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A Guide to
Gulf War Veterans' Health:
1998 Continuing Medical Education Program

Independent Study
Release:
March 1998

Sponsored by
Department of Veterans Affairs
Employee Education System

This is a Veterans Health Administration System-Wide Training Program,
sponsored by the Employee Education System in cooperation with the
Office of Employee Education and the Office of Public Health and Environmental Hazards,
Department of Veterans Affairs. It is produced by the Employee Education System. 2_
2 Page 3 4
b
A Guide to Gulf War Veterans' Health
Contents Page
Program Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vi
Accreditation Statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .viii
Independent Study Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ix
Content Materials
1 History of Operations Desert Shield and Desert Storm . . . . . . . . .1
2 VA Healthcare Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
3 Department of Defense Comprehensive Clinical
Evaluation for Gulf War Veterans . . . . . . . . . . . . . . . . . . . . . . . .11

4 Depleted Uranium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
5 Research on Gulf War Veterans' Illnesses . . . . . . . . . . . . . . . . . .25
6 Chemical Warfare Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
7 Some Hypotheses Regarding Illnesses in Gulf War Veterans . . . .67

Supplemental Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71
Additional References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .77
Independent Study Program Evaluation . . . . . . . . . . . . . . . . . . . . . . . . .79
Independent Study Continuing Medical Education Test . . . . . . . . . . . . .83
Scantron Forms 3_
3 Page 4 5
c
A Guide to Gulf War Veterans' Health
© 1998
Department of Veterans Affairs
Employee Education System
St. Louis Center (14B/ JB)
VA Medical Center
#1 Jefferson Barracks Drive
St. Louis, MO 63125

Program Contents:
� History of Operations Desert Shield and Storm

� VA Healthcare Programs � Department of Defense
Comprehensive Clinical Evaluation
Program for Gulf War Veterans

� Depleted Uranium � Research on Gulf War Veterans'

Illnesses
� Chemical Warfare Agents � Some Hypotheses Regarding

Illnesses in Gulf War Veterans

Program Implementation:
1. Read the program materials.
2. Complete the registration.
3. Complete the CME test questions.
4. Complete the program evaluation.
5. A passing score of 70% on the CME
test is required to receive credit. This
test may be retaken one time.

6. The estimated study time for this
program is six hours.

This Program includes:
� independent study � test for CME credits

� program evaluation
This activity was planned and produced in
accordance with the ACCME Essentials.

This program will no longer be
authorized for CME credit after
March 1999. 4_
4 Page 5 6
vi
A Guide to Gulf War Veterans' Health
Purpose: This independent study is designed to provide an
introduction to issues regarding Gulf War (GW) veterans'
health. It will provide an overview of the Gulf War
experience, the Department of Veterans Affairs (VA) and
the Department of Defense (DoD) health programs
available for Gulf veterans, and the common symptoms
and diagnoses of these veterans. Emphasis is placed on
providing the most recent available information from
clinical and scientific studies of Gulf War veterans'
illnesses.

Objectives: After reading this independent study, the participants will
be able to:

1. recognize the most common symptoms and diagnoses
of GW veterans,

2. describe current GW veterans' programs available
through VA and DoD, and

3. discuss recent research studies and findings
concerning health of GW veterans.

Target Audience: This independent study is designed for all VA physicians. 5_
5 Page 6 7
vii
A Guide to Gulf War Veterans' Health
Planning Committee
Karen Jones, R. N., M. S.
Education & Performance Development
Division, Employee Education System
St. Louis Center
VA Medical Center, St. Louis, MO

Susan Mather, M. D., M. P. H.
Chief, Office of Public Health and
Environmental Hazards Officer
Department of Veterans Affairs
Washington, DC

Frances M. Murphy, M. D., M. P. H.
Director, Environmental Agents Service
Department of Veterans Affairs
Washington, DC

Susan K. Sverha, M. S. N.
Educational Services & Partnerships Division
Employee Education System
Department of Veterans Affairs
Washington, DC

Editor
Frances M. Murphy, M. D., M. P. H.
Director, Environmental Agents Service
Department of Veterans Affairs
Washington, DC

Program Director
Karen Jones, R. N., M. S.
Education & Performance Development
Division, Employee Education System,
St. Louis Center
VA Medical Center, St. Louis, MO

Program Assistant
Lynda Gavaghan
Site & Logistical Support Division
Employee Education System, St. Louis Center
VA Medical Center, St. Louis, MO

Jane Clanton, B. F. A., M. B. A.
Learning Technology & Media Development
Division, Employee Education System
St. Louis Center
VA Medical Center, St. Louis, MO

Deborah A. Dorsey, M. Ed.
Learning Technology & Media Development
Division, Employee Education System
St. Louis Center
VA Medical Center, St. Louis, MO

Lisa McClanahan
Learning Technology & Media Development
Division, Employee Education System
Salt Lake Center
VA Medical Center, Salt Lake City, UT

Editorial Staff
Michael Howe, M. S. L. S.
Medical Librarian
VA Medical Center, San Francisco, CA

John E. Kraemer, M. H. A.
Senior Program Analyst
Environmental Agents Service
Department of Veterans Affairs
Washington, DC

Donald J. Rosenblum
Deputy Director
Environmental Agents Service
Department of Veterans Affairs
Washington, DC 6_
6 Page 7 8
viii
A Guide to Gulf War Veterans' Health
Accreditation
The Department of Veterans Affairs Employee
Education System is accredited by the
Accreditation Council for Continuing Medical
Education to sponsor continuing medical
education for physicians. This activity was
planned and produced in accordance with the
ACCME Essentials.

Continuing Education Credit
The Department of Veterans Affairs Employee
Education System designates this continuing
medical education activity for a maximum of six
hours in category I credit towards the AMA
Physicians' Recognition Award. Each physician
should claim only those hours of credit that he/ she
actually spent in the educational activity. The
Department of Veterans Affairs Employee
Education System maintains responsibility for the
program. A certificate of attendance will be
awarded to VA employees and accreditation
records will be on file with the Department of
Veterans Affairs Employee Education System.

Disclosure Policy Statement
It is the policy of the Department of Veterans
Affairs, Employee Education System, to ensure
balance, independence, objectivity, and scientific
rigor in all its educational programs. All faculty
participating in these programs are expected to
disclose to the program audiences any real or
apparent conflict of interest related to the content
of their presentation.

Report of Training
It is the program participant's responsibility to
submit VA Form 5-4691 (Report of Employee
Training) to Human Resources Management
Service in order for this training to be coded into
their personnel record.

VA Application Procedure
To receive credit for this course, you must read the
independent study, complete the Registration , the
Test and Program Evaluation. If you have attained
a passing score of at least 70%, a certificate will be
mailed to you after your test has been graded
(approximately 6-8 weeks).. The test may be
retaken one time.

This program will no longer be authorized for
CME credit after March 1999.

AMA Continuing Education Credit 7_
7 Page 8 9
ix
A Guide to Gulf War Veterans' Health
Chapter 1
History of Operations Desert Shield
and Desert Storm

Chapter 2
VA Gulf War Healthcare Programs
a. Gulf War Registry Health Examination
Program

b. Referral Center Programs
c. Spouses and Children Examination
Program

Comprehensive Clinical Evaluation of
20,000 Persian Gulf War Veterans
(journal article summary)

Chapter 4
Depleted Uranium
General Information
Health Effects
VA Depleted Uranium Follow-up
VA Depleted Uranium Follow-up Program
Consultation Information

Guidelines for Clinicians

Chapter 5
Research on Gulf War Veterans' Illnesses
a. Mortality Study
Mortality Among U. S. Veterans of the
Persian Gulf War
(journal article summary)

b. Morbidity Study
The Postwar Hospitalization Experience of
U. S. Veterans of the Persian Gulf War
(journal article summary)

c. Reproductive Outcome Study
The Risk of Birth Defects Among Children
of Persian Gulf War Veterans
(journal article summary)

No Evidence of Increase in Birth Defects
and Health Problems Among Children
Born to Persian Gulf War Veterans in
Mississippi
(journal article summary)

d. Infectious Diseases
The Impact of Infectious Diseases on the
Health of U. S. Troops Deployed to the
Persian Gulf during Operations Desert
Shield and Desert Storm
(journal article summary)

Assessment of Arthropod Vectors of
Infectious Diseases in areas of U. S. Troop
Deployment in the Persian Gulf
(journal article summary)

Visceral Infection Caused by Leishmania
Tropica in Veterans of Operation Desert
Storm
(journal article summary)

e. Unexplained Illness/ Symptoms
Unexplained Illness Among Persian Gulf
War Veterans in an Air National Guard
Unit: Preliminary Report -August 1990-
March 1995
(journal article summary)

f. Psychological Health
Psychological Health of Gulf War-Era
Military Personnel
(journal article summary)

Psychological Symptoms and Psychiatric
Diagnoses in Operation Desert Storm
Troops Serving Graves Registration Duty
(journal article summary)

War Zone Stress, Personal Resources, and
PTSD in Persian Gulf War Returnees
(journal article summary)

Independent Study Outline 8_
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x
A Guide to Gulf War Veterans' Health
Chapter 5 cont.
Research on Gulf War Veterans' Illnesses
f. Psychological Health
Assessment of Psychological Distress in
Persian Gulf Troops: Ethnicity and Gender
Comparisons
(journal article summary)

Reassessing War Stress: Exposure and the
Persian Gulf War
(journal article summary)

g. Pyridostigmine Bromide
Acute Oral Toxicity Study of
Pyridostigmine Bromide, Permethrin and
DEET in the Laboratory Rat.
Toxicological Study 75-48-2665
(journal article summary)

Neurotoxicity Resulting from Coexposure
to Pyridostigmine Bromide, DEET and
Permethrin: Implications of Gulf War
Chemical Exposures
(journal article summary)

Chapter 6
Chemical Warfare Agents
Long-Term Health Effects Associated with
Subclinical Exposures to GB and Mustard
(journal article summary)

Chapter 7
Some Hypotheses Regarding Illnesses in
Persian Gulf War Veterans
(journal article summary) 9_
9 Page 10 11
On August 2, 1990, Iraq invaded Kuwait. In
accordance with United Nations Resolutions 660,
the United States promptly responded by sending
troops to the Gulf region to help in the defense of
neighboring countries and to reverse the Iraqi
aggression against Kuwait. The mission was called
Desert Shield.

On August 8, 1990, the United States began
deployment of almost 697,000 troops to the
Southwest Asia theater of operations. The pace of
military build-up was unprecedented. Furthermore,
the Gulf War presented U. S. forces with many
other new challenges including the deployment of
large numbers of reserve and National Guard
forces (approximately 17%) as well as active duty
personnel, and deployment of a uniquely large
number of women to combat support functions
(7.2%). The demographic characteristics of the
U. S. military forces are presented in Table I.

About five months later, on January 16, 1991, the
air war began, and Operation Desert Shield turned
into Operation Desert Storm. On February 24,
1991, the ground war began for U. S. military
personnel. One hundred hours later, on February
28, 1991, the fighting ended. While Iraqi forces
suffered terrible personnel casualties, the coalition
forces, lead by the U. S., succeeded in liberating
Kuwait and sustained far fewer combat casualties
than had been anticipated. Many had expected
thousands of U. S. fatalities. Well under a tenth of
one percent of the U. S. 697,000 U. S. troops
deployed were lost during the quick and decisive
war. Furthermore, the incidence of non-battle
injuries and diseases was very low in comparison
with other wars or military engagements. The low
morbidity was attributed to preventive medicine
efforts, minimal contact with local populations,
and almost no consumption of alcohol.

In contrast to the decisive victory, living
conditions were far from hospitable. U. S. troops
entered an extremely hot and bleak desert
environment where their numbers were initially
dwarfed by the large Iraqi force. A significant
number of U. S. military personnel in the region
spent months isolated in the desert, under constant
stress, and uncertain if and when they might return
home. The troops were more than 7,000 miles

from the U. S. They had few amenities and lived
under arduous and austere conditions. The
weather, initially extremely hot, changed to cold
and damp conditions by the time the Gulf War
actually began.

Troops were housed in crowded warehouses,
military compounds, and tents, which accorded
little privacy. Prepackaged meals were sometimes
their principal diet. Sanitation was far from ideal.
Latrines and communal washing facilities were
common. Desert filth flies were ubiquitous.

Considering the living conditions that Gulf War
(GW) veterans were exposed to while in
Southwest Asia, it is not surprising that some of
them now have medical problems. In addition, it is
important to keep in mind that GW veterans were
potentially exposed to a wide range of toxic
substances and environmental hazards. There has
been a great deal of speculation about what may
have caused the illnesses that GW veterans are
currently experiencing. VA and other departments
and agencies are evaluating possible causes. (See
Chapter 5, which focuses on scientific research
efforts.)

Most symptoms experienced by GW veterans can
be easily diagnosed and effectively treated. Other
symptoms have proven difficult to diagnose. These
symptoms have been attributed by veterans to one
or more of the following exposures: chemical or
biological warfare agents, pyridostigmine bromide
prophylaxis, vaccinations for botulinum toxoid and
anthrax, infectious diseases, depleted uranium, oil
well fires, pesticides, chemical agent-resistant
coatings (CARC) paint, stress and a combination
of these exposures.

One major concern that has generated considerable
interest in Congress and the news media is
exposure to chemical and biological warfare
agents. Iraq was known to have used chemical
weapons in other recent conflicts. In anticipation
of their use in the Gulf War, tens of thousands of
chemical agent sensors were used to detect the
presence of these agents during the War.
Unfortunately, chemical warfare sensors are also
sensitive to numerous other substances.
Consequently, there was an extraordinarily high
rate of alarms.

