sources including water according to Technical Bulletins, Medical (TB MEDs) 530, 576, and 577/NAVMED P-5010-10/AFMAN 48-138_IP and multiservice publications using the operational risk model described in FM 5-19. Documenting and disseminating information using appropriate risk communication techniques, and archiving available data according to Joint (MCM 0028-07) and Service guidance will be beneficial in identifying and procuring food items or dairy products and will help ensure food sources meet regulatory requirements.

## Prevention

3-41. Currently, no preexposure or postexposure prophylaxis is available.  Prevention incorporates PVNTMED/public health personnel ensuring food service operations are following sanitary procedures and water sources are properly disinfected.

## Biological Warfare Clinical Presentation Incubation Period

3-42. Glanders is 10 to 14 days following endemic exposure; high-dosed inhalation exposure is 1 to 4 days.
Melioidosis is 1 to 21 days.

## Signs And Symptoms

3-43. Following an aerosol attack, this disease will most likely present as an acute pulmonary infection.
Infection can vary from a mild bronchitis to a severe necrotizing pneumonia.  The illness may begin abruptly, or with a vague prodrome featuring headache, anorexia, and myalgia.  Fever, often in excess of 102 Fahrenheit (F), is common.  Localizing symptoms may include pleuritic or dull aching chest pain, and a cough (which may be either productive with purulent or bloody sputum, or nonproductive).  Physical findings may be minimal but can feature pulmonary rales.  Acute pulmonary disease can progress and result in bacteremia and acute septicemic disease.

3-44. The acute septicemic disease may follow a terminal course with death occurring in 7 to 10 days.
Case-fatality rate for acute septicemic disease exceeds 90 percent.  Symptoms may include severe dyspnea, headache, pharyngitis, diarrhea, and a pustular rash.  Physical findings may include high fever, tachypnea, hypotension, flushing of the skin, cyanosis, and rash (the rash may begin as a generalized papular rash that may progress to a pustular exanthem).  Chest findings are variable; palpable hepatosplenomegaly may be present.

3-45. Pulmonary infection can result in chronic disease, with clinical and radiographic features similar to those of tuberculosis.  Chronic suppurative disease can complicate metastatic infection to other organs including the brain, myocardium, liver, bone, spleen, lymph nodes, and eyes.

## Diagnosis

3-46. Microscopic evaluation of exudate will feature poorly staining gram-negative bacilli; methylene blue or Wright's stain will disclose a "safety pin" bipolar appearance.  Standard bacteriologic culture methods can identify both *B. mallei* and *B. pseudomallei*.  Diagnosis can also be confirmed by serologic tests, with the limitations that single low titers are nondiagnostic and negative serology does not exclude the diagnosis.  Given the possible presentation of an acute pneumonia and the above findings on sputum studies, the most important item in a differential diagnosis, especially in a BW context, would be plague. Chest x-rays may disclose infiltrates involving the upper lobes, with consolidation and cavitation.  Pleural effusions and pleural-based masses are unusual radiographic findings.  Leukocyte count can vary from normal to 20,000 white blood cells/cubic millimeter.  When cultures for B. mallei or *B. pseudomallei* are submitted, laboratory personnel must be alerted, as these cultures must be processed at a Biosafety Level 3
facility.

## Treatment

3-47. Medical management is as follows:


All glanders and melioidosis cases should be treated with initial intensive therapy regardless of
severity (mild cases may rapidly progress to septicemia) and should be treated at least 2 weeks of either ceftazidime IV therapy, meropenem IV or imipenem IV followed by a minimum of three months of oral therapy such as doxycycline and trimethoprim-sulfamethoxazole.

For extrapulmonary suppurative disease, the antibiotic therapy should be administered for 6 to
12 months.  Surgical drainage of abscesses is indicated.

The addition of streptomycin is indicated if presentation (acute pneumonia) and sputum studies suggest plague.

## Prognosis

3-48. The extent of infection will vary with inoculum, individual's underlying state of health, availability of protective mask or other respiratory protective devices, and other factors.  Late activation or recrudescence can result years or decades later.

## Control Of Patients, Contacts, And Treatment Areas

3-49. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Control measures are discussed below:


Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.

Apply standard precautions in management of patients and contacts.  Contact precautions are indicated while caring for patients with skin involvement.

Melioidosis, glanders, and smallpox may present with diffuse pustular rashes; strict isolation and quarantine would be indicated until smallpox can be excluded.  Contact precautions are indicated
while caring for patients with skin involvement.

Melioidosis, glanders, and plague may present as acute pulmonary disease with purulent sputum. Respiratory isolation pending exclusion of plague is prudent if sputum studies disclose gramnegative bacilli with bipolar safety pin when using Wright's or methylene blue stains.

## Medical Evacuation

3-50. Patients may be evacuated using standard precautions following the exclusion of smallpox and plague.  Contact precautions are indicated for patients with skin involvement.

## Plague Etiologic Agent

3-51. Yersinia pestis (*Y. pestis*) is a gram-negative coccobacillus of the family *Enterobacteriaceae*.

## Reservoir

3-52. The primary reservoir is rodents.  Domestic cats and wild carnivores can also transmit plague to humans.

## Transmission

3-53. In endemic or epidemic plague, the disease is transmitted via infected fleas from rodent to human, dog or cat to human, or person to person.  Respiratory droplet transmission can occur person to person or cat to person.  Respiratory transmission is enhanced in humid climates.  Plague may also be transmitted via cat bites or scratches.  Domestic cats and wild carnivores are susceptible to the disease and may propagate the disease by bites, scratches, or respiratory droplets.

## Endemic Disease

3-54. The following three forms of plague are typically observed in man: bubonic, pneumonic, and septicemic:


Bubonic plague is the most common form of naturally occurring plague characterized by the
acute onset of fever and prostration in association with acute, painful, swollen lymph nodes (buboes), clinically consistent with lymphadenitis, in the region draining the site of the fleabite. Therefore, a minority of bubonic plague cases may develop septicemic plague.  Furthermore, pneumonia due to hematogenous metastasis occurs in approximately 25 percent of cases, a
clinical condition known as secondary pneumonic plague.  Person-to-person spread does not occur with the bubonic form of plague.


Primary pneumonic plague occurs after inhalation of organisms, which may occur via aerosol transmission from a person or animal with secondary or primary pneumonic plague.  Pneumonic
plague is the only form of plague disease which readily spreads from person to person.  Buboes are absent in the pneumonic form of disease and the fatality rate is nearly 100 percent if the disease is not promptly treated with appropriate antibiotics (within 24 hours after onset of symptoms).

Septicemic plague may evolve from any form of plague.  It features the acute onset of bacteremia, septic shock, and thrombosis with or without antecedent lymphadenitis.  Prognosis
for pneumonic and septicemic pneumonic plague is poor; the fatality rate is 100 percent for untreated cases.

## Biological Warfare Agent Delivery

3-55. The primary threat is by aerosol release resulting in pneumonic plague.

## Environmental Detection

3-56. Refer to paragraph 3-7 for information on environmental detection. A plague BW attack may result in simultaneous onset of disease in humans, rodent reservoirs, and possibly domestic and wild animals not usually associated with plague.

## Prevention Repellents

3-57. Use of insect repellents approved for human use (for example, N,N-diethyl-meta-toluamide), will provide a level of protection from bites by infected fleas.  Additionally, use of permethrin-impregnated clothing will assist in flea control by killing adult fleas.

## Immunization

3-58. No FDA-licensed plague vaccine is currently available.  However, there is a vaccine that is in advanced development.

## Preexposure Prophylaxis

3-59. Administer ciprofloxacin 500 mg orally every 12 hours or doxycycline 100 mg orally every 12 hours beginning when a BW attack is imminent or suspected; discontinue if the employment of plague BW can be excluded.

## Postexposure Prophylaxis

3-60. Administer doxycycline 100 mg orally every 12 hours for one week or ciprofloxacin 500 mg orally every 12 hours for one week.

## Biological Warfare Clinical Presentation Incubation Period

3-61. As low as one day.

## Signs And Symptoms

3-62.  Following an aerosol release of the organisms, unprotected individuals will present with acute pneumonic plague featuring high fever, systemic toxicity, productive cough, and hemoptysis.  Patients may present with disseminated intravascular coagulation (DIC) with resultant thrombosis and digital gangrene.
However, hemorrhagic complications of DIC in plague are rare.  Further, an aerosol attack of plague could result in an epidemic of bubonic plague if rodent hosts and flea vectors are present in the vicinity of the attack.

## Diagnosis

3-63. Initial diagnosis of plague is based primarily on clinical suspicion.  A presumptive diagnosis can be made microscopically by identification of the coccobacillus in gram-negative, Wright-, Giemsa-, or Wayson-stained smears from lymph node needle aspirate, sputum, blood, or cerebrospinal fluid (CSF) samples.  The Wayson stain demonstrates a bipolar staining bacillus (light blue bacillus with dark blue polar bodies), giving the appearance of a *safety pin*.  Immunofluorescent staining is also useful.

3-64. Definitive diagnosis relies on culturing the organism from blood, sputum, or bubo aspirates.  The organism grows slowly at normal incubation temperatures and may be misidentified by automated systems because of delayed biochemical reactions.  It may be cultured on blood agar, MacConkey agar, or infusion broth.  Most naturally occurring strains of *Y. pestis* produce an F1-antigen in vivo, which can be detected in serum samples by immunoassay.  A passive hemagglutination testing demonstrating fourfold rise in antibody titer in patient serum or a single titer 1:128 in an unvaccinated patient with a compatible illness is considered diagnostic (convalescent serum generally should be obtained 4 to 6 weeks later as early antibiotics may delay seroconversion for several weeks).  Polymerase chain reaction is not sufficiently developed for routine use, but it is a very sensitive and specific technique that is currently able to identify as few as 10 organisms per milliliter (ml or mL).  A presumptive identification of *Y. pestis* can be made using PCR or antigen-capture enzyme-linked immunosorbent assay.

## Treatment

3-65. Medical management is as follows:


Supportive care.  Supportive care should include IV hydration, supplemental oxygen, and respiratory support as indicated.

Specific therapy.  Administer one of the following:

Streptomycin, 15 mg/kg lean body mass intramuscular every 12 hours for 10 to 14 days.

Gentamicin, 5 mg/kg lean body mass IV every 24 hours for 10 to 14 days.

Gentamicin, 2 mg/kg loading dose followed by 1.7 mg/kg lean body mass IV every 8 hours
for 10 to 14 days.

Ciprofloxacin, 400 mg IV every 12 hours. Oral therapy may be given (750 mg orally every
12 hours) after the patient is clinically improved, for completion of a 10- to 14-day course of therapy.

Doxycycline, 200 mg IV loading dose followed by 100 mg IV every 12 hours.  Oral
therapy may be given (100 mg orally every 12 hours) after the patient is clinically improved, for completion of a 10- to 14-day course of therapy.

Plague meningitis.  Administer chloramphenicol 25 mg/kg IV loading dose, followed by 15 mg/kg IV every 6 hours.  Oral therapy may be given after the patient is clinically improved, for completion of a 10- to 14-day course of therapy.

## Prognosis

3-66. Pneumonic plague is invariably fatal if antibiotic therapy is delayed more than one day after the onset of symptoms.

## Control Of Patients, Contacts, And Treatment Areas

3-67. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.
Pneumonic plague is a very contagious disease.  The following must be applied for all cases:


Report case(s) to the line commanders and command surgeon.

Employ standard precautions for disease control.  For suspected pneumonic plague (BW
presentation), apply respiratory droplet isolation for a minimum of the first 48 hours of therapy.
If plague pneumonia is confirmed, continue respiratory droplet isolation until sputum cultures are negative.

Employ measures to minimize personnel contact with rodents (proper food storage, trash disposal, and elimination of rodent nests); enforce the use of topical insect repellents and the use of insecticides in and around troop encampments to kill fleas, thus decreasing the risk of secondary transmission.  Eliminate fleas from patients and their personal effects.

Administer postexposure prophylaxis to personnel who have come in close contact.

Conduct terminal disinfection of all items used in the care of patients.  The standard disinfectants available at MTFs will inactivate *Y. pestis*.

## Medical Evacuation

3-68. Quarantine patients.  Evacuate only with other plague cases.  Employ respiratory droplet precautions in addition to standard precautions for patients with pneumonic plague until sputum cultures are negative. Do not evacuate across international borders unless authorized by the theater command surgeon.

## Q Fever Etiologic Agent

3-69. Coxiella *burnetii* is a rickettsial organism that is highly resistant to heat and desiccation.  The organism is highly communicable via aerosol.

## Reservoir

3-70. The reservoir is sheep, goats, cattle, dogs, cats, some wild mammals, birds, and ticks.  Infected animals usually do not develop the disease, but shed significant numbers of organisms in placental tissues and body fluids.

## Transmission

3-71. The organisms are usually transmitted via aerosols containing dust from areas contaminated by placentas, amniotic fluid, excreta from infected animals, aerosols generated by processing products of infected animals, direct contact with infected animals, and/or ingestion of unpasteurized milk.  Q fever has also been transmitted by inhaling aerosols generated from manure, straw, contaminated laundry, and vehicles.  The role of ticks as vectors of human disease is unclear, but they may transmit the disease to humans by dropping organisms on the body at the site of their bite.

## Endemic Disease

3-72. Acute Q fever can present as an undifferentiated febrile illness, as an atypical pneumonia, or as a rapidly progressive pneumonia.  Complications in patients with Q fever are discussed below:


The atypical pneumonia presentation features fever, fatigue, chills, sweats, and myalgia. Approximately 75 percent of patients will complain of severe headache.  There is a relative absence of respiratory symptoms; coughing occurs in approximately 25 percent of patients with radiography confirmed pneumonia.  Physical examination of the chest is usually normal; inspiratory rales may be present.  Patients with the rapidly progressive pneumonic presentation may feature auscultatory findings consistent with consolidation.  Q fever pneumonia can result in development of hyponatremia due to the syndrome of inappropriate antidiuretic hormone.

Neurologic complications of Q fever include aseptic meningitis or encephalitis in approximately one percent of cases.  Other complications have included cranial nerve palsies, behavioral disturbances, cerebellar and extrapyramidal disease, and Miller Fisher syndrome.  Other rare
extrapulmonary complications have included hemolytic anemia and glomerulonephritis.

Significant amount of Q fever cases will develop acute hepatitis (Q fever hepatitis).  The acute hepatitis can present with fever and abnormal liver function tests with the absence of pulmonary symptoms, signs, or radiographic abnormalities.  A liver biopsy may disclose granulomatous hepatitis with a highly suggestive histologic appearance.  The granuloma will present as a dense
fibrin ring surrounded by a central lipid vacuole (doughnut granuloma).

The most common complication of chronic Q fever is endocarditis.  Patients with valvulopathies or other anatomic abnormalities of the vascular tree are at increased risk.  Routine blood cultures
will be negative.  Fever may be absent.  Typical findings include clubbing of the fingernails, hepatosplenomegaly in approximately 50 percent of cases, arterial embolic phenomena in 33 percent of cases, and purpura due to leukocytoclastic vasculitis in approximately 20 percent of cases.

## Biological Warfare Agent Delivery

3-73. The primary threat is by aerosol or through contamination of food.

## Environmental Detection

3-74. Refer to paragraph 3-7 for information on environmental detection.

## Prevention

3-75. Service members should only consume pasteurized dairy products and should heat all foods sufficiently to destroy the organisms.  To enhance overall prevention in food service operations, refer to TB MED 530 or to respective Service publication.

## Preexposure Prophylaxis

3-76. Currently no approve FDA vaccine for preexposure however, there is a vaccine in advanced development.

## Postexposure Chemoprophylaxis

3-77. Chemoprophylaxis (tetracycline 500 mg orally every 6 hours for 5 days, or doxycycline 100 mg orally every 12 hours for 5 days) is effective if started 8 to 12 days postexposure.

Note.  Chemoprophylaxis is not effective if given immediately (1 to 7 days) postexposure; it merely delays the onset of disease.

## Biological Warfare Clinical Presentation Incubation Period

3-78. Longer range is up to 3 weeks.

## Signs And Symptoms

3-79. See endemic disease, above.

## Diagnosis

3-80. Laboratory confirmation is accomplished by serologic testing for antibody titers.  Acute Q fever results in high titers to Phase II antigen and lower antibody titers to Phase I antigen, while the antibody titers to Phase I antigen is higher during chronic Q fever.  An ELISA test for immunoglobulin Class M (IgM) and immunoglobulin Class G (IgG) antibody maybe available at reference laboratories.  A single high titer may be diagnostic as early as 10 to 14 days into the illness.  A four-fold rise in titer in paired acute/convalescent sera is diagnostic of acute Q fever but requires a baseline and repeat sample in 2 to 4
weeks.  Chronic Q fever is confirmed by complement fixation titer of 1:200 or greater to Phase I antigen.

## Chapter 3

Cultures for *coxiella burnetii* are technically difficult, hazardous, and generally not done.  *Coxiella burnetii*
can be identified on biopsy specimens (tissue) by immunofluorescent stain or electron microscopy. Nonspecific laboratory findings may include leukocytosis in one third of the patients.  Elevations aminotransferase levels (2 to 3 times the upper limit of normal) are typical.  Bilirubin is usually normal.

3-81. Chest x-ray findings are abnormal in approximately one half of symptomatic cases and may include pleural effusions in up to 35 percent of cases, nonsegmental and segmented pleural-based opacities, increased interstitial markings, and hilar adenopathy.

3-82. Differential diagnosis should include the diverse causes of either rapidly progressive or atypical pneumonia.

## Treatment

3-83. Medical management is as follows:


Acute Q fever.  While acute Q fever may run a brief, self-limited course without therapy,
suspected cases of acute Q fever should be treated to reduce the risk of development of chronic disease.  Therapeutics for acute Q fever are to

Administer doxycycline 100 mg orally every 12 hours for 15 to 21 days.

Administer tetracycline 500 mg every 6 hours for 14 to 21 days.

Quinolones are an option but not recommended for the treatment of children.

Chronic Q fever.  Therapy for Q fever endocarditis and other forms of chronic Q fever is complex, controversial, and beyond the scope of this manual.  However, recommended regimens have included doxycycline combined with rifampin, ofloxacin, or trimethoprim/sulfa and continued for at least 2 years.  Antibody titers should be monitored every 6 months during therapy.  Monitoring should be continued every 3 months for the first 2 years after therapy. Valve replacement is often necessary to cure Q fever endocarditis; however, this procedure
should be reserved for hemodynamic indications or embolic complications.

## Prognosis

3-84. Q fever usually results in a self-limited febrile illness of 2 to 14 days in duration.  Previously healthy individuals would be expected to make a complete recovery.  Fulminant pneumonia and chronic Q fever (including endocarditis and neurologic sequelae) are uncommon.

## Control Of Patients, Contacts, And Treatment Areas

3-85. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  The Q fever is not communicable person to person.  Observe standard precautions when handling patients. Unlike most other potential biological weapons, heavy environmental contamination with *coxiella burnetii* could pose a long-term risk due to environmental persistence.  Dusts generated from the contaminated environment may continue to transmit the disease.  Exposed clothing and equipment should be decontaminated.

## Medical Evacuation

3-86. Patients may be evacuated with other classes of patients.

## Tularemia Etiologic Agent

3-87. Francisella tularensis (*F. tularensis*) is an aerobic catalase-positive, gram-negative coccobacillus.

## Reservoir

3-88. *Francisella tularensis* is maintained in numerous and diverse mammalian (rabbits, hares, rodents)
and tick reservoirs.  *Francisella tularensis* is limited to the northern hemisphere.  Type A (the predominant strain in North America) is more virulent than Type B (the predominant strain in Northern Europe).

## Transmission

3-89. Transmission is by arthropod vectors (ticks and deerflies; also mosquitoes in Sweden, Finland, and the former Soviet Union), direct contact with infected animals, aerosols generated by skinning/processing infected animals, and ingestion of contaminated food or water.  The organisms may also be transmitted by aerosol as a BW agent.

## Endemic Disease

3-90. Clinical syndromes vary with portal of entry, inoculum, strain virulence, and the host's underlying state of health.  Infection may be subclinical or fulminant.  With the exception of typhoidal tularemia, the clinical syndromes are characterized by the combination of focal processes featuring ulceration at the portal of entry, and regional adenopathy involving the node groups draining the portal of entry.  Signs and symptoms of tularemia are discussed below:


Ulceroglandular tularemia is most often acquired through the inoculation of the skin or mucous membranes with blood or tissue fluids of infected animals.  It is characterized by usually sudden
onset of fever, chills, headache, cough, and myalgia concurrent with the appearance of a painful papule at the site of inoculation.

Pharyngeal tularemia presents as an acute pharyngitis following ingestion of contaminated food or water.  The chief complaint is a severe sore throat.  Physical findings include fever, exudative pharyngitis and/or tonsillitis, and possibly pharyngeal ulcers.  Also, findings may include a
pharyngeal membrane similar to that seen in diphtheria.  Regional adenopathy may present in cervical, preauricular, and retropharyngeal node groups with occasional abscess formation.

Oculoglandular disease presents following inoculation of the conjunctivae via aerosol, splashes, or direct contact (contaminated fingers).  This disease presents as an acute conjunctivitis and may feature small conjunctival ulcers or papules.  Complications may include corneal ulceration and dacryocystitis, but visual loss is rare.  Regional adenopathy is a conspicuous feature of this illness, with preauricular or preparotid adenopathy.  Severe cases of adenopathy may mimic parotiditis.  Differential diagnosis should include other causes of Parinaud oculoglandular syndrome, including adenovirus infection, cat scratch disease, syphilis, herpetic infection, and pyogenic bacterial infection.
3-91. Following aerosol exposure, an undifferentiated febrile illness (typhoidal tularemia) or an acute pneumonia featuring fever, coughing, substernal chest tightness, and pleuritic chest pain may present. Usually, coughing is nonproductive; hemoptysis is rare.  Physical findings may vary.  Examination may be normal, or disclose rales, friction rubs, or findings consistent with consolidation or effusions.

## Biological Warfare Agent Delivery

3-92. The primary threat is by aerosol release, or by contamination of food or water supplies.

## Environmental Detection

3-93. Refer to paragraph 3-7 for information on environmental detection.

## Prevention

3-94. The military protective mask provides protection of the respiratory tract from exposure to aerosol organisms.  All food must be thoroughly heated before consumption to kill any organisms.  Water must be thoroughly disinfected before consumption.

## Preexposure Prophylaxi

3-95. There is no FDA-approved vaccine however, there is a vaccine in advanced development.
Chemoprophylaxis given for anthrax or plague (ciprofloxacin, doxycycline) may confer protection against tularemia, based on in vitro susceptibilities.

## Postexposure Prophylaxis

3-96. Following a BW attack, administer doxycycline 100 mg orally every 12 hours for 2 weeks.
Chemoprophylaxis is not recommended following potential natural exposures (tick bite, rabbit, or other animal exposures).

## Biological Warfare Clinical Presentation Incubation Period

3-97. One to 21 days (usually 3 to 5 days).

## Signs And Symptoms

3-98. The BW agent presentations of tularemia will be the pneumonic and typhoidal forms.
Oculoglandular disease could possibly occur following inoculation of the conjunctivae.

## Diagnosis

3-99. Serologic testing is the preferred procedure for laboratory confirmation. Confirmation of diagnosis requires a four-fold increase in titer; serologies may need to be repeated at 7-to-10 day intervals.
Agglutination tests and ELISA are also available.  A gram stain of expectorated sputum is usually unrewarding; generally, the organism is not visualized on stains of clinical specimens.  Cultures are not advised for diagnostic purposes.  The organism does not grow on standard bacteriologic growth media. Francisella tularensis can be cultured on special supportive media containing cystine or another sulfhydryl source.  However, cultures of the organism pose a significant occupational hazard to laboratory personnel. When cultures for *F. tularensis* are submitted, laboratory personnel must be alerted, as these cultures must be processed at a Biosafety Level 3 facility.  Blood specimens may be submitted for mouse/egg inoculation.

3-100. Radiographic findings are nonspecific and may include subsegmental or lobar infiltrates, apical or miliary infiltrates, cavitation, pleural effusions, and hilar adenopathy.

## Treatment

3-101. Medical management is as follows:  Supportive care may include respiratory support and hydration.  Open lesions should be covered and topical antibiotics applied.  Antibiotic therapy may be one of the following:


Administer streptomycin 1 gm intramuscular every 12 hours for 10 days.

Administer gentamicin 5 mg/kg intramuscular or IV daily for 10 days.

Administer ciprofloxacin 400 mg IV every 12 hours for 10 days as an alternative.

Administer doxycycline 100 mg IV twice daily for 14 to 21 days (longer course) as an alternative.

## Prognosis

3-102. Inhalation tularemia can lead to fulminant pneumonia with case-fatality of 30 to 60 percent without treatment.

## Control Of Patients, Contacts, And Treatment Areas

3-103. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions.  Tularemia is not communicable person to person.

## Medical Evacuation

3-104. Patients may be evacuated.  Observe standard precautions during evacuation.

## Cholera Etiologic Agent

3-105. An acute bacterial enteric disease, *Vibrio cholerae* serogroups O1 and O139 are associated with the epidemiological characteristics and clinical picture of cholera.

## Reservoir

3-106. The main reservoir is humans. Recent evidence indicates that environmental reservoirs exist, apparently in association with copepods and chironomids.  The dispersal of endozoochorus and epizoochorous (invertebrates) via waterfowl is an important process for *V. cholerae* dissemination.

## Transmission

3-107. It is acquired through ingestion of an infective dose of contaminated food or water.  Water usually is contaminated by feces of infected individuals.  Contamination of drinking water occurs usually at source, during transportation or during storage at home.  Food may also be contaminated by soiled hands during preparation.

## Endemic Disease

3-108. Conditions leading to epidemics exist in many developing countries where cholera is either endemic or a recurring problem in a large number of areas.  Typical settings for cholera are periurban slums where basic urban infrastructure is missing.  Manmade or natural disasters such as complex emergencies and floods resulting in population movements as well as overcrowded refugee camps are conducive to explosive outbreaks with high-fatality rates.

## Biological Warfare Agent Delivery

3-109. The primary threat is aerosol release into food and water supply.

## Environmental Detection

3-110. Refer to paragraph 3-7 for information on environmental detection.

## Prevention

3-111. Currently, no preexposure or postexposure prophylaxis is available.  Prevention incorporates PVNTMED/public health personnel ensuring food service operations are following sanitary procedures and water sources are properly disinfected.