A Guide to Gulf War Veterans' Health
Chapter One: History of Operations Desert Shield and Desert Storm 10_
10 Page 11 12
2
A Guide to Gulf War Veterans' Health
Table I
Percent Distribution of Military Characteristics of VA Registry Participants and
Gulf War Participants

Military Components
Active 54.6 83.3
Reserve 20.3 10.4

National Guard 18.8 6.3
Unknown 6.4 �

Branch of Service
Army 72.3 50.4
Marine Corps 12.2 14.9

Navy 7.7 22.7
Air Force 7.3 11.9

Coast Guard 0.3 0.1
Unknown 0.3 �

Rank
Enlisted 88.0 89.1
Officer 12.0 10.9

Gender
Men 89.6 92.5
Women 10.4 7.2

Race/ Ethnicity
White 65.0 67.7
Black 22.9 22.6
Other 12.1 9.7

Mean Age (years)
(in 1991) 30.5 28.0

Source: Defense Manpower Data Center, Department of Defense 11_
11 Page 12 13
3
A Guide to Gulf War Veterans' Health
A related concern is pyridostigmine bromide, a
medication used for decades in treating patients
with myasthenia gravis. During the Gulf War, U. S.
troops used it for the first time as an
investigational new drug for pretreatment of nerve
gas exposure.

Some veterans are worried that certain vaccines,
specifically the immunizations for botulinum
toxoid and anthrax, may have caused long-term
illnesses in some veterans. Another fear is endemic
infectious diseases such as leishmaniasis,
Q fever, and brucellosis. Concerns about the
transmission of leishmaniasis led to a temporary
suspension of blood donations by GW veterans.

A unique environmental hazard of the War was
exposure to depleted uranium (DU) munitions that
were used for their armor penetrating ability. Some
U. S. troops were exposed to DU during friendly
fire incidents; others were exposed to DU while
fighting a fire in a munitions storage area and/ or
while servicing vehicles hit by DU munitions.

Iraqi soldiers started numerous oil well fires in
Kuwait at the end of the war. These fires produced
dense clouds of soot, liquid aerosols, and gases.

The smoke from these fires blackened the sky for
days and heightened concern about respiratory
problems in GW veterans.

Numerous pesticides were used in Southwest Asia.
While no cases of acute pesticide poisoning are
known to have occurred during these operations,
the possibility that certain pesticides could have
increased the acute toxic effects of pyridostigmine
is being investigated.

Vehicles and equipment were painted with CARC
before arriving or in the theater of operations.
CARCs contain toluene diisocyanate, which could
lead to pulmonary effects, including asthma. A
very small number of GW veterans are thought to
have had exposure to CARC while painting
vehicles.

With thousands of ill GW veterans and so many
potential causes, VA, in concert with other federal
departments and agencies, has been proactive in
developing a comprehensive program to respond
to veterans' needs. The succeeding chapter
describes our healthcare, surveillance and medical
treatment initiatives. 12_
12 Page 13 14

A Guide to Gulf War Veterans' Health 13_
13 Page 14 15
A. VA Gulf War Veterans Health Examination
Registry Return to FAQ's

Almost 697,000 active duty service members and
activated reserve and National Guard from the
United States served in the Gulf theater of
operations during operations Desert Shield and
Desert Storm. Returning U. S. troops began
reporting a variety of illnesses which they initially
attributed to inhalation of fumes and smoke from
burning Kuwaiti oil well fires. Many other risk
factors were eventually raised by veterans.
Differences in military specialty determined the
kinds of elements to which troops were exposed.
These exposure concerns include:

� smoke from oil well fires � smoke or fumes from tent heaters

� passive cigarette smoke from others � diesel and/ or other petrochemical fumes
� exposure to burning trash/ feces � skin exposure to diesel or other
petrochemical fuel
� CARC (Chemical Agent Resistant Compound)

� other paint, solvents and petrochemical substances
� depleted uranium � microwaves

� pesticide or personal insect repellents including creams, sprays and pet flea
collars
� nerve gas or other nerve agents � pyridostigmine bromide used to protect

against nerve agents
� mustard gas or other agents � food and drink contaminated with smoke,

oil or other chemical
� potable and bathing water contaminated with smoke, oil, and/ or other chemical

� endemic infections � multiple immunizations, including against
anthrax and botulism
In August 1992, in response to veterans' health
concerns, VA developed a health surveillance

system which evolved into the Persian Gulf
Registry Health Examination Program.

Persian Gulf Registry
The Persian Gulf Registry Health Examination
Program offers a free, complete physical
examination with basic laboratory studies to every
GW veteran. A complete medical history is also
performed and documented in the veteran's
medical record. To date, almost 81,000 veterans
have responded to VA's outreach program
encouraging them to obtain a free physical
examination. A centralized registry (list of
participants who have had these examinations) is
maintained to enable VA to keep veterans informed
on research findings or new compensation policies
through periodic newsletters. This clinical
database is called the Persian Gulf Veterans Health
Registry, which in addition to allowing VA to
communicate with GW veterans, provides a
mechanism to catalogue prominent symptoms,
reported exposures, and diagnoses. The voluntary,
self-selected nature of the database make it
valuable for health surveillance; however, it is not
designed or intended to be a research tool and
therefore, the results cannot be generalized to
represent all GW veterans' illnesses. Each VA
medical center has an assigned Registry
Coordinator and a Registry Physician.

Protocol
The standard Registry examination protocol
(Protocol for Conducting the Physical
Examination and Ordering Diagnostic Studies)
consists of the laboratory tests and consultations
that physicians use to evaluate the symptoms
reported by GW veterans during their initial
physical examination. This basic examination
protocol extracts information about symptoms and
exposures, and directs baseline laboratory studies,
including blood count, urinalysis and a set of
blood chemistry tests. VA has expanded this
standard protocol as more experience has been
gained about the health of GW veterans. In
addition to this core laboratory work, for every
veteran taking the Registry examination,

A Guide to Gulf War Veterans' Health
Chapter Two: VA Healthcare Programs 14_
14 Page 15 16
physicians order additional tests and specialty
consultations as symptoms dictate. If a veteran's
symptoms remain unexplained, VA provides an
expanded assessment protocol, which is in essence
a set of clinical guidelines for use in evaluating ill-defined
or unexplained illnesses of GW veterans.
An unexplained illness for this purpose is one or
more symptoms that do not conform to the
characteristic set of signs or symptoms allowing a
conventional diagnosis to be made, but are causing
a decline in the veteran's functional status or
quality of life.

This set of clinical guidelines, the Uniform Case
Assessment Protocol (UCAP), suggests 22
additional baseline tests and auxiliary specialty
consultations and outlines supplementary
diagnostic procedures based on the specific
symptoms of the veterans and the clinical
judgment of the Veterans' Registry Physician. The
UCAP was originally developed in 1993 for use by
the VA's Referral Centers (described in Section B),
but is now standardized and used in VA and
Department of Defense (DoD) medical centers
nationwide. In January 1996, the Institute of
Medicine (IOM) completed a two-year study of
DoD's Persian Gulf Comprehensive Clinical
Evaluation Program (CCEP). The CCEP was
developed to respond to the health problems
experienced by active duty military personnel
following their service in the Persian Gulf. It
provides an in-depth systematic medical
evaluation for DoD personnel utilizing the UCAP.
The IOM's final report included the following
recommendations and comments regarding the
CCEP/ UCAP:

� The CCEP clinical protocol is a thorough, systematic approach to the diagnosis of a
wide spectrum of diseases.
� The results of the CCEP can and should be used for several purposes, including
education, improving the medical protocol
itself, and evaluating patient outcomes.

The required forms that must be completed as part
of the Persian Gulf Registry Health Examination
Program are: Standard Form (SF) 88, Report of
Medical Examination, VA Form 10-9009A,
Persian Gulf Registry Code Sheet, and SF 509,

Progress Notes (for follow-up). These are
maintained in the veteran's Consolidated Health
Record (CHR). Completion of the forms should be
accomplished by, or under the direct supervision
of, a Veterans' Registry Physician.

In VA and DoD registries, no significant variation
in occurrence of major categories of medical
problems has been identified, but there has been a
wide distribution of major categories of diagnosis.
The International Classification of Diseases,
9th Edition, Clinical Modification (ICD-9-CM),
does not provide sufficient codes to correctly
identify all symptoms and diagnoses. Several new
coding designations have been created to correct
this problem. Form 10-9009A lists a number of
diseases and exposures endemic to the Gulf area to
help familiarize examining physicians with some
of the health problems and/ or diseases they should
consider when rendering diagnoses.

Enrollment
While GW veterans cannot gain inclusion to the
Persian Gulf Health Examination Registry merely
by requesting to be added to the list, the
individuals who have taken advantage of the
physical examination program become part of a
larger Persian Gulf consolidated "Registry" or
roster of GW veterans. Eligibility under Public
Law 102-585 (Title VII), the "Persian Gulf War
Veterans Health Status Act" (enacted November 4,
1992), allows for GW participants to be included
in the consolidated roster if they meet one of the
following criteria:

1. apply for health services from VA,
2. file a claim for compensation from VA on
the basis of any which may be associated
with GW service,

3. die and are survived by a spouse, child or
parent who files a VA claim for
dependency and indemnity compensation
(survivors' benefits) on the basis of GW
service,

4. request a special VA Registry health
examination (authorized by this law), or

A Guide to Gulf War Veterans' Health 15_
15 Page 16 17
5. receive a health examination from the
Department of Defense similar to the
VA Registry examination, and request
inclusion in the VA Registry.

Currently, more than 200,000 veterans are
included on the consolidated roster. VA uses this
roster for outreach to GW veterans.

Results
Not all of the almost 67,000 GW veterans who
have received a free Registry physical examination
are ill. The self-reported health status of 52,835 of

these individuals shows that 32.2% report their
health was very good/ good, 40.8% report their
health was good, and 25.6% report their health was
poor/ very poor. The 10 most frequent complaints
of these 52,835 Registry veterans, and the
distribution of diagnoses are shown in Tables I
and II.

A Guide to Gulf War Veterans' Health
Table I
Ten Most Frequent Complaints Among the 52,835 Veterans on the Persian Gulf Registry

Complaints Frequency Percent*
Fatigue 10,847 20.5
Skin Rash 9,719 18.4

Headache 9,525 18.0
Muscle, Joint Pain 8,871 16.8

Loss of Memory and Other General Symptoms 7,406 14.0
Shortness of Breath 4,190 7.9

Sleep Disturbances 3,111 5.9
Diarrhea and Other GI Symptoms 2,416 4.6

Other Symptoms (Involving Skin and Integumentary Tissue) 1,916 3.6
Chest Pain 1,847 3.5

No Complaint 6,496 12.3

*Percent of 52,835 veterans
(Data as of August 1997, prepared by Office of Public Health and Environmental Hazards) 16_
16 Page 17 18
Limitations
The VA's Persian Gulf Registry Health
Examination Program is a clinical care program
offering a voluntary health examination to every
GW veteran concerned about their health status.
The computerized clinical database developed
from these examination results provides valuable
information about types of symptoms and illnesses
experienced by GW participants. However, since
the Registry database consists of a self-selected
population, lacks an appropriate comparison or
control group, and is subject to recall bias, it
cannot be used to identify the etiology of a disease
or estimate prevalence. The Persian Gulf Registry
Health Examination Program is not a research tool,
but the information it generates may eventually
suggest areas to be explored in directed scientific
epidemiologic research studies.

B. Referral Centers
For GW veterans with severe symptoms that
remain unexplained after taking a Registry health
examination, the local VA physician may refer
them to one of VA's four Persian Gulf Referral
Centers. VA determined that for these veterans, it
is desirable to provide hospital stays to allow for
observation, multidisciplinary consultation,
documentation of occupational and exposure
histories, and opportunity for frequent re-examination.

Locations
Created in 1992, the first centers were located at
VA medical centers in Washington, D. C., Houston
and Los Angeles. In June 1995, an additional
Persian Gulf Referral Center was designated at
Birmingham, AL. The referral centers were
selected on the basis of clinical and academic

A Guide to Gulf War Veterans' Health
Table II
Distribution of Diagnoses for the 52,835 Veterans on the Persian Gulf Registry

Diagnosis Number Percent
Infectious Diseases 3,715 7.0
Neoplasm 232 0.4

Mental Disorders 7,995 15.1
Nervous System 4,398 8.3

Circulatory System 3,747 7.1
Respiratory System 7,540 14.3

Digestive System 6,028 11.4
Genitourinary System 1,774 3.4

Skin & Subcutaneous Tissue 7,144 13.5
Musculoskeletal and Connective Tissue 13,299 25.2

Injury and Poisoning 2,485 4.7
No Medical Diagnosis 13,998 26.5

(Data as of August 1997, prepared by Office of Public Health and Environmental Hazards) 17_
17 Page 18 19
expertise in such areas as neuropsychology,
immunology, toxicology, and pulmonary and
infectious diseases.

Referral
The majority of the veterans who have reported to
their local VA medical center for a health
examination have been successfully diagnosed
there. The decision to send a veteran to a referral
center is made by the local medical center
physician in consultation with a referral center
physician. The number of veterans requiring
transfer to a referral center has been relatively
small. More than 400 have been assessed at the
referral centers thus far. Most of these individuals
have been ultimately diagnosed with known or
definable illness. Individuals who feel they may
benefit from a referral center evaluation should
contact their local VA physician.

Unexplained Illnesses
The prevalence of unexplained illnesses among
GW veterans is uncertain. Although most GW
veterans are diagnosed and treated, some
experience such chronic symptoms as fatigue,
memory loss, or joint pain. Some respond to well-accepted
symptomatic treatments even though
their doctors have not identified a pathogenic
agent or underlying illness. There appears to be no
unifying exposure that would account for all
unexplained illnesses. Several panels of private-sector
medical and scientific experts and
government physicians have been unable to
identify any unique symptom complex or new
illness such as that incorrectly referred to as
"Persian Gulf Syndrome."

On April 1, 1996, VA initiated a special program to
fund health examination for some spouses and
children of GW Veterans Registry participants.
The results of these examinations, which are
conducted under contract by non-VA physicians in
non-VA medical facilities, are included in the

Registry. This program was established by Public
Law 103-446 which originally authorized funding
for six months. The legislation has recently been
amended to extend funding through December 31,
1998.

Eligibility
Under this authority, VA can provide examinations
to any individual, who:

a. is the spouse or child of a veteran, is listed
in the Persian Gulf War Veterans Registry
established under P. L. 102-585, Section
702; and is suffering from illness or
disorder.

b. is suffering from, or may have suffered
from, an illness or disorder (including
birth defect, miscarriage, or stillbirth)
which cannot be disassociated from the
veteran's service in the Southwest Asia
theater of operations.

c. has granted VA permission to include in
the Registry relevant medical data from
the evaluation.

Administration
Individuals wishing to participate can register for
the program by calling the VA Persian Gulf War
Helpline (1-800-PGW-VETS). Helpline personnel
enter the required information into a computer
database which is forwarded to VA Headquarter's
Environmental Agents Service. Information on
participants whose eligibility is confirmed is then
forwarded to the appropriate Veterans Integrated
Service Network (VISN) office. Each Network
Director designated at least one tertiary care center
in his/ her VISN to participate. The 35 designated
VAMCs establish a contract with their affiliated
university to perform the protocol examinations.
Examinations are performed by a board-certified/
eligible physician. Payment for the
examinations performed under this program are
authorized only after the contract physician
submits all forms and completed code sheets to the
responsible VAMC.

A Guide to Gulf War Veterans' Health 18_
18 Page 19 20
Protocols
The protocol for examination of GW veterans'
spouses involves a signed informed consent form,
VA Form 10-21002a, Consent to Participate in
VA's Registry Examination Program for Spouses
and Children of Persian Gulf Veterans, VA Form
10-9009c, Persian Gulf Registry Code Sheet
(Spouse or Child of Persian Gulf Veteran), and VA
Form 10-21002d, Adult Symptom Checklist. A
physical examination is completed and recorded
on the adult standardized exam form, VA Form 10-
21002b, Funded GW Spouses and Children
Examination Program. Diagnostic testing includes
a complete blood count, blood chemistries (chem
20), urinalysis, and, for women, a Pap smear, and
breast and pelvic examination. Upon completion
of the evaluation, VA Form 10-9009c is completed
and signed by the examining physician.

The protocol for children of GW veterans includes
a detailed medical history including symptoms and
developmental history. A physical examination is
completed and recorded on the juvenile
standardized examination form, VA Form 10-
21002c, Funded GW Spouses and Children
Examination Program. No routine diagnostic
testing is required by the protocol.

Alternative Program
Eligible family members of GW veterans may
have their medical information entered into the
Persian Gulf Registry database by undergoing a

physical examination from their private physician.
The physician must complete a Registry code
sheet containing the protocol examination
information and submit it to VA for entry into the
database. The veteran or family member choosing
this option must assume the cost of the protocol
examination and code sheet completion.

Informed Consent
Requiring participants to sign an informed consent
form (VA Form 10-21002a) not only permits VA to
enter their health information into the Registry
database, it also serves to inform them that no
follow-up examinations or treatment are provided.

Currently, GW veterans are granted, by legislative
mandate, special eligibility status for VA
healthcare. If a condition is found, which the VA
examining physician determines could possibly be
related to an exposure which occurred during
service in the Gulf War, that condition will be
treated and medical care provided at no cost to the
veteran. If the physician determines that the
condition could not in any way be associated with
an exposure during GW service, the physician
enters this medical opinion in the veteran's
consolidated health record. A traumatic injury
sustained years after service is an example of such
a condition.

A Guide to Gulf War Veterans' Health 19_
19 Page 20 21
In 1994, in response to GW veterans' concerns
about possible health effects of service in
Operations Desert Shield and Desert Storm, the
Department of Defense (DoD) developed a special
clinical examination program, the Comprehensive
Clinical Evaluation Program or CCEP. Individuals
eligible for the CCEP include GW veterans
currently on active duty or retired, members of the
full-time National Guard who are GW veterans,
and GW veterans who are members of the Ready
Reserve/ Individual Ready Reserve/ Standby
Reserve or Reserve components and their family
members. This examination program was modeled
after the Department of Veterans Affairs Persian

Gulf Registry Health Examination and provides
comparable clinical guidelines and evaluations.
Both DoD's CCEP and VA's Registry were
designed primarily as a clinical rather than a
research program. Self-selection of patients,
inability to validate self-reported exposures, and
lack of an appropriate control group limit our
ability to draw generalizable conclusions from
these examination programs. However, the large
numbers of individuals examined and the
systematic examination process provide important
clinical insight into the variety of illnesses suffered
by GW veterans and a source of hypotheses for
future research.

Introduction 20_
20 Page 21 22
Background
During the six years since the end of the Gulf War
on February 28, 1991, some veterans of
Operations Desert Shield and Desert Storm have
presented with a diversity of unexplained somatic
symptoms. Although various potential etiologies
have been postulated, no single cause of these
symptoms has been demonstrated. In response to
the health concerns of GW veterans, DoD
instituted the CCEP on June 7, 1994. Although not
designed as a research study, the CCEP neverthe-less
provided valuable clinical information about
the health of this population. This report is an
analysis of the findings from the comprehensive
clinical evaluation of 20,000 GW veterans.

Methods
Starting on August 8, 1990, the U. S. deployed
697,000 troops to the Gulf region; by May 1991,
most had returned. Troops who remained on active
duty after the war were provided complete
healthcare. In addition, the physical condition of
active duty U. S. troops is assessed continuously
with physical fitness tests every six to 12 months,
routine dental and gynecological examinations,
and a complete medical examination at least every
five years. Prior to leaving active duty, military
personnel are medically screened and undergo a
physical examination.

The 285,000 GW veterans still on active duty
when the CCEP was initiated were encouraged to
participate if they had any health questions or
concerns. The CCEP provided a two-phase clinical
evaluation supervised by a board-certified
physician. All participants were provided a Phase I
examination. For those without current medical

problems or who had health problems that could
be satisfactorily explained, no additional
evaluation was conducted. If referral consultations
and specialized tests were clinically indicated,
participants proceeded to Phase II examination at
one of 14 DoD regional medical centers. At the
conclusion of the CCEP evaluation process,
examining physicians provided a primary
diagnosis and additional secondary diagnoses
based on clinical importance. After review by
accredited medical record coders, up to seven
diagnoses were coded using the International
Classification of Diseases-Ninth Revision, Clinical
Modification (ICD-9-CM) and entered into the
data base.

Results
As of April 1, 1996, a total of 20,000 GW veterans
had completed CCEP examinations with 12% of
participants undergoing specialized Phase II
evaluations. The types of primary and secondary
diagnoses among CCEP participants varied widely.
For broad ICD-9-CM classifications, the three
most common primary diagnoses were "diseases
of the musculoskeletal system and connective
tissue" (18.6%), "mental disorders" (18.3%), and
"symptoms, signs, and ill-defined conditions"
(17.8%). Nine percent of participants were found
to be "healthy" without a clinically significant new
illness.

Among the 3,558 participants with a primary
diagnosis of "symptoms, signs, and ill-defined
conditions," no single ICD-9-CM subcategory
predominated. These veterans had a wide variety
of symptoms, with fatigue, headache, memory
problems, and sleep disturbances being the most
frequent presenting complaints.

A Guide to Gulf War Veterans' Health
Reference: A Comprehensive Clinical Evaluation of 20,000 Gulf War Veterans
Military Medicine. 1997 Mar; 162( 3): 149-155.

Authors: Stephen C. Joseph, M. D., M. P. H. and the Comprehensive Clinical Evaluation
Program Evaluation Team 21_
21 Page 22 23
Among all 20,000 CCEP participants, the
examinations revealed the following diagnoses:
connective tissue disease as either a primary or
secondary diagnosis (74 participants); disorders of
immunity (5 with selective immunoglobulin A
immunodeficiency and 1 with selective
immunoglobulin M immunodeficiency); skin
cancer (9), lymphoma/ leukemia (22), other types
of cancers (30); glomerulonephritis (13) and renal
insufficiency (12); interstitial pulmonary fibrosis
(14); and polyneuropathy (8) or peripheral
neuropathy (34). Common skin infections
accounted for 60% of primary infectious disease
diagnoses. A common or distinctive organic
pathology was not identified among over 800
veterans with neuromuscular symptoms who had
extensive neuropsychological evaluations.

All elicited exposures were reported frequently,
including: exposure to diesel and other fuels
(88%); use of pyridostigmine bromide pills (74%);
exposure to oil well fire smoke (71%); personal
use of insect repellents (66%); anthrax (49%) and
botulinum (26%) vaccinations; and observing
combat casualties (57%) or actual combat (38%).

Discussion
This large patient series demonstrated a wide range
of well-known illnesses among GW veterans
requesting evaluation, with no single illness
predominating and no clinical indication of a new
or unique syndrome. In addition, the types of
medical conditions that would result from
postulated Gulf War environmental hazards were
diagnosed infrequently, including: neurologic
disease from possible chemical weapons or
pesticide exposure, interstitial pulmonary disease
from smoke or sand inhalation, renal disease from
heavy metal exposure, and immunologic
dysfunction from various combinations of
exposures. These findings are consistent with
medical surveillance data collected during the Gulf
deployment. Also, the absence of clinical data
indicating a new or unique illness is consistent
with the findings of three previous review panels

that did not identify a distinctive syndrome related
to GW service.

A relatively large percentage of CCEP participants
had a psychological condition as either a primary
(18%) or secondary (18%) diagnosis. Also a large
number of troops had musculoskeletal conditions.
The third common diagnostic category,
"symptoms, signs, and ill-defined conditions," did
not appear to represent a group of veterans with a
distinctive illness. CCEP participants in this
diagnostic category varied substantially in clinical
presentation; no characteristic physical sign or
laboratory abnormality was identified.

These clinical findings have to be carefully
qualified by the fact that the CCEP was not
designed as a research study. In addition, a rare or
minimally pathogenic illness could have been
missed or not adequately captured in the data base
because of diagnostic weakness of the ICD-9-CM
coding system. Nevertheless, any widespread
serious physiologic disease should have been
detected in this very large patient series. It also is
unlikely that debilitating disease would remain
undetected among active duty troops not
participating in the CCEP because of the military's
emphasis on readiness and preventive medicine,
including regular physical evaluations of troops.
Because the CCEP primarily involved active duty
troops, any illness that predominated among
Reserve/ National Guard personnel or veterans who
had been discharged from the military would have
been under-represented in the CCEP population.
However, no new or unique illness has been
identified.

Although a new or unique illness was not
identified, the findings of the CCEP nevertheless
provide important clinical information. In the
evaluation of GW veterans, physicians will need to
be alert for a wide range of illnesses because the
diversity of medical and psychological problems
that occur in any sizable adult population was
found in this cohort. In addition, the findings of
the CCEP provide reassurance for GW veterans

A Guide to Gulf War Veterans' Health 22_
22 Page 23 24
since effective treatments are available for most
commonly diagnosed health problems. Inability in
this and prior clinical evaluations to find a
characteristic organic sign of a new or unique
disease among GW veterans will result in research
limitations not encountered in studies of well-characterized
diseases. Most importantly, a
specific case-definition based on criteria that can
be objectively measured cannot be developed
without a characteristic sign of pathology. Any
definition of illness will have to be based on self-reported
symptoms which are subject to
confounding and recall bias in a population that
has been the focus of widespread publicity about
possible harmful exposures and ill health.

Veterans' health questions remain unresolved
because the causes, frequency, and long-term

sequelae of nonspecific somatic symptoms are not
adequately understood. Until they are better
understood, it will be difficult to thoroughly
determine the health of any large adult population,
whether military or civilian.

A Guide to Gulf War Veterans' Health 23_
23 faq.htmlPage 24 25
Depleted Uranium (DU) is the component of
natural uranium ore left after the U235 is removed
for use as fuel in nuclear power reactors.
Consequently, DU has approximately half the
radioactivity of naturally occurring mineral
deposits of uranium. DU also has nephrotoxicity
and neurotoxicity related to its heavy metal
properties.

In recent years, the United States Armed Forces
have used DU in manufacture of projectiles and
armor for vehicles. It is used in anti-tank
munitions because of its highly effective
penetrating capabilities and as protective armor
plating due to its extremely dense properties.

During the Gulf War, some U. S. tanks and
airplanes fired DU munitions which produced
shrapnel and an aerosolized dust upon impact with
armor. A friendly fire incident injured
approximately three dozen U. S troops in a Bradley
fighting vehicle. Other GW veterans had potential
exposure to DU during reclamation,
decontamination and restoration of damaged
vehicles.