## Biological Warfare Clinical Presentation Incubation Period

3-112. From a few hours to 5 days, usually 2 to 3 days.

## Signs And Symptoms

3-113. Following an aerosol attack, this disease will most likely present as an acute watery diarrhea with or without vomiting in any patient.  No respiratory disease is expected.  In untreated cases, rapid dehydration, acidosis, circulatory collapse, hypoglycemia in children, and renal failure can rapidly lead to death.

## Diagnosis

3-114. It is confirmed by isolating *Vibrio cholerae* of the serogroup O1 or O139 from feces.  Vibrio cholerae grows well on standard culture media, the most widely used of which is Thiosulfate Citrate Bile Salts Sucrose agar.  The strains are further characterized by O1 and O139 specific antisera.  Strains that agglutinate in O1 antisera are further characterized for stereotype.  If laboratory facilities are not nearby or immediately available, Cary Blair transport medium can be used to transport or store a fecal or rectal swab.
For clinical purposes, a quick presumptive diagnosis can be made by darkfield or phase microscopic visualization of the vibrios moving like shooting stars, inhibited by preservative-free, serotype-specific antiserum.  For epidemiological purposes, a presumptive diagnosis can be based on the demonstration of a significant rise in titer of antitoxic and vibriocidal antibodies.

## Treatment

3-115. The cornerstone of cholera treatment is timely and adequate rehydration.  As rehydration therapy becomes increasingly effective, patients who survive from hypovolemic shock and severe dehydration may manifest certain complications, such as hypoglycemia, that must be recognized and treated promptly.
Medical management is as follows:


Treat with oral rehydration solution that contains glucose 75 millimoles per liter (mmol/L); sodium chloride (NaCl) 75 mmol/L; potassium chloride (KC1) 20 mmol/L; and trisodium citrate dehydrate 10 mmol/L.

Severely dehydrated patients or patients in shock should be given rapid IV rehydration with a balanced multielectrolyte solution containing approximately 130 milliequivalents per liter (mEq/L) of sodium (Na)+, 25-48 mEq/L of potassium+.  Useful solutions include Ringer lactate (4 grams NaCl, 1 gm KC1, 6.5 grams sodium acetate and 8 grams glucose/L), and Dacca
solution (5 grams NaCl, 4 grams sodium bicarbonate (NaHCO3) and 1 gram KC1/L) which can be prepared locally in an emergency.

In severe cases, appropriate antimicrobial agents can shorten the duration of diarrhea, reduce the
volume of rehydration solutions required, and shorten the duration of vibrio excretion.  Adults are given tetracycline 500 mg 4 times a day, and children 1.25 mg/kg 4 times daily, for 3 days. For adults, a single dose of 300 mg of doxycyline is a good alternative treatment.  Where tetracycline-resistant strains of *Vibrio cholerae* are prevalent, alternative antimicrobial regimens include furazolidone (100 mg 4 times daily for adults and 1.23 mg/kg 4 times daily for children, for 3 days); or erythromycin (250 mg 4 times daily for adults and 30 mg/kg 4 times daily for children, for 3 days).  Ciproflaxin, 250 mg once a day for 3 days, is also useful for adults.

Since individual strains of *Vibrio cholerae* O1 or O139 may be resistant to any of these
antimicrobials, knowledge of the sensitivity of local strains to these agents, if available, should be able to guide the choice of the antimicrobial therapy.

## Prognosis

3-116. Patients with milder cases of cholera usually recover on their own in three to six days without additional complications.  They may eliminate the bacteria in their feces for up to two weeks.  Chronic carriers of the disease are rare.  With prompt fluid and electrolyte replacement, the death rate in patients with severe cholera is less than 1 percent. Untreated, the death rate can be greater than 50 percent.  The difficulty in treating severe cholera does not lie in not knowing how to treat it but rather in getting medical care to the sick in underdeveloped areas of the world where medical resources are limited.

## Control Of Patients, Contacts, And Treatment Areas

3-117. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in management of patients and contacts.  Contact precautions are indicated while caring for patients.  Hospitalization with universal precautions is desirable for severely ill patients; strict isolation is not necessary.  Less severe cases can be managed on an outpatient basis with oral rehydration and an appropriate antimicrobial agent to prevent the spread of the disease.  Cholera wards can be operated even when crowded without hazard to staff and visitors, provided standard precautions are observed for hand washing and cleanliness and for the circulation of staff and visitors.  Fly control should be practiced.

## Medical Evacuation

3-118. Patients may be evacuated using standard precautions.

This page intentionally left blank.


## Chapter 4 Viral Agents Viruses

4-1. Viruses are the simplest type of microorganism and consist of a nucleocapsid protein coat containing genetic material, either ribonucleic acid or DNA.  Potential viral BW agents include smallpox; Venezuelan, Western, and Eastern Equine Encephalitis; and VHF.

## Smallpox Etiologic Agent

4-2. Smallpox (caused by variola major, a member of the Orthopoxvirus genus) is very contagious to humans.  A relatively mild form of smallpox, called alastrim (caused by variola minor), and featuring limited systemic toxicity and a milder exanthem was seen in parts of southern Africa, Europe, and Latin America.  Other Orthopoxviruses, including cowpox, monkeypox, and vaccinia are also pathogenic to humans.  Theoretically, recombinant poxviruses could be developed from animal poxviruses or vaccinia, and used as biological weapons.

## Reservoir

4-3. Humans were the only natural reservoir of variola.  Variola was eradicated as an endemic human pathogen, but known laboratory cultures of variola are maintained under security at the CDC, Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (Koltsovo, Russia).

## Transmission

4-4. Usually occurred by respiratory droplet transmission following close face-to-face contact.  Smallpox was also transmitted by direct contact with skin lesions or drainage or with contaminated objects.  Although uncommon, airborne transmission (long distance) also occurred.

## Endemic Disease

4-5. Smallpox has been eradicated as an endemic disease.  The last naturally acquired reported cases occurred in October 1977, in Somalia.  However, if variola is delivered as a BW agent, it could result in the reemergence of smallpox.  Once reestablished as an endemic disease, it could again be spread by respiratory droplet or droplet nuclei, or by contact with scabs, lesion drainage, and contaminated objects.

## Biological Warfare Agent Delivery

4-6. The primary threat is delivery by aerosol release.

## Environmental Detection

4-7. The CBRN reconnaissance teams or other bioenvironmental engineering personnel operating similar detection equipment perform detection procedures.  Medical personnel collect specimens for laboratory analysis and confirmation.

## Prevention Preexposure Prophylaxis

4-8. There are no routine immunizations of U.S. forces for smallpox.  When the threat indicates, senior leadership may direct vaccination of personnel with vaccinia according to the guidelines from the Health Affairs Policy 08-004 (http://www.vaccines.mil/documents/1182SPX_Update_Clinical_Policy.pdf.)
Note.  Contraindications to preexposure prophylaxis include age <12 months, pregnancy, intention to become pregnant within 4 weeks, impaired immunity, human immunodeficiency virus infection, cardiac disease,  history of eczema, psoriasis or other chronic dermatoses, and individuals with household or other close contacts with the above conditions.  Refer to Health Affairs Policy 08-004 for a full discussion of contraindications.

## Postexposure Prophylaxis

4-9. All individuals exposed to or suspected of being exposed to smallpox BW agents should have active or passive immunization.  Contacts that are not immunized or those immunized more than 3 years prior to exposure should be given vaccination as soon as possible (within 1 to 7 days) following exposure.  Limited data obtained during the era of endemic smallpox suggested that vaccinia combined with vaccinia immunoglobulin (VIG) was slightly more effective than vaccinia alone for postexposure immunoprophylaxis.  If postexposure immunoprophylaxis cannot be given within 7 days of exposure, the administration of the combination of vaccinia and VIG is an option.  Considerations when administering VIG are discussed below:


For contacts with pregnancy or eczema at increased risk for vaccine side effects, the route of administration of VIG product is given either intravenously or intramuscularly.  The IV route (6000 units/kg) is much more acceptable from patient tolerability standpoint.  The combination
of vaccine and VIG may be considered (this would represent an off-label use) for patients vaccinated during pregnancy, or at risk for complications.  Vaccinia immunoglobulin should be administered in divided doses at multiple locations over 24 to 36 hours.

Under routine circumstances, VIG is indicated for the treatment or modification of certain
conditions induced by the smallpox vaccine.  Consultation with a board certified infectiousdisease or allergy-immunology specialist is required before administration according to Health Affairs Policy 08-004.  The Vaccine Health Care Centers Network (Vaccine Clinical Call Center 866-210-6469) will provide and coordinate professional consultation services to optimize clinical use of IV-VIG, and then maintain a case file of patients treated with IV-VIG.

For information on how to obtain IV-VIG through DOD channels, call the Military Vaccine
Agency at 877-GET-VACC, DSN 761-4245.  Physicians at military facilities may request VIG by calling the USAMRIID at 301-619-2257 or 888-USA-RIID and ask for the physician on call.
Note.  The Department of Health and Human Services guidance on smallpox vaccination is as follows:  "During a smallpox emergency, all contraindications to vaccination would be reconsidered in the light of the risk of smallpox exposure.  Persons would be advised by public health authorities on recommendations for vaccination."


Possible side effects of vaccine (vaccine is a live virus) are the potential to cause disease in vaccinees and their contacts, especially those with conditions outlined above. Inadvertent inoculation of other skin surfaces can occur.  Inadvertent inoculation of the eyes can result in severe conjunctivitis, keratitis, and corneal ulceration.  Consult an ophthalmologist.

Generalized vaccinia is a rare idiosyncratic reaction featuring mild constitutional symptoms and a generalized vesicular rash.  Vaccinia cannot be cultured from the vesicles or from the serum of patients with this condition.  Pathogenesis is unknown, but is possibly due to an immunopathologic mechanism.  Usually, this is a self-limited reaction and no therapy is indicated, but VIG may be indicated for severe cases.  A VAERS report should be submitted for any unexpected or serious event occurring after smallpox vaccination as well as adverse events
occurring in persons following close contact with a vaccine recipient.  For more information, refer to Chapter 2.


Idiosyncratic reactions of varying severity were seen that require supportive care.  These included generalized urticarial exanthems, such as erythema multiforme and Stevens-Johnson
syndrome, an immune-complex-mediated hypersensitivity complex.

Encephalitis occurs in approximately two individuals per million receiving the vaccine.  This
complication produced a case-fatality rate of up to 30 percent and neurologic sequelae in survivors.  The pathogenesis is unknown but is probably due to an immunopathologic mechanism because vaccinia cannot be cultured from cerebrospinal fluid or brain tissue of
patients.  Treatment is supportive.

Eczema vaccinatum is a severe dermatitis featuring replication of vaccinia at sites of eczema, psoriasis, burns, or other chronic or severe cutaneous lesions.  The route of administration of VIG product is given either intravenously or intramuscularly.  The IV route (6000 units/kg) over a 24- to 36-hour period until no new lesions appear is more acceptable from a patient tolerability
standpoint.

Vaccinia necrosum has occurred in immunocompromised vaccinees.  This condition features an
intense local reaction at the site of the vaccination, progressing to local necrosis.  The lesion can
progress by local extension and metastasize to distant sites on the skin; it is potentially fatal. Therapy is the same as Eczema vaccinatum over a 24- to 36-hour period until definite clinical
improvement is apparent.

Availability of IV Cidofovir and newer antiviral drug ST 246 as IND treatment for cases of
severe vaccinia reactions refractory to VIG.  For treatment protocol, contact CDC Emergency
Operations Center (800-CDC-INFO) (800-232-4636), TTY:  888-232-6348 24 hours/every day.

Fetal vaccinia may result from giving vaccinia to females during pregnancy.  The prognosis for the fetus is poor, resulting in stillbirth.

## Biological Warfare Clinical Presentation Incubation Period

4-10. The incubation period is 7 to 17 days, commonly 10 to 12 days.

## Signs And Symptoms

4-11. Smallpox begins as a febrile prodrome of 2 to 4 days duration, featuring the acute onset of fever, rigors, malaise, headache, backache, and vomiting.  Other features of the prodrome included delirium and a transient erythematous macular rash, each occurring in approximately 15 percent of patients.  The characteristic exanthematous phase begins with an acute papular dermatitis on the face, hands, and forearms, then spreading to the lower extremities and the trunk.  Distribution of the rash is centrifugal, with face and distal extremities involved earlier and to a greater extent than proximal extremities or trunk.  The lesions progress in a synchronous manner from papule to vesicle to pustule.  Scabs form in 8 to 14 days and slough off in 14 to 28 days after the onset of the rash.  The sloughing leaves depressed depigmented scars.
Enanthems involving the upper aerodigestive tract may also occur.

4-12. Variants include flat-type smallpox, featuring severe systemic toxicity and large flat maculopapular lesions with a soft, velvety, nonindurated texture.  The most severe clinical presentation of smallpox is the hemorrhagic variant, featuring severe systemic toxicity, and diffuse ecchymosis and purpura.  This variant is associated with a high-titer viremia and absent or negligible antibody responses and patients usually died before the characteristic papules or vesicles appeared.  A relatively mild form of smallpox, featuring limited systemic toxicity and a milder exanthem was seen in parts of southern Africa, Europe, and Latin America.  It was due to a less virulent strain of variola (variola minor or alastrim).

4-13. Complications of smallpox include encephalitis in one per 500 cases, with high rates of mortality and neurologic sequelae among survivors.  Keratitis with corneal ulceration leading to blindness occurred in one percent of cases.  Pulmonary edema could complicate the course of hemorrhagic and flat-type variants.

## Diagnosis

4-14. Differential diagnosis of a vesicular or pustular exanthem may include consideration of other infections (varicella, enteroviruses, rickettsialpox, septicemic melioidosis) or autoimmune diseases
(dermatitis herpetiformis, bullous erythema multiforme, and so forth).  Cytologic examination of specimens obtained from the bases of unroofed vesicles may disclose eosinophilic inclusions (Guarnieri bodies) which are sites of viral replication in the cytoplasm.  Poxviruses may also be identified by electron microscopy of specimens obtained from skin lesions; however, these methods will not differentiate poxviruses.  Clinical specimens (serum, respiratory secretions, specimens obtained from skin lesions or crusts) may be sent to the laboratory for culture.  The virus may also be cultured from the blood during the prodrome.  Poxviruses may be identified by differential growth characteristics in tissue culture.  The use of genetic typing methods such as PCR will lead to a specific diagnosis.

## Treatment

4-15. Medical management:  provide supportive care.  There are products currently in development for the treatment of orthopox viruses; however, these products are not FDA-approved.

## Prognosis

4-16. Case-fatality rate for smallpox (variola major) was historically 20 to 40 percent and higher during pregnancy or the neonatal period.  Case fatality for the flat-type variant was approximately 95 percent in the unimmunized and 66 percent in previously immunized patients.  The hemorrhagic variant was nearly always fatal.  Case fatality for variola minor (alastrim) is less than 1 percent.

## Control Of Patients, Contacts, And Treatment Areas

4-17. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Control measures are discussed below:


Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.

Strict (standard, contact, and airborne) isolation and quarantine of all patients must be maintained until scabs have separated.  Smallpox can also be spread through direct contact with infected bodily fluids or contaminated objects such as bedding or clothing.  Indirect spread is
less common.  Rarely, smallpox has been spread by virus carried in the air in enclosed settings. Deposit all oral and nasal discharges in a paper container and burn.  Sterilize (autoclave or boil) all bedclothes and other fabrics that are exposed to the patient.  Spray or mop all floors, walls, and other hard surfaces in the patient isolation area with a disinfectant solution (phenolic and quaternary ammonium compounds, formalin, or a 5 percent chlorine solution).  Allow the disinfectant to remain on the surfaces for at least 4 hours.

Guidance on patient contacts are discussed below:

The reappearance of a single case of smallpox would be a global emergency.  Immediately
report all occurrences to Military Public Health.

Quarantine all direct contacts with any case and maintain daily surveillance for 17 days
after last known contact with a case.  Vaccinate all contacts, including health care workers, if
they have not been immunized or received a booster within 3 years.

Conduct an epidemiological investigation to identify all potentially exposed personnel.
Quarantine identified personnel for the remainder of the incubation period; usually 7 to 12 days following the appearance of index cases.

## Medical Evacuation

4-18. Smallpox is an internationally quarantinable disease.  Apply strict quarantine measures.  Isolate all smallpox patients in cohorts.  Do not evacuate smallpox patients unless directed by major command authority.

## Venezuelan Equine Encephalitis Etiologic Agent

4-19. The VEE virus is a mosquitoborne alphavirus.  It is closely related to EEE and WEE viruses.

## Reservoir

4-20. Enzootic serotypes are maintained in a rodent-mosquito cycle.  Enzootic strains are frequently transmitted to humans living in endemic disease areas via mosquito bites.  However, enzootic strains are generally not virulent for horses.  Epizootic serotypes are thought to arise from enzootic strains by mutation.  In contrast to enzootic strains, epizootic strains are highly virulent for equidae (horses, mules, donkeys).  Horses serve as amplifying hosts of epizootic (but not enzootic) strains, providing a source of virus for mosquitoes, which transmit virus to humans.  Epizootic strains of the VEE virus occur in northern South America, Central America (including Mexico), and Trinidad.  Enzootic strains exist in southern Florida.  The WEE is found in North, Central, and South America, but most cases have been reported from the plains regions of the western and central U.S.  The EEE virus occurs in the eastern half of the U.S. Western and eastern equine encephalitis viruses are similar to the VEE complex, are often difficult to distinguish clinically, and share similar aspects of transmission and epidemiology.  The human infective dose for VEE is thought to be approximately 10 to 100 organisms, which is one of the principal reasons that VEE is considered a militarily effective BW agent.

## Transmission

4-21. *Alphaviruses* are a large group of viruses that are spread by certain invertebrate animals, mainly bloodsucking insects.  In the U.S., *alphaviruses* are usually spread by infected mosquitoes.  Birds are often the source of infection for mosquitoes, which can sometimes spread the infection to horses, other animals, and people.  There is no evidence of human-to-human or horse-to-human transmission.  These encephalitic alphaviruses are highly infectious by aerosol, making them extremely hazardous in the laboratory.
Aerosolized exposure is not the normal route of exposure and it is unknown if any cases of aerosolized transmission have occurred.

## Endemic Disease

4-22. The epizootic VEE virus has an incubation period of 1 to 6 days (WEE, 5 to 10 days; EEE, 3 to 10
days).  The usual presentation is an undifferentiated febrile illness with fever, malaise, and headache.
Other symptoms that may appear include myalgia (72 percent), vomiting (50 percent), drowsiness (40 percent), chills (20 percent), sore throat (20 percent), and diarrhea (20 percent).  Fever can remit but recur the following day.  Patients may be incapacitated by malaise and fatigue for 1 to 2 weeks.  Less than 1 percent of adults will develop severe encephalitis featuring meningismus, ataxia, seizures, and coma;
paralysis and neurologic sequelae may result in survivors.  Susceptibility in humans is high (90 to 100 percent) and nearly 100 percent of those infected develop overt illnesses.  The case-fatality rate in adults is approximately 1 percent of all cases, but may reach 10 percent with CNS involvement.  The incidence of CNS disease and fatality rate are expected to be greater in the event of aerosol exposure.

## Biological Warfare Agent Delivery

4-23. The primary threat is delivery by aerosol release.  The intentional release of infected mosquitoes may also present a BW threat.

## Environmental Detection

4-24. The CBRN reconnaissance teams collect aerosol samples; medical personnel collect medical specimens; and veterinary personnel may collect specimen from equines for laboratory analysis and confirmation.  A natural epidemic would usually be preceded by equine disease (outside of its natural geographic range, it would suggest a possible BW attack or importation of infected horses or mosquito vectors).  A BW attack will most likely result in human disease as a primary event, or the simultaneous onset of disease in humans and equines.  A BW attack in an area with equines and mosquito vectors may also initiate an epizootic/epidemic.

## Prevention Preexposure Prophylaxis

4-25. No FDA-approved vaccine is available.  A live attenuated vaccine (TC-83) and an inactivated vaccine (TC-84) are available as an IND only used in the Special Immunizations Program to protect laboratory workers.  For WEE and EEE, a vaccine is available for horses but not for humans.

## Postexposure Prophylaxis

4-26. There are no postexposure prophylaxes available.

## Biological Warfare Clinical Presentation Incubation Period

4-27. For VEE is 1 to 6 days; WEE is 5 to 10; EEE is 3 to 10; onset of symptoms is sudden.

## Signs And Symptoms

4-28. For signs and symptoms, see paragraph 4-17 above (endemic disease).

## Diagnosis

4-29. Perform serologic tests to measure antibody titers.  A single high titer IgM value 5 to 7 days after the onset of illness is supportive; a four-fold rise in antibody titer in paired acute and convalescent sera is diagnostic.  Identification of the virus in clinical specimens (serum,  pharynx, and CSF) by PCR and ECL is under investigation.  Viral cultures may confirm the diagnosis if serum or pharynx samples are sent early during the illness (a low titer viremia is present during the first 24 to 72 hours of illness and pharyngeal cultures may contain virus up to 8 days); however, cultures will be negative later in the clinical course and in those who have progressed to encephalitis.  Nonspecific laboratory findings include lymphopenia and occasionally, neutropenia and mild thrombocytopenia.  Enzyme levels (aspartate aminotransferase and lactate dehydrogenase) are usually elevated and a CSF pleocytosis may be present.

Note.  Report all cases to the line commander, command surgeon, and PVNTMED/public health/
bioenvironmental engineering assets.  PVNTMED/public health assets or field sanitation teams can assist with vector (mosquito) control.

## Treatment

4-30. Medical management is as follows:

There is no specific antiviral therapy.

Administer anticonvulsive therapy for patients with seizures and other supportive care measures as indicated.

## Prognosis

4-31. The VEE virus is an incapacitating agent.  While acute morbidity is severe, most patients recover.
However, animal studies demonstrate that aerosol exposure leads to viral attachment to olfactory nerve endings and direct invasion of the CNS via the olfactory nerve, resulting in a high incidence of CNS disease.  As with VEE and EEE, WEE affects the CNS.  This suggests that in contrast to the mosquitoborne disease, VEE, EEE, and WEE resulting from a BW attack would be more likely to cause CNS involvement and could be associated with higher morbidity and mortality.

## Control Of Patients, Contacts, And Treatment Areas

4-32. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Control measures are discussed below:


Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.

Apply standard precautions for infection control.

Observe standard precautions.  Control mosquito vectors and vaccinate horses in the vicinity. The VEE virus is not communicable person to person.

## Medical Evacuation

4-33. Patients may be evacuated with all other classes of patients.

## Viral Hemorrhagic Fevers Etiologic Agent

4-34. The VHF viruses belong to four distinct families of lipid-enveloped viruses with single-stranded ribonucleic acid genomes.  Viral hemorrhagic fevers are caused by viruses of four distinct families: Arenaviruses, Filoviruses, Bunyaviruses, and *Flaviviruses*.  They are unified by their potential to present as a severe febrile illness accompanied by shock and hemorrhagic diathesis.  The taxonomy, ecology, and epidemiology of these viruses along with the VHF reservoir and transmission information are summarized in Table 4-1.  Transmission of VHFs varies with the specific virus.  All of the VHF agents (with the exception of dengue and yellow fever) are infectious hazards when delivered by aerosol causing severe disease and with an extremely high rate of mortality.  For these reasons, the VHF agents are considered a significant threat for BW use.

| Virus                 |
|-----------------------|
| Arenaviridae Family   |
| New World Complex     |
| Junin                 |
| Machupo               |
| Guanarito             |
| Sabia                 |
|                       |
| Old World Complex     |
| Lassa                 |
|                       |
| Bunyaviridae Family   |
|                       |
|                       |
| S. America            |
| S. America            |
| S. America            |
| S. America            |
|                       |
|                       |
| W. Africa             |
|                       |
|                       |
|                       |
|                       |
|                       |
| Argentina VHF         |
| Bolivian VHF          |
| Venezuelan VHF        |
| Brazilian VHF         |
|                       |
|                       |
| Lassa fever           |
|                       |
|                       |
|                       |
|                       |
|                       |
| Aerosol, fomites      |
| Aerosol, fomites      |
| Aerosol, fomites      |
| Aerosol, fomites      |
|                       |
|                       |
| Aerosol, fomites      |
|                       |
|                       |
|                       |
|                       |
|                       |
| Rodent                |
| Rodent                |
| Rodent                |
| Unknown               |
|                       |
|                       |
| Rodent                |
|                       |
|                       |
|                       |
| Mosquito, aerosol or  |
| fomites from          |
| slaughtering infected |
| animals               |
| Mosquito, aerosol or  |
| fomites from          |
| slaughtering infected |
| animals               |
| Africa                |
|                       |
|                       |
|                       |
| Africa, Middle        |
| East, E. Europe       |
|                       |
|                       |
| Mosquito              |
|                       |
|                       |
|                       |
| Ticks                 |
|                       |
|                       |
|                       |
| Rift Valley fever     |
|                       |
|                       |
|                       |
| Crimean-Congo VHF     |
|                       |
|                       |
|                       |
| VHF with renal syn-   |
| drome                 |
| Aerosol, fomites      |
|                       |
| VHF with pulmonary    |
| syndrome              |
|                       |
| Phlebovirus genus     |
| Rift Valley           |
|                       |
|                       |
|                       |
| Nairovirus genus      |
|                       |
|                       |
| Hantavirus genus      |
| Hantaan               |
|                       |
|                       |
|                       |
|                       |
| Aerosol, fomites      |
|                       |
|                       |
| VHF with renal        |
| syndrome              |
| Aerosol, fomites      |
|                       |
| Asia, Europe          |
|                       |
| N. and S. America     |
|                       |
|                       |
| E. Europe             |
|                       |
| Rodent                |
|                       |
| Rodent                |
|                       |
|                       |
| Rodent                |
|                       |
| Worldwide             |
|                       |
| VHF with renal        |
| syndrome              |
| Dobrava               |
|                       |
| Seoul                 |
|                       |
| Aerosol, fomites      |
|                       |
| Rodent                |
|                       |
| Puumala               |
| Nephropathia          |
| endemica              |
| Aerosol, fomites      |
|                       |
| Europe                |
|                       |
| Rodent                |
|                       |
|                       |
|                       |
|                       |
| Filoviridae Family    |
| Africa, Asia          |
| Ebola VHF8            |
|                       |
| Unknown               |
| Ebola                 |
|                       |
| Unknown               |
| Marburg VHF           |
| Marburg               |
| Flaviviridae Family   |
| Unknown               |
|                       |
|                       |
|                       |
|                       |
| Mosquitoborne         |
| Yellow fever          |
| Yellow fever          |
| Unknown               |
|                       |
|                       |
|                       |
| Mosquito              |
| Mosquito,             |
| primate               |
| Africa                |
|                       |
|                       |
|                       |
| S. America, Africa    |
|                       |
| Dengue, dengue VHF    |
| Mosquito,             |
| Humans                |
| Mosquito              |
|                       |
| Tropics and           |
| subtropics            |
|                       |
| Dengue                |
|                       |
| Tickborne             |
| Tick                  |
| Kyasanur Forest       |
| Kyasanur Forest       |
| Disease               |
| Rodent,               |
| monkey                |
| India                 |
|                       |
| Siberia               |
|                       |
| Tick                  |
| Omsk VHF              |
| Rodent                |
| Omsk                  |

## Reservoir

4-35. For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs.  Each of the VHF families share a number of features such as their survival is dependent on an animal or insect host called the natural reservoir; the viruses are geographically restricted to the areas where their host species live; and humans are not the natural reservoir for any of these viruses.  Humans are infected when they come into contact with infected hosts.  However, with some viruses, after the accidental transmission from the host, humans can transmit the virus to one another.  Refer to Table 4-1 for more information.

## Transmission

4-36. The viruses carried in rodent reservoirs are transmitted when humans have contact with urine, fecal matter, saliva, or other body excretions from infected rodents.  The viruses associated with arthropod vectors are spread most often when the vector mosquito or tick bites a human, or when a human crushes a tick.  However, some of these vectors may spread the virus to animals or livestock.  Humans then become infected when they care for or slaughter the animals.  Some viruses that cause hemorrhagic fever can spread from one person to another, once an initial person has become infected.  This type of secondary transmission of the virus can occur directly, through close contact with infected people or their body fluids. It can also occur indirectly, through contact with objects contaminated with infected body fluids.  For example, contaminated syringes and needles have played an important role in spreading infection in outbreaks of *Ebolavirus* hemorrhagic fever and Lassa fever.  Refer to Table 4-1 for more information.

## Endemic Disease

4-37. Viral hemorrhagic fever is a clinical syndrome featuring fever, myalgia, malaise, and hemorrhage, and in some cases, hypotension, shock, and death.  Viral pathogenesis is complex, incompletely understood, and varies among specific viruses.  Some infections result in immune complex deposition which activates complement and other inflammatory cascades.  This process damages vascular endothelium, results in capillary leak, and deregulates vascular smooth muscle tone.  These lead to hypotension, shock, and end-organ failures.  Some of these diseases activate coagulation cascades and result in DIC.  Hemorrhage can also be enhanced by specific end-organ failures.  For example, yellow fever can cause massive hepatic necrosis resulting in a deficiency of vitamin K-dependent clotting factors.  The uremia complicating the acute renal failure of HFRS leads to platelet dysfunction, further promoting hemorrhage.  The final common pathway of VHF is damage to the vascular endothelium.

## Biological Warfare Agent Delivery

4-38. The primary threat is delivery by aerosol release.

## Environmental Detection

4-39. The CBRN reconnaissance teams collect aerosol samples; medical personnel collect medical specimens; veterinary/PVNTMED/public health personnel collect vector samples; and PVNTMED/public health/bioenvironmental engineering personnel collect suspect or contaminated water samples for supporting laboratory analyses and confirmations.  Veterinary personnel may collect specimens from animals for laboratory analysis and confirmation.

## Prevention Preexposure Prophylaxis

4-40. Yellow fever is the only FDA-approved VHF vaccine.  For preexposure prophylaxis, ensure all Service members have received their yellow fever vaccinations.  Investigational vaccines for Argentine hemorrhagic fever (such as Junin virus) and Rift Valley fever are available as INDs.  Argentine hemorrhagic fever live attenuated vaccine has been safely used and has proven effective with greater than
95 percent efficacy.  Ebola vaccine and therapeutics is in advanced development.

## Postexposure Chemoprophylaxis

4-41. Prophylactic antiviral therapy is not recommended for persons exposed to any hemorrhagic fever viruses (including Lassa virus) in the absence of clinical illness.  Instead, exposed persons should be placed under medical surveillance.

## Biological Warfare Clinical Presentation Incubation Period

4-42. The incubation is typically described as 2 to 21 days.

## Signs And Symptoms

4-43. Viral hemorrhagic fevers are illnesses characterized by fever and bleeding diathesis.  Initial clinical features may include flushing of the face and chest, petechiae, hypotension, frank bleeding, and shock.
Malaise, myalgias, headache, vomiting, and diarrhea occur frequently.  Refer to Table 4-2 for more information on comparison of VHF agents and diseases.


Characteristic
features
Countermeasures
Virus
Incubation
(days)
Mortality
Nosocomial
transmission
Flavivirus
No No No
Overall 5% to
7%, hospitalized patients 20%, if severe
second
phase develops 50%. 3% to 5% 0.5% to 10%
17-D
live
attenuated
vaccine very effective in prevention,
no
postexposure
countermeasure available. Formalin-inactivated vaccine available in India. Tickborne
encephalitis
vaccines (not available in U.S.) may offer some cross-protection.
Often biphasic severe
second
phase
with
bleeding,
very
high
bilirubin
and
transaminases,
jaundice,
renal failure. Flu-like syndrome with addition of cough, GI symptoms,
hemorrhage, bradycardia. Frequent sequelae of hearing loss, neuropsych
complaints,
alopecia.
Yellow
fever Kyansur Forrest Disease Omsk Hemorrhagic fever

3 to 6
2 to 9
2 to 9
Severe illness, maculopapular rash, profuse bleeding and DIC.
Filoviruses
Common Yes
50% to 90% for Sudan/Zaire 23% to 93%
2 to 21
2 to 14
Ebola Marburg
Anecdotal success with immune
serum
transfusion.

Vaccine
and
therapeutics in advanced development. Therapeutics
in
advanced development.
Bunyaviruses
Yes No No
3 to 12
2 to 6

9 to 35
30% 1%, for hemorrhagic
disease
50% 5%
for
Asian
HFRS
Crimean- Congo Hemorrhagic fever Rift Valley fever Hanta (Hantaan, Dobrava, Seoul,
Puumala)
Often
prominent
petechial/ecchymotic rash. Hemorrhagic disease rare,
classically
associated with retinitis and
encephalitis.
Significant
threat
to
livestockepidemics of abortion and death of young. Prominent
renal
disease, marked polyuric
phase
during
recovery, usually elevated
white
blood
cells.
Anecdotal success with ribavirin. Formalin-inactivated vaccine (3 boosters). Live
attenuated
viral
strain MP-12. Effective locally produced vaccines in Asia (not available
in
U.S.).
Experi-mental vaccine at
USAMRIID.

Ribavirin
effective in randomized, controlled clinical trial.
Arenaviruses
Yes Rare Rare
5 to 16
7 to 14
9 to 15
Lassa Junin Machupo
Frequent
inapparent/
mild infection, hearing loss in convalescence common. Prominent
GI
complaints, late neurologic syndrome. Similar to Argentine hemorrhagic fever.
Overall 1% to 2%, hospitalized patients 15% to 25% 15% to 30% 30%
Ribavirin
effective
in
clinical trial with nonrandomized controls. Live
attenuated
Junin
vaccine strain (Candid 1) developed by USAMRIID and available as an IND. Therapeutics
in
advanced development. Immune plasma effective, ribavirin probably effective, Candid 1 vaccine protects monkeys.

## Diagnosis

4-44. Definitive diagnosis is usually made at a reference laboratory with advanced biocontaminant capability.  Serologic methods include IgM antibody capture and ELISA techniques to detect the antigen.
Tissue can be submitted for immunohistochemical staining, electron microscopy, or for genetic typing.
Serum and other clinical specimens should be forwarded for viral culture under maximum containment (Biosafety Level 4).  Laboratory findings are nonspecific and variable.  In general, these result in thrombocytopenia and leukopenia.  Elevated liver function tests and other nonspecific laboratory findings may be present.  The blood urea nitrogen will be related to the circulatory status with the exception of HFRS in which the kidneys are target organs of the hantaviruses.  Differential diagnosis includes diseases such as typhoid fever, meningococcemia, leptospirosis, malaria, vasculitic diseases, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and the diverse etiologies of DIC.

## Treatment

4-45. Medical management is as follows:


Supportive care is essential for patients with all types of VHF to include

Maintenance of fluid and electrolyte balance with hemodynamic monitoring as needed.

Mechanical ventilation as indicated.

Dialysis as indicated.

Steroids could be considered in certain situations.

Appropriate therapy for secondary infections.

Management of severe bleeding complications is controversial.  Potential therapies include clotting factor concentrates, platelets, fresh frozen plasma, and heparin for DIC.  Convalescent human plasma has been shown to be effective in the treatment of Argentine hemorrhagic fever and has been suggested for treatment of other New World arenavirus infections.

No antiviral drugs are approved by the FDA for treating VHFs.  Although Ribavirin is FDA licensed and indicated for treatment of hepatitis C, Ribavirin therapy for arenavirus and bunyavirus hemorrhagic fevers is not FDA-approved.  Ribavirin appears to be effective in animals and could be used cautiously in humans.  Antiviral agents have not been shown to be effective, and are not recommended, for infections caused by Filoviruses (Ebola and Marburg hemorrhagic fever), Flaviviruses (yellow fever, Kyasanur Forest disease, and Omsk hemorrhagic fever).  Refer to Table 4-3 for the recommended regimens for use of ribavirin.

|                                        | Patient group                     | Contained-casualty setting    |
|----------------------------------------|-----------------------------------|-------------------------------|
| Mass casualty setting                  |                                  |                               |
| Adults (including preg-                |                                   |                               |
| nant women)                           |                                   |                               |
| Loading dose of 30 mg/kg (maximum      |                                   |                               |
| dose, 2 gm) IV once, then:             |                                   |                               |
|                                        | - 16 mg/kg (maximum dose, 1 gm)   |                               |
| IV every 6 hrs for 4 days.             |                                   |                               |
|                                        | - 8 mg/kg (maximum dose, 500 mg)  |                               |
| IV every 8 hrs for 6 days.             |                                   |                               |
| Loading dose of 2,000 mg by mouth      |                                   |                               |
| once, then:                            |                                   |                               |
|                                        | - ~Weight >75 kg:  1,200 mg/day   |                               |
| by mouth in 2 divided doses for 10     |                                   |                               |
| days.                                 |                                   |                               |
|                                        | - ~Weight <75 kg:  1,000 mg/day   |                               |
| by mouth in divided doses (400 mg in   |                                   |                               |
| a.m. and 600 mg in p.m.) for 10 days. |                                   |                               |
| Loading dose of 30 mg/kg by mouth      |                                   |                               |
| once, then:                            |                                   |                               |
|                                        | - 15 mg/kg/day by mouth in 2      |                               |
| divided doses for 10 days.             |                                   |                               |
| Children                               | Loading dose of 30 mg/kg (maximum |                               |
| dose, 2 gm) IV once, then:             |                                   |                               |
|                                        | - 16 mg/kg (maximum dose, 1 gm)   |                               |
| IV every 6 hrs for 4 days.             |                                   |                               |
|                                        | - 8 mg/kg (maximum dose, 500 mg   |                               |
| IV) every 8 hrs for 6 days.            |                                   |                               |

*These are the recommendations of the Working Group on Civilian Biodefense; ribavirin is not approved by the U.S. FDA for treatment of viral hemorrhagic fever and must be used under an IND protocol, although in a mass casualty setting this requirement may need to be modified. The decision to use oral rather than parenteral medication will depend on available resources. Generally, ribavirin is contraindicated in pregnant women; however, the Working Group believes that the benefits appear to outweigh the fetal risk of ribavirin therapy.  Also, the mortality of viral hemorrhagic fever appears to be higher in pregnancy. A 1,000-mg dosage per day given in 3 divided doses has been used to treat patients with Lassa fever; however, this regimen cannot be used in the U.S., because the current available formulation of ribavirin is 200 mg capsules, which cannot be broken open.

## Prognosis

4-46. Prognosis varies from agent to agent; case-fatality rates range from less than 0.5 percent (Omsk hemorrhagic fever) to 93 percent (Marburg).  Survivors may be left with long-term sequelae (such as blindness, neurosensory hearing loss, and other neurologic, retinal, and ocular involvement).  Refer to Table 4-4 for more information on case-fatality rates and complications.


| Case-fatality rate                               | Complications                                      |
|--------------------------------------------------|----------------------------------------------------|
|                                                  |                                                    |
| Generally occur at least 2 weeks after illness   |                                                    |
| onset.                                           |                                                    |
|                                                  | Migratory arthralgias.                             |
|                                                  | Ocular disease (unilateral vision loss, uveitis).  |
|                                                  | Suppurative parotitis.                             |
|                                                  | Orchitis.                                          |
|                                                  | Hearing loss.                                      |
|                                                  | Pericarditis.                                      |
|                                                  | Illness-induced abortion among pregnant            |
|                                                  |                                                    |
| Ebola hemorrhagic fever                          |                                                    |
| Varies by virus subtype:                         |                                                    |
|                                                  | Zaire, 57% to 90%.                                 |
|                                                  | Sudan, about 50%.                                  |
|                                                  | Cote d'Ivoire, not established.                    |
|                                                  | Reston, 0% (not known to cause clinical disease in |
|                                                  |                                                    |
| In 1995 Democratic Republic of Congo outbreak:   |                                                    |
| mean number of days from symptom onset to death, |                                                    |
| 9.6 days (range, 0 to 34 days).                  |                                                    |
|                                                  |                                                    |
|                                                  |                                                    |
|                                                  |                                                    |
| Marburg hemorrhagic fever                        |                                                    |
| Varies by outbreak (23% to 93%).                 |                                                    |
|                                                  |                                                    |
| Generally occur at least 2 weeks after illness   |                                                    |
| onset.                                           |                                                    |
|                                                  | Orchitis.                                          |
|                                                  | Alopecia.                                          |
|                                                  | Uveitis.                                           |
|                                                  | Recurrent hepatitis.                               |
|                                                  |                                                    |
| Lassa fever                                      |                                                    |
| Overall mortality (including nonhospitalized     |                                                    |
|                                                  | patients)1% to 2%.                                |
| Hospitalized patients15% to 25%.                |                                                    |
| Series of 150 hospitalized patients9%.          |                                                    |
| Series of 441 hospitalized patients16.5%.       |                                                    |
|                                                  |                                                    |
|                                                  |                                                    |
|                                                  |                                                    |
| Generally occur in 2                             |                                                    |
| d                                                |                                                    |
| and 3                                            |                                                    |
| rd                                               |                                                    |
| week of illness.                                 |                                                    |
|                                                  | 8                                                  |
| th                                               |                                                    |
| cranial nerve damage with hearing loss           |                                                    |
|                                                  |                                                    |
|                                                  |                                                    |
|                                                  | Pericarditis (about 2% of patients in one          |
|                                                  |                                                    |
|                                                  | Transient alopecia during convalescence.           |
|                                                  | Illness-induced abortion among pregnant            |
|                                                  |                                                    |
|                                                  | Uveitis and orchitis (uncommon).                   |
|                                                  |                                                    |
| Transient alopecia and nail furrows may occur.   |                                                    |
| Most patients who survive recover without        |                                                    |
|                                                  | sequelae,                                          |
|                                                  | require several weeks.                             |
| New World hemorrhagic fever                      |                                                    |
| Junin (Argentine hemorrhagic fever)15% to 30%.  |                                                    |
| Machupo (Bolivian hemorrhagic fever)30%.        |                                                    |
| Guanarito (Venezuelan hemorrhagic fever)25%.    |                                                    |
| Sabia (Brazilian hemorrhagic fever)33% (only 3  |                                                    |
|                                                  | cases identified, 1 fatal).                        |
| Whitewater Arroyo100% (only 3 cases identified; |                                                    |
|                                                  | all fatal).                                        |
| Case-fatality rate                               | Complications                                  |
|--------------------------------------------------|------------------------------------------------|
|                                                  |                                                |
| Blindness following retinitis.                   |                                                |
| Neurologic sequelae following encephalitis.      |                                                |
| Rift Valley fever                                |                                                |
| Overall:  <1%.                                   |                                                |
| For hemorrhagic disease, about 50%.              |                                                |
| In 2000 outbreak in Saudi Arabia17% among       |                                                |
|                                                  | symptomatic                                    |
|                                                  | hospitalized patients admitted to Rift Valley  |
|                                                  | fever unit at local referral hospital.         |
| Death usually due to hepatic necrosis and DIC.   |                                                |
|                                                  |                                                |
| Myocarditis.                                     |                                                |
| Yellow fever                                     |                                                |
| Overall5% to 7%.                                |                                                |
| Hospitalized patients or in some epidemicsabout |                                                |
|                                                  | 20%.                                           |
| Patients                                         | in                                             |
|                                                  | (jaundice, bleeding manifestations)about 50%. |
|                                                  |                                                |
| Transient alopecia may occur.                    |                                                |
| Omsk hemorrhagic fever                           |                                                |
| 0.5% to 10%.                                     |                                                |

Source:  Center for Infectious Disease Research and Policy Copyright Regents of the University of Minnesota.

## Control Of Patients, Contacts, And Treatment Areas

4-47. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Control measures are discussed below:


Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.

Report suspected cases of VHFs outside the U.S. to PVNTMED/public health personnel immediately.  Yellow fever is an internationally quarantinable disease.

The following recommendations apply to patients with suspected or proven arenavirus, filovirus, or Crimean-Congo VHF virus infections:  these patients should be isolated in private rooms or isolation tents; if private rooms are not available, only other patients with the same disease should be in the same room; a negative air flow room should be used, if possible, if the patient has significant cough, hemorrhage, or diarrhea.  Limit exposure to caregivers only; other staff members and visitors should not be allowed in the room to avoid injuries/nosocomial exposures. Caregivers should be the most skilled/experienced staff.

The following recommendations apply to patients with suspected or proven arenavirus, filovirus, or Crimean-Congo VHF virus infections: all caregivers must wear gloves and gowns; anyone
coming within 3 feet of the patient should also wear a minimum of a National Institute for Occupational Safety and Health approved N-95 respirator (or a surgical N-95 respirator jointly approved by both FDA and National Institute for Occupational Safety and Health) and eye/face protection (for example, face shield, goggles or eyeglasses with side shields).  When caring for
patients with prominent cough, vomiting, diarrhea, or hemorrhage, caregivers should wear, as a minimum, a National Institute for Occupational Safety and Health approved P-100 particulate respirator (for example, powered air-purifying respirator) with a high-efficiency particulate air or P-100 filter, or a full facepiece positive pressure supplied air respirator.  Any use of military or commercial respirators must be part of the Service-specific respirator program to include
appropriate fit testing, training, and medical clearance.

Sewage, bulk blood, suctioned fluids, secretions, and excretions should be autoclaved, processed in a chemical toilet, or treated with a 5 percent chlorine solution for at least 5 minutes in bedpan or commode prior to flushing.

Guidance on patient contacts are discussed below:

Casual contacts.  There is no known risk of transmission to casual contacts, such as
travelers in the same airplane.

Close contacts.  Close contacts, such as household members, physicians, nursing care, and
individuals handling laboratory specimens, increase the possibility of contracting the disease. Close contacts should have their temperature recorded twice daily for 3 weeks postexposure.
Close contacts should receive postexposure evaluation/treatment if fever (above 101F) or other
systemic symptoms present within 3 weeks of exposure.

High-risk contacts.  High-risk contacts include anyone who has mucous membrane or
percutaneous exposures.  High-risk contacts with mucous membrane exposure should copiously irrigate with water or eyewash solution for at least 15 minutes.  For cutaneous exposure,
individuals should frequently wash affected skin surfaces with soap and water; an antiseptic
solution or handwashing agent may also be considered to provide better removal of any contamination on the exposed surfaces.  High-risk contacts with exposure to Lassa fever and
Crimean-Congo VHF should
- Call USAMRIID at 1-888-USA-RIID (1-888-872-7443) during duty hours if there are
any questions.  After duty hours, contact (301) 619-2257 (DSN 343), and ask to speak with the on-call medical staff.  Refer to Table 4-3 for ribavirin therapy.
- Record their temperature twice daily for 3 weeks postexposure. - Receive further evaluation/treatment if fever (greater than 101F) or other systemic
symptoms present within 3 weeks of exposure.

## Medical Evacuation

4-48. Medical evacuation may result in increased morbidity and mortality.  Strict isolation must be used for all patients evacuated.  Obtain approval from the senior medical authority before evacuation.

## Chapter 5 Toxin Agents Toxins

5-1. Toxins are poisonous byproducts of living organisms.  They are very stable and produce severe illness when ingested, inhaled, or introduced into the body by any other means.  Some toxins are susceptible to heat, while others are heat stable.  Their effects on the human body range from minor illness to death.  Toxins may be much more toxic (based on weight) than chemical agents.

## Clostridium Botulinum Toxin Etiologic Agent

5-2. Botulinum toxins are a group of seven related neurotoxins produced by the spore forming bacillus, Clostridium botulinum.  The spores are ubiquitous; they germinate to give rise to vegetative bacteria that produce toxins during anaerobic incubation.  Industrial-scale fermentation can produce large quantities of toxin for use as a BW agent.  There are three forms of naturally occurring botulismfoodborne, infantile, and wound.  Botulinum toxin is the most potent neurotoxin known; paradoxically it has been used therapeutically to treat spastic conditions (strabismus, blepharospasm, torticollis, and tetanus).  Botulinum toxin consists of two polypeptide subunits (A and B chains).  The B subunit binds to a receptor on the axons of motor neurons.  The toxin is taken into the axon, where the A chain exerts its cytotoxic effect; it inactivates the axon, preventing release of acetylcholine and neuromuscular transmission (presynaptic inhibition).  Recovery follows only after the neuron develops a new axon, which can take months.  The presynaptic inhibition affects both autonomic (muscarinic) and motor (nicotinic) receptors.

## Reservoir

5-3. The reservoir is soil, animals, and fish.  The organisms can be recovered from honey and other agricultural products.  High-risk foods are primarily improperly canned foods and dried meat or fish.

## Transmission

5-4. Consumption of food contaminated with the *C. botulinum* toxin.

## Endemic Disease Foodborne

5-5. The food is contaminated with the bacterial spores.  These spores germinate and produce toxin.
Ingestion of the toxin now present in the food causes the clinical syndrome of botulism.  Inadequately heating vegetables and fruits during canning or inadequate heating before serving is the primary mode of transmission.  Other natural sources of intoxication include smoked sausage, seafood, salmon, and fermented salmon eggs.

## Infantile

5-6. Germination of spores leading to colonization and toxin production may occur in the infantile GI
tract due to anatomic, physiologic, and microbiologic factors present during the first year of life. Clostridium botulinum spores survive transit through the stomach in infants, relative to achlorhydria; spores can then germinate and colonize the intestinal tract in the absence of well-established GI tract microflora. Parents are advised not to feed infants honey, molasses, and other foods potentially high in *C. botulinum*
spore content to prevent this disease.  This form of botulism is a rare disease of adults, but may occur in cases of underlying anatomic or physiologic abnormalities of the GI, or alteration of the normal GI tract flora (such as after antibiotic exposure).

## Wound

5-7. Wound botulism is due to the germination of *C. botulinum* spores and in-situ toxin production in traumatic wounds.  The spores may be introduced by organisms entering during wounding, by drug abusers through injection sites, and by cocaine abusers inhaling the spores into ischemic nasal ulcers and sinuses.
Botulism can feature milder presentations limited to cranial nerve palsies and mild GI symptoms related to autonomic dysfunction.  Botulism should be considered in the differential diagnosis of patients presenting with symptoms of cranial nerve neuropathies, especially if numerous patients present simultaneously.

## Biological Warfare Agent Delivery

5-8. The primary threat is delivery by aerosol release.  Inhalation challenge does not occur naturally, but can be used in a BW attack.  Aerosol dispersion has delivered lethal intoxication to experimental animals.
The BW agent may also be delivered through contaminated food or water.

## Environmental Detection

5-9. The CBRN reconnaissance teams collect aerosol samples; medical personnel collect medical specimens; veterinary/PVNTMED/public health personnel collect suspect or contaminated food samples; and PVNTMED/public health/bioenvironmental engineering personnel collect suspect or contaminated water samples for supporting laboratory analyses and confirmations.

## Prevention Preexposure Prophylaxis

5-10. There is no FDA-licensed vaccine currently available, however, vaccines for types A and B are in advanced development. A pentavalent (types A, B, C, D, and E) toxoid vaccine has been developed as a preexposure prophylaxis.  This vaccine is safe and effective in animal studies, and has been demonstrated to be safe in human volunteers.  The vaccine remains under an IND status since it is not feasible to test for efficacy in humans.  The pentavalent botulinum toxoid vaccine is given at 0, 2, and 12 weeks with annual booster doses thereafter.     Vaccines for types A and B are in advanced development.

## Postexposure Prophylaxis

5-11. Currently, postexposure prophylaxis is not available.  Animal experiments demonstrate that botulinum antitoxin is effective; however, human data or practice guidelines are not available.  Botulinum antitoxin should be considered in extraordinary circumstances.

## Biological Warfare Clinical Presentation Incubation Period

5-12. The incubation period for foodborne botulism is usually 24 to 36 hours. The incubation period for infantile botulism is unknown.  The incubation period for wound botulism may take up to 2 weeks to appear.  The onset of symptoms of inhalation botulism usually occurs 12 to 36 hours after exposure but can vary according to the amount of toxin absorbed and could be reduced to hours following a BW attack.

## Signs And Symptoms

5-13. The autonomic features of botulism are typical anticholinergic signs and symptoms: dry mouth, ileus, constipation, and urinary retention.  Nausea and vomiting may occur as nonspecific sequelae of ileus. Dilated pupils (mydriasis) occur in approximately 50 percent of cases.

5-14. The motor complications of botulism feature a descending paralysis, usually beginning with cranial nerve palsies leading to blurred vision, diplopia, dysphonia, and dysphagia.  Collapse of the upper airway may occur due to weakness of the oropharyngeal musculature.  As the descending motor weakness involves the diaphragm and accessory muscles of respiration, respiratory failure may occur.