In 1993, VA established a special medical
surveillance program at the Baltimore VA medical
center to follow those GW veterans identified by
the U. S. Army to have retained DU shrapnel. The
program provides periodic evaluations to monitor
for potential adverse health consequences of
retained depleted uranium fragments.

A Guide to Gulf War Veterans' Health
Chapter Four: Depleted Uranium Return to FAQ's
Introduction 24_
24 Page 25 26
What is Depleted Uranium?
Depleted uranium is derived from the heavy metal
uranium, which occurs naturally as mineral
deposits which are mined and processed primarily
for use as fuel in nuclear power reactors. Naturally
occurring uranium (U nat) deposits contain over
99% U238, with small amounts of U235 and
U234. U238 has a half life of 4.5 billion years but
has very low radioactivity. Depleted uranium is the
natural uranium left over from the concentration
and extraction of U235. It contains even less U235
than naturally occurring ores. The spent uranium
which is about half as radioactive as natural
uranium is the "depleted uranium." (Voelz)

How does the military use Depleted Uranium?
In recent years, the United States Armed Forces
have used depleted uranium (DU) in the
manufacture of both projectiles and armor.
Uranium's high density and pyrophoric or easily
combustible properties makes it, in projectiles,
capable of penetrating armor made with less dense
metals. Conversely, armor constructed with DU
provides a high degree of shielding and resistance
to penetration. During the Gulf War, depleted
uranium containing munitions were used on a very
large scale for the first time. In the manufacture of
projectiles and armor, depleted uranium is alloyed
with small amounts of other metals such as
molybdenum, titanium, zirconium and niobium.
(DoD, 1993)

How were soldiers exposed to DU?
When a vehicle is impacted and penetrated by a
DU projectile, the projectile splits into small
shards, bursts into flames, and fills the insides of
the vehicle with flying metal, fumes, and
particulates. The inside of the damaged vehicle
remains contaminated. In the event of a vehicular
fire, the heat of the fire can cause any onboard DU

ammunition to oxidize. Soldiers in struck vehicles
may inhale airborne DU particles (or other
combustion products), ingest DU particles, and
experience wound contamination by DU. Crew
members may be left with multiple tiny fragments
of uranium scattered through their muscle and soft
tissue. Other soldiers may exposed during
operations to salvage tanks that had been disabled
by DU rounds or have potential exposure from
brief "sightseeing" entry into damaged vehicles.

Who was exposed to DU in the Gulf War?
At present only a limited number of U. S. veterans
are known to have been directly wounded by DU
weapons. An initial check by the Army's Office of
the Surgeon General (OTSG) has revealed that
there are approximately 22 soldiers whose records
indicated shrapnel fragments that might contain
DU. There are an additional 13 soldiers with
potential DU exposure who were wounded and
hospitalized but were not specifically identified as
having shrapnel.

It is possible that some other allied personnel were
wounded by DU munitions. US forces continue to
use DU munitions and may employ them in future
conflicts. DU penetrators are now available in
international arms markets, and may become
widely available to armies around the globe. Other
groups with potential exposure to DU include
personnel involved in the assessment, reclamation,
decontamination and restoration of damaged
vehicles as well as workers involved in the
maintenance or modification of armored vehicles.

Are there civilian groups exposed to DU?
Workers involved in the manufacture and testing
of DU munitions and fabrication of armor, as well
as those involved in the assembly of vehicles, may
also form a potentially exposed population.
Environmental contamination of soil, water, air

A Guide to Gulf War Veterans' Health
Depleted Uranium: General Information 25_
25 Page 26 27
and food may pose a risk to the general population
from DU penetrators, fragments or dust scattered
on battlefields and training grounds. The potential
for stateside environmental contamination of soil,
water, air and food remains as well. In 1991,
according to the Wall Street Journal, an estimated
705 million pounds of DU were stockpiled in the
U. S. Consideration of other uses of DU, including
use as a replacement for lead in bird shot, yacht
keels and ballast, and aircraft and missile
counterweights, suggest the possibility of future
exposed populations.

References:
Voelz, George L., Chapter 13 Uranium in
Hazardous Material Toxicology Eds. Sullivan,
John B. and Krieger, Gary R. Williams and
Wilkins, Baltimore, MD 1992.

Health Effects of Depleted Uranium -Fact
Sheet, Department of Defense, June 11, 1993.
Copies can be obtained by calling
703-697-3189.

A Guide to Gulf War Veterans' Health 26_
26 Page 27 28
How does DU enter the body?
The uptake and distribution of uranium is in some
ways analogous to other heavy metals, such as
lead, mercury, arsenic, and cadmium and can enter
the body through any of the three common routes
of absorption. The principal entry route is through
inhalation of DU vapor and fine dust
contamination with DU. Dermal exposure as a
result of DU dust contamination of skin or a
wound is also possible. Imbedded, retained DU
shrapnel may be dissolved and also be absorbed
and distributed throughout the body. Depleted
uranium dust can be ingested as well, but is not a
likely significant exposure route unless exposure is
ongoing.

Research on the human health effects of DU
exposure in military occupations is limited,
especially regarding DU's potential chemical
(rather than radiologic) toxicity. There are, for
example, no published epidemiological studies of
soldiers exposed to depleted uranium dust or vapor
in war time settings. Most of the knowledge about
human effects is derived from studies of uranium
miners and associated occupations which is not
precisely, but generally relevant to DU exposed
veterans. For example, uranium miners and millers
have exposure to uranium but also possibly to
radon, as well as other toxic substances present in
the mines or the ores that are milled, making their
health effects experience not directly comparable
to those DU exposed. Additionally, exposure
intensity and duration of these other occupations
are not directly comparable to exposure scenarios
in military settings, limiting the applicability of
observed health effects in the DU exposure setting.

Acute toxic effects of uranium exposure are
manifested primarily in the respiratory system and
kidney. In wartime situations, there is the
possibility of acute exposure to DU when DU
munitions or shielding explode and burn. It is
theorized that soldiers, particularly soldiers inside
of tanks, may inhale excessive amounts of DU
vapor and dusts raising the question about local
effects in the lung as well as systemic effects
incurred through an inhalation exposure.

Chronic exposure is thought to affect primarily the
kidney. The few chronic studies in the literature (as
summarized by Voelz) document renal tubular
changes without clear clinical implications. Other
epidemiological studies of uranium millers and
miners shows an increased risk of renal disease.
Animal studies have documented both tubular and
glomerular lesions in rats given uranium
compounds orally. These lesions increased with
higher doses of uranium. (From ATSDR Tox
Profile p 43). This finding is consistent with the
known health effects of other heavy metals. It is
unknown if low level, chronic exposure to DU will
cause renal disease.

Chronic exposure by inhalation presents a
potential radiologic hazard to the lung. Uranium
miners have a long occupational history of
inhaling uranium dust in closed spaces. There is an
increased risk of lung cancer among uranium
miners but this is thought to be due to the
simultaneous exposure to radon. The animal data
are insufficient to determine whether inhalation of
natural uranium causes lung cancer in animals.

Concerns about genotoxicity, mutagenicity and
reproductive effects are only beginning to be
studied, and definitive answers to these questions
will almost certainly take much more work.
Animal cell lines treated with uranium in one
study have shown possible genotoxic and/ or
mutagenic changes. Reproductive effects in
humans exposed to uranium have not been studied.

A Guide to Gulf War Veterans' Health
Depleted Uranium: Health Effects 27_
27 Page 28 29
The ATSDR Toxicological Profile on Uranium
summarizes the existing animal and human data on
uranium. (See ordering information in the Section
on Further Reading)

Is Depleted Uranium radioactive?
External exposures, that is when DU is not taken
directly into the body, result in minimal radiation
exposure because DU has low levels of
radioactivity. The Department of Defense has
developed estimates of radiation exposure as
follows:

Bare DU penetrator dose at distance of one
meter = 0.7 mrem/ hour of exposure

Soldier would have to stand near bare
penetrator for 700 hours to exceed allowed
radiation levels for the general public. (500
mrem/ year)

Holding a bare penetrator for 93 hours would
exceed quarterly radiation level limit allowed
for occupational exposures.

A soldier in a fully uploaded tank with DU
munitions (0.5mrem/ hour) is within allowed
standards of radiation exposure for the general
public.( DoD, 1993)

Internal exposure, whether via inhalation,
ingestion, wound contamination or retained
shrapnel warrants concern. Internalized DU
radioactive particles "� are unable to penetrate
skin, but can travel short distance in the body and
cause damage�"[ ATSDR Toxicological Profile,
1990]. Concerns about cell damage from exposure
to the radioactivity of depleted uranium should be
tempered with the knowledge that DU is
minimally radioactive and is even less radioactive
than naturally occurring uranium which is found in
the soil. Nonetheless, an assessment of exposure,
whether the exposure is internal, and a
commitment to regular follow-up are prudent
clinical and public health activities.

The original concern about health effects from DU
exposure was primarily the potential radiologic
hazard that exists. Separate from its radiologic
properties however, uranium is also a heavy metal,
a chemical toxicant which exhibits some adverse
health effects similar to other heavy metals, such
as lead and cadmium. The kidney effects, for
example (proximal tubular and, possibly,
glomerular) are likely a result of the chemical
toxicity of uranium, rather than its radiologic
toxicity. The mutagenicity data, although
extremely limited, are also probably due to
uraniumÌs chemical properties. This distinction is
important because it suggests possible health
outcomes in an affected population, as well as a
knowledge base (which exists for other heavy
metals) with which to compare the extremely
limited findings observed in the DU exposed
participants.

Insights into successful interventions, treatment
strategies and refined prognoses may also be
gained from the heavy metal literature. The
chemical nature of DU will thus be an additional
focus for the on-going follow-up program.

References:
Agency for Toxic Substances and Disease
Registry., U. S. Public Health Service. 1990.
Toxicologic Profile for Uranium. PB91-180
471, US. Department of Commerce, National
Technical Information Service. Customer
Service (703) 487-4660.

Health Effects of Depleted Uranium -Fact
Sheet, Department of Defense, June 11, 1993.
Copies can be obtained by calling
(703) 697-3189.

Voelz, George L., Chapter 13 Uranium in
Hazardous Material Toxicology Eds. Sullivan,
John B. and Krieger, Gary R. Williams and
Wilkins, Baltimore, MD 1992.

A Guide to Gulf War Veterans' Health 28_
28 Page 29 30
What is the Depleted Uranium Follow-up
Program?

The VA Depleted Uranium (DU) Follow-up
Program at the Baltimore VA Medical Center is a
clinical surveillance program for identifying,
characterizing and following individuals with
retained DU fragments.

The specific aims of the project are to provide on-going
clinical surveillance of GW veterans with
known or suspected imbedded DU fragments, DU
contaminated wounds or significant amounts of
inhaled DU. This clinical surveillance will detect
health effects, if any, of DU containing shrapnel,
and provide recommendations for treatment to
participating veterans and physicians caring for
them.

Focused research into the toxicological and
radiological effects of DU is intended to improve
the scientific basis for advice about fragment
removal, to better model uranium absorption,
distribution in tissue, and excretion, and to develop
improved methods to assess uranium dose in vivo.
In addition, the program hopes to improve
methods of detection of toxic effects from low
dose uranium exposure.

Thirty-three participants, who had been on or in
U. S. Army vehicles when struck by DU containing
munitions, were evaluated at the Baltimore VA
Medical Center in 1993 and 1994 and continue to
be followed by the Program. Approximately half
of the participants remain on active duty.

What is the Program doing for the participants?
All participants were evaluated at the Baltimore
VA Medical Center and underwent a
comprehensive medical and psychological
evaluation, as well as a full body radiologic
shrapnel survey. While those individuals with
evidence of retained shrapnel showed increased
excretion of uranium, no association between
uranium excretion and clinically detectable
adverse effects has been documented. Efforts to
improve both the assessment of uranium dose and
the detection of toxic effects continue. The
Program has facilitated the assignment of primary
care providers for the veterans in the group and
interfaces with those primary care providers as
needed.

Consultation: A toll-free telephone number has
been made available to participants, as well as
their family members and healthcare providers, for
consultation and assistance in a variety of clinical
and personal issues. The staff have expertise and
experience in the area of environmental and
occupational health, particularly with regard to the
effects of heavy metal exposure.

The DU program has developed a collaboration of
VA and non-VA academic experts in the field of
exposure characterization and outcome
measurement. A team of specialists in
environmental and occupational health,
epidemiology, toxicology, radiobiology, physics,
psychiatry, neuropsychology, and reproductive
health have worked individually and collectively
to develop and adapt diagnostic tools to better
evaluate, treat and counsel this unique group of
soldiers and veterans.

A Guide to Gulf War Veterans' Health
Depleted Uranium: VA Follow-up Program 29_
29 Page 30 31
What kinds of outreach and assistance efforts
have been provided to non-participants and the
community at large?

Consultation: The program has been involved in
outreach activities to other VA medical centers,
serving as a clearinghouse for questions raised by
veterans about uranium exposures. These inquiries
involve veterans who were not wounded but may
have inhaled or been in proximity to uranium
because of their active duty participation during
the Gulf War or during maintenance, clean up and
repair of vehicles containing depleted uranium.

While at much lower risk than program
participants, these individuals still have questions
for their VA physicians. The Program aids their
physicians with advice about the best methods to
assess the risks of past depleted uranium exposure
and how to assess these exposures clinically.

Communication: The staff of the DU Program
serve as a resource for requests for information
from healthcare providers, government and private
sector news publications, VA Headquarters, the
Presidential Advisory Committee on Persian Gulf
War Veterans' Illnesses, and others.

A Guide to Gulf War Veterans' Health 30_
30 Page 31 32
What can I do if a patient suspects possible past
DU exposure as a result of military service in
the Gulf War?

The staff of the DU Program has a unique
expertise in the evaluation of risk, clinical
assessment and treatment of exposure to depleted
uranium. Based on their experience with DU and
other heavy metal exposures, they are available to
provide:

� general information regarding depleted uranium

� determination of possible exposure � assessment of risk

� guidance in determining appropriate medical testing
� assistance in obtaining and interpreting urine uranium results
� advice for counseling DU-exposed personnel
� referral to other specialists for individualized problem solving

Points of contact for DU Program
To contact the DU Follow up Program:
Call 1-800-815-7533
or write
Depleted Uranium Program (11DUP)
Baltimore Veterans Affairs Medical Center
10 N. Greene Street
Baltimore, MD 21201

A Guide to Gulf War Veterans' Health
Depleted Uranium: Consultation Information 31_
31 Page 32 33
Tips for Taking the History
Listen for the patients' concerns about their Gulf
War exposures and experiences. Veterans are
hearing information and advice from a wide
variety of sources. Encourage the patient to ask
questions and express their concerns. Given the
amount of public discussion of possible sequelae,
it is not surprising that veterans will wonder about
the possible significance and prognosis of any type
of new symptom in themselves or their family
members. In the first round of evaluations, we
uncovered serious concerns about the possible
significance of problems as common and generally
benign as otitis media in toddlers and tinea
versicolor. Such concerns and apprehensions won't
be relieved if they do not get discussed.

Ask the patient to provide a detailed description of
all occupations, including the current occupation.
Focus on the situation that resulted in potential DU
exposure. Probe for specific details about duties,
the equipment used, the nature of the site, the
protective equipment worn, the training required
and the hazard information provided. Obtain
information about how and why the veteran
believes he or she was exposed to DU. Patients can
often provide quite accurate and detailed exposure
information.

It is always important to determine the length of
time the patient may have been exposed. For
example, how many hours did the soldier spend

cleaning tanks potentially contaminated with DU
dust. Determine if the exposure occurred via
inhalation, ingestion or dermal (wound
contamination). The clinician can reassure most
concerned patients by pointing out that in the
cohort with imbedded, retained DU shrapnel, no
adverse health conditions have been detected. The
clinician should emphasize that retained shrapnel
represents continuous, internal exposure and, as
such, is more potentially hazardous than other
military exposures as currently understood. The
clinician can further re-assure the patient by
assessing uranium excretion when indicated by the
individual's exposure history. (See next section.)

Laboratory Tests for Uranium
The only practical, biologic measure readily
available to assess uranium exposure clinically is
to measure urine excretion of uranium. If internal
DU exposure is suspected, the clinician should call
the DU Program to discuss the specific patient
case. The DU Program at the Baltimore VAMC
will facilitate processing and interpretation of the
results. The results are available in four to six
weeks and the clinician will be called with the
results and interpretation. Other possible methods
for assessing DU exposure and body burden are
being developed and are not appropriate for
routine, clinical use.

A Guide to Gulf War Veterans' Health
Depleted Uranium: Guidelines for Clinicians 32_
32 Page 33 34
Uranium and Depleted Uranium
Agency for Toxic Substances and Disease
Registry., U. S. Public Health Service. 1990.
Toxicologic Profile for Uranium. PB91-180 471,
US. Department of Commerce, National Technical
Information Service. Customer Service 703-487-
4660.

Armed Forces Radiobiology Research Institute.
Technical Report 93-3, Depleted Uranium:
Questions and Answers. Prepared by: CDR Eric E.
Kearsely, MSC, USN and LTC Eric G. Daxon,
MS, USA

Health and Environmental Consequences of
Depleted Uranium Use by the U. S. Army,
Summary Report to Congress, Prepared by U. S.
Army Environmental Policy Institute, June 1994.

Health Effects of Depleted Uranium -Fact Sheet,
Department of Defense, June 11, 1993. Copies
can be obtained by calling 703-697-3189.

Voelz, George L., Chapter 13 Uranium in
Hazardous Material Toxicology. Eds. Sullivan,
John B. and Krieger, Gary R. Williams and
Wilkins, Baltimore, MD 1992.

Gulf War Illness
Institute of Medicine, Committee to Review the
Health Consequences of Service During the
Persian Gulf War. Health Consequences of Service
During the Persian Gulf War: Initial Findings and
Recommendations for Immediate Action
(Washington, DC: National Academy Press, 1995)

Presidential Advisory Committee on Gulf War
Veterans Illnesses: Interim Report. Washington,
DC: U. S. Government Printing Office, February
1996)

On the Internet
GulfLINK (http:// www. dtic. dla. mil/ gulflink/) is
the World Wide Web information system of the
Persian Gulf War Veterans Illnesses Task Force
which provides to the public information
concerning the illnesses affecting Gulf War
veterans. Information is updated periodically and
covers a wide range of topics. For example, recent
searches produced access to information such as
Federal Activities Related to the Health of Persian
Gulf Veterans: Dept. of Veterans Affairs, March
1995 which details VA and DoD research on
depleted uranium, as well as testimony from the
Presidential Advisory Committee on Gulf War
Veterans' Illnesses on August 6, 1996.

A Guide to Gulf War Veterans' Health
Depleted Uranium: Further Reading 33_
33 Page 34 35
On August 31, 1993, in response to Public Law
102-585, President William J. Clinton asked the
Secretary of Veterans Affairs to take the lead in
coordinating research into the health consequences
of GW service. VA is committed to investigating
all possible causes and treatments for health
problems in troops who served in the Gulf War.
The President has declared that federal researchers
should "leave no stone unturned" in the search for
answers to the questions raised by GW veterans
and their families about the long-term health
effects of military service in the Gulf War.

The Departments of Defense and Health and
Human Services also are pursuing important
research efforts. More than 90 federally-funded
projects are in progress, and others have been
completed. Nearly half of all GW research is being
conducted at VA hospitals and affiliated medical
schools. Important VA research projects include a
long-term mortality study of GW veterans, and a
national health survey of GW veterans and their
families. In 1994, VA established three national
environmental hazards research centers. These
centers are exploring the possible health
consequences of military service in the Gulf War.
Some projects are relatively small, while others
involve thousands of participants.

Researchers are considering an array of possible
causes including, but not limited to, oil well fires,
vaccinations, infections, chemicals, pesticides,
microwaves, depleted uranium, and chemical and
biological warfare agents. All potential causes are
receiving serious consideration and appropriate
investigation. In 1996, VA established a fourth
environmental hazards research center which is
focusing on the possibility of reproductive
problems related to military service.

A number of endemic and routine infectious agents
have been investigated as potential causative
agents for GW veterans' illnesses. In 1991, a small
number of GW veterans returned from Southwest
Asia with infectious diseases that have been
diagnosed and treated. Infections with viruses,
viscerotrophic leishmaniasis, mycoplasma,

microsporidia, and nonculturable bacteria are
among the agents some individuals have
hypothetically linked but not conclusively shown
to cause the illnesses of GW veterans. Extensive
medical testing to date has not found an
association link between the infectious agents and
the illnesses GW veterans are now reporting. The
Centers for Disease Control and Prevention (CDC)
have reviewed the available evidence and has
determined that at this time that there is no
scientific evidence to suggest that illnesses among
GW veterans are caused by infectious agents.
Numerous research studies are underway to
investigate this matter further.

Veterans and their families are concerned that the
children of GW veterans may have an increased
risk of birth defects. These fears have been fueled
by anecdotal reports on birth defects in the popular
media. While we do not now have a conclusive
answer to this important question, this possibility
is being thoroughly investigated. In January 1996,
Military Medicine published the results of a small-scale
study by investigators from the VA Medical
Center in Jackson, MS, and the Mississippi State
Department of Health. This collaborative research
effort was conducted in response to a newspaper
report of an apparent cluster of birth defects and
other health problems among children born to
veterans of two Mississippi National Guard units
after their return from the Gulf War. The medical
records of all children conceived by and born to
veterans of these units after deployment were
reviewed. Observed numbers of birth defects and
other health problems were compared with
expected numbers using rates from birth defect
surveillance systems and previous surveys.

The total number of all types of birth defects was
not greater than expected. However, because of the
small numbers in this study, investigators could
not determine whether the number of specific birth
defects was greater, equal or smaller than
expected. Investigators reported that the frequency
of premature birth, low birth weight, and other
health problems appeared similar to that in the
general population.

A Guide to Gulf War Veterans' Health
Chapter Five: Research on Gulf War Veterans' Illnesses
Introduction 34_
34 Page 35 36
In June 1997, The New England Journal of
Medicine published a much larger study of the
risks of birth defects among children of GW
veterans. Researchers evaluated the routinely
collected data on all live births at 135 military
hospitals in 1991, 1992, and 1993. Records of
more than 75,000 newborns were reviewed for any
birth defect and for defects defined as severe on
the basis of specific diagnoses and the criteria of
the CDC.

During the study period, 33,998 infants were born
to GW veterans and 41,463 to non-deployed
veterans at these hospitals. Investigators found that
the overall risk of any birth defect and the risk of
severe defects was similar to those reported in
civilian population. Furthermore, there was no
significant association for either men or women
between service in the Gulf War and the risk of
any birth defect or of severe birth defects in their
children (NEJM, 1997; 336: 1650-1656).

The VA's national health survey of GW veterans
and their families is in progress. Phase I is a
survey of 15,000 GW veterans and a comparison
group of 15,000 Gulf-era veterans who were not
deployed to the theater of operations to assess
prevalence of symptoms and medical conditions
was completed in August 1996. Phase II consists
of 8,000 telephone interviews and a review of
4,000 medical records. Phase III will involve
physical examinations of veterans and their
families. Investigators hope to learn a great deal
about the problems experienced by the offspring of
GW veterans from this survey.

In November 1996, VA established an
Environmental Hazards Research Center at the VA
Medical Center in Louisville, KY, specifically to
focus research on the potential reproductive and
development hazards of military service. The
Center's overall goal is to determine whether
exposures to hazardous substances affects
reproductive capacity and causes developmental
abnormalities in the children of veterans.

GW veterans have reported multisystem symptoms
and been diagnosed with a wide spectrum of
medical conditions, both diagnosed and
undiagnosed. A CDC survey of GW veterans

found that deployed GW veterans have a
significantly increased rate of symptom reporting
when compared to their non-deployed counterparts
[MMWR, 1995 Jun 16;( 23): 443-447]. A large
population based telephone survey of Iowa
veterans showed that those deployed to the Gulf
War have a higher prevalence of self-reported
symptoms compared to the non-deployed veterans.
Those symptoms include those consistent with
depression, PTSD, chronic fatigue, cognitive
dysfunction, bronchitis, asthma and fibromyalgia.
Although the investigators identified potential
relationships between the self-reported symptoms
and exposures, there were no consistent patterns
noted between the exposures and the health
outcomes reported [JAMA, 1997; 277( 3): 238-245].
However, Haley et al., in a study of the 24th Naval
Reserve Construction Battalion, indicated that
these self-reported symptoms could be aggregated
by factor analysis into six distinct syndromes. The
three most prominent syndromes were associated
with exposures to pyridostigmine, pesticides, and
possible chemical warfare agents. In the opinion of
the investigators, these syndromes were suggestive
of a possible neurologic basis for the symptoms
[JAMA, 1997; 227( 3): 215-237]. Serious limitations
in these studies mitigate against drawing definitive
conclusions from this work including non-representative
sampling, small sample size, self-reported
exposures, and in the later study, poor
response rates. Follow-up investigations to this
preliminary work are being planned.

Other investigators have also studied
pyridostigmine bromide as a possible risk factor
for development of health problems in GW
veterans. Pyridostigmine bromide is a carbamate
acetylcholinesterase inhibitor. Pyridostigmine
bromide has been used as a nerve agent protective
measure against organophosphate chemical
warfare nerve agents. U. S. forces followed the
doctrine of only using pyridostigmine bromide
when a nerve agent threat was assessed to be
imminent. On orders of a responsible division or
corps-level commander, 30 mg pyridostigmine
tablets would be taken orally every eight hours.
Like nerve agents, carbamates inhibit the
enzymatic activity of acetylcholinesterase (AChE).
Unlike chemical warfare nerve agents, the

A Guide to Gulf War Veterans' Health 35_
35 Page 36 37
interaction between carbamates and the active site
of AChE is spontaneously reversible.
Carbamoylated AChE is protected from attack by
nerve agents because the active site of the enzyme
is not accessible to binding of nerve agent
molecules. Pyridostigmine pre-treatment that
results in carbamoylation of 20% to 40% of the
AChE does not significantly impair
neurotransmission or normal functioning of the
soldier. Prompt post-exposure treatment with
atropine and an oxime reactivator is needed for
pyridostigmine bromide to be effective.
Pyridostigmine has been used safely for many
years in treatment of myasthenia gravis.

Studies of possible interactions of pyridostigmine
administered together with the insect repellent
diethyltoluamide (DEET) and the insecticide
permethrin have demonstrated possible synergistic
toxicity. The relevance of these reports to the
experience of GW veterans is unknown since
systemic administration of the interacting
compounds was at least 10,000 fold in excess of
the maximum potential exposure to U. S. troops in
Operation Desert Storm. Low dose studies have
been funded and are underway. A recent animal
study found that stress may enhance the blood-brain
barrier permeability of pyridostigmine
bromide and enhance the resultant neuronal
excitability [Nature Medicine, 1996; 2( 12): 1382-
1385].