5-15. Sensory symptoms usually do not occur.  Botulinum toxins do not cross the blood/brain barrier and do not cause CNS disease.  However, the psychological sequelae of botulism may be severe and require specific intervention.

## Diagnosis

5-16. Botulism is primarily a clinical diagnosis based on symptoms of botulism (descending paralysis with cranial nerve dysfunction) that may be supported by epidemiologic or nerve conduction studies as treatment of antitoxin must be given as early as possible to have greatest effect, and confirmatory tests for botulism take days.  Nerve conduction studies and single-fiber electromyography can confirm the diagnosis, although these modalities may not be readily available in a tactical setting.  Nerve conduction tests are not diagnostic but only supportive and facilitation may be abnormal in only 65 percent of cases and single-fiber electromyography in only 15 percent.  Edrophonium test results can be positive in botulism as well as in myasthenia gravis; therefore, this test may not be useful due to the lack of specificity.
Laboratory confirmation may be obtained by the use of an ELISA or ECL test to detect toxin antigen.  The assay may be used to test specimens of implicated food or water, or samples obtained from the environment.  Clinical specimens submitted for study may include serum, gastric aspirates, stool, and respiratory secretions.  A simple bioassay (mouse neutralization) confirms the diagnosis if an aliquot of a clinical specimen from the patient produces descending paralysis when injected into a laboratory mouse. Antibody tests are not useful for botulism, as the amount of antigen required to stimulate an antibody response exceeds the lethal dose.

## Treatment

5-17. Medical management is as follows:


Treatment of botulism consists of supportive care, and passive immunization with botulinum antitoxin.  Botulinum antitoxins are most effective if given early as the antitoxin only neutralized circulating botulinum toxin and has no effect on the toxin already bound.  Early administration of antitoxin has been associated with decreased duration of mechanical ventilation and decrease in the number of hospitalized days.  Antibiotics are also recommended for wound botulism (includes sinusitis), as well as incision and debridement of the wound.  Ideally, the wound should be debrided after administration of antitoxin as the debridement and irrigation may result in increase of toxin into the bloodstream that would need to be neutralized.

The decision to give antitoxin is based on a presumptive diagnosis of botulism, based on clinical signs and symptoms consistent with botulism.  The diagnosis may be supported by epidemiology risk factors and electrodiagnostic testing, and exclusion of other causes of paralysis.  Before 2006, antitoxin was not recommended if greater than 7 days after the onset of neurological symptoms and if symptoms were not progressing.  After an outbreak of botulism associated with
high levels of toxin in carrot juice (resulted in serum toxin 10 times higher than any previous case and toxin still present in the serum at days 12 and 25 postingestion in two subjects), the
recommendations were changed to consider antitoxin even if greater than 7 days postingestion and stable neurological findings.  This is highly recommended after a known high dose of toxin exposure.   Another recommendation to consider is a follow-up serum toxin assay and a second dose of botulinum antitoxin if the individual is still toxemic.

The current antitoxin for adults is an investigational hepatavalent despeciated antitoxin that contains antitoxin against all 7 toxin serotypes (A-G), known as H-BAT and currently only
available from the CDC. The despeciated antitoxin product is based on two despeciated hepatavalent products produced by USAMRIID (HE-BAT and Hfab-BAT) that have been demonstrated to be protective against botulinum toxin in animal models and were given to humans without occurrence of serious adverse events.  The despeciated antitoxins are prepared
by cleaving the species specific Fc fragments from the immune globulin, for the purpose of reducing allergic reactions due to horse protein.  However, 2 percent of horse antigen product
still remains; there is still a risk of hypersensitivity reactions. The HE-BAT USAMRIID product is available on protocol in the DOD.  However, the Cangene H-BAT is the recommended treatment of choice, if readily available (Cangene H-BAT product not available outside the U.S.).  Before administration of an investigational heptavalent botulinum immune globulin, one must have institutional review board approval.  Because of the risk of severe allergic reactions
(anaphylaxis, angioedema), the product must be administered in a medical setting with available trained medical personnel who are able to treat a possible anaphylactic reaction and with equipment to handle anaphylaxis readily available (intubation equipment, epinephrine, and IV access established).


While the despeciated antitoxin products may be given to infants, Baby-BIG (an FDA-approved human antitoxin for treatment of botulism due to serotypes A and B) or an investigational human antitoxin E product (both available from the California Department of Public Health) are the recommended treatment of choice (unless intoxication is from a serotype other than A, B, or E), as the human antitoxin does not contain horse protein (reduces risk of anaphylaxis and avoids sensitization of infant to horse protein for life) and has a longer serum half-life than the
despeciated products.  The FDA-approved botulinum antitoxin is no longer available at the CDC.
Note.  Aminoglycosides and clindamycin may further impair neuromuscular transmission and may lead to clinical deterioration if used for patients with botulism.

## Prognosis

5-18. Botulism can result in severe morbidity; untreated botulism is frequently fatal.  Complications include descending paralysis, with possible respiratory failure.  Case fatality is approximately 60 percent without respiratory intensive care.  However, with respiratory supportive care, prognosis is favorable, with case-fatality rates at approximately 5 percent.  Recovery may be prolonged, requiring up to three months for signs of initial improvement and up to one year for complete symptomatic recovery.  Psychological sequelae may be severe and require specific interventions.

## Control Of Patients, Contacts, And Treatment Areas

5-19. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  The patient can be evacuated.  Employ standard precautions; botulism is not communicable person to person.

## Medical Evacuation

5-20. Patients may be evacuated with other classes of patients.  Observe standard precautions for evacuation.

## Clostridium Perfringens Toxins Etiologic Agent

5-21. *Clostridium perfringens* is a common gram-positive, spore forming, anaerobic bacillus that produces five toxin types (A, B, C, D, and E).  These toxin types produce four major toxinsalpha, beta, epsilon, and iota.  Spores are relatively heat stable, readily germinate, and multiply during storage at ambient temperature, slow cooling, or inadequate rewarming.  A high inoculum (greater than 100,000 colonyforming units/gm of food) is usually required to produce enteric disease.

## Reservoir

5-22. The reservoir is soil and the GI tract of healthy persons and animals.

## Transmission

5-23. Gas gangrene results from wound contamination with soil containing spores of *C. perfringens*.
Clostridial food poisoning follows ingestion of foods contaminated with soil or feces and then stored under conditions that allow germination and replication of the organism-yielding toxin.

## Endemic Disease

5-24. The diseases produced by these toxins depend upon the site of *C. perfringens* colonization or infection and toxin production.  For example, wound infection results in gas gangrene, while ingesting contaminated food results in clostridial food poisoning, or in susceptible hosts, enteritis necroticans. Clostridial food poisoning is usually a brief, self-limited disease, featuring the abrupt onset of nausea, abdominal colic, and diarrhea; vomiting and fever are rare.  Individuals can develop gas gangrene by having wounds contaminated with soil containing bacterial spores.  The spores germinate, resulting in bacterial toxin production.  Gas gangrene (clostridial myonecrosis) features necrosis of skeletal muscle and overlying soft tissue thus constituting a surgical emergency.

## Biological Warfare Agent Delivery

5-25. The primary threat is delivery of *C. perfringens* alpha or epsilon toxin as an aerosol to the respiratory tract.  This would result in pulmonary disease, vastly different from the naturally occurring diseases associated with *C. perfringens*.  These toxins may also be delivered in combination with other toxins to produce a variety of clinical effects.

## Environmental Detection

5-26. The CBRN reconnaissance teams or other bioenvironmental engineering personnel operating similar detection equipment perform detection procedures.  Medical personnel collect specimens to include pulmonary secretions for laboratory analysis and confirmation.

## Prevention

5-27. There is no preexposure or postexposure prophylaxis for *C. perfringens*.

## Biological Warfare Clinical Presentation Incubation Period

5-28. The incubation period is 1 to 6 hours.

## Signs And Symptoms

5-29. Aerosol challenges of *C. perfringens* alpha toxin produce lethal pulmonary disease in laboratory animals.  The *C. perfringens* alpha toxin is a highly toxic phospholipase, which will result in severe injury to the exposed respiratory tract.  An aerosol delivery can produce a severe pulmonary capillary leak, resulting in adult respiratory distress syndrome, and respiratory failure.  Absorbed toxin can lead to intravascular hemolysis, thrombocytopenia, and liver damage.  The *C. perfringens* epsilon toxin is naturally associated with veterinary disease.  Aerosol forms of epsilon toxin may cause neurotoxic symptoms.

## Diagnosis

5-30. Acute serum and tissue specimens should be collected and transported to the designated reference laboratory for toxin immunoassay.  Clinical laboratory findings could include anemia, thrombocytopenia, abnormal liver function tests, and hypoxia.  The differential diagnosis should include other causes of adult respiratory distress syndrome such as chemical warfare agent (phosgene or mustard) exposure, inhalation injury due to ricin or SEB.  Pulmonary disease will be less severe.  Hemolysis, thrombocytopenia, or liver damage should not occur due to SEB.

## Treatment

5-31. Medical management is as follows:


Medical management consists of supportive care.

Patients may require assisted ventilation to relieve the respiratory effects.  There are no specific
antitoxins or antidotes available.

## Prognosis

5-32. The organism itself is sensitive to penicillin, and consequently, this is the current drug of choice.
Recent data indicate that Clindamycin or Rifampicin may suppress toxin production and provide superior results in animal models.

## Control Of Patients, Contacts, And Treatment Areas

5-33. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in patient care.  The *C. perfringens* toxin is not communicable person to person.

## Medical Evacuation

5-34. Patients may be evacuated.  Apply standard precautions during evacuation.

## Ricin Etiologic Agent

5-35. Ricin is a potent cytotoxin derived from the beans of the castor plant (*Ricinus communis*).  Over one million tons of castor beans are processed annually in the production of castor oil, which is used for medicinal and industrial purposes including the production of aircraft and marine engine lubricants, dyes, and paints.  The waste mash from this process is approximately 5 percent ricin by weight.  Consequently, large quantities of ricin are easily and inexpensively produced.  Ricin consists of two glycoprotein chains (A and B) bound together by a disulfide bond.  The A-chain is a potent ribosome-inactivating protein that inhibits intracellular protein synthesis.  The B-chain possesses lectin-like properties that bind the heterodimer to cellular surfaces and initiate endocytic uptake of the protein complex.  Once inside the cell, the disulfide bond is reductively cleaved. Ricin's A-chain is then able to attack the ribosomes.

## Reservoir

5-36. Castor beans.

## Transmission

5-37. Transmission has been by inhalation of dust or waste mash containing the toxin during industrial operations.  Also, transmitted through ingestion of castor bean meal or percutaneous injection.

## Endemic Disease

5-38. There is no real endemic disease from Ricin in the environment.  Endemic disease occurs from ingestion of castor beans.  Clinical features vary according to the route of intoxication and toxin dose. Accidental sublethal aerosol exposures occurred during the 1940's.  Patients presented with acute onset of fever, chest tightness, cough, dyspnea, nausea, and arthralgias 4 to 8 hours after exposure.  The onset of profuse sweating several hours later was the sign of termination of most of the symptoms.  Lethal aerosol exposures in humans have not been reported; however, aerosol exposures in experimental animals result in necrosis of upper and lower respiratory epithelium, and perivascular and alveolar edema.  Respiratory tract exposure to a large dose will produce necrosis of the entire exposed respiratory tract; pulmonary capillary leaks result in extravasation of protein-rich fluid into the alveoli, resulting in pulmonary edema, adult respiratory distress syndrome, and respiratory failure.  Ingestion results in necrosis of the GI epithelium, local hemorrhage, and hepatic, splenic, and renal necrosis.  Intramuscular injection of ricin usually results in necrosis of the muscle and local lymph nodes and may also have other sites involved due to systemic absorption such as visceral organ involvement.

## Biological Warfare Agent Delivery

5-39. The primary threat is delivery of the BW agent by aerosol release.  Ricin is less toxic than botulinum.
The agent may also be delivered through contamination of food and water supplies.

## Environmental Detection

5-40. Refer to paragraph 5-9 for information on environmental detection.  Specific ELISA and ECL tests of serum and respiratory secretions, or immunohistochemical stains of tissue may be used where available to confirm the diagnosis.  Ricin is an extremely immunogenic toxin, and paired acute and convalescent sera should be obtained from survivors to measure antibody response.  Polymerase chain reaction can detect castor bean DNA in most ricin preparations.

## Prevention Preexposure Prophylaxis

5-41. Preexposure prophylaxis is not available; however, candidate vaccines are under development.

## Postexposure Prophylaxis

5-42. Postexposure prophylaxis is not available.

## Biological Warfare Clinical Presentation Incubation Period

5-43. The incubation period is 18 to 24 hours.

## Signs And Symptoms

5-44. See endemic disease above.

## Diagnosis

5-45. Serum and respiratory secretions may be submitted for antigen detection (ELISA). Immunohistochemical stains of tissue may also be available.  Paired acute and convalescent sera for antibody studies can be submitted from survivors.  Nonspecific laboratory and radiographic findings may include neutrophilic leukocytosis, and bilateral interstitial infiltrates compatible with noncardiogenic pulmonary edema.  Differential diagnosis of respiratory disease would include phosgene exposure, SEB, hantavirus pulmonary syndrome, atypical pneumonias including Q fever and tularemia, and diverse causes of adult respiratory distress syndrome.

## Treatment

5-46. Medical management is as follows:


Supportive care including intensive care measures such as supplemental oxygen, endotracheal
intubation and mechanical ventilation, positive end-expiratory pressure, and hemodynamic monitoring may be required for respiratory disease.

Gastrointestinal intoxication is best managed by vigorous gastric decontamination with lavage
and superactivated charcoal, followed by use of cathartics such as magnesium citrate.  Volume and electrolyte replacement of GI tract fluid loss is important.

In percutaneous exposures, treatment would be primarily supportive, managing specific organ system failures.

Specific therapeutic drugs are not currently available.

## Prognosis

5-47. Prognosis depends on the route and intensity of exposure.  High morbidity and long term sequelae may result from significant exposure.  Active immunization and passive antibody prophylaxis are under study, as both are effective in protecting animals from death following exposure by IV or respiratory routes.

## Control Of Patients, Contacts, And Treatment Areas

5-48. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in patient care.  Ricin poisoning is not communicable person to person.

## Medical Evacuation

5-49. Patients may be evacuated.  Apply standard precautions during evacuation.

## Saxitoxin Etiologic Agent

5-50. Saxitoxin is the parent compound of a group of related neurotoxins produced by marine dinoflagellates for the genera Alexandrium (previously Gonyaulax), Pyrodinium, and Gymnodinium, as well as others.

## Reservoir

5-51. Shellfish, big reef fish, certain octopods, and certain snails.

## Transmission

5-52. Saxitoxin is transmitted to humans by ingesting bivalve mollusks such as clams, mussels, and scallops, which accumulate dinoflagellates during filter feeding.

## Endemic Disease

5-53. Paralytic shellfish poisoning is a severe, life-threatening neuromuscular condition.  Saxitoxin is rapidly absorbed from the GI tract following ingestion of contaminated shellfish.  Saxitoxin binds to the sodium channels of nerve and muscle tissue, preventing propagation of action potentials in excitable cells. This leads to neuromuscular dysfunction, and in severe cases, death due to respiratory paralysis and respiratory failure.  In contrast to botulism, sensory and CNS symptoms are present in addition to motor symptoms.  Symptoms begin as early as 10 minutes to several hours after ingestion, depending on the ingested dose and host factors.  Initial symptoms include numbness and tingling of the lips, tongue, and fingertips; followed by numbness of the neck and extremities and motor incoordination.  Cranial nerve involvement can result in diplopia, speech, and swallowing difficulties.  Other symptoms may include light-headedness, dizziness, weakness, confusion, memory loss, and headache.  Flaccid paralysis and respiratory failure are life-threatening complications, and occur within 2 to 12 hours after ingestion.  The toxin is rapidly cleared by renal excretion; however, complete neurologic recovery may require 7 to 14 days.

## Biological Warfare Agent Delivery

5-54. The primary threat is delivery by aerosol release. Saxitoxin may also be delivered by projectiles or by contamination of food and water.  Contamination of food and water supplies would be on a very limited basis.

## Environmental Detection

5-55. Refer to paragraph 5-9 for information on environmental detection.

## Prevention Preexposure Prophylaxis

5-56. There is no preexposure prophylaxis available.  Avoidance of potentially contaminated food and water will protect individuals from the effects of ingested toxins.

## Postexposure Prophylaxis

5-57. There is no postexposure prophylaxis available.

## Biological Warfare Clinical Presentation Incubation

5-58. Minutes to hours.

## Signs And Symptoms

5-59. Clinical features would be similar to those discussed above for endemic disease; animal experiments using aerosol challenges suggest that the clinical course following inhalation is accelerated and that death occurs within minutes following exposure.

## Diagnosis

5-60. Diagnosis is confirmed by antigen (toxin) detection by ELISA test or mouse bioassay.  Clinical specimens which may be submitted for toxin assay include stomach contents, serum, and in a BW context, respiratory secretions.  Specific toxins can be identified by high-performance liquid chromatography. Routine clinical laboratory findings are not specific for saxitoxin poisoning.  Cardiac conduction disturbances may develop; however, these electrocardiographic findings are nonspecific.  The differential diagnosis of saxitoxin poisoning includes ciguatoxin (ciguatera) and tetrodotoxin ingestion.  Ciguatoxin occurs following ingestion of large finned reef fish, and in contrast to saxitoxin, will result in more severe GI symptoms (nausea, vomiting, diarrhea), and in a peculiar reversal of temperature sensationhot feels cold, cold feels hot.  Tetrodotoxin occurs following ingestion of puffer fish.  Tetrodotoxin poisoning symptoms include neurologic (such as muscle weakness) and cardiopulmonary (such as hypotension) manifestations.

## Treatment

5-61. Medical management is as follows:


Supportive care is essential.  Airway management and mechanical respiratory support is required for severe intoxication.

Standard management of poison ingestion, including superactivated charcoal, should be used following oral ingestion.

## Prognosis

5-62. Severe cases risk death from pulmonary edema and respiratory failure.

## Control Of Patients, Contacts, And Treatment Areas

5-63. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in patient care.  Saxitoxin is not transmitted person to person.

## Medical Evacuation

5-64. Patients may be evacuated.  Apply standard precautions during evacuation.

## Staphylococcal Enterotoxin B Etiologic Agent

5-65. Staphylococcal enterotoxin B is one of numerous exotoxins produced by Staphylococcus (S.) *aureus*.
Up to one-half of all clinical isolates of *S. aureus* produce exotoxins; related toxins include toxic shock syndrome toxin-1 and exfoliative toxins.  The SEB toxin is heat-stable and is the second most common source of outbreaks of food poisoning.

## Reservoir

5-66. The reservoir of *S. aureus* is human (especially food handlers with infected cuts on their hands, abscesses, acne eruptions, nasal discharges, or normal appearing skin) and contaminated milk or milk products.  The SEB is usually produced in foods contaminated with *S. aureus*.

## Transmission

5-67. Ingestion of food, milk, or milk products containing preformed toxin.

## Endemic Disease

5-68. Staphylococcal food poisoning features the acute onset of fever, nausea, vomiting, and diarrhea within hours of intoxication.  The toxin increases intestinal peristalsis; severe nausea and vomiting may be due to stimulation of the CNS.  The SEB belong to a class of potent immune stimulants known as bacterial superantigens.  Superantigens bind to monocytes at major histocompatibility complex type II receptors rather than the usual antigen binding receptors.  This leads to the direct stimulation of large populations of T-helper cells while bypassing the usual antigen processing and presentation.  This results in a brisk cascade of proinflammatory cytokines and recruitment of other immune effector cells, and a relatively deficient activation of counter-regulatory negative feedback loops.  This results in an intense inflammatory response that can injure host tissues.

## Biological Warfare Agent Delivery

5-69. The primary threat is SEB aerosol release.  The SEB may also be employed by sabotage contamination of food and/or water supplies.

## Environmental Detection

5-70. Refer to paragraph 5-9 for information on environmental detection.  Also, ELISA, ECL, and PCR (to detect staphylococcal genes) can be used on environmental samples to confirm SEB intoxication.

## Prevention Preexposure Prophylaxis

5-71. Currently, there is no preexposure prophylaxis available.  Protecting food and water supplies from contamination and avoiding potentially contaminated food and water will protect individuals from the effects of ingested toxins.

## Postexposure Prophylaxis

5-72. Currently postexposure prophylaxis is not available; however, IV immunoglobulin can attenuate experimental disease in experimental animals if given within 4 to 8 hours postexposure.  There are no current human data or practice guidelines.

## Biological Warfare Clinical Presentation Incubation Period

5-73. Intoxication begins after a latent period of 3 to 12 hours after inhalation or 4 to 10 hours for GI
illness.

## Signs And Symptoms

5-74. Illness due to poisoning of food or water supplies will present as acute GI illness.  Illness due to inhalation will result in respiratory tract disease not encountered in the endemic disease.  This is due to the activation of proinflammatory cytokine cascades in the lungs, leading to pulmonary capillary leak and pulmonary edema.  Symptoms after inhalation include high fever, headache, myalgia, nonproductive cough, and in severe cases, dyspnea.  The fever, respiratory symptoms, chest x-ray findings, and high white blood cells may mimic an acute infectious pneumonia.  Some subjects may have chest pain.  Symptoms plateau and do not progressively get worse; however, the symptoms may persist for several weeks.

## Diagnosis

5-75. Diagnosis includes performing toxin assay (antigen detection) on suspect food or water and on environmental samples collected following a suspect BW attack.  Clinical specimens that could be sent for toxin assay include serum and respiratory secretions.  However, the toxin may not be detectable before the onset of symptoms.  Acute and convalescent sera for antibody tests will confirm the diagnosis.  Nonspecific findings may include leukocytosis, elevated sedimentation rate, and in severe cases, chest x-ray abnormalities featuring pulmonary edema.  Differential diagnosis include pneumonia due to viruses, mycoplasmas, Chlamydia pneumoniae, *Coxiella burnetii*, hantavirus pulmonary syndrome, chemical warfare agent inhalation injury (mustard, phosgene), and in severe cases, other diverse causes of noncardiogenic pulmonary edema and adult respiratory distress syndrome.

## Treatment

5-76. Medical management is as follows:


Medical management is primarily supportive care; symptomatic relief may be provided by the
use of acetaminophen and cough suppressants.

Severe cases will require intensive care including respiratory support, hemodynamic monitoring, and possibly diuretics and vasopressors.

## Prognosis

5-77. Staphylococcal enterotoxin B is considered an incapacitating agent; most patients may be expected to make a full recovery, although most patients will be unfit for duty for 1 to 2 weeks.  Patients with pulmonary edema and respiratory failure will be at risk for mortality.

## Control Of Patients, Contacts, And Treatment Areas

5-78. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in patient care.  Staphylococcal enterotoxin B is not communicable person to person.

## Medical Evacuation

5-79.  Patients may be evacuated.  Observe standard precautions in patient movement.

## Trichothecene Mycotoxins Etiologic Agent

5-80. Trichothecene mycotoxins are a diverse group of over 40 compounds produced by fungi of the genus Fusarium, a common grain mold.  These toxins inhibit protein and DNA synthesis, mitochondrial respiration, and alter cell membrane structure and function.  Naturally occurring mycotoxicosis occurs in livestock following ingestion of grains contaminated with molds.

## Reservoir

5-81. Moldy grain and cereals.

## Transmission

5-82. Ingestion of moldy grains and cereals.

## Endemic Disease

5-83. While there have been no laboratory-confirmed cases of human disease due to trichothecene mycotoxins, these toxins are thought to have caused an epidemic of foodborne illness in Russia during World War II due to the ingestion of foods prepared from moldy grain.  The syndrome was officially named alimentary toxic aleukia.  Symptoms of the disease include vomiting, diarrhea, fever, skin inflammation, leucopenia, multiple hemorrhage, necrotic angina, sepsis, vertigo, visual disturbances, and exhaustion of the bone marrow.

## Biological Warfare Agent Delivery

5-84. The toxin may be delivered by aerosol release or through contamination of food and water supplies.
These toxins are the agents allegedly delivered via aerosol during the Yellow Rain attacks in Afghanistan and Southeast Asia during the 1970s and 1980s.  The trichothecene mycotoxins are the only potential BW
agents that can harm and be absorbed through intact skin.

## Environmental Detection

5-85. Refer to paragraph 5-9 for information on environmental detection.

## Prevention Preexposure Prophylaxis

5-86. As a preexposure prophylaxis, the use of topical antivesicant cream or ointment may provide limited protection of skin surfaces.  Food and water contaminated with mycotoxins must not be consumed.

## Postexposure Prophylaxis

5-87. There is no postexposure prophylaxis.

## Biological Warfare Clinical Presentation Incubation/Time To Intoxication

5-88. Time to intoxication is minutes after exposure.

## Signs And Symptoms

5-89. The BW disease presentation will vary according to the portal of entry and delivered dose.
Mycotoxins are highly cytotoxic and may be viewed as bone marrow suppressive toxin.  Additionally, the toxin can have effects similar to vesicants, especially mustard agents.  Delivery to the skin may cause a burning skin pain, redness, tenderness, blistering, and progression to skin necrosis with eschar formation and sloughing.  Respiratory exposure may result in nasal itching with pain, rhinorrhea, sneezing, epistaxis, dyspnea, wheezing, and cough.  Exposure of the conjunctivae and other mucosal surfaces may result in local burning pain and redness, followed by necrosis.  Gastrointestinal exposure would be expected to result in nausea, vomiting, crampy abdominal pain, and watery or bloody diarrhea.  Systemic absorption may follow delivery via any route and would result in late toxicity of decreased blood cell counts, predisposing to bleeding and sepsis.

## Diagnosis

5-90. Serum and urine should be sent for antigen detection.  The parent toxin and metabolites (50 to 75
percent) are eliminated in urine and feces within 24 hours; however, metabolites can be detected as late as
28 days after exposure.

## Treatment

5-91. Medical management is as follows:


Following oral ingestion, standard therapy for poison ingestion including the use of superactivated charcoal is indicated.  Other measures of supportive care depend upon the organ
system involved (for example, respiratory support for respiratory involvement and standard burn care for cutaneous involvement).

All medical interventions are supportive; there are no antidotes or other specific therapies available.
Note.  If the Service member is unprotected during an attack, the outer uniform should be removed as soon as possible.  The skin should be thoroughly washed with soap and water.  This may reduce dermal toxicity, even if delayed 4 to 6 hours after exposure.  The M291 skin decontamination kit or the RSDL can also be used to remove skin-adherent trichothecene.

## Prognosis

5-92. Prognosis following the development of symptoms is poor.

## Control Of Patients, Contacts, And Treatment Areas

5-93. Control of patients, contacts, and treatment areas is critical in preventing spread of the disease.
Forward notifiable event case reports to the AFHSC for incorporation in the centralized DMSS.  Apply standard precautions in patient care.  Mycotoxins are not transmitted person to person.

## Medical Evacuation

5-94. Patients may be evacuated.  Observe standard precautions during evacuation.
This page intentionally left blank.


## Chapter 6 Identification Technologies Identification Methods For Biological Warfare Agents

6-1. The DOD has recognized since the inception of its BW agent detection program that the accurate and low-risk methodology for the detection, identification, and analysis of BW agents involves a layered, technologies-based strategy.  Referred to as orthogonal approach, this is a coordinated system using multiple technologies in the analysis of samples/specimens integrated with intelligence/surveillance and clinical information.  The advantages and disadvantages of orthogonal testing are as follows:


Advantages of orthogonal testing are

Increased confidence value of analysis.

Successful identification of BW agent is possible even if one of the test methodologies fails
or is defeated.

Required for theater validation and definitive BW testing.

Disadvantages of orthogonal testing are

More extensive concept of operations required to integrate the technologies and interpret
the data.

Personnel will likely require more training and will be required to achieve broader technical
proficiency.

Increased complexity of testing scheme.

More costly than single test methods for BW detection and identification.
6-2. Methods of identification of BW agents include

Isolation of the etiological agent by culture (possible in one to two days for some BW agents).

Handheld antibody-based assays, also called lateral flow immunoassays (LFIs).

Detection of toxin by animal inoculation or in vitro methods.

Antibody detection (specific IgM may appear within 3 days).

Antigen detection via enzyme immunoassay (such as ELISA) or other sensitive assay methods
such as immunofluorescence (for example ECL).

Genome detection employing DNA probes or PCR.

Detection of metabolic or degradation products of the infectious agent or toxin in clinical specimens.

Electron microscopy.

## Common Technology Lateral Flow Immunoassays Or Handheld Assays

6-3. Lateral flow immunoassays are simple, antibody-based assays used to presumptively identify BW
agents.  Similar to a pregnancy test kit, they are inexpensive, generally reliable, and easy to use.  A capture antibody (for antigen detection) or antigen (for antibody detection) is bound to the membrane, and a second antibody labeled with a visible marker element is placed on a sample application pad.  As the sample flows across the membrane, antigen or antibody present in the sample binds to the labeled antibody and is captured as the complex passes the bound antibody or antigen.  The LFIs are the primary identification component of several fielded systems: Joint Biological Point Detection System, Joint Portal Shield, and the Dry Filter Unit.  The LFI is designed to be used only on nonporous surfaces (such as metal, plastic, and glass) and are not designed to be the sole method of identification or for diagnostic use.  The advantages and disadvantages of using LFIs are as follows:


Advantages of using LFIs are

Easy to use.

Excellent for environmental samples.

No power requirements.

Toxin assays very sensitive.

Inexpensive and portable.

Disadvantages of using LFIs are

Cross-reactivity.

Lack of controls.

Sample nonspecifically binds to capture antibody (false positive).

Antigen detector antibody capture antibody complex does not form (false negative).

Detector antibody antispecies complex does not form (false negative).

Hook effect; unlabeled excess antigen binds to capture antibody (false negative).

Must be temperature controlled to maintain its shelf life.

## Enzyme-Linked Immunosorbent Assays

6-4. The ELISA is one of the most widely used and best understood immunoassay technologies.  Agentspecific antigen or host-derived antibody is captured onto a plastic multiwell plate by an antibody or antigen previously bound to the plate surface (capture moiety).  Bound antigen or antibody is then detected using a secondary antibody (the detector antibody).  The detector antibody can be directly labeled with a signal-generating molecule or it can be detected with another antibody labeled with an enzyme.  These enzymes catalyze a chemical reaction with substrate, which results in a colorimetric change.  The intensity of this color can be measured by a modified spectrophotometer that determines the extent of the reaction by using a specific wavelength of light.  In many cases, the assay can be interpreted without instrumentation by simply viewing the color that appears in the reaction vessel.  The advantages and disadvantages of ELISA are as follows:


Advantages of ELISA are

Easily configured for various applications.

Excellent for toxin identification.

Limited power requirement.

Inexpensive and portable.

Disadvantages of ELISA are

Labor intensive.

Takes 3-5 hours.

Lack of sensitivity.

False positive and negative results.

## Electrochemiluminescence Assay

6-5. The ECL assays exploit labeled antibodies that emit light when electrochemically stimulated.  One ECL system makes use of antigen-capture assays, a chemiluminescent label (a ruthenium-based complex), and magnetic beads to concentrate target agents.  These beads are coated with capture antibody, and in the presence of BW agent, immune complexes are formed between the agent and the labeled detector antibody. The application of an electric field results in a rapid electron transfer reaction between the substrate (tripropylamine) and the ruthenium label.  Excitation with as little as 1.5 V results in light emission, which in turn is detected.  The advantages and disadvantages of ECL are as follows:


Advantages of ECL are

Speed.

Sensitivity compared to other immunoassays.

Accuracy.

Precision over a wide dynamic range.

Disadvantages of ECL are

Generally does not determine viability.

Not as sensitive as culture and PCR.

False positives and negatives.

## Detection Of Nucleic Acid By Pcr

6-6. The PCR is a simple, in vitro chemical reaction that permits the synthesis of almost limitless quantities of a targeted nucleic acid sequence.  The reaction consists of the target DNA, two oligonucleotide primers that flank the target DNA sequence to be amplified, and a heat-stable DNA polymerase.  The reaction is subjected to repeated cycles of defined temperature changes that help to facilitate denaturation of the template DNA, annealing of the primers to the target DNA, and extension of the primers so that the target DNA sequence is replicated.  The DOD has fielded a PCR technology through the Joint Biological Agent Identification and Diagnostic System program of record.  Information regarding PCR technology are discussed below:


Real-time PCR.  The improvement of assay throughput came with the development of assay
chemistries that allowed the PCR reaction to be monitored during the exponential amplification phase on fast thermocyclers.  The PCR products are detected as they accumulate in real time during the amplification process.

Reverse-transcriptase PCR (RT-PCR).  The RT-PCR was developed to amplify specific ribonucleic acid targets.  In this process, extracted ribonucleic acid is first converted to
complementary DNA by reverse transcription, and then the complementary DNA is amplified by PCR.  The advantages and disadvantages of real-time PCR are as follows:

Advantages of real-time PCR are

Accuracy.

Sensitivity.

Speed.

Wide range of validated/operationally tested reagents available.

Disadvantages of real-time PCR are

Does not determine viability.

Detection methods must be validated against environmental and genetic near neighbors.

Requires a degree of technical expertise.

Requires more controls, particularly inhibition.

Prone to contamination.

Reagent storage requirements.

Does not directly identify toxins.

## Transition From Three Levels To Four Levels Of Cbrn Identification

6-7. There has been an initiative by the CBRN multiservice doctrine group of which the Army CBRN
School is the lead agent, to transition the CBRN levels of confidence analyses from three to four levels.
Refer to Figure 6-1 for more information.  This initiative was based on a study that was conducted and developed by the Joint Environmental Surveillance Working Group (published as U.S. Army Public Health Command Technical Information Paper 64-003-0310) and currently incorporated in Army Techniques, Publication (ATP) 3-11.37/MCWP 3-37.4/NTTP 3-11.29/AFTTP 3-2.44 (FM 3-11.19/FM 3-11.86).  For the purpose of this manual, the discussion will be concentrated on the BW agent levels of confidence analyses.  For more information on the three levels of confidence analysis, refer to FM 4-02.7/MCRP
4-11.1F/NTTP 4-02.7/AFTTP 3-42.3.


|                                                                                           | Previous Levels of    | Current Levels     |                             | Medical Decisions    |
|-------------------------------------------------------------------------------------------|-----------------------|--------------------|-----------------------------|----------------------|
|                                                                                           | Identification        | of Identification  | Possible Medical Tasks      | and Actions          |
| _________________________________________________________________________________________ |                       |                    |                             |                      |
|                                                                                           |                       |                    |                             |                      |
|                                                                                           | Definitive            | Definitive         | Targeted treatment          | Strategic            |
|                                                                                           |                       |                    |                             |                      |
|                                                                                           |                       |                    | Prophylaxis/treatment/      |                      |
|                                                                                           | Field Confirmatory    | Theater Validation | reporting/sample evacuation | Operational          |
|                                                                                           |                       |                    | to definitive laboratory    |                      |
|                                                                                           |                       |                    |                             |                      |
|                                                                                           |                       |                    | Prophylaxis/treatment/      |                      |
|                                                                                           |                       | Field Confirmatory | reporting/sample evacuation | Tactical/Operational |
|                                                                                           |                       |                    | to theater or definitive    |                      |
|                                                                                           |                       |                    | laboratory                  |                      |
|                                                                                           |                       |                    |                             |                      |
|                                                                                           | Presumptive           | Presumptive        | Sampling/Reporting          | Tactical             |
|                                                                                           |                       |                    |                             |                      |
| Sample Flow                                                                               |                       |                    |                             |                      |

Note.  Forward deployed Navy medical assets including the forward deployable preventive medicine unit and those aboard aircraft carriers, nuclear, amphibious assault ships (general purpose), and amphibious assault ships (dock) will continue to operate within a three-tiered system and conduct both *Field Confirmatory* and *Theater Validation* level analyses on suspected BW materials within the same laboratories.

6-8. Presumptive identification definition:  The employment of technologies with limited specificity and sensitivity by general purpose forces in a field environment to determine the presence of a chemical, biological, radiological, and/or nuclear hazard with a low level of confidence and the degree of certainty necessary to support immediate tactical decisions.

6-9. Presumptive identification descriptor:  Presumptive identification is obtained using commonly fielded devices/materials/technologies available to general purpose forces to indicate/warn of the possible presence of a CBRN/target substance.  It provides important information to support warning decisions and actions, such as taking avoidance, protection, and decontamination measures.
6-10. Field confirmatory identification definition:  The employment of technologies with increased specificity and sensitivity by technical forces in a field environment to identify chemical, biological, radiological, and/or nuclear hazards with a moderate level of confidence and the degree of certainty necessary to support follow-on tactical decisions.

6-11. Field confirmatory identification descriptor:  Field confirmatory identification is obtained using fielded devices/materials/technologies available to specially trained personnel and units in a field environment that includes collection and analyses of samples to substantiate the presence and type of a CBRN/target substance at a given location.  Field confirmatory identification can be used to prove (or disprove) previous presumptive results.  It results in higher confidence levels to support tactical decisionmaking, such as refining avoidance, protection and decontamination measures, and immediate treatment.

6-12. Theater validation identification definition:  The employment of multiple independent established protocols and technologies by scientific experts in the controlled environment of a fixed or mobile/transportable laboratory to characterize a chemical, biological, radiological, and/or nuclear hazard with a high level of confidence and the degree of certainty necessary to support operational-level decisions.

6-13. Theater validation identification descriptor:  Using accepted quality assurance measures, theater validation quantifies the CBRN sample.  It provides additional critical information to support timely and effective decisions regarding avoidance, protection and decontamination measures, and medical prophylaxis and treatment for affected units and personnel.  It can also support preliminary attribution to implicate or support trace analytics for the source of the identified CBRN material.

6-14. Definitive identification definition:  The employment of multiple state-of-the-art independent established protocols and technologies by scientific experts in a nationally recognized laboratory to determine the unambiguous identity of a chemical, biological, radiological, and/or nuclear hazard with the highest level of confidence and degree of certainty necessary to support strategic-level decisions.

6-15. Definitive identification descriptor:  Definitive identification supports attribution to implicate or point to the source of the identified material.  It uses the highest level of quality assurance measures.

6-16. Refer to Figure 6-2 for more information on the four levels of identification analyses and refer to Table 6-1 for more information on associated medical applications/tasks.

6-17. For more detailed information regarding sample management and sample routing involving the four levels of CBRN hazard identification, refer to ATP 3-11.37/MCWP 3-37.4/NTTP 3-11.29/AFTTP 3-2.44
(FM 3-11.19/FM 3-11.86).

| Level                                                                               | Associated medical applications/tasks    |
|-------------------------------------------------------------------------------------|------------------------------------------|
| Presumptive                                                                         |                                          |
| Use of devices/materials/technologies to indicate/warn of the possible presence of  |                                          |
| a BW agent.  This detection is to support a real-time tactical decision (such as,   |                                          |
| avoid/retreat from area; mitigate hazard/decon; maintain/upgrade protective         |                                          |
| equipment; request/initiate additional sampling and analyses).  Due to associated,  |                                          |
| limited reliability/low confidence in devices/materials/technologies and related    |                                          |
| procedures,                                                                         | this                                     |
| intelligence/information and often uses two or more different forms of presumptive  |                                          |
| detection technology.  This level may be unnecessary if field confirmatory          |                                          |
| capabilities are readily available.                                                 |                                          |
| Field Confirmatory                                                                  |                                          |
| The processes/procedures that include collection and analyses of sample(s) to       |                                          |
| determine presence, type, possible extent of a BW agent to support tactical or      |                                          |
| operationally relevant decisions (such as, confirm or disprove presumptive results; |                                          |
| downgrade protective equipment; support intelligence targeting).  Usually this task |                                          |
| is performed by specialized teams.  This level may be unnecessary if theater        |                                          |
| validation assets are readily available as they provide a higher degree of          |                                          |
| confidence and specificity.                                                         |                                          |
| Theater Validation                                                                  |                                          |
| The processes/procedures that include collection and analyses of sample(s) used     |                                          |
| to validate the presence and type and possible extent of a BW agent to support      |                                          |
| tactical, operational, and possibly strategic decisions (such as, decontamination  |                                          |
| "how clean is clean;" determine type of protection required; determine enemy        |                                          |
| capabilities).  Usually, this task is performed by highly specialized personnel and |                                          |
| facilities/technologies and, therefore, requires some additional time/logistics for |                                          |
| sample processing/shipping.  Use of results from theater validation assets may be   |                                          |
| determined (for example by combatant commanders) to be adequate so that             |                                          |
| definitive detection is not required.                                               |                                          |
| Definitive                                                                          |                                          |
| The processes/procedures that include collection and analyses of sample(s) to       |                                          |
| demonstrate the highest level of confidence and specificity regarding the presence, |                                          |
| type, and possible extent of a target substance.  Only specified, nationally        |                                          |
| recognized reference laboratories can conduct the analyses, but the limiting factor |                                          |
| may be how well samples were collected/packaged and transported by field            |                                          |
| elements.  Due to the limited capacity of these laboratories, operational plans and |                                          |
| orders should identify the conditions under which such a level of detection would   |                                          |
| be required and ensure documentation of the process by which quality samples        |                                          |
| would reach such facilities.                                                        |                                          |

## Department Of Defense Laboratory Network

6-18. A coordinated and operational system of DOD laboratories, programs, and activities possessing analytic and/or response capabilities are currently established and maintained to provide timely, highquality, actionable results for early detection, confirmation, and effective consequence management of acts of terrorism or warfare involving CBRN agents, an emerging infectious disease, and other all-hazards events requiring an integrated laboratory response.  The system of laboratories, programs, and activities ensure a clear delineation of current and needed capabilities as follows:


Improve data collection, interrogation, fusion, and networking.

Harmonize, validate, and enhance quality control of laboratory protocols and methods.

Standardize reporting of results.

Provide a unified DOD position on related issues external to the DOD.
6-19. The DOD has a substantial detection, diagnostic, analysis, and reporting capability for CBRN, other all-hazards agents of military significance, and emerging infectious diseases.  For certain agents, the DOD
constitutes the only national resource to accomplish these tasks.  These DOD capabilities will benefit from the coordination and integration provided by the DOD Laboratory Network.  The establishment of the DOD Laboratory Network provides the mechanism for enhancing intra- and interagency collaboration.

6-20. The DOD Laboratory Network functions as an active member network of the Federal Interagency Integrated Consortium of Laboratory Networks and its Network Coordinating Group.

## Laboratory Response Network

6-21. The Laboratory Response Network is an early warning network to detect the covert use of pathogenic agents.  It uses procedures established by the CDC and is based on grouping laboratories into one of four different levels, A through D, according to their ability to support the diagnostic needs presented by a bioterrorism event.

6-22. Level A laboratories have minimal agent identification capabilities.  Their primary role is to rule out and refer to their nearest Level B laboratory.  Level B laboratories perform identification, confirmation, and susceptibility testing.  Levels A and B are designated as sentinel laboratories under the new Laboratory Response Network designation.  Level C laboratories include state and other large-facility laboratories with advanced capacity for testing to include dome molecular techniques and are designated as a reference laboratory.  Level D laboratories include the CDC, USAMRIID, and Naval Medical Research Center and are designated as national laboratories.  These designated national laboratories are  Biological Safety Level 4 laboratories and have special surge capacity, as well as advanced molecular typing techniques.  In DOD, most clinical laboratories have microbiological capability and participate in the Laboratory Response Network.  All operate at least at the sentinel level while medical centers participate at the reference level.


This page intentionally left blank.


## Appendix A Specimen Collection, Handling, And Transport Biological Warfare Agent Characteristics

A-1. Environmental sampling is critical and essential in order to facilitate identification of BW agents.
Both medical personnel (such as PVNTMED, veterinary, and public health assets) and nonmedical personnel (such as CBRN and bioenvironmental engineering assets) collect and test environmental samples (for example, air, soil, water, food, plants) for BW agents.  See ATP 3-11.37/MCWP 3-37.4/NTTP
3-11.29/AFTTP 3-2.44 (FM 3-11.19/FM 3-11.86) for further discussions on environmental sampling.

A-2. Medical personnel have the primary responsibility for collecting and testing clinical specimens (for example, human blood, tissue, urine) for BW agents.  Most clinical specimens are collected on an individual patient in order to support a clinical diagnosis.

## Warning Decontamination Of Each Layer Of Packaging Is Crucial To Avoid The Spread Of Contamination (Which Can Occur During The Sampling And Packaging Process) To Uncontaminated Areas, Facilities, And Personnel.

A-3. Success or failure in providing a timely medical response to a BW attack will depend upon the rapidity and accuracy of the diagnostic effort, together with the passage of timely information from those units/organizations involved in environmental sampling.  Close coordination and cooperation between CBRN and medical staff will be vital to optimize sampling.  Refer to Table A-1 for information on characteristics of BW agents.

Note.  The guidance for processing/transporting specimens through designated laboratories, implementing chain of custody requirements, and the resupply process (equipment and supplies) should be clearly identified in appropriate operational plans.

Disease
Transmit human to human
Infective or Toxic dose (aerosol)
Incubation period
Duration of illness
Lethality (approximate case-fatality rates)
Anthrax (Inhalational)
No
8,000 to 50,000
Range 1 to 43 days
3 to 5 days (usually fatal if untreated) Weeks to months
< 5% untreated
Very stable
No vaccine
Brucellosis
No
10 to 100 organisms
5 to 60 days (usually 1 to 2 months)
Death in 7 to 10 days in septicemic form
Glanders
Low
Unknown, potentially low
10 to 14 days (endemic exposure); 1 to 4 days (inhalation exposure)
Melioidosis
Low
Unknown, potentially low
1 to 21 days (up to years)
Death in 2 to 3 days with septicemic form (untreated)
Plague
High, Pneumonic
500 to 15,000 organisms
1 to 7 days (usually 2 to 3 days)
1 to 6 days (usually fatal)
Tularemia
No
10 to 50 organisms
1 to 21 days (average 3 to 5 days)
 2 weeks
Low if untreated
For months in moist soil or other media
Q Fever
Rare
1 to 10 organisms
Up to 3 weeks
2 to 14 days
Very low
For months on wood and sand
7 to 17 days (average 12)
4 weeks
High to moderate
Very stable
Vaccine available
Smallpox
High
Assumed low (10 to 100) organisms
Venezuelan Equine Encephalitis
Low
10 to 100 organisms
1 to 6 days
Days to weeks
Low
Relatively unstable
No vaccine (IND for Special Immunizations Program)
Viral Hemorrhagic Fevers
Moderate
1 to 10 organisms
2 to 21 days
Death between 7 to 16 days
12 to 36 hours
Death in 24 to 72 hours; lasts months if not lethal
Botulism
No
0.001 g/kg is
LD50 for Type A
(parenteral), 0.003 g/kg (aerosol)
Hours
< 1%
Resistant to freezing
No vaccine
Staph Enterotoxin B
No
0.03 g/person (80 kg) incapacitation
3 to 12 hours after inhalation
Persistence of organism
Vaccine current status
High
Very stable spores remain viable for > 40 years in soil
Vaccine available preexposure 5 doses
> 50%
Very stable
No vaccine
No vaccine
19 to 50% for severe disease
Very stable; survives indefinitely in warm moist soil or stagnant water
High unless treated within 12 to 24 hours
For up to 1 year in soil; 270 days in live tissue
No vaccine (IND in advanced development)
No vaccine (IND for Special Immunizations Program) No vaccine (IND for Special Immunizations Program)
High to moderate depends on agent
Relatively unstable depends on agent
Vaccine for yellow fever (IND for Argentine hemorrhagic fever and Rift Valley fever)
High without respiratory support
For weeks in nonmoving water and food
No vaccine (Pentavalent IND vaccine discontinued by CDC)
Disease
Transmit human to human
Infective or Toxic dose (aerosol)
Persistence of organism
Vaccine current status
Incubation period
Duration of illness
Lethality (approximate case-fatality rates)
High
Stable
No vaccine (In Phase 1 clinical trial)
Ricin
No
 500 g/person
18 to 24
hours
Days (death within 10 to 12 days for ingestion)
No vaccine
T-2 Mycotoxins
No
Moderate
2 to 4 hours
Days to months
Moderate
For years at room temperature Very stable
No vaccine
1 to 6 hours
1 to 2 days
Low for C. Perfringens Infection Unknown for C. Perfringens epsilon toxin
C. Perfringens
No
More than 100,000 organisms/ grams of ingested food required to produce toxin in the human intestine
Cleared in 12 to 24 hours
No vaccine
Saxitoxin
No
8 g/kg is LD50
in mice
30 minutes to several hours
7 to 14 days
Dosedependent (0.2 milligrams lethal dose)
Cholera
Rare
10 to 500 organisms
4 hours to 5 days (usually 2 to 3 days)
 1 week
Low with treatment; high without
Unstable in aerosols and freshwater. Stable in saltwater
Two oral vaccines available in 60 countries, not available in the U.S.

## Specimen Collection

A-4. A blood culture with routine media will readily detect bacterial agents, although specialized media may be required for some.  Both aerobic and anaerobic cultures should be obtained.  Cultures and impression smears should be taken from involved lymph nodes, sputum, pleural fluid, CSF, tissues, or body fluids as clinically indicated.

A-5. Acute serum (at least 3 ml for suspected infectious agents and at least 20 ml serum for suspected intoxications) should be collected as early as possible after onset of symptoms.  Blood specimens also should be obtained from exposed persons who are not yet symptomatic.  Convalescent sera from survivors and sera from asymptomatic unit members should be obtained 3 to 4 weeks later.

A-6. Tissue specimens obtained at autopsy should be collected in multiple aliquots; minimally, one (25 to
50 gm) to freeze for microbiology or toxicology testing and one in formalin for histopathology testing. Where possible, additional specimens for other procedures, such as immunofluorescence or PCR studies, should be obtained.  Organs sampled should include lung, mediastinal lymph nodes, spleen, liver, and other tissues as clinically indicated.  Gross lesions and adjacent normal tissue should be taken from affected areas in any organ.  Postmortem blood (up to 20 ml) should be obtained and submitted as serum and clot or cells. Refer to Chapter 1, JP 4-06, and Technical Guide 195 for more information on necessity and precautions of contaminated human remains autopsies.

A-7. Table A-2 provides information on the types and amounts of specimens to collect from personnel exposed to aerosolized BW agents.  Proper collection of specimens is dependent on the time frame following exposure.  These time frames are not rigid and will vary according to the concentration of the agent used, the agent strain, and predisposing health factors of the patient.  Specimen collection for "early postexposure, clinical, and convalescent/terminal/postmortem" time frame is discussed below:


Early postexposure.  Specimens must be taken when it is known that an individual has been exposed to a bioagent aerosol; aggressively attempt to obtain specimen as indicated.

Clinical.  Specimens must be taken from those individuals presenting with clinical symptoms.

Convalescent/terminal/postmortem.  Specimens must be taken during convalescence, the terminal stages of infection or toxicosis or postmortem during autopsy.