War-related stressors are a unique human
experience. During Operations Desert Shield and
Desert Storm, in addition to the experience of
being in actual combat, U. S. troops experienced
many other forms of stress, including short
deployment notice, family and employment-related
concerns, uncertainty about the length of
the deployment, environmental exposures, poor

living conditions, anticipation of a high casualty
and death rate, casualties and dead bodies, and the
constant threat of chemical and biologic warfare
attack. Post-deployment also resulted in stressful
conditions for returning forces. Acute stress
reactions and posttraumatic stress disorder are not
the only conditions that arise after wartime
experiences. Based on years of clinical observation
and scientific study, it is recognized that stress
may have physical as well as psychological
consequences. Stress is known to affect the
endocrine, immune, cardiovascular and nervous
systems. For this reason, the Presidential Advisory
Committee concluded in its final report that stress
"� is likely to be an important contributing factor
to the broad range of physiological and
psychological illnesses currently being reported by
Gulf War veterans."( ISBN 0-16-048942-3, 1997).

A DoD study of the post-war hospitalization
experience of GW veterans [NEJM, 1996; 335
(20): 1505-1513] indicates that, at least among
active duty personnel, the rate of hospitalizations
of GW veterans does not exceed the
hospitalization rates in their non-deployed
counterparts. This suggests that GW veterans are
not experiencing an excess of illnesses of a
severity that would lead to hospitalization. Caution
must be exercised, however, in drawing a more
general conclusion because the study does not
account for veterans who may have left the
military, nor does it account for individuals who
are hospitalized in nonmilitary facilities.

In the remainder of this chapter, research studies
published related to the health risks and illnesses
of GW veterans are summarized.

A Guide to Gulf War Veterans' Health 36_
36 Page 37 38
Background
Since the 1990-1991 Gulf War, there has been
concern that U. S. war veterans may have
experienced adverse health consequences,
including increased mortality due to external
causes (motor vehicle accidents and accidents of
other types, suicide, and homicide). The authors
conducted a retrospective cohort study of mortality
in which they compared the postwar mortality of
GW veterans with that of veterans from the era of
the Gulf War who did not serve in that conflict.
This study complements the DoD study of non-battle
related deaths among GW troops who
remained on active duty.

Methods
The study subjects were all 695,516 military
personnel who served in the Gulf War area from
August 1990 to April 1991. A control group of
746,291 military personnel consisted of a stratified
random sample of approximately half of all
personnel on active duty in the National Guard and
in the military reserves who served from
September 1990 to April 1991 but did not go to the
Gulf. The vital status of each GW veteran from the
date the veteran left the Gulf area was determined
with a VA database. Death certificates were
obtained and causes of death were coded. The data
obtained were analyzed in three stages:

1. the relative frequency of death overall, as well
as death due to specific causes, was compared
between the GW veterans and the controls on
the basis of the number of person-years at risk;

2. the Cox proportional-hazards model was used
to account for possible confounding and the
effect of selected covariates on the risk of a
veteran's dying from a specific cause,
according to the time since that veteran's entry
into the cohort; and

3. the cause-specific mortality of GW veterans
and other veterans was compared with the
number of deaths expected in the overall U. S.
population after adjustment for age, sex, race,
and year of death.

Results
The demographic and military characteristics of
the GW veterans were similar to those of the
controls with the exception of the year of birth,
sex, and type of unit. After controlling for potential
confounders (age, sex, race, and military
variables), the GW veterans had significantly
higher mortality from all causes than the other
veterans. The excess deaths were entirely
attributable to external causes, including all types
of accidents and motor vehicle accidents. There
was no observed excess of suicides, homicides, or
deaths from disease-related causes. The risk of
death from infectious and parasitic diseases was
significantly lower among the GW veterans than
among the other veterans.

Relative-risk estimates derived from the Cox
proportional-hazards model showed that overall
mortality and mortality from all external causes,
including accidents of all types and motor vehicle
accidents, continued to be significantly elevated
among the GW veterans as compared with the
controls. In men, the risk of disease-related
mortality was lower among GW veterans than
among controls. The effect of being mobilized
without being sent to the Persian Gulf did not
appear to affect the overall mortality or the risk of
death from external causes, even after adjustment
for the type of unit, age, sex, race, and branch of
service. As compared with the general population
of the United States, the GW veterans and the non-GW
veterans both had significantly lower cause-specific
standardized mortality ratios. Deaths

A Guide to Gulf War Veterans' Health
5A: Mortality Study
Reference: Mortality Among U. S. Veterans of the Persian Gulf War
New England Journal of Medicine. 1996; 335( 20): 1498-1504.

Authors: Han K. Kang, Dr. P. H., and Tim A. Bullman, M. S., Department of Veterans Affairs,
Environmental Epidemiology Service, Washington, DC 37_
37 Page 38 39
among both groups of veterans occurred at a rate
no more than half that expected in the U. S.
population after adjustment for age, sex, race, and
year of death.

Women sent to the Gulf War area also had a
significant excess of deaths from all external
causes, including accidents. The adjusted rate ratio
was higher among female than among male
veterans. In contrast, the rate ratio for deaths from
disease-related causes was almost the same among
female veterans as among male veterans. Being
mobilized without actually serving in the Persian
Gulf areas appears to have affected the mortality
rates of women more than those of men. Women
who were deployed somewhere (but who did not
serve in the Gulf) had a higher, but not a
significantly higher, rate of death from all causes
than non-mobilized women, a higher rate of death
from external causes, and a higher rate of death
from accidents after adjustment for the type of
unit, age, race, and branch of service. Female GW
veterans had a higher (but not significantly higher)
risk of death from external causes, including
accidents, than their female peers in the general
U. S. population. The rate of death among the
female GW veterans was 43 percent higher than
expected, whereas among other female veterans
the risk was 31 percent lower than expected.

Discussion
GW veterans have had a significantly higher
mortality than other veterans who served during
the same period. Accidental deaths accounted for
most of this increase. Neither the suicide rate nor
the homicide rate was elevated among GW
veterans. Mortality due to illness was not higher in
GW veterans than in other veterans. The
significant excess mortality from external causes
among GW veterans as compared with controls is
similar to what has been observed in studies of
veterans of other wars. The underlying reasons for
the excess of deaths due to external causes among
war veterans are not well understood.

The authors note that serious flaws in the design
and execution of the study are an unlikely
explanation for their findings. To minimize

statistical variation due to sampling, the study
included all GW veterans and almost half of all
military personnel who were not sent to the
Persian Gulf. The interpretation of the study
findings is somewhat confounded by the
possibility that military personnel who were
seriously ill or recovering from major surgery
would not have been deployed to the Persian Gulf
area. Another limitation of the study is the reliance
on death certificates rather than medical records
for information on causes of death. A further
possible limitation is the lack of data on potential
risk factors, such as a history of smoking and/ or
drinking, and preexisting mental disorders.

The effect of the Gulf War on postwar mortality
appears to be greater among female veterans. Both
male and female veterans of the conflict had
higher rates of mortality from external causes than
the controls, but the increase was greater among
women. In contrast, there was no excess of deaths
from disease among either male or female GW
veterans. Mobilization without actual service in
the Persian Gulf area had no substantial effect on
the mortality of GW veterans as a group. Among
women, however, those who were mobilized had a
higher risk of death from each category of external
causes than those who were not mobilized,
although the risk was not significantly higher.

In summary, as compared with non-GW veterans,
veterans of the conflict in the Persian Gulf had
significant excesses of death from external causes
(mainly accidents), but not from disease-related
causes. Their risk of death remained less than half
that expected in their civilian counterparts. The
findings are consistent with the postwar mortality
observed in veterans in previous wars.

A Guide to Gulf War Veterans' Health 38_
38 Page 39 40
Background
Since the Gulf War ended in 1991, many veterans
of that conflict have reported diverse, unexplained
symptoms. Thus far, clinical evaluations have not
implicated specific exposures or a recognized
disease process as causing the multiple symptoms,
nor have they identified a new illness. To evaluate
the health of GW veterans, the authors studied
veterans' post-war hospitalization experience and
compared it with that of other military personnel
serving at the same time who did not go to the
Persian Gulf.

Methods
The authors used a retrospective cohort approach
and data from Department of Defense hospitals to
study the hospitalizations of 547,076 veterans of
the Gulf War who were serving in the Army, Navy,
Marine Corps, and Air Force and 618,335 other
veterans from the same era who did not serve in
the Gulf War. The hospitalization records included
up to eight discharge diagnoses which were coded
by using the International Classification of
Diseases, 9th Revision, Clinical Modification
(ICD-9-CM). For this report, multivariate logistic-regression
models were used to analyze the risks
for overall hospitalization and hospitalization for a
diagnosis in each of 14 broad ICD-9-CM
categories (not including diagnoses involving the
reproductive system) for three periods from
August 1991 through September 1993 (a total of
45 comparisons).

Results
GW veterans were at slightly lower risk of
hospitalization for any cause than other veterans
two years before the war, but the risk did not differ
after the war. The odds of hospitalization due to

diagnoses in the ICD-9-CM categories differed
between the two cohorts with GW veterans at
greater risk in five models: neoplasms (in 1991),
diseases of the genitourinary system (in 1991),
diseases of the blood and blood-forming organs (in
1992), and mental disorders (in both 1992 and
1993). The ten most frequent diagnoses in each of
the five models accounted for 68 to 100 percent of
the diagnoses in their respective categories:

1. The 10 most frequent discharge diagnoses
involving neoplasms in the last five months of
1991 were mostly for benign conditions and
showed no significant difference in rates
between GW veterans and other veterans. The
one exception was testicular cancer, but the
event was rare and GW veterans were not
hospitalized significantly more often with this
diagnosis than other veterans in 1992.

2. Female GW veterans were at slightly greater
risk for hospitalization for disorders of the
genitourinary system than other female
veterans during the last five months of 1991.
Specifically, they were at increased risk for
inflammatory diseases of the ovary, fallopian
tube, pelvic cellular tissue, and peritoneum
and for infertility.

3. Male GW veterans were at slightly higher risk
of hospitalization than other male veterans for
redundant prepuce and phimosis, a diagnosis
often associated with hospitalization for
circumcision.

4. Both male and female GW veterans were at
slightly increased risk of being hospitalized for
"other disorders of the breast," a nonspecific
diagnosis.

5. Hospitalizations in 1992 for diseases of the
blood and blood-forming organs were usually
for anemia. However, when pregnancy-related

A Guide to Gulf War Veterans' Health
5B: Morbidity Studies
Reference: The Postwar Hospitalization Experience of U. S. Veterans of the Persian Gulf War
New England Journal of Medicine. 1996; 335( 20): 1505-1513.

Authors: Gregory C. Gray, Bruce D. Coate, Christy M. Anderson, Han K. Kang, S. William Berg,
F. Stephen Wignall, James D. Knoke, Elizabeth Barrett-Connor 39_
39 Page 40 41
hospitalizations (as a result of a postwar baby
boom among GW veterans) were removed
from consideration, the resulting values
showed no increase in risk among GW
veterans. This suggests that the increase in risk
was primarily due to anemias associated with
pregnancy.

6. Finally, the 10 most frequent diagnoses of
mental disorders in 1992 and 1993 were
examined. GW veterans were hospitalized
significantly more often than other veterans
for conditions related to alcohol and drug use
and for adjustment reactions.

Discussion
Comparisons between the two groups in this study
yielded few surprises. The increased overall risk of
hospitalization among women is consistent with
the findings of a previous study of hospitalizations
in the Navy. The increased rates of hospitalization
after the war for conditions related to drug and
alcohol use and adjustment reactions have been
reported in other groups of combat veterans.
Finally, the comparisons of separation rates are
consistent with the results of other recent mortality
studies that have not shown GW veterans to have a
higher overall or disease-related risk of death than
other veterans.

The prewar selection effect is understandable in
that the services permit recently hospitalized
personnel to remain attached to their operational
units while they convalesce, but the limited-duty
status of these personnel makes them ineligible for
deployment. The data suggest that this selection
effect is transient and that the reduction in the risk
of hospitalization seen before the war disappeared
shortly after the war. After a prewar-hospitalization
covariate was created to control for this selection
effect in the multivariate models, the odds ratios in
the two cohorts remained essentially the same.

Some differences were found in the risks
associated with specific diagnostic categories and
rates of specific diagnoses. These differences were
not consistent over time and do not suggest an

emerging illness associated with GW service.
Many of the observed differences between cohorts
with regard to rates of diagnoses suggest that
medical care for some conditions was deferred
until after the war. This is true with regard to the
diagnosis of redundant prepuce and phimosis,
which usually means that elective circumcision
was performed. Deferred diagnostic evaluation or
surgery probably also accounts for the slight
increases in the rates of various benign neoplasms
and of hospitalizations for inflammatory disease or
infertility in women that occurred immediately
after the war. Because no known associations
between an exposure and the appearance of a
neoplasm have such a short latency period and
because women are hospitalized for infertility only
after months, if not years, of outpatient medical
care, it is difficult to implicate GW service in
causing these conditions. It is more likely that GW
veterans waited until they were home before
undergoing elective hospitalization.

In conclusion, the authors constructed multivariate
logistic-regression models for hospitalization both
overall and for conditions assigned to any of 14
broad diagnostic categories in each of three
postwar periods. The risk associated with 16 of
these 45 comparisons differed between GW
veterans and other veterans. In five of these 16
cases, the risk of hospitalization was higher among
GW veterans, but the increases were inconsistent
over time and were probably due to deferred
medical care, a post-war baby boom, chance, or
mental conditions known to be associated with
war. The data suggest that GW veterans who
remained on active duty were not at increased risk
for unexplained hospitalization during the 25
months after the war.