Note.  Several choices are offered for blood specimens based on availability of the blood collection tubes.  Do not send blood in all the tubes listed, but merely choose one.  Tiger-top tubes that have been centrifuged are preferred over red-top clot tubes with serum removed from the clot, but the latter will suffice.  Blood culture bottles are also preferred over citrated blood for bacterial cultures.  See FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3 for additional information on specimen collection procedures.

| Early postexposure                  | Clinical    |
|-------------------------------------|-------------|
| Convalescent/terminal/              |             |
| postmortem                          |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Serum (TT or RT) for toxin assays.  |             |
| Blood (E) for PCR.                  |             |
| Blood (BC or C) for cultures.       |             |
| Anthrax                             |             |
| 0 to 24 hours.                      |             |
| Nasal and throat swabs, and         |             |
| induced respiratory secretions for  |             |
| culture, FA, and PCR.               |             |
|                                     |             |
| 3 to 10 days.                       |             |
| Serum (TT or RT) for toxin          |             |
| assays.                             |             |
| Blood (BC or C) for culture.        |             |
| Pathology specimens.                |             |
|                                     |             |
| > 6 days.                           |             |
| Serum (TT or RT) for IgM, later     |             |
| for IgG.                            |             |
| Pathology specimens.                |             |
| Plague                              |             |
| 0 to 24 hour.                       |             |
| Nasal                               | swabs,      |
| induced respiratory secretions for  |             |
| culture, FA, and PCR.               |             |
|                                     |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Blood (BC and C) for culture and    |             |
| bloody sputum (C) for FA.  Serum    |             |
| (TT or RT) for F-1 antigen assays.  |             |
| Blood (E) for PCR.                  |             |
|                                     |             |
| > 6 days.                           |             |
| Serum (TT or RT) for IgM and        |             |
| later IgG, agglutination titers.    |             |
| Pathology specimens.                |             |
| Tularemia                           |             |
| 0 to 24 hours.                      |             |
| Nasal swabs, sputum, and            |             |
| induced respiratory secretions for  |             |
| culture, FA, and PCR.               |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Blood (BC or C) for culture.        |             |
| Blood (E) for PCR.                  |             |
| Sputum for FA and PCR.              |             |
|                                     |             |
| Melioidosis/Glanders                |             |
| 0 to 24 hours.                      |             |
| Nasal swabs, sputum, and            |             |
| induced respiratory secretions for  |             |
| culture and PCR.                    |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Blood (BC or C) for culture.        |             |
| Blood (E) for PCR.                  |             |
| Sputum and drainage from skin       |             |
| lesions for PCR and culture.        |             |
|                                     |             |
| > 6 days.                           |             |
| Blood (BC or C) and tissue for      |             |
| culture.                            |             |
| Serum (TT or RT) for                |             |
| immunoassays.                       |             |
| Pathology specimens.                |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Blood (BC or C) for culture.        |             |
| Blood (E) for PCR.                  |             |
| Brucellosis                         |             |
| 0 to 24 hours.                      |             |
| Nasal swabs, sputum, and            |             |
| induced respiratory secretions for  |             |
| culture and PCR.                    |             |
|                                     |             |
| > 6 days.                           |             |
| Blood (BC or C) and tissue for      |             |
| culture.                            |             |
| Serum (TT or RT) for                |             |
| immunoassays.                       |             |
| Pathology specimens.                |             |
|                                     |             |
| 2 to 5 days.                        |             |
| Blood (BC or C) for culture in eggs |             |
| or mouse inoculation.               |             |
| Blood (E) for PCR.                  |             |
|                                     |             |
| > 6 days.                           |             |
| Blood (BC or C) for culture in      |             |
| eggs or mouse inoculation.          |             |
| Pathology specimens.                |             |
| Q Fever                             |             |
| 0 to 24 hours.                      |             |
| Nasal swabs, sputum, and            |             |
| induced respiratory secretions for  |             |
| culture and PCR.                    |             |
|                                     |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Nasal swabs and respiratory         |             |
| secretions for PCR (contaminating   |             |
| bacterial DNA) and toxin assays.    |             |
|                                     |             |
| > 6 days.                           |             |
| Usually no IgM or IgG.              |             |
| Pathology specimens (liver and      |             |
| spleen for toxin detection).        |             |
| Botulism                            |             |
| 0 to 24 hours.                      |             |
| Nasal swabs and induced             |             |
| respiratory secretions for PCR      |             |
| (contaminating bacterial DNA)       |             |
| and toxin assays.  Serum (TT or     |             |
| RT) for toxin assays.               |             |
| BC    | blood culture                                        |     |         |     |     | IgG                       | immunoglobulin Class G    |
|-------|------------------------------------------------------|-----|---------|-----|-----|---------------------------|---------------------------|
| C     | citrated blood                                       |     |         |     |     | IgM                       | immunoglobulin Class M    |
| DNA   | deoxyribonucleic acid                                |     |         |     | PCR | polymerase chain reaction |                           |
| E     | ethylenediaminetetra-acetic acid/electron microscopy | RT  | red top |     |     |                           |                           |
| F-1   | fraction-1                                           |     |         |     |     | TT                        | tiger top                 |
| FA    | fluorescent antibody                                 |     |         |     |     |                           |                           |
|       |                                                      |     |         |     |     |                           |                           |
| Early postexposure                  | Clinical    |
|-------------------------------------|-------------|
| Convalescent/terminal/              |             |
| postmortem                          |             |
| Ricin intoxication                  |             |
| 0 to 24 hours.                      |             |
| Nasal                               | swabs,      |
| respiratory secretions for PCR      |             |
| (contaminating castor bean DNA)     |             |
| and toxin assays.                   |             |
| Serum (TT or RT) for toxin          |             |
| assays.                             |             |
|                                     |             |
| 36 to 48 hours.                     |             |
| Serum (TT or RT) for toxin          |             |
| assays.                             |             |
| Tissue for immunohistological       |             |
| staining.                           |             |
| Pathology specimens.                |             |
|                                     |             |
| SEB toxin                           |             |
| 0 to 3 hours.                       |             |
| Nasal                               | swabs,      |
| respiratory secretions for PCR      |             |
| (contaminating                      | bacterial   |
| and toxin assays.                   |             |
| Serum (TT or RT) for toxin          |             |
| assays.                             |             |
|                                     |             |
| 2 to 6 hours.                       |             |
| Urine for immunoassays.  Nasal      |             |
| swabs and induced respiratory       |             |
| secretions for PCR                  |             |
| (contaminating bacterial DNA)       |             |
| and toxin assays.  Serum (TT or     |             |
| RT) for toxin assays.               |             |
|                                     |             |
| 1 to 5 days.                        |             |
| Serum (TT or RT) and tissue for     |             |
| toxin detection.                    |             |
| T-2 Mycotoxin intoxication          |             |
| 0 to 24 hours postexposure.         |             |
| Nasal and throat swabs and          |             |
| induced respiratory secretions for  |             |
| immunoassays,                       | HPLC/mass   |
| spectrometry.                       |             |
| Equine encephalomyelitis            |             |
| (VEE, EEE, and WEE viruses)         |             |
| 0 to 24 hours.                      |             |
| Nasal                               | swabs       |
| respiratory secretions for RT-PCR   |             |
| and viral culture.                  |             |
|                                     |             |
|                                     |             |
| 24 to 72 hours.                     |             |
| Serum (TT or RT) and throat for     |             |
| culture.                            |             |
| Serum (E, C, H, TT, or RT) for      |             |
| RT-PCR.  Throat swabs up to 5       |             |
| days for culture then CSF Serum     |             |
| (TT or RT) for antigen ELISA.       |             |
|                                     |             |
| 2 to 5 days.                        |             |
| Serum (TT or RT) for viral culture. |             |
|                                     |             |
| Pox                                 |             |
| (Smallpox and monkeypox)            |             |
| 0 to 24 hours.                      |             |
| Nasal                               | swabs       |
| respiratory secretions for PCR      |             |
| and viral culture.                  |             |
|                                     |             |
|                                     |             |
| 2 to 5 days.                        |             |
| Serum (TT or RT) for viral culture. |             |
|                                     |             |
| Ebola                               |             |
| 0 to 24 hours.                      |             |
| Nasal                               | swabs       |
| respiratory secretions for RT-PCR   |             |
| and viral culture.                  |             |
|                                     |             |

## Legend:

| C     | citrated blood                                       |     |                                 |     |                                               | IgG                          | immunoglobulin Class G    |
|-------|------------------------------------------------------|-----|---------------------------------|-----|-----------------------------------------------|------------------------------|---------------------------|
| CSF   | cerebrospinal fluid                                  |     |                                 |     | IgM                                           | immunoglobulin Class M       |                           |
| DNA   | deoxyribonucleic acid                                |     |                                 |     | PCR                                           | polymerase chain reaction    |                           |
| E     | ethylenediaminetetra-acetic acid/electron microscopy | RT  | red top, if TT is not available |     |                                               |                              |                           |
| EEE   | eastern equine encephalitis                          |     |                                 |     | RT-PCR reverse transcriptase/polymerase chain |                              |                           |
| ELISA | enzyme-linked immunosorbent assay                    |     |                                 |     | reaction                                      |                              |                           |
| EM    | electron microscopy                                  |     |                                 |     | SEB                                           | staphylococcal enterotoxin B |                           |
| H     | heparin                                              |     |                                 |     |                                               |                              | TT                        |
| HPLC  | high-pressure liquid chromatography                  |     |                                 | VEE | Venezuelan equine encephalitis                |                              |                           |
|       |                                                      |     |                                 |     |                                               |                              | WEE                       |
|       |                                                      |     |                                 |     |                                               |                              |                           | > 6 days. Serum (TT or RT) for IgM and IgG in survivors. > 6 days. Serum for IgM and IgG. > 6 days postexposure. Urine for detection of toxin metabolites. > 6 days. Serum (TT or RT) for IgM. Pathology specimens plus brain. > 6 days. Serum (TT or RT) for viral culture. Drainage from skin lesions/scrapings for microscopy, EM, viral culture, and PCR. Pathology specimens. > 6 days. Serum (TT or RT) for viral culture. Pathology specimens plus adrenal gland.

## Specimen Labeling

A-8. Each container should be labeled with name, numerical identities, type of specimen, and date of collection.  Routine laboratory slips should be included with each specimen.  Included should be


A brief description of the illness and/or gross autopsy findings.

Place, date, and time of exposure/symptom onset/death.

Name of persons submitting sample/specimen.

The individual's unit and/or location.
A-9. Clinical and operational data should be included for all specimens, together with a form to establish chain of custody.  This requirement must be strongly and clearly delineated since evidence may well be politically or militarily sensitive.

## Specimen Packaging

A-10. All specimens from suspected BW casualties should be submitted through the designated laboratory chain for processing.  Specimens must be clearly marked for special testing and the chain of custody procedures maintained.  Each specimen will be placed in a watertight receptacle made of glass, plastic, or metal with a screw cap closure, the screw cap will be reinforced with adhesive tape.  Serum specimens will be placed individually in a second plastic vial or zip-top bag to prevent leakage.  Absorbent material (such as vermiculite) sufficient to absorb the entire content of the primary receptacle is placed between the primary and secondary packaging; for serum specimens placed in a plastic vial, the absorbent material will be placed between the plastic vial and another secondary container/packaging material.  The secondary container/packaging should be of a materiel that prevents leakage.  The entire contents should be placed in an insulated shipping container with cold packs or dry ice.  When ice is used, the outer package must be leakproof.  When dry ice is used, the outer container must permit release of carbon dioxide gas.  For transportation out of theater, the specimens must be packaged in an International Air Transportation Association or Department of Transportation 49, Code of Federal Regulation 173-approved container.

A-11. It is the responsibility of the physician at forward MTFs or the laboratory officer, in concert with a physician at a hospital, to ensure that suspect specimens are submitted correctly and expeditiously to an appropriate diagnostic laboratory.

A-12. Specimens sent rapidly (less than 24 hours) to analytical laboratories require only wet ice or refrigeration at 2 to 8C.  However, if the time span increases beyond 24 hours, contact the USAMRIID; telephone hot line (1-888-USA-RIID/872-7443) for other shipping requirements such as shipment on dry ice or in liquid nitrogen.  Several choices are offered on blood specimen based on availability of the blood collection tubes.  Do not send blood in all the tubes listed, but merely choose one.  Tiger-top tubes that have been centrifuged are preferred over red-top clot tubes with serum removed from the clot, but the latter will suffice.  Blood culture bottles are also preferred over citrated blood for bacterial cultures.

## Specimen Transport

A-13. International regulations.  The international regulations for the transport of infectious substances by any mode of transport are based upon the recommendations made by the Committee of Experts on the Transport of Dangerous Goods, a committee of the United Nations (UN) Economic and Social Council. The recommendations are presented in the form of Model Regulations.  For more information refer to the World Health Organization Guidance on Regulations for the Transport of Infectious Substances.

A-14. National regulations.  Many countries adopt the UN Model Regulations in their entirety to stand as their national dangerous goods legislation.  Some countries apply variations.  National authorities should provide details of their own national requirements.

A-15. Infectious substances.  For the purposes of transport, infectious substances are defined as substances which are known or are reasonably expected to contain pathogens. Pathogens are defined as microorganisms (including bacteria, viruses, rickettsiae, parasites, fungi) and other agents such as prions, which can cause disease in humans or animals. The definition is applied to all specimens except those explicitly excluded.  Infectious substances are divided into two categories


Infectious substance, Category A.  An infectious substance which is transported in a form that, when exposure to it occurs, is capable of causing permanent disability, life-threatening or fatal
disease in otherwise healthy humans or animals.

Infectious substances meeting these criteria which cause disease in humans or both in
humans and animals shall be assigned to UN number UN 2814. Infectious substances which cause disease only in animals shall be assigned to UN 2900.

Assignment to UN 2814 or UN 2900 shall be based on the known medical history and
symptoms of the source human or animal, endemic local conditions, or professional judgment concerning individual circumstances of the source human or animal.  See Table A-3 for more information on infectious substances, Category A.
Note.  The proper shipping name of UN 2814 is infectious substance, affecting humans. The proper shipping name for UN 2900 is infectious substance, affecting animals.

| UN 2814                                       | UN 2900               |
|-----------------------------------------------|-----------------------|
| African swine fever virus (cultures only)     |                       |
| Avian paramyxovirus Type 1Velogenic          |                       |
| Newcastle disease virus (cultures only)       |                       |
| Foot and mouth disease virus (cultures only)  |                       |
| Pestes des petits ruminants                   | virus (cultures only) |
| Goatpox virus (cultures only)                 |                       |
| Swine vesicular disease virus (cultures only) |                       |
| B. anthracis                                  | (cultures only)       |
| C. botulinum                                  | (cultures only)       |
| Ebola virus                                   |                       |
| F. tularensis                                 | (cultures only)       |
| HBV (cultures only)                           |                       |
| Human immunodeficiency virus (cultures only)  |                       |
| Lassa virus                                   |                       |
| Marburg virus                                 |                       |
| M. tuberculosis                               |                       |
| R. rickettsii                                 |                       |
| Variola virus                                 |                       |
| Yellow fever virus (cultures only)            |                       |
| Y. pestis                                     | (cultures only)       |



Infectious substance, Category B.  An infectious substance which does not meet the criteria for
inclusion in Category A.  Infectious substances in Category B shall be assigned to UN 3373.
Note.  The proper shipping name of UN 3373 is biological substance, Category B.

A-16. For more information on the transport of infectious substances, refer to the World Health Organization Guidance on Regulations for the Transport of Infectious Substances; Department of the Army Guidance for the Shipment of Biological Select Agents and Toxins; AR 50-1; Code of Federal Regulations Title 49; and AFMAN 24-204.  For more information regarding the DOD transportation guidelines, refer to Defense Transportation Regulation 4500.9-R.

## Chain Of Custody Responsibilities

A-17. A strict chain of custody must be maintained for every specimen collected.  Use Department of the Army (DA) Form 4137 (Evidence/Property Custody Document) or Office of Chief of Naval Operations (OPNAV) Form 5580/22 (Evidence/Property Custody Receipt) or Department of Defense (DD) Form 1911 (Materiel Courier Receipt) for each specimen collected.  The DA Form 4137 or OPNAV Form 5580/22 or DD Form 1911 must accompany the specimen during transport from the point of collection to the final receiving laboratory.  Each time the specimen is transferred to another individual, the receiving person must sign the document to show that they have received and inventoried the specimen.  When a DA Form
4137 or OPNAV Form 5580/22 or DD Form 1911 is not available, the information must be recorded in such a manner that a clear chain of custody can be verified.  Regardless of whether the DA Form 4137 or OPNAV Form 5580/22 or DD Form 1911 or another record document is used, the document will provide the answer to the following questions


When was the specimen collected?

What is the description of the sample (vapor, liquid, solid) and how much?

Who has maintained custody of the specimen?

What has been done with the specimen at each change of custody?


## Caution

Each change of custody must be recorded with date and time of change.

A-18. Specimens being shipped to a laboratory for confirmation of a BW attack should follow this standard chain of custody


Sampling unit.

Unit Intelligence Officer (U.S. Army), medical operations officer, or other designated person.

Technical escort unit or other command-designated escort personnel.

In-theater supporting medical laboratory, if in operation.

Continental U.S. laboratory.


This page intentionally left blank.


## Appendix B Patient Decontamination General Principles

B-1. Casualties presenting to the MTF with symptoms or disease due to BW agent exposure may not require decontamination due to the time delay between BW agent exposure and onset of symptoms.  To a large degree, external contamination would likely have dissipated any large contamination of BW agent on the patient's clothing or body.  The following are examples of when decontamination may be required:


Intentional release of persistent aerosolized BW agent such as crop duster.

Presence of unidentified powders found in clothing or skin.
B-2. Certain CBRN scenarios involve the intentional release of a persistent aerosolized BW agent that presents not only as an immediate hazard on exposed skin or clothing, but also has the potential of being a reaerosolization hazard (this is particularly a concern from the aerosol release of anthrax spores or toxins).
B-3. Patients who present themselves for decontamination may suffer from the effects of exposure to a BW agent.  They may have conventional wounds, psychological effects, combat and operational stress reactions, or any combination of these.  It is also likely that worried-well will present themselves.  In addition, patients may have heat injuries induced by extended time spent in IPE/PPE.  It is important to quickly determine whether there is potential for residual contamination on a patient or in their bodily fluids for the suspected BW agent; and to determine if there may be a continued hazard to the patient or pose a cross-contamination to responders/MTF personnel.  While not all CBRN agents/scenarios require decontamination, when in doubt utilize most protective personal protection and decontamination actions feasible.

B-4. External clothing removal and rinsing of exposed skin and hair with water or soap and water (most preferred method) is generally considered adequate decontamination for most BW agents.
Note.  Each Service is aware that the potential scenario exists in which contaminated personnel might arrive at an MTF.  Therefore, all arriving casualties should be evaluated for decontamination and each Service should be prepared to receive such casualties.

B-5. Refer to FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3 for details on patient decontamination.
Note.  Do not let patient decontamination interfere with immediate lifesaving treatment.

## Decontamination Materials

B-6. Physical removal of contaminants is the primary method of decontamination for personnel.  Physical removal includes washing and wiping, but never vigorous scrubbing that could abrade the skin.  Skin abrasions whether through rubbing or harmful chemical reaction (for example, when 5 percent hypochlorite is mistakenly used as a decontamination solution on the skin) allow agents to move more rapidly through the skin barrier.

## Skin Liquid Soap And Water

B-7. This is the most preferred method.  This is a low-cost material that removes agents by washing them away.  It is effective for removing biological contaminants.  It does not kill BW agents.  Water runoff must be collected and treated before disposal.  Fat-based soaps and emulsifiers (for example, baby shampoo, castile liquid soap, or soft soap) are much more effective than liquid or powder detergents.  Detergents tend to dry the skin and should not be used.  Soap and water is best used during patient thorough decontamination, but can also be used for immediate (gross) and operational patient decontamination if available and practical.  It is not practical to use soap and water on the joint service lightweight integrated suit technology or similar protective garments as it will dampen the garment and reduce its protective capabilities.  It is also not advisable to use hot water for skin decontamination since it will open skin pores allowing BW agents to easily penetrate and absorb into the skin.  For better results, use tepid or lukewarm water with soap.

## Water

B-8. Water is the next preferred method.  In the absence of soap, a copious amount of water is effective in removing biological contaminants, helping loosen the agent, and helping lift it off of the skin with washing. Tepid or lukewarm water should be used and not hot water.

## Other Locally Available Absorbent Material

B-9. Any material that can absorb a liquid and then be brushed or scraped from the skin without abrading it, can be used as an effective skin or equipment decontaminant to remove liquid agents.  Soft towel, baby wipes, clean sawdust, clay, dirt, baking powder, or fuller's earth, can be put on the agent found on the skin or equipment, allowed to be absorbed, and then carefully wiped away.  Large quantities of liquid agent can be removed from clothing and skin by initially scraping it off with an uncontaminated stick or similar device.  Clean sand can be used on equipment but it is not advisable to be used on skin since it might be too abrasive and may cause the skin pores to open thus absorbing the BW agent.

## Reactive Skin Decontamination Lotion

B-10. The RSDL is a liquid decontaminant dispensed on a sponge.  The FDA has cleared RSDL for the removal or neutralization of many chemical warfare agents plus T-2 Mycotoxin from the skin.  The RSDL can be used for the decontamination of intact skin around wounds, but is not approved for the decontamination of wounds.  For more information regarding RSDL, refer to FM 4-02.285/MCRP 4-11.1A/NTRP 4-02.22/AFTTP(I) 3-2.69.

## Hypochlorite Solution

B-11. The 0.5 percent hypochlorite (12 percent, dilute household hypochlorite) solution is not recommended for BW agent skin decontamination.  A 0.5 percent hypochlorite concentration poses risk of causing skin irritation and opens skin pores.  Using copious amounts of soap and water is preferred and will better loosen the agent and help lift it off of the skin with washing.
Note.  The use of 0.5 percent hypochlorite (12 percent, dilute household hypochlorite) solution is not recommended for BW agent skin decontamination.

## Wounds

B-12. Clean or sterile water (such as an IV bag of saline) is the most appropriate material for the irrigation of the eyes and contaminated open wounds.  Soft tissue closed wounds can be irrigated with clean water, IV saline, or soap and water.  Deeper wounds, such as contaminated abdominal or thoracic cavity wounds or contaminated open intracranial (head) injuries should not be irrigated in the field.

B-13. Wound irrigation does not necessarily completely decontaminate the wound, but can help dislodge foreign material (such as pieces of clothing or metal which could hold agent) for recovery by aspiration with a large bore evacuator, forceps, or other no-touch technique.

## Equipment Hypochlorite Solution

B-14. The 5 percent hypochlorite (full strength household liquid hypochlorite) solution is effective for decontaminating equipment contaminated by BW agents.  The 5 percent hypochlorite solution works by rinsing away the agent while causing an oxidative, burning, chemical reaction with the agent which will neutralize and kill BW agents.  This solution should never be allowed to touch the skin as its alkalinity will redden, burn, and damage skin.  Equipment decontaminated with hypochlorite should be thoroughly rinsed with water or soap and water before use.  It is important that hypochlorite not be used on sensitive electronic equipment as it will cause oxidation and rust the equipment.  This highly reactive oxidant solution will react with some chemicals.

## Caution

Five percent hypochlorite (full strength household liquid hypochlorite) solution is highly reactive and oxidative.  It should NEVER be used on skin.  It can damage sensitive electrical equipment.  Equipment decontaminated with hypochlorite solution must be thoroughly rinsed with clean water before use.

## Soap And Water

B-15. Generous amounts of soap and water work well to decontaminate equipment contaminated by biological contaminants.   It removes BW agents, but will not destroy anthrax spores.  Runoff should be collected and killed with hypochlorite or sporicides.

Note.  Soap and water does not destroy biological contamination.  Water runoff should be collected.

## Detection Device Used During Patient Decontamination

B-16. There are currently no handheld detectors for BW agents that would be appropriate for patient decontamination operations.

This page intentionally left blank.


## Appendix C Medical Management And Treatment In Biological Warfare Operations Objectives Of Health Service Support In Biological Warfare Operations

C-1. The objectives of health service support in BW operations are to


Avoid spreading infectious diseases to staff or other patients.

Return to duty the maximum number of personnel as soon as possible.

Manage casualties so that BW traumatic injuries, diseases, illnesses, infections, or intoxications are minimized.

Protect persons handling contaminated casualties or working in contaminated areas.

Avoid spreading contamination in ambulances, other evacuation vehicles and aircraft, MTFs, and adjoining areas.

Continue the MTF's operations to maintain normal services unrelated to the medical treatment of BW agent illnesses and injuries.

## Planning For The Management And Treatment Of Biologically Contaminated Casualties

C-2. The initial management and treatment of casualties contaminated with a BW agent will vary with the tactical situation and the nature of the contaminant.  Therefore, each MTF must have a plan and put it into effect immediately, then modify it to meet each specific situation.  Patient decontamination sites are collocated with an MTF.  This ensures that medical supervision of patient decontamination is available. Specifics on management of BW contaminated patients at the MTF are found in FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3.

C-3. Each MTF must be prepared to treat

Biological warfare agent casualties generated within the geographical area of the MTF.

Patients suffering from a combination of injuries/illnesses (such as BW and conventional injuries and BW and endemic disease).

Patients suffering from battle injuries and diseases and nonbattle injuries that have not been exposed to any BW agents.

Enemy prisoners of war, detained persons, and noncombatants, when directed.

## Emergency Medical Treatment Of Biologically Contaminated Casualties

C-4. Biological warfare agent casualties received at an MTF may also have traumatic wounds or illnesses due to other causes.  Management of these patients must minimize the BW agent injuries without aggravating their traumatic wounds or illnesses.

C-5. Triage of arriving casualties is extremely important.  A decision is made whether treatment or decontamination of the casualty requires priority.  Airway management and/or control of hemorrhage may be equal to or more urgent than treatment for BW agent poisoning.  Therefore, treatment measures may have to be performed in rapid sequence with decontamination or by simultaneous team actions.

C-6. When a contaminated casualty has another injury or illness resulting in respiratory difficulty, hemorrhage, or shock, the order of priority for emergency action is as follows


Control bleeding and provide ventilation assistance for respiratory failure.

Decontaminate the casualty.

Administer additional medical treatment for shock, wounds, and illnesses so severe that delay may be life- or limb-threatening.

Evacuate the casualty as soon as possible, if necessary.
C-7. The medical management precautions are discussed below.  Also, refer to Table C-1 for medical management precautions for select BW agent diseases.


Universal/standard precautions:  frequent handwashing, gloves, and splash protection which includes mask, gown, and eye protection.

Contact precautions:  include universal/standard precautions plus isolating patients in a private
room.

Droplet precautions: include universal/standard precautions plus isolating patients in a private room.  Respiratory protection consists of at least an N-95 filtering facepiece respirator when
working within 3 feet of an infected patient.  Have patient wear surgical mask.

Airborne precautions: include universal/standard precautions plus isolating patients in a negative
air-pressure room.  Respiratory protection consists of at least an N-95 filtering facepiece respirator or better.  Have patient wear mask.

Universal/
standard
precautions
Contact precautions
Droplet precautions
Airborne/contact
precautions
Smallpox Viral hemorrhagic fevers
(for example, Ebola or

Marburg)
Brucellosis (if draining lesions)
Melioidosis
Glanders Influenza Viral encephalitis Plague (pneumonic)
(until patient is

treated for 3 days)
Anthrax Cholera Q fever Shigellosis Tularemia Typhoid fever Typhus Toxins

## Training

C-8. Commanders must ensure that medical personnel and decontamination team members are trained to manage, decontaminate, and treat BW agent casualties.

C-9. Personnel must be trained to protect themselves from BW agent injuries.  In addition, provisions must be made for practice exercises to enable them to accomplish their responsibilities with speed and accuracy.  Training emphasis should be placed on


Employing individual protection.

Practicing immediate decontamination procedures.