A Guide to Gulf War Veterans' Health 40_
40 Page 41 42
Introduction
During the six years since the Gulf War, there has
been concern that the veterans health was
adversely affected, and there have been claims that
the children of GW veterans suffer from an
increased rate of birth defects. This study found no
evidence of an increase risk of birth defects among
the children of GW veterans.

Methods
Of the 696,562 military personnel deployed for at
least one day to Operations Desert Shield and
Desert Storm from August 8, 1990 to July 31,
1991, 579,931 were active duty members of the
Army, Navy, Air Force or Marine Corps and were
considered eligible for inclusion in the study. A
comparison group composed of 700,000 service
members who were not deployed to the Gulf
region� approximately half of all such
personnel� was selected from the total population
of military personnel. Reservists were excluded,
since neither they nor their dependents were
eligible for care in military hospitals after the
military member was released from active duty.
Military data on administration, demographics and
hospitalization were obtained from the Department
of Defense databases.

For GW veterans, all live births that occurred
before October 1, 1993, with an estimated
conception date after return from the Gulf region
were included. For the comparison non-deployed
group, all live births that occurred before October
1, 1993, with an estimated conception date after
December 31, 1990 were included. Hospitalization
data included up to eight diagnoses coded to five
digits by the medical records personnel using the
International Classification of Diseases, 9th
revision, Clinical Modification (ICD -9-CM). Data
on babies included sex and birth date but did not

include birth weight or gestational age. Births paid
for by the military that occurred in civilian
facilities were identified and used for estimates of
fertility and total number of live births.

The primary outcome assessed in the study was the
occurrence of birth defects. Two secondary
outcomes were also analyzed: the number of live
births per 1000 population and the ratio of male to
female babies. "Birth defects" for the purposes of
this study were defined in two ways. First, a very
sensitive definition of "any birth defect" as defined
by the Metropolitan Atlanta Congenital Defects
Program which includes virtually all ICD-9-CM
codes related to congenital malformations (740 to
759), as well as neoplasms and hereditary diseases.
The second definition, "severe birth defects," was
based on the specific defects considered by the
CDC to be frequent and severe enough to represent
a public health problem.

Exposure was defined only as deployment to the
Gulf region. Deployment was analyzed by three-month
increments in the duration of deployment
and as a continuous variable based on the number
of days of deployment.

Results
A total of 543,541 male and 35,164 female GW
veterans and 613,762 male and 86,192 female
nondeployed veterans were included in the study.
Of the identified births that occurred during the
study period, 58% of the births of wives of male
GW veterans and 7% of the births of wives of
male nondeployed veterans occurred in military
hospitals. Essentially all (over 99%) of the live
births to female service members occurred in
military medical facilities. There were 30,151
children born in military hospitals to the wives of
29,468 male GW veterans and 32,638 born to the
wives of 31,646 non-deployed veterans. Among

A Guide to Gulf War Veterans' Health
5C: Reproductive Outcomes
Reference: The Risk of Birth Defects Among Children of Persian Gulf War Veterans
New England Journal of Medicine. 1997; 336: 1650-1656.

Authors: David N, Cowan, Ph. D., M. P. H., Robert F. DeFraites. M. D., M. P. H., Gregory Gray, M. D.,
M. P. H. Mary Goldenbaum, M. L. S., Samuel M. Wishik, M. D., M. P. H. 41_
41 Page 42 43
women service members, 3,847 live births
occurred in 3,722 GW veterans and 8,825 to 8,494
non-deployed veterans. Male GW veterans were
about one year younger on average than their non-deployed
counterparts at the time of their child's
birth. Male and female GW veterans were
significantly more likely than the non-deployed
veterans to be single, black, in the Army, and of
enlisted rank. Female GW veterans were, on
average, about seven months younger than the
non-deployed veterans and six months younger at
child birth.

Among the men identified in the original
population, the rate of live births was 95.4 per
1000 for deployed and 93.29 per 1000 for non-deployed
veterans. Among women the rates of live
births were 109.40 per 1000 and 102.39 per 1000
for deployed and non-deployed veterans,
respectively. Significantly more births occurred for
male and female GW veterans than for non-deployed
veterans. In addition, the male to female
ratios for the children of GW veterans were not
found to be significantly different than the children
of non-deployed veterans.

For male service members, no positive association
was identified between GW service and the risk of
any birth defect. However, among female veterans,
there was a statistically significant increase in risk
of birth defects for Gulf veterans, with a relative
risk of 1.12( 95% CI, 1.00 to 1.25). After
adjustment for marital status, race or ethnicity, and
branch of service, there was no significant
association between GW service and the risk of
birth defects, suggesting that the univariate
association could be due to confounding. No linear
trend of increasing risk with increasing time spent
in the Gulf region was demonstrated in this study.
Nor was there any change in risk associated with
the interval between return from the Gulf region
and the babies' date of birth. Moreover, there was
no significant association between GW service and
risk of severe birth defects for the children of
either male (RR = 1.03, 95% CI = 0.92 -1.15) or
female (RR = 0.92, 95% CI = 0.90 -1.10)
veterans.

Discussion
The study was designed to test the hypothesis that
children born to GW veterans were at increased
overall risk of birth defects. The study findings do
not support that hypothesis, since most of the
univariate relative risks and all of the adjusted
odds ratios were close to 1.0. While the risk of any
birth defect was slightly higher among the children
of female GW veterans, this finding appears to be
the result of confounding by race or ethnicity,
marital status, and branch of service. The risk of
birth defects in both the deployed and the non-deployed
military populations approximated the
risk in a civilian population.

This study has some definable limitations. Only
children born in military hospitals were included
which accounts for approximately 68% of all the
births to active duty military personnel during the
study period. Births to reserve component
members or individuals who left active duty before
the study period were excluded. Only birth defects
evident at birth and coded on the birth discharge
summary were included. Diagnoses made
subsequently or in nonmilitary settings were not
analyzed.

Despite these limitations, the findings of this study
provide substantial evidence that the children of
GW veterans do not have an increased risk of birth
defects. In addition, there is no evidence for
decreased fertility in GW veterans and there are no
significant differences in the sex ratios of babies of
GW veterans.

A Guide to Gulf War Veterans' Health 42_
42 Page 43 44
Background
In late November 1993, the local Jackson,
Mississippi, newspaper reported an apparent
cluster of birth defects and other health problems
among children born to veterans of two
Mississippi National Guard units after their return
from the Gulf War. According to the wife of one
veteran, 12 children out of 15 were affected. A
variety of reported birth defects and health
problems was reported, but detailed information
was not immediately available.

From December 1993 through May 1994, the
Department of Veterans Affairs, Jackson,
Mississippi, the Mississippi State Department of
Health, and the Centers for Disease Control and
Prevention conducted a collaborative investigation
to determine whether an excess number of birth
defects occurred among children born to this group
of veterans and, if so, whether etiologic/ pathologic
patterns in the birth defects could be observed.

Methods
Mississippi has approximately 5,000 National
Guardsmen in 124 National Guard units; 65 of
these units were mobilized for the Gulf War, and
approximately 1,000 personnel were sent to the
Middle East. The reported cases of birth defects
and health problems in children came only from
veterans in two units based in southeast
Mississippi. Therefore, the survey was restricted to
all of the service personnel from these two units.
Of 282 veterans in the two units, initial phone
contact was made with 254 (90%). The remaining
28 had left the National Guard and could not be
contacted. In this group, 67 veterans or their
spouses gave a history of pregnancy since return
from deployment in the Gulf War.

Because the veterans and their spouses/ significant
others were concerned about birth defects,
premature births, and other health problems in
their children (e. g. respiratory infections, otitis
media, blood disorders, and jaundice), the medical
records of all children conceived by and born to
veterans of the two units after deployment were
reviewed. Of the 54 births for which medical
records were obtained, 29 (54%) were male, and
30 (56%) were white. As of May 1994, the ages of
the children ranged from three to 26 months.
Maternal ages ranged from 18 to 41 years (mean
25). The mother was the veteran in six of the
families, including one family in which both
parents were veterans.

Standard case definitions for birth defects, low
birth weight, and premature birth were used, but
diagnoses written in the medical records were
accepted. A case was defined as a serious
structural congenital malformation diagnosed
during the first year of life. A serious malformation
was one that could be associated with premature
death, cause substantial handicap, or require
surgery or extensive medical care. Any structural
congenital malformation not meeting the previous
definition was classified as a minor birth defect. A
case of low birth weight was defined as a birth
weight of less than five pounds, eight ounces. A
premature birth was defined as birth of an infant at
less than 37 weeks gestation.

To obtain baseline rates for comparison, data were
used from the three major U. S. birth defect
surveillance systems that survey segments of the
general population. Because many of the families
expressed concern about the high frequency of
non-congenital health problems in their children,
the authors compared the observed numbers of
some of these conditions in this group with the

A Guide to Gulf War Veterans' Health
5C: Reproductive Outcomes
Reference: No Evidence of Increase in Birth Defects and Health Problems among Children
Born to Persian Gulf War Veterans in Mississippi
Military Medicine. 1996 Jan; 161( 1): 1� 6.

Authors: Alan D. Penman, Bureau of Preventive Health, State Department of Health, 2423 North
State Street, Jackson, MS 39215; Russell S. Tarver, Department of Veterans Affairs
Medical Center, 1500 East Woodrow Wilson, Jackson, MS 39216 43_
43 Page 44 45
numbers expected using rates from published
studies or generally accepted rates.

Results
Three cases of major birth defect were found: one
case of craniosynostosis and perimembranous
ventricular septal defect in an infant born at 37
weeks gestation; one case of posterior urethral
valves with hydronephrosis in a full-term infant;
and one case of bilateral trigger fingers in a full-term
infant. Two cases of minor birth defect were
found: one case of pulmonary stenosis that was
judged to be hemodynamically insignificant and
one case of single umbilical artery without
associated abnormalities. No stillbirths or deaths
were noted.

Five cases of low birth weight were observed.
Multiple other conditions occurring in the post-neonatal
period were reported by the parents in the
telephone survey or noted in the clinical records.
The number of cases of each condition or problem
was minimal. A total of 38 children had a mean of
2.3 office visits for upper respiratory infection in
the first year of life. A total of 26 children in this
group made an average of 2.1 office visits for otitis
media during the first year of life.

Discussion
The frequency of premature birth and/ or low birth
weight in the study group when compared with
that of other groups should be interpreted with
caution because:

1. The study could not account for confounding
by all the well-known factors that can increase
the risk for conceiving and giving birth to an
infant with a congenital malformation.

2. The small size of the study population and the
occurrence of only one case of each of five
different types of birth defects (i. e. three major
and two minor) makes the calculation of
individual rates for the purpose of comparison
difficult.

3. Low birth weight is associated with an
increased frequency of congenital
abnormalities, but none were observed among

the low birth weight babies in this group.
4. The amount of morbidity from respiratory
infections and otitis media observed during the
first year of life in this group of children was
not excessive.

5. Diagnoses stated in the medical records were
accepted without further verification.
However, with few exceptions, no major
discrepancies were noted between the health
problems reported by the parents and the
diagnoses recorded by the physicians or, in the
cases of those children referred for further
investigation/ surgery, between physicians.

6. The lack of data concerning the 28 families
who could not be contacted is a possible
source of bias. No information could be
obtained on how many births occurred in this
group nor what the outcomes were. If this
nonparticipant group had healthy children,
their omission from the study would make the
observed rates higher than they actually were.

Conclusions
The authors found no increase in the total number
of all types of birth defects among children
conceived by and born to this group of GW
veterans after deployment (i. e., the rate of birth
defects of all types in children born to this group
of veterans was similar to that expected in the
general population). However, because of the
small numbers involved, the authors could not
determine whether the occurrence of any specific
birth defect observed among this group of children
differed from what was expected. Perhaps the most
significant finding was that a variety of birth
defects was observed, and clustering of any one
type or affected system did not occur.
Furthermore, no known genetic or chromosomal
abnormality or teratogen was common to the
various defects.

A Guide to Gulf War Veterans' Health 44_
44 Page 45 46
Summary
An assessment was conducted of the impact of
infectious diseases on the 697,000 U. S. troops
deployed to the Persian Gulf during 1990� 1991 in
Operations Desert Shield and Desert Storm.
Published reports and data were obtained from the
U. S. Navy's weekly surveillance system of
outpatient visits among approximately 40,000
Marine Corps ground troops deployed to
northeastern Saudi Arabia. As indicated by
statistical data, the disease nonbattle injury rate,
which includes infectious diseases, was lower
during this military campaign than in any major
war involving U. S. military personnel.
Nondisabling acute enteric and respiratory
infections, however, were a frequent occurrence.

Gastroenteritis
Diarrheal disease was the leading cause of
infectious disease morbidity among U. S. troops. At
the beginning of the rapid buildup of troops when
the weather was very hot, outbreaks of acute
diarrhea were common, and more than 50% of the
troops in some initially deployed units reported an
epidemic of acute diarrhea. The major risk factor
for diarrheal disease among initially deployed
ground troops was consumption of fresh fruits and
vegetables obtained from neighboring countries.
Viral gastroenteritis also was a cause of morbidity
among troops, but no confirmed, acute case of
cholera, typhoid fever, amoebic dysentery, or
giardiasis was reported among troops.