Providing emergency medical treatment.

Performing casualty decontamination.

Evacuating decontaminated casualties.

Evacuating contaminated casualties.

Sorting and receiving contaminated casualties into a system designed for the treatment of both contaminated and uncontaminated casualties.

Practicing techniques for patient lifting and litter transfer.

## Medical Treatment Facilities

C-10. Medical treatment facilities must be prepared to receive mass casualties caused by exposure to BW
agents.  A mass casualty situation exists when the number and type of casualties exceed the local medical support capabilities for their care.  If the unit follows conventional operational standing operating procedures, an overwhelming backlog of work will rapidly accumulate.  Such backlogs can result in unnecessary loss of life and limb.  Therefore, all medical planners must prepare plans for mass casualty situations and all units must be trained and equipped for these plans.  The unit must be ready to operate with minimal confusion.  Medical units must provide medical treatment to these casualties and supervise their decontamination.  Normally, individual Service members are responsible for their own decontamination.  For casualties who are injured and unable to decontaminate themselves, this process has to be performed by buddy aid, by unit personnel at a troop decontamination site, or at an MTF by nonmedical personnel from the supported units.

C-11. At U.S. Army Roles 1 and 2 units, the supported unit commander must provide at least 8 nonmedical personnel to perform patient decontamination.  At U.S. Army Roles 2 and 3 combat support hospitals, at least a 20-man patient decontamination augmentation team or 20 nonmedical personnel must be provided to perform patient decontamination.  The base cluster commander or units within the geographical area of the hospital must provide the 20 nonmedical personnel.

C-12. For the purpose of this publication, USN Role 1 MTFs include battle dressing stations and medical departments of U.S. naval vessels, and battalion aid stations in support of the Fleet Marine Forces, regardless of the presence of a physician.  Where this manual differs from USN and USMC doctrine, such doctrine shall have precedence.

C-13. In the USAF, the Expeditionary Medical Support (EMEDS) provides a rapid, deployable medical response force.  The basic EMEDS provides a Role 2 capability and has 4 holding beds, EMEDS + 10 is a Role 3 capability with 10 inpatient beds, and EMEDS + 25 is a Role 3 capability with 25 inpatient beds. The EMEDS concept may also be modified to provide specialty teams with medical counterCBRN or other capabilities.  Collective protectionEMEDS is an add-on capability that allows continued operations in a CBRN environment with a protected air and water supply.  Medical personnel must supervise patient decontamination personnel to ensure patient conditions are not aggravated by decontamination process. Supervising medical personnel must make the final determination on the completeness of patient decontamination.

C-14. The higher headquarters of the contaminated unit (battalion, brigade, or echelons above brigade) will coordinate and provide nonmedical personnel augmentees to support the medical unit with patient decontamination.  The USAF coordinates with their higher headquarters for support only when not supported by an expeditionary medical decontamination team.  The expeditionary medical decontamination teams will generally support a 10-bed or larger USAF expeditionary medical support MTF in a CBRN
environment.
C-15. Commanders must be aware that military personnel who become BW medical casualties will most likely require medical treatment for more than 7 days and it is unlikely that they will be recovered to 75 percent capacity to permit return to duty until after a lengthy convalescent period.  In-theater commanders must make arrangements for medical evacuation of BW casualties and arrangement for replacement personnel.  Continental U.S. commanders must prepare for at least a 10-day forecast of patient loads from theater commanders and identify resources for treatment and recovery of BW patients.  Special resources and transportation requirements will be required for casualties exposed to internationally quarantinable diseases.

C-16. The MTF should attempt to identify the BW agent using diagnostic laboratory resources they have available.  The MTF should be prepared to seek advice and send specimens to reachback capabilities such as Laboratory Response Network reference laboratories and Laboratory Response Network nationally recognized reference laboratories.  Medical personnel should also coordinate with any environmental laboratories in the theater such as the forward deployable preventive medicine unit or the area medical laboratory to confer on biological threats they may have identified from environmental sampling.

C-17. For information on the employment, physical properties, infectivity, detection, and control of BW
agents, see AFMAN 10-2503 and Air Force Visual Aid 10-2511.  Basically, protection consists of denying access of the agent to the respiratory and digestive systems and immunization of individuals.  Skin and wound contamination is of secondary importance.

C-18. If a real-time field detection/identification capability is not present, recognition of BW agents must be based on epidemiology and symptoms.  Once illness begins to appear, the presence of an airborne BW
agent should be relatively obvious because of the large numbers of casualties and the absence of a common exposure source such as food or water.  However, food and/or water may also serve as a vehicle of transmission.  Some indications of an attack are


Point-source epidemiology with a record number of sick and dying patients presenting within a short period of time (within 12 to 48 hours).

Very high attack rates (60 to 90 percent of personnel are affected/symptomatic).

A high incidence of pulmonary involvement signaling an aerosol route of infection.  This would apply to such agents as plague, tularemia, anthrax, and Q fever where the usual form of infection
is not pulmonary.

Impossible epidemiology, for example, if the Crimean-Congo VHF occurred in Alaska or New York, or VEE in England, a man-made epidemic would be extremely likely.

Record fatality rates which would be expected for many agents, since a large number of victims would receive doses of organisms far beyond what could possibly occur in nature.  This is especially true of an aerosol attack.

Localized areas of disease epidemics occurring in an area or sector downwind.

Multiple infections at a single site with unusual pathogens.

Increased numbers of dead animals of all species, such as rats for plague or horses with equine encephalitis viruses.

Protection of those working in indoor environments or environments with filtered air.

The near simultaneous outbreak of similar or different epidemics at the same site or at different sites in a theater of operations or at military installations around the world.

Direct evidence, such as finding an unexploded munitions or a contaminated exploded munitions; admission by hostile forces or terrorists that BW weapons are being used; witnessing
an attack; or intelligence information reporting use of BW agents by hostile forces from covert agents working within those hostile forces.

## Medical Logistics Support

C-19. A CBRN incident can place significant demands on the medical logistics support system.  Medical operations depend upon logistics for supply/resupply and patient movement resources.  The CBRN hazards present unique challenges to the medical logistics support because of the potential for contamination and higher consumption rates.  The medical planning staff will consider the following logistical requirements


Chemical-, biological-, radiological-, and nuclear-specific consumables, supplies that may be
depleted quickly, or assets particularly vulnerable to CBRN contamination.

Identification of suitable substitutions for standard medical material and equipment for casualty management.

Testing of food and water, ambient environment, and medical supplies for CBRN contamination.

Protection of food, water, medical supplies, and assets from contamination.

Management of decontamination assets.

Support requirements related to the CBRN casualty evacuation policy.

Procedures for handling CBRN contaminated remains, contaminated medical waste, and
decontamination rinse waters.

Locations of critical supplies such as CBRN medical/pharmaceutical stockpiles.

Coordination of host-nation support.
C-20. The CBRN contaminated medical waste requires disposal considerations or procedures in addition to medical waste typical of trauma-related injuries.  Enhanced considerations or procedures may be required to mitigate the potential impact on medical operations.  A CBRN event has the potential to generate large quantities of hazardous waste.  The medical planning staff will provide advice on CBRN hazards and associated mitigation requirements for the disposal of medical waste.  Coordination between Services is necessary with respect to the decontamination, handling, and disposal of hazardous waste.  Proper planning and education of medical personnel is necessary to ensure that personnel, facilities, and other medical resources are adequately protected from unnecessary exposure.

C-21. Host nations may be capable of supporting waste management but may have unique standards and regulations with respect to CBRN contaminated waste.  The medical planning staff should consider hostnation requirements when planning or contracting for waste management operations.  The medical planning staff will provide advice on procedures for handling contaminated or potentially contaminated human remains.  Refer to Chapter 1 for more information on the considerations for the management of contaminated human remains.

C-22. The medical planning staff will be directly involved in the assessment of medical host -nation support capabilities and development of agreements in the medical field.  The use of local resources will be authorized or coordinated with national medical personnel on the ground.  The medical planning staff should consider resource availability; equipment compatibility; interoperability of medical support structures (both military and civilian); acceptability of procedures; and quality of medical care available.
The medical planning staff should also consider the logistical demands of host-nation hospitals during a CBRN event.  The lack of preexisting host nation support agreements that address CBRN medical planning places an additional burden on the force when providing medical support.  The situation may be compounded by the lack of infrastructure in areas where these types of operations may be conducted, resulting in competition between contractors for scarce resources.

C-23. The medical planning staff will identify resources and capabilities that are scarce or unavailable.
Some shortfalls may be alleviated by contracted local civilian resources.  Resources and services such as casualty care facilities or evacuation assets (for example, use of airstrips or ports) may be contracted through host-nation civilian contractors.

C-24. For many situations, the required numbers of consumable medical supplies may be adequate.
However, the diversity of the potential casualty population during a CBRN incident may require a greater variety and quantity of medical supplies.  Stockpiled CBRN response materiel should be strategically located to facilitate distribution and the inventory and monitoring of expiration dated items.  Logistics planning should consider the needs of infants, children, expectant women, and the elderly.

## Strategic National Stockpile

C-25. An act of terrorism (or a large scale natural disaster) targeting the U.S. civilian population will require rapid access to large quantities of pharmaceuticals and medical supplies.  Such quantities may not be readily available unless special stockpiles are created.  No one can anticipate exactly where a terrorist will strike and few state or local governments have the resources to create sufficient stockpiles on their own.  Therefore, a national stockpile has been created as a resource for all.

C-26. In 1999, Congress charged the Department of Health and Human Services and the CDC with the establishment of the National Pharmaceutical Stockpile.  The mission was to provide a resupply of large quantities of essential medical materiel to states and communities during an emergency within 12 hours of the federal decision to deploy.

C-27. The Homeland Security Act of 2002 tasked the Department of Homeland Security with defining the goals and performance requirements of the Strategic National Stockpile Program, as well as managing the actual deployment of assets.  The National Pharmaceutical Stockpile became the Strategic National Stockpile Program managed jointly by Department of Homeland Security and Department of Health and Human Services.  The Strategic National Stockpile Program works with governmental and nongovernmental partners to upgrade the nation's public health capacity to respond to a national emergency.  Critical to the success of this initiative is ensuring capacity is developed at federal, state, and local levels to receive, stage, and dispense Strategic National Stockpile assets.

This page intentionally left blank.


## Appendix D Biological Warfare Agents Clinical Diagnostic Algorithm General

D-1. Medical personnel must be familiar with the signs and symptoms of BW agent casualties.  With current technology, it is likely that a BW attack will be completed before the local commander, or his medical advisor, is aware that it has taken place.  The medical officer must attempt to distinguish between an epidemic of natural origin and a BW attack.

D-2. Medical and tactical intelligence channels should communicate with each other as early as possible.
Threat information on potential enemy force use of BW weapons/agents is important for planning and executing health service support operations.  Once BW agents have been used, identification of agents will be important to medical intelligence channels for operational purposes.

D-3. Medical units should rely on information not only from detectors and intelligence sources, but also from the casualties themselves.  This applies particularly to BW weapons/agents since at present there are no rapid methods of detection or identification.  Some of the problems in the recognition and diagnosis of casualties suffering from the effects of BW operations are discussed here.  Medical personnel must remember that the signs and symptoms of most BW agents are identical to or similar to those of endemic and epidemic diseases.  The nature and timing of symptoms will vary with the route of exposure.  Although most BW agents require days to manifest, some agents produce their effects in a few hours.  It is important that the fullest and earliest information be given to medical units when the enemy has used BW weapons/agents.  This information is used to facilitate the diagnosis of individual cases, to initiate immediate treatment, and to permit the arrangement for the reception of casualties.

## Types Of Casualties

D-4. On the BW battlefield, the following types of casualties may be seen:


Conventional casualties with no BW injury and with no contamination of their clothing and equipment.

Conventional casualties with no BW injury but with contamination of their clothing and equipment.

Biological warfare agent casualties with no other injury.

Mixed casualties with conventional and BW injuries.  Since BW munitions often include burst charges, such injuries may occur as part of a BW agent attack.  They may also be present when
the BW injury and conventional injury occur at different times.  Other types of mixed casualties may be from nuclear or chemical weapons used as well as the biological weapons.  Also, mixed casualties may result when biological injuries are combined with natural illnesses (infectious disease still accounts for the majority of casualties in conventional warfare).

Casualties suffering combat and operational stress reactions.  Combat and operational stress reactions occur often in warfare, but may be more frequent where CBRN threats exist.  The
Service member will have the additional stress of isolation and fatigue from wearing the chemical protective ensemble and experience the fear of CBRN agents.  See FM 4-02.51 for additional information on combat and operational stress reactions.  Some of the causes of
combat and operational stress reactions are as follows:

Some BW agent treatments can have undesirable side effects when taken inappropriately,
or in large enough quantities.  Antibiotics kill desirable bacteria in the digestive tract, causing abdominal pain and frequent bowel movements.  Medical personnel must monitor patients for these effects.

Wearing the protective ensemble makes dissipation of excess body heat more difficult.
Wearing the mask also makes water intake difficult.  Both will increase the probability of heat injury (heat exhaustion or heat stroke).

Medical staff, other personnel, and patients may be infected from patients with contagious
diseases caused by BW agents.

## Recognize Biological Warfare Casualties

D-5. It is unlikely that BW agents will produce single casualties under field conditions.  Also, a BW attack should be suspected with any sudden increase in the numbers of unexplained casualties presenting with the same signs and symptoms.  If BW operations are unlikely, and if relatively few Service members are affected, an endemic or epidemic disease may be more probable (for example, salmonella food poisoning).
If the number of cases continues to present over an extended period, as opposed to a large number presenting in one or two days, a naturally occurring epidemic is suspected.

D-6. Under operational conditions, the psychological effects may complicate the medical situation.  To determine if a BW agent has caused the casualty, the medical officer should ask questions along the following lines


Was the casualty wearing protective equipment at the time of the exposure?

Was there any aircraft or artillery bombardment in the area at the time of the attack?

Was there anyone in the area dispersing a suspicious spray or vapor from portable or vehiclemounted devices?

Were there any suspicious persons around the unit water supply or in the unit food service area?

Was there any evidence of spray, liquid droplets, or suspicious persons in the area?

Was anyone else affected and if so, what are the effects?
D-7. To recognize a BW attack, the identity of the agent must be determined.  The medical officer should consider the following:


Groups of patients from a specific unit/area presenting with the same illness signs and symptoms in a short period of time (hours to days).

Signs and symptoms not associated with any known endemic diseases in the area of operations.
D-8. The medical officer should also question the patient about the delay or rapidity of the onset of symptoms as follows:


Was there any delay between exposure or contamination and the onset of effects?  If so, how long was the delay?

Did the effects persist after adjustment of the protective mask?

Has the casualty used any self-injection device or did anyone else use any injection devices on
the casualty?  If so, did the symptoms improve or deteriorate?

Is the casualty's behavior normal?
D-9. To assess the dose of the agent received by the patient, determine the following

Was the casualty exercising or at rest?

Was the casualty in the open or under cover?

How long was the suspect BW agent inhaled/ingested?

How long was the interval between suspected contamination and decontamination?

How long ago was the suspected exposure before symptoms started to appear?
D-10. Follow these ten steps in the management of biological casualties on the battlefield

Maintain an index of suspicion.

Protect yourself.

Assess the patient.

Decontaminate as appropriate.

Establish a diagnosis.

Render prompt treatment.

Practice good infection control.

Alert the proper authorities.

Assist in the epidemiologic investigation and manage the psychological consequences.

Maintain proficiency and spread the word.
D-11. Refer to Figure D-1 for a clinical algorithm for the diagnosis of BW agent-induced casualties.

Notes:
1 Epidemiologic clues may assist in maintenance of an index of suspicion.

2 Did symptoms occur immediately following a suspected exposure?

| EEE   | Eastern equine encephalitis   | UG   | ulceroglandular                |
|-------|-------------------------------|------|--------------------------------|
| JE    | Japanese encephalitis         | VEE  | Venezuelan equine encephalitis |
| SEB   | staphylococcal enterotoxin B  | VHF  | viral hemorrhagic fever        |

This page intentionally left blank.


## Glossary Section I - Acronyms And Abbreviations



AFHSC
Armed Forces Health Surveillance Center
AFMAN
Air Force manual
AMedP
Allied medical publication
ATP
Army techniques publication
ATTP
Army tactics, techniques, and procedures
BW
biological warfare
C
centigrade
C.
Clostridium
CAC
common access card
CBRN
chemical, biological, radiological, and nuclear
CDC
Centers for Disease Control and Prevention
CIDRAP
Center for Infectious Disease Research and Policy
CNS
central nervous system
CSF
cerebrospinal fluid
DA
Department of the Army
DD
Department of Defense (official forms only)
DIC
disseminated intravascular coagulation
DMSS
Defense Medical Surveillance System
DNA
deoxyribonucleic acid
DOD
Department of Defense
DODD
Department of Defense directive
DODI
Department of Defense instructions
ECL
electrochemiluminescence
EEE
Eastern equine encephalitis
ELISA
enzyme-linked immunosorbent assays
EMEDS
Expeditionary Medical Support
F
Fahrenheit
FDA
Food and Drug Administration
FM
field manual
GI
gastrointestinal
gm
gram
HFRS
hemorrhagic fever with renal syndrome
hr
hour
IgG
immunoglobulin Class G
IgM
immunoglobulin Class M
IND
investigational new drug
IPE
individual protective equipment
IV
intravenous
JP
joint publication
KC1
potassium chloride

## Glossary

kg
kilogram
L
liter
LFI
lateral flow immunoassay
MCM
memorandum for the chairman
MCO
Marine Corps order
mEq
milliequivalents
mg
milligram
mmol
millimole
ml/mL
milliliter
MTF
medical treatment facility
Na
sodium
NaCl
sodium chloride
NATO
North Atlantic Treaty Organization
NAVSUP-P
Navy supplement publication
NBC
nuclear, biological, and chemical (only in legacy terms and documents)
NBIC
National Biosurveillance Integration Center
OPNAV
Office of the Chief of Naval Operations
PCR
polymerase chain reaction
PIU
patient isolation unit
PPE
personal protective equipment
PVNTMED
preventive medicine
RSDL
reactive skin decontamination lotion
RT-PCR
reverse-transcriptase polymerase chain reaction
SEB
staphylococcal enterotoxin B
STANAG
standardization agreement (NATO)
TB MED
technical bulletin, medical
TM
technical manual
UN
United Nations
U.S.
United States
USAF
United States Air Force
USAMEDDC&S
United States Army Medical Department Center and School
USAMRIID
United States Army Medical Research Institute of Infectious Diseases
USMC
United States Marine Corps
USN
United States Navy
VAERS
Vaccine Adverse Event Reporting System
VEE
Venezuelan equine encephalitis
VHF
viral hemorrhagic fever
VIG
vaccinia immunoglobulin
WEE
Western equine encephalitis

## Section Ii - Terms And Definitions

biological weapon An item of materiel which projects, disperses, or disseminates a biological agent including arthropod vectors.  (JP 1-02.  Source:  JP 3-11.)

chemical, biological, radiological, and nuclear defense Measures taken to minimize or negate the vulnerabilities and or effects of a chemical, biological, radiological, or nuclear incident.  Also called CBRN defense.  (JP 1-02.  Source:  JP 3-11.)
contamination
1.  The deposit, absorption, or adsorption of radioactive material, or of biological or chemical agents on or by structures, areas, personnel, or objects.  2.  (Department of Defense only) Food and/or water made unfit for consumption by humans or animals because of the presence of environmental chemicals, radioactive elements, bacteria or organisms, the byproduct of the growth of bacteria or organisms, the decomposing material (to include the food substance itself), or waste in the food or water.  (JP 1-02.  Source:  JP 3-11.)
contamination control A combination of preparatory and responsive measures designed to limit the vulnerability of forces to chemical, biological, radiological, nuclear, and toxic industrial hazards and to avoid contain, control exposure to, and where possible, neutralize them.  (JP 1-02.  Source:  JP 3-11.)
decontamination The process of making any person, object, or area safe by absorbing, destroying, neutralizing, making harmless, or removing chemical or biological agents, or by removing radioactive material clinging to or around it.  (JP 1-02.  Source:  JP 3-11.)
force health protection Measures to promote, improve, or conserve the mental and physical well-being of Service members.  These measures enable a healthy and fit force, prevent injury and illness, and protect the force from health hazards.  Also called FHP.  (JP 1-02. Source:  JP 4-02.)
health service support All services performed, provided, or arranged to promote, improve, conserve, or restore the mental or physical well-being of personnel. These services include, but are not limited to, the management of health services resources, such as manpower, monies, and facilities; preventive and curative health measures; evacuation of the wounded, injured, or sick; selection of the medically fit and disposition of the medically unfit; blood management; medical supply, equipment, and maintenance thereof; combat stress control; and medical, dental, veterinary, laboratory, optometric, nutrition therapy, and medical intelligence services. Also called HSS.  (JP 1-02.  Source:  JP 4-02.)
individual protective equipment In chemical, biological, radiological, or nuclear operations, the personal clothing and equipment required to protect an individual from chemical, biological, and radiological hazards and some nuclear hazards.  Also called IPE.  (JP 1-02.  Source:  JP 3-11.)
medical evacuation The timely and efficient movement of the wounded, injured, or ill, while providing en route medical care to and between medical treatment facilities.  Also called MEDEVAC.  (FM 4-02)
patient decontamination The removal and/or the neutralization of hazardous levels of chemical, biological, radiological, and nuclear contamination from patients at a medical treatment facility.  Patient decontamination is performed under the supervision of medical personnel to prevent further injury to the patient and to maintain the patient's health status during the decontamination process.  Patient decontamination serves multiple purposes; it protects the patient from further injury, it prevents exposing medical personnel to the contamination, and it prevents contamination of the medical treatment facility.  (FM 4-02.7)
personal protective equipment The equipment provided to shield or isolate a person from the chemical, physical, and thermal hazards that can be encountered at a hazardous materials incident.  Personal protective equipment includes both personal protective clothing and respiratory protection.  See also individual protective equipment.  (JP 1-02. Source:  JP 3-11.)

This page intentionally left blank.


## References Sources Used These Are The Sources Quoted Or Paraphrased In This Publication. Geneva Convention This Publication Is Available Online At:

http://www.icrc.org/Web/Eng/siteeng0.nsf/htmlall/genevaconventions.

Convention (I) for the Amelioration of the Condition of the Wounded and Sick in Armed Forces in the Field, 12 August 1949.

NATO STANAGS
These documents are available online at:  https://nsa.nato.int (password required).
2048, Chemical Methods of Insect and Rodent Control*AMedP-3*(B), 30 June 2006.
2136, *Minimum Standards of Water Potability During Field OperationsAMedP-18*, Edition 5,
22 October 2007.
2242, Policy for the Chemoprophylaxis and Immunotherapy of NATO Personnel Against Biological
Warfare Agents, Edition 1, 10 May 2005.
2462, NATO Handbook on the Medical Aspects of NBC Defensive Operations (Biological)*AMedP-6(C)*,
Volume II, Edition 1, 11 May 2005.
2873, Concept of Operations of Medical Support in Chemical, Biological, Radiological, and Nuclear
EnvironmentsAMedP-7(D), Edition 4, 6 December 2007.
2879, *Principles of Medical Policy in the Management of a Mass Casualty Situation*, Edition 3,
7 September 1998.
4632, *Deployable NBC Analytical Laboratory*, Edition 1, 12 August 2005.
EXECUTIVE ORDER/DIRECTIVE
These documents are available online at: http://www.fas.org/irp/offdocs/pdd39.htm.

Executive Order 13375, Amendment to Executive Order 13295 Relating to Certain Influenza Viruses and Quarantinable Communicable Diseases, 11 July 2009. http://www.gpo.gov/fdsys/pkg/FR-2005-
04-05/pdf/05-6907.pdf.

Presidential Decision Directive/NSC-39, *U.S. Policy on Counterterrorism (U)*, 21 June 1995.

## United States Code United States Codes Can Be Found At:  Http://Www.Gpoaccess.Gov/Uscode/Index.Html. Title 49, United States Code, *Transportation*.

FEDERAL ACTS
These documents are available online at:  http://www.state.gov.

Homeland Security Act of 2002, 25 November 2002. Implementing Recommendations of the 9/11 Commission Act of 2007, 3 August 2007.

Pandemic and All-Hazards Preparedness Act, 19 December 2006.

Public Health Security and Bioterrorism Preparedness and Response Act of 2002, 12 June 2002.

## References

DEPARTMENT OF DEFENSE PUBLICATIONS
Department of Defense publications are available online at:  http://www.dtic.mil/whs/directives/.
Defense Transportation Regulation 4500.9-R, Defense Transportation Regulation Part II, Cargo Movement, June 2008. http://www.transcom.mil/dtr/part-ii/.

DODD 5154.24, *Armed Forces Institute of Pathology (AFIP)*, 3 October 2001. DODD 6490.02E, *Comprehensive Health Surveillance*, 8 February 2012.

DODI 3020.52, DOD Installation Chemical, Biological, Radiological, Nuclear, and High-Yield Explosive
(CBRNE) Preparedness Standards, 18 May 2012.

DODI 5200.08, Security of DOD Installations and Resources and the DOD Physical Security Review Board (PSRB), 10 December 2005.

DODI 6055.1, DOD Safety and Occupational Health *(SOH) Program*, 19 August 1998.

DODI 6200.03, *Public Health Emergency Management Within the Department of Defense*, 5 March 2010. DODI 6490.03, *Deployment Health*, 11 August 2006. Health Affairs Policy 08-004, Update to Clinical Policy for the Department of Defense Smallpox Vaccination Program, 1 April 2008.

 http://www.vaccines.mil/documents/1182SPX_Update_Clinical_Policy.pdf.

JOINT PUBLICATIONS
Joint publications are available online at http://www.dtic.mil/doctrine/new_pubs/jointpub.htm.

MCMs are available at https://www.dtic.mil/cjcs_directives/index.htm.

JP 3-11, *Operations in Chemical, Biological, Radiological, and Nuclear (CBRN) Environments,* 26 August
2008.

JP 4-02, *Health Service Support*, 31 October 2006.

JP 4-06, *Mortuary Affairs in Joint Operations*, 12 October 2011.

MCM 0026-02, *Chemical Warfare (CW) Agent Exposure Planning Guidance*, 29 April 2002.
(Restricted by the Joint Staff Office of Primary Responsibility.)
MCM 0028-07, *Procedures for Deployment Health Surveillance*, 2 November 2007.

MULTISERVICE PUBLICATIONS
These publications are available online at:  https://armypubs.us.army.mil.
AFMAN 24-204/TM 38-250/NAVSUP PUB 505/MCO P4030.19J/DLAI 4145.3, Preparing Hazardous
Materials for Military Air Shipments, 3 December 2012.
AR 40-12/SECNAVINST 6210.2A/AFR 161-4, *Quarantine Regulations of the Armed Forces*, 24 January
1992.
ATP 3-11.37/MCWP 3-37.4/NTTP 3-11.29/AFTTP 3-2.44, Multi-service Tactics, Techniques, and
Procedures for Chemical, Biological, Radiological, and Nuclear Reconnaissance and Surveillance, 25 March 2013.
FM 3-11.4 (FM 3-4)/MCWP 3-37.2/NTTP 3-11.27/AFTTP (I) 3-2.46, Multiservice Tactics, Techniques,
and Procedures for Nuclear, Biological, and Chemical (NBC) Protection, 2 June 2003.
FM 3-11.5/MCWP 3-37.3/NTTP 3-11.26/AFTTP(I) 3-2.60, Multiservice Tactics, Techniques, and
Procedures for Chemical, Biological, Radiological, and Nuclear Decontamination, 4 April 2006.
FM 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3, Multiservice Tactics, Techniques, and Procedures
for Health Service Support in a Chemical, Biological, Radiological, and Nuclear Environment,
15 July 2009.
FM 4-02.285 (FM 8-285)/MCRP 4-11.1A/NTRP 4-02.22/AFTTP(I) 3-2.69, Multiservice Tactics,
Techniques, and Procedures for Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries, 18 September 2007.
TB MED 577/NAVMED P-5010-10/AFMAN 48-138_IP, Sanitary Control and Surveillance of Field
Water Supplies, 1 May 2010.
ARMY PUBLICATIONS
Most of these publications are available online at: http://www.apd.army.mil/.

AR 50-1, *Biological Surety*, July 28, 2008. ATTP 4-02, *Army Health System*, 7 October 2011.

FM 4-02.2, *Medical Evacuation*, 8 May 2007. FM 4-02.51, *Combat and Operational Stress Control*, 6 July 2006. FM 5-19, *Composite Risk Management*, 21 August 2006. FM 6-22.5, *Combat and Operational Stress Control Manual for Leaders and Soldiers*, 18 March 2009. FM 7-15, *The Army Universal Task List*, 27 February 2009. TB MED 530, *Occupational and Environmental Health Food Sanitation*, 30 October 2002. TB MED 576, Occupational and Environmental Health Sanitary Control and Surveillance of Water Supplies at Fixed Installations, 15 March 1982.

Technical Information Paper, 64-003-0310, Recommended Hazard Identification, Detection, and Analyses Definitions for Military Occupational and Environmental Health and Chemical, Biological, and Radiation Applications.

http://phc.amedd.army.mil/Pages/Library.aspx?Series=PHC+Technical+Information+Paper.
United States Army Center for Health Promotion and Preventive Medicine, Technical Guide 195, Safety
and Health Guidance for Mortuary Affairs Operations:  Infectious Materials and CBRN Handling,
May 2009.
http://phc.amedd.army.mil/topics/workplacehealth/ms/Pages/FactSheets%20and%20Technical%20Guides.

aspx.

USAMRIID, *USAMRIID's Medical Management of Biological Casualties Handbook*, Seventh Edition, September 2011.
http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%207th%20Edition%20-
%20Sep%202011.pdf.

## Marine Corps Publications This Publication Is Available Online At:  Http://Www.Quantico.Usmc.Mil/Activities/?Section=Cmm.

MCO 3900.15B, *Marine Corps Expeditionary Force Development System (EFDS)*, 10 March 2008.

NAVY PUBLICATIONS
These publications are available online at: http://www.med.navy.mil/directives/pages/default.aspx and https://navalforms.documentservices.dla.mil/.

NAVMED P-5010-9, *Manual of Preventive Medicine, Chapter 9, Preventive Medicine for Ground Forces*, June 1991.

OPNAV Form 5580/22, *Evidence/Property Custody Receipt*.

AIR FORCE PUBLICATIONS
These publications are available online at: http://www.e-publishing.af.mil.

Air Force Institute for Operational Health
(https://kx.afms.mil/kxweb/dotmil/kj.do?functionalArea=USAF_SAM).

Air Force Instruction 33-360, *Publications and Forms Management*, 1 July 2008.

AFMAN 10-2503, Operations in a Chemical, Biological, Radiological, Nuclear, and High-Yield Explosive
(CBRNE) Environment, 6 July 2011.

AFTTP 3-42.3, *Health Service Support in Nuclear, Biological, and Chemical Environments*, 26 August
2002.

Air Force Visual Aid 10-2511, USAF Standardized Attack Warning Signals for CBRNE Medium and High Threat Areas, 5 August 2011.

## References

OTHER SOURCES
Borden Institute, The Textbooks of Military Medicine, Medical Aspects of Chemical and Biological
Warfare, 1997 (http://www.bordeninstitute.army.mil/published_volumes/chemBio/chembio.html).
Borio, L, et al, Journal of the American Medical Association, Hemorrhagic Fever Viruses as Biological
Weapons: Medical and Public Health Management, August 7, 2002.
Ceislak, T.J., Rowe, J.R., Kortepeter, M.G., et al, A Field-Expedient Algorithmic Approach of the Clinical
Management of Chemical and Biological Casualties  (Manuscript).
Centers for Disease Control and Prevention, Guideline for Isolation Precautions:  Preventing Transmission
of Infectious Agents in Healthcare Settings, 2007.
Centers for Disease Control and Prevention, Management of Multidrug-Resistant Organisms in Healthcare
Settings, 2006.
Chu, M, *Laboratory Manual of Plague Diagnostic Tests*, Centers of Disease Control and Prevention and
World Health Organization, 2000.
Department of Homeland Security, *National Response Plan*, 22 March 2008. Department of Homeland Security, *The National Strategy for Homeland Security*, October 2007. Department of Transportation, Emergency Response Guidebook (A Guidebook for First Responders
During the Initial Phase of a Dangerous Goods/Hazardous Materials Transportation Incident),
2008.  This guidebook can be obtained at http://hazmat.dot.gov/pubs/erg/gydebook.htm.
Emergency War Surgery, Third United States Revision, 2004.  (http://www.bordeninstitute.army.mil).
Henretig, F.M., Cieslak, T. J., Kortepeter, M.G., and Fleisher, G.R., Medical Management of the Suspected
Victim of Bioterrorism:  An Algorithm Approach to the Undifferentiated Patient.  Emerg Med Clin N Am 2002; 20: 351-64.
Infectious Substances Shipping Guidelines (9052-07), International Air Transport Association, 2006.
Loiez C, Herwegh S, Wallet F, Armand S, Guinet F, Courcol RJ: Detection of Yersinia pestis in sputum by
real-time PCR, J Clin Microbiol, 2003.
Morbidity and Mortality Report, Recognition of Illness Associated with the Intentional Release of a
Biologic Agent, Centers for Disease Control and Prevention, 2001; 50(41); 893-7.
Pilch, Fran, *The Worried Well:  Strategies for Installation Commanders*.  Colorado Springs:  U.S. Air Force
Academy, Institute for National Security Studies, 2004.  72pp. (UG638.5 F703 no.53).
Radnedge L, Gamez-Chin S, McCready PM, Worsham PL, Andersen GL, Identification of nucleotide
sequences for the specific and rapid detection of Yersinia pestis, Appl Environ Microbiol, 2001.
The Scowcroft Memorandum*, U.S. Compliance with the Biological Weapons Convention, 23* December
1975.
Sheth AN, et al, *Enteric Diseases Epidemiology Branch*, Centers for Disease Control and Prevention, 2008,
asheth@cdc.gov.
Siegel JD, et al, Healthcare Infection Control Practices Advisory Committee Guideline for Isolation
Precautions:  Preventing Transmission of Infectious Agents in Healthcare Settings, June 2007.
World Health Organization, ST/SG/AC.10/1/Rev.15, Recommendations on the Transport of Dangerous
Goods, 2007.
World Health Organization, International Statistical Classification of Diseases and Related Health
Problems, 10th revision, 2007.
World Health Organization, WHO/HSE/IHR/2010.8, Guidance on Regulations for the Transport of
Infectious Substances, 2011-2012.
DOCUMENTS NEEDED
These documents must be available to the intended users of this publication.  These forms are available at:
http://www.dtic.mil/whs/directives/infomgt/forms/formsprogram.htm and http://www.apd.army.mil/Forms/browse_forms.asp.

JP 1-02, *Department of Defense Dictionary of Military and Associated Terms,* 8 November 2010.

DD Form 1380, *U.S. Field Medical Card*. (Available through normal forms supply channels.)
DD Form 1911, *Materiel Courier Receipt*.

DA Form 4137, *Evidence/Property Custody Document*. FM 1-02 (FM 101-5-1)/MCRP 5-12A, *Operational Terms and Graphics*, 21 September 2004.

## Readings Recommended These Sources Contain Relevant Supplemental Information.

NATO STANAGS
These documents are available online at:  https://nsa.nato.int (password required).
2037, *National Military Strategies for Vaccination of NATO ForcesAMedP-23*, Edition 9, 16 December
2008.
2068, *Emergency War Surgery*, Edition 5, 12 September 2005. 2070, *Emergency War Burial Procedures*, Edition 4, 6 April 1999. 2126, *First-Aid Dressings, First Aid Kits and Emergency Medical Care Kits*, Edition 6, 10 December 2009.
2478, *Medical Support Planning for Nuclear, Biological, and Chemical Environments*, Edition 1,
10 February 200.6
2529, Rapidly Deployable Outbreak Investigation Team (RDOIT) for Suspected Use of Biological Warfare
Agents, Edition 1, 29 October 2009.
2553, *NATO Planning Guide for the Estimation of CBRN CasualtiesAMedP-8(C)*, Edition 1, 3 March
2011.
2827, *Materials Handling in the Field*, Edition 6, 22 April 2010. 2954, *Training of Medical Personnel for NBC Defence Operations*, Edition 2, 12 May 2006.
DEPARTMENT OF DEFENSE PUBLICATIONS
Department of Defense publications are available online at:  http://www.dtic.mil/whs/directives/.

DODD 4500.54.E, *DOD Foreign Clearance Program (FCP)*, 28 December 2009.

DODI 6200.02, Application of Food and Drug Administration (FDA) Rules to Department of Defense Force Health Protection Programs, 27 February 2008.

MULTISERVICE PUBLICATIONS
These publications are available online at:  https://armypubs.us.army.mil/.
AR 40-562/BUMEDINST 6230.15A/AFJI 48-110/CG COMDTINST M6230.4F, Immunizations and
Chemoprophylaxis, 29 September 2006.
FM 3-11.9/MCRP 3-37.1B/NTRP 3-11.32/AFTTP(I) 3-2.55, Potential Military Chemical/Biological
Agents and Compounds, 10 January 2005.
FM 3-11.21/MCRP 3-37.2C/NTTP 3-11.24/AFTTP (I) 3-2.37, Multiservice Tactics, Techniques, and
Procedures for Chemical, Biological, Radiological, and Nuclear Consequence Management Operations, 1 April 2008.
TB MED 502/DALM 1000.2, *Occupational and Environmental Health Respiratory Protection Program*,
15 February 1982.
TM 3-4240-288-12&P/NAVFAC P-475, Operator's and Unit Maintenance Manual Including Repair Parts
and Special Tools List for Collective Protection Equipment Nuclear, Biological, and Chemical, Simplified, M20, 20 August 1987.
TM 4-02.33/NAVMED P-5038, *Control of Communicable Diseases Manual*, 19th Edition, 1 June 2009.
TM 9-4120-411-14/TO 35E9-314-1, Operator, Unit, Direct Support and General Support Maintenance
Manual for Field Deployable Environmental Control Unit Model FDECU-2 and Model FDECU-3, 1 May 2000.

## References Army Publications These Publications Are Available Online At: Https://Armypubs.Us.Army.Mil/ And At:

http://phc.amedd.army.mil/Pages/Library.aspx.

FM 3-11.20 (FM 9-20), *Technical Escort Battalion Operations*, 29 August 2007.

FM 4-02.1, *Army Medical Logistics*, 8 December 2009. FM 4-02.10, *Theater Hospitalization*, 3 January 2005. FM 4-02.17, *Preventive Medicine Services*, 28 August 2000.

FM 4-02.18, *Veterinary ServiceTactics, Techniques, and Procedures*, 30 December 2004.

FM 4-20.64, *Mortuary Affairs Operations*, 9 January 2007. FM 8-10-6, *Medical Evacuation in a Theater of OperationsTactics, Techniques, and Procedures*,
14 April 2000.

FM 8-55, *Planning for Health Service Support*, 9 September 1994.

FM 10-52, *Water Supply in Theaters of Operations*, 11 July 1990. TM 10-5410-228-10, *Operator's Manual for Chemical Biological Protective Shelter (CBPS) System*,
19 March 2004.

TM 10-5410-283-14&P, Operator's, Unit, Direct Support, and General Support Maintenance Manual
(Including Repair Parts and Special Tools List) Chemically Protected Deployable Medical System (CPDEPMEDS) and CPDEPMEDS Training Set, 30 November 2001.

United States Army Center for Health Promotion and Preventive Medicine, Technical Guide 244, The Medical CBRN Battlebook, October 2008.

## Marine Corps Publications Mco 3500.27B, *Operational Risk Management (Orm)*, 20 August 2004. Http://Www.Marines.Mil/News/Publications/Electroniclibrary/Tabid/13081/Article/129134/Mco- 350027B.Aspx.

NAVY PUBLICATIONS
These publications are available online at:  http://www.med.navy.mil/directives/pages/default.aspx, https://ndls.nwdc.navy.mil,  https://doni.daps.dla.mil/allinstructions.aspx  and https://navalforms.documentservices.dla.mil/.

NAVSUP P-409, Military Standard Requisitioning and Issue Procedures (MILSTRIP) and Military Standard Transaction Reporting and Accounting Procedures (MILSTRAP) Desk Guide, 9 May
2003.

NTTP 3-20.31, *Surface Ship Survivability*, October 2004.

NTTP 3-20.31.470, Naval Ships Technical Manual, Chapter 470, Shipboard Biological Warfare/Chemical Warfare Defense and Countermeasures, Rev.004, 1 November 2006.

OPNAVINST 5090.1C, *Environmental Readiness Program Manual*, 30 October 2007. Tactical Memorandum (TACMEMO) 3-11.1-02, Guide to Biological Warfare Defense and Bioterrorism
Afloat and Ashore, 23 October 2002.

AIR FORCE PUBLICATIONS
These publications are available online https://kx.afms.mil/doctrine and http://www.e-publishing.af.mil/.

Air Force Doctrine Document 2-1.8, *Counter-Chemical, Biological, Radiological, and Nuclear Operations*,
26 January 2007.

Air Force Instruction 10-2501, *Air Force Emergency Management Program Planning and Operations*,
24 January 2007.

AFMAN 10-2502 *Air Force Incident Management System (AFIMS) Standards and Procedures*,
25 September 2009.

Air Force Policy Directive 10-26, *Counter-Chemical, Biological, Radiological and Nuclear Operations*,
26 September 2007.

AFTTP 3-42.5, *Aeromedical Evacuation (AE),* 1 November 2003.

AFTTP 3-42.22, *Contagious Casualty Management*, 7 May 2007.

AFTTP 3-42.23, *Preventive and Aerospace Medicine (PAM) Teams*, 22 February 2006.

AFTTP 3-42.32, Home Station Medical Response to Chemical, Biological, Radiological, and Nuclear
(CBRN) Events, 13 August 2009.

AFTTP 3-42.33, *Expeditionary Medical Decontamination Team,* 7 April 2005.

AFTTP 3-42.71, *Expeditionary Medical Support (EMEDS),* 27 July 2006.

## Web Sites

http://phc.amedd.army.mil/topics/workplacehealth/ih/Pages/IHTechnicalGuides.aspx.

http://afhsc.army.mil/reportableEvents.

http://www.cdc.gov/nchs/icd/icd10cm.htm.

https://doehsportal.apgea.army.milwww.vaers.hhs.gov.

http://www.vaccines.mil/documents/1182SPX_Update_Clinical_Policy.pdf.

http://ecfr.gpoaccess.gov/.

http://phc.amedd.army.mil/Pages/default.aspx.
http://phc.amedd.army.mil/Pages/Library.aspx.

http://www.cdc.gov/ncidod/dhqp/pdf/isolation2007.pdf.

http://www.cidrap.umn.edu.

http://www.pdhealth.mil.


The copyright owners listed here have granted permission to reproduce material from their works.  Other sources of quotations are listed in the source notes. Center for Infectious Disease Research and Policy (CIDRAP), Copyright Regents of the University of Minnesota (http://www.cidrap.umn.edu).

No endorsement by the Government is expressed or implied with any URL associated with a non-Government web site.

This page intentionally left blank.


## Index

References are to paragraph numbers unless otherwise stated.

| E                               |          |
|---------------------------------|----------|
| Ebola, Table 1-2, 1-89, 1-97,   |          |
| Table 4-12, 4-43, Table        |          |
| 4-4, Table A-3, Table C-1       |          |
| ECL.                            | See      |
| nescence.                       |          |
| electrochemiluminescence,       |          |
| 4-28, 5-16, 5-40, 5-69, 6-2,    |          |
| 6-5                             |          |
| ELISA.                          | See      |
| munosorbent assays.             |          |
| employment,  1-14, 1-18, 1-28,  |          |
| 1-33, 3-59, 6-8, 6-10, 6-12,    |          |
| 6-14, C-14, C-17                |          |
| enzyme-linked immunosorbent     |          |
| assays, 1-92, 3-80, 3-97,       |          |
| 4-42, 5-16, 5-40, 5-44, 5-59,   |          |
| 5-69, 6-2, 6-4                  |          |
| epidemic curve,  2-78, Figure  |          |
| 2-1                             |          |
|                                 |          |
| F                               |          |
| filovirus, 4-45                 |          |
|                                 |          |
| G                               |          |
| gastrointestinal anthrax, 3-12, |          |
| Table 3-5                       |          |
| gastropharyngeal                | anthrax, |
| 3-12, Table 3-3                 |          |
| glanders,  Table 1-23, 1-89,   |          |
| 3-1, 3-3536, 3-38, 3-47,       |          |
| 3-49, Table C-1                 |          |
|                                 |          |
| H                               |          |
| hantavirus, 1-21, 1-23, Table   |          |
| 4-1, 5-44, 5-74                 |          |
| human remains, 1-87, 1-89,      |          |
| A-6, C-21                       |          |
|                                 |          |
| I                               |          |
| IND.                            | See      |
| drug.                           |          |
| infection control, 1-32, 1-98,  |          |
| 4-31, D-8                       |          |
| infectious substance,  A-15,    |          |
| Table A-3                       |          |
| influenza, 1-21, Table 1-2,     |          |
| 1-70, 1-97, 2-6, 2-15, 2-17,    |          |
| Table C-1                       |          |

 inhalational
anthrax,
1-36,
Table 2-1, 3-10, Table 3-1 2, Table 3-56
investigational new drug, 1-35,
1-7071, 1,-74,  4-8, 4-24, Table 4-23, 5-10
isolation,  1-5153, 1-66, 1-
68, 1-90, 1-9596, 2-9, 2- 18, 3-49, 3-67, 3-118, 4-16, 4-4546, 6-2, D-3

L
laboratory response network,
2-21, Figure 6-2, 6-2122
lateral flow immunoassay, 63 levels of identification, 6-16
17, Figure 6-12
LFI.  See lateral flow immunoassay.

M
Marburg,
Table
1-2,
1-97,
Table
4-12,
4-4344,
Table 4-4, Table A-3, Table C-1
Melioidosis, Table 1-2, 3-1,
3-3536, 3-38, 3-47, 3-49, 4-13, Table C-1
mycotoxin, Table 1-23, 1-30,
5-79, 5-8283, 5-85, 5-87, 5-91, Table A-2, B-10

N
novel threat, 1-19
P
pathogen, 1-11, 1-15, 1-19,
1-21, 1-23, Table 1-1, 1-25, 1-31, 1-41, 1-89, 2-4, Table 2-1, 2-1617, 3-1, 3-19, 4-3, A-15, C-18
patient isolation unit, 1-99
100
PCR.  See polymerase chain
reaction.
personal protective equipment,
1-38, 1-4245, 1-64, 1-88, B-3
PIU.  See patient isolation unit.
A
anthrax, 1-6, 1-20, Table 1-2
3, 1-3536, 1-66, 2-1, Table 2-1, 2-6, 3-1, 3-46, 3-8 11, Table 3-16, 3-1216, 3-18, 3-94, Table A-12, B-2, B-15, Table C-1, C-18
arenavirus, 1-70, 4-43, 4-45 Argentine hemorrhagic fever,
Table 1-2, 1-35, 4-39, 4-43, Table 4-4

B
bacteria, 1-2, 1-7, 1-17, Table
1-1, 3-1, 3-8, 3-22, 5-1, A-7, D-1
bacterial agents, Table 1-3,
1-36, 3-186, A-4
Biological Weapons Convention, 1-5, 1-19
BioPHusion, 2-356 BioSense, 2-378 BioWatch, 2-34 botulinum toxin, 1-35, 1-96,
5-2, 5-4, 5-17
brucellosis, Table 1-23, 3-1,
3-2324, 3-2627, 3-30, 3-32, 3-34, Table A-12, Table C-1
bunyavirus, 1-70, 4-43
C
case-fatality rate, 3-5, 3-16,
3-32, 3-44, Table 3-6, 4-8, 4-15, 4-21, Table 4-4, Table A-1
chain of custody, 2-5, A-3,
A-910, A-1718
cholera, Table 1-23, 1-97,
3-1, 3-103, 3-106, 3-116 118, Table C-1
Cidofovir, 1-70, 3-120 classification, 1-22, Table 1-1,
2-15, 2-27
cutaneous anthrax, 3-5, Table
3-5

## Index

plague, Table 1-23, 1-35
36, 1-9698, Table 2-1, 3-1, 3-4647, 3-4950, 3-52 56,
3-5859,
3-6263,
3-6568, 3-94, Table C-1, C-18
polymerase
chain
reaction,
1-92, 3-13, Table 3-5, 3-30, 3-64, 4-13, 4-28, 5-69, 6-2, 6-56, 6-10, A-6
PPE.  See personal protective
equipment.
psychological effects, 1-82
84, 1-86, B-3, D-6
public health, 1-6, 1-8, 1-10,
1-12, 1-14, 1-34, 1-9091, 1-97, 2-2, 2-45, 2-10, 2-16, 2-23, 2-27, 2-32, 2-3637, 3-7, 3-25, 3-41, 3-110, 4-9, 4-17, 4-29, 4-39, 4-46, 5-9, 5-17, A-1, C-27

Q
Q fever, Table 1-23, 1-78,
1-89, 3-1, 3-69, 3-7172, 3-80, 3-8385, 5-44, Table C-1, C-18
quarantine,
1-3,
1-5253,
1-66, 1-80, 1-90, 1-94, 1-96, 3-49, 3-68, 4-1617

R
reaerosolization,
1-2829,
1-66, B-2
restriction of movement, 1-3,
1-32, 1-52, 1-76, 1-90
T
toxin, 1-11, 1-31, 1-35, 1-79,
3-4, 5-2, 5-47, 5-1112, 5-1617, 5-21, 5-2325, 5-2930, 5-3233, 5-37 38, 5-40, 5-52, 5-59, 5-64, 5-6667, 5-74, 5-83, 5-87 88, 6-2, 6-4
triage, 1-66, 1-84, 2-13 trichothecene, 5-8283, 5-89 tularemia,  Table 1-23, 1-36,
1-78,
1-87,
3-1,
3-87,
3-9091,
3-94,
3-96,
3-100101, 5-44, Table C-1, C-18

V
VEE.  See Venezuelan Equine
Encephalitis.
Venezuelan Equine Encephalitis, 1-35, 1-78, 4-1920, 4-22, 4-27, 4-3132, Table A-2, C-18
VHF.  See viral hemorrhagic
fever.
viral hemorrhagic fever, 1-96,
4-1, 4-34, Table 4-1, 4-35, 4-37, 4-42, 4-44, 4-46, C-18

Y
yellow fever, Table 1-2, 1-35,
1-78, 1-97, 4-34, Table 4-1, 4-37, 4-40, Table 4-2, 4-44, 4-46, Table 4-4, Table A-3

reverse-transcriptase
polymerase chain reaction, 6-7, Table A-2
Rift Valley fever, Table 1-2,
1-35, 1-70, Table 4-1, Table 4-4
RT-PCR.

See
reversetranscriptase
polymerase
chain reaction.

S
sample collection, 2-18, 2-43 sample management, 6-17 saxitoxin, 1-17, Table 1-23,
5-49, 5-5153, 5-59, 5-62
SEB.

See
staphylococcal
Enterotoxin B.
smallpox, Table 1-23, 1-35,
1-70, 1-89, 1-9698, Table 2-1,
3-4950,
4-12,
4-45, 4-813, 4-1618, Table C-1
specimen collection, 2-2, Table
3-5, Figure 6-2, A-1, A-4, A-7, Table A-2
staphylococcal Enterotoxin B,
1-31, 5-30, 5-44, 5-6465, 5-6769
surveillance, 1-18, 2-6, 2-10,
2-12,
2-1417,
2-23,
2-2526, 2-2930, 2-32, 2-3738, 3-25, 4-17, 4-40,
6-1, 6-7, 6-17


                                                            25 March 2013

By Order of the Secretary of the Army:

                                           RAYMOND T. ODIERNO

                                          General, United States Army

                                                Chief of Staff

Official:



    JOYCE E. MORROW
Administrative Assistant to the

    Secretary of the Army
             1212801


DISTRIBUTION:
Active Army, Army National Guard, and United States Army Reserve: Not to be
distributed. Electronic media only.

By Order of the Secretary of the Air Force

    JAMES D. COLLIER
   Colonel, USAF, MC, CFS
  Assistant Surgeon General
   Health Care Operations
 Office of the Surgeon General


Air Force Distribution:

ACCESSIBILITY:  Publications and forms are available for downloading or ordering on the
e-Publishing Web site at http://afpubs.hq.af.mil


Marine Corps Distribution:  PCN:  144 000080 00