Respiratory Disease
Acute, common cold-type respiratory complaints
were a widespread cause of minor morbidity
during both Operations Desert Shield and Desert
Storm especially during periods of initial

deployment and crowding. A major concern was
that respiratory disease would result from exposure
to the sand in this region. A survey of 2,598 U. S.
troops, however, indicated that upper respiratory
symptoms, other than chronic rhinorrhea, were
most common among the minority of troops who
resided in air-conditioned buildings.

Leishmaniasis
To date, 12 cases of visceral and 20 cases of
cutaneous leishmania infection have been reported
among U. S. GW veterans who were deployed to
Saudi Arabia, Kuwait, and southern Iraq.
Leishmania tropica was found in cases of visceral
disease and Leishmania major in cutaneous cases
in which parasites could be cultured and evaluated.
There are several possible reasons for a low
number of cases of cutaneous and visceral
leishmaniasis:

1. insecticides and repellents were used against
arthropod vectors in areas where group troops
were camped;

2. most combat troops were stationed in the open
desert rather than in oases or urban areas
where the sandfly vector and the primary
leishmania host, desert rodents, thrive; and

3. the troop buildup did not occur until the cooler
winter season which is the lowest period of
sandfly activity.

Other Arthropod-Borne Infections
No outbreak of febrile disease consistent with
sandfly fever or other arthropod-borne disease was
reported or observed in the U. S. Navy disease
surveillance system of 40,000 Marine Corps
personnel. The reasons why U. S. troops were at
low risk of sandfly fever may be related to the low

A Guide to Gulf War Veterans' Health
5D: Infectious Diseases
Reference: The Impact of Infectious Diseases on the Health of U. S. Troops Deployed to the Persian
Gulf During Operations Desert Shield and Desert Storm
Clinical Infectious Diseases. 1995 June; 20( 6): 1497� 1504.

Authors: Kenneth C. Hyams, Kevin Hanson, F. Stephen Wignall, Joel Escamilla,
Edward C. Oldfield 45_
45 Page 46 47
number of cases of leishmaniasis because these
two diseases are transmitted by the same sandfly
vector. Use of insecticides and limited sandfly
activity during the cold winter months, when most
troops were deployed, would have lessened the
risk of transmission of both diseases. Furthermore,
because of differences in geographic location, the
risk of sandfly fever may not have been as great
for Desert Storm troops who were deployed in the
open deserts of Saudi Arabia. The low occurrence
of arboviral infections and leishmaniasis indicated
a very low risk overall of arthropod-borne
diseases.

Other Infectious Diseases
Infectious diseases that historically have plagued
military populations--malaria, sexually transmitted
diseases, and viral hepatitis� were not a problem
during this deployment. Only seven cases of
malaria were reported; STDs were an infrequent
finding because of very limited contact between
U. S. troops and other populations; and only a few
cases of Hepatitis A and B were observed. No
diagnosis of brucellosis and only three cases of
Coxiella burnetii infection, which are endemic in
the Middle East, have been reported. There have
been no reported cases of schistosomiasis,
echinococcosis, or active tuberculosis, but there
were two cases of meningococcal disease.

Unexplained Illnesses
Since the end of the Gulf War, several thousand
veterans from widely diverse military units have
complained of chronic nonspecific symptoms,
which have not been readily explained. The most
common complaints have been chronic fatigue,
headache, muscle and joint pain, shortness of
breath, intermittent diarrhea, cough, and
neuropsychological complaints, including sleep
disturbance, difficulty concentrating, forgetfulness,
irritability, and depression. No documented fever,
characteristic skin rash, or consistent abnormality
in results of laboratory tests currently have been
identified. A number of possibilities have been
considered as causes of these unexplained
illnesses: various infectious diseases (e. g. visceral

leishmaniasis, brucellosis, Q fever, Lyme disease,
tuberculosis, and retroviral infections); biological
warfare agents; an unknown or emerging
infectious disease; and chronic fatigue syndrome.
Because most veterans became ill several weeks to
more than a year after returning to the U. S. (rather
than after an illness while in the Persian Gulf)
epidemic neuromyasthenia is considered an
unlikely explanation for chronic fatigue and other
generalized symptoms.

Conclusion
The fact that infectious diseases were not a major
cause of lost manpower, unlike the experience of
Western troops in the Persian Gulf during World
War II, can be attributed to a combination of
factors: the presence of a comprehensive
infrastructure of medical care, extensive
preventive medicine efforts, and several fortuitous
circumstances, principally isolation of troops in
barren desert locations and cooler winter
conditions during the height of the troop buildup.
Although U. S. troops were at low risk of
incapacitation from infectious diseases during the
Gulf War, other military campaigns may not be so
fortunate. Chance events (e. g. time of year and
geographic location of deployment) can have a
major impact on the risk of transmission of
infectious diseases and result in higher morbidity
among deployed troops. The U. S. military must
continue to support an aggressive program of
preventive medicine, which is guided during
deployments by continuous disease surveillance
and on-site laboratory analyses. In addition, it is
critical for the military to maintain an infectious
diseases research program to develop new
vaccines, improved medical treatments, and more
accurate and rapid diagnostic tests.

A Guide to Gulf War Veterans' Health 46_
46 Page 47 48
Background
Beginning in August 1990, approximately 800,000
coalition troops were deployed to the Persian Gulf
during Operations Desert Shield and Desert Storm.
There was substantial concern that coalition troops
would be adversely affected by arthropod-borne
infectious diseases, particularly sand fly fever and
cutaneous leishmaniasis, because of high
morbidity rates in the Persian Gulf during World
War II. In sharp contrast to WWII, however, there
were no reports of sand fly fever among coalition
forces and only 31 cases of leishmaniasis among
697,000 U. S. troops. Consistent with the low
incidence of arthropod-borne diseases the
suspected vectors of the agents for these diseases
appeared to be scarce in areas where coalition
troops were deployed.

To determine the reason why troops were at low
risk of arthropod-borne diseases and to further
evaluate the risk of infection for troops who are
currently deployed in this region, an entomologic
survey was conducted between January and
September, 1992, in 12 areas of U. S. troop
deployment in Kuwait and Saudi Arabia.

Materials and Methods
The survey was conducted in 12 locations (four in
Kuwait and eight in Saudi Arabia) where U. S.
military personnel were located in 1992. The 12
sites were chosen based on diversity of ecologic
conditions, the presence of U. S. troops, and
accessibility. In Kuwait, all survey areas were near
the Persian Gulf coast and in Saudi Arabia, sites
5-10 were near the Persian Gulf coast, and sites 11
and 12 were inland adjacent to the city of Riyadh.

Four collecting trips were made during 1992. Sand
flies were collected using oiled-paper traps;
mosquitoes, sand flies, and other host-seeking
dipterans were collected using CDC light traps.
Tweezers were used to collect host-seeking ticks
from the desert floor. Ticks were also collected
from trapped rodents. Vials containing
cryopreserved sand flies were rapidly thawed in
warm water. Female sand flies were examined
under a dissecting microscope on a sterile glass
slide in a drop of sterile PBS for the presence of
promastigotes.

In addition to these collections, rodents were also
captured and combed for ectoparasites and
carefully examined for Leishmania lesions. Rodent
sera were tested for antibodies to Rickettsia conorii
and R. typhi.

Results
A total of 1,556 arthropods was collected.
Mosquitoes accounted for 78.7% (1,224) of
collected arthropods, sand flies for 15.2% (236),
Culicoides for 3.6% (56), and ticks for 2.4%. Six
species of mosquitoes were identified, eight
species of sand flies, at least one species of
Culicoides, and three species of Hyalomma ticks.

The majority (87%) of specimens was collected
during the hot, late summer period in August and
September, 1992. The largest number of sand fly
specimens were collected from the coast of
Kuwait, whereas mosquitoes were found both
along the coast and further inland around Riyadh.
A total of 856 arthropods was processed in 50
pools for virus isolation; all pools were negative
by plaque assay in Vero cell culture. Due to the

A Guide to Gulf War Veterans' Health
5D: Infectious Diseases
Reference: Assessment of Arthropod Vectors of Infectious Diseases in Areas of U. S. Troop
Deployment in the Persian Gulf
American Journal of Tropical Medicine and Hygiene. 1996 Jan; 54( 1): 49-53.

Authors: Stanton E. Cope, George W. Schultz, Allen L. Richards, Harry M. Savage,
Gordon C. Smith, Carl J. Mitchell, David J. Fryauff, Joseph M. Conlon,
Jeffrey A. Corneil, Kenneth C. Hyams 47_
47 Page 48 49
small numbers collected, only 25 sand flies were
dissected for evidence of Leishmania infection; all
were negative.

Among 52 captured mammals, there were 35 Mus
musculus; eight Gerbillus species; eight Meriones
crassus; and one hedgehog. The rodents appeared
healthy and few ectoparasites were found; no
external lesions were noted. There was no
serologic reactivity to R. conorii or R. typhi
antigen preparations among the captured rodents.

Discussion
The survey demonstrated the presence of the
principal sand fly vector in areas of U. S. troop
deployment in Kuwait and Saudi Arabia. In
addition, the suspected mosquito vectors of the
West Nile and Rift Valley fever, and the tick vector
of Crimean-Congo hemorrhagic fever were
detected. However, there was no evidence of
arboviruses or Leishmania among collected
arthropod vectors and trapped rodents.

Due to the limited extent of the survey and the
focal nature of vectors and animal hosts of
infectious agents, the risk of arboviral and
Leishmania infection could not be estimated from
the results of the survey. Although vectors of
arthropod-borne disease agents were found in
numerous locations, the low incidence of these
infectious diseases among more than 500,000
coalition ground troops indicate that the risk was
very low during Operations Desert Shield/ Storm.

There are several possible reasons for the low risk
of arthropod-borne infectious diseases among GW
troops in an area where suspected vectors
frequently were found:

1. the use of insecticides, repellents, and other
protective measures would have lessened the
risk;

2. most combat troops were deployed to the open
desert where sand fly activity and host rodents
are minimal; and

3. most troops were deployed during the cooler,
winter period when sand fly and mosquito
activity is lowest.

Reports of L. tropica infection causing mildly
symptomatic visceral disease (viscerotropic
leishmaniasis) among 12 U. S. GW veterans,
however, were unexpected. Although there have
been scattered reports of visceral L. tropica
infection, this disease has not been reported
previously in Saudi Arabia and Kuwait. The
species of sand fly that serves as a vector of
viscerotropic leishmaniasis has not been
determined. A likely candidate is P. sergenti;
however, this species was not found in this survey.

A Guide to Gulf War Veterans' Health 48_
48 Page 49 50
Background
Visceral leishmaniasis (kala-azar), usually caused
by Leishmania donovani, has rarely been reported
from eastern Saudi Arabia, so it was not expected
to affect the soldiers of Operation Desert Storm.
Kala-azar presents as a chronic febrile illness with
emaciation, marked hepatosplenomegaly,
pancytopenia, and hyperglobulinemia. In this
article, the authors described eight American
soldiers who had a systemic leishmanial infection
that differed from kala-azar in that the infected
organism was L. tropica rather than L. donavani.
These patients did not have the classic signs or
symptoms of kala-azar.

Methods
The authors evaluated eight soldiers with visceral
leishmania infection. Patient One was evacuated
from Saudi Arabia with an unknown febrile illness.
Patients Two (abrupt onset of fever, rigors,
nonproductive cough, and malaise one month after
his return from Saudi Arabia), Three (onset of
watery diarrhea, nausea, and diffuse abdominal
pain two months after his return from Saudi
Arabia), and Seven (sudden onset of fever, rigors,
malaise, and right-lower-quadrant pain with
diarrhea one month after returning from Saudi
Arabia) were directly referred early in the course
of their illnesses because of their symptoms.
Patient Four was in the same unit as Patient Two,
and his illness was diagnosed during a serologic
survey. Patients Five and Six (gradual onset of
malaise, fatigue, anorexia, nausea, abdominal pain,
headaches, nonproductive cough, arthralgias, and
myalgias seven months after returning from Saudi
Arabia) were in the same unit as Patient One and

were identified during a serologic survey. Patient
Eight was referred because of a febrile illness.

Titers of antibody to leishmania were determined
by immunofluorescence assays. Mononuclear cells
obtained by density sedimentation of bone marrow
aspirates were analyzed by an indirect
immunofluorescence assay incorporating a
monoclonal antibody specific for leishmanial
organisms. Bone marrow samples were obtained
from the iliac crest by needle aspiration. Cultured
promastigotes were isolated and characterized by
isoenzyme analysis.

Results
The patients with visceral leishmaniasis described
in this article all presented between November
1990 and April 1992. Their median age was 32.5
years (range, 21 to 40), and all were males. For the
maximal incubation period, defined as the interval
between arrival in Saudi Arabia and the onset of
symptoms, the median was seven months (range,
two to 14); for the minimal incubation period,
defined as the time between departure from Saudi
Arabia and the onset of clinical illness, the median
was two months (range, one to seven). In Patient
One, the incubation period was two months since
he became ill while in Saudi Arabia.

None of the eight soldiers had classic signs or
symptoms of visceral leishmaniasis (kala-azar).
Seven soldiers had unexplained fever, chronic
fatigue, malaise, cough, intermittent diarrhea, or
abdominal pain that began up to seven months
after they returned to the United States; one had no
symptoms. Five had adenopathy or mild, transient
hepatosplenomegaly. None had cutaneous
manifestations. Diagnoses were made by bone

A Guide to Gulf War Veterans' Health
5D: Infectious Diseases
Reference: Visceral Infection Caused by Leishmania tropica in Veterans of Operation Desert Storm
New England Journal of Medicine. 1993 May 13; 328( 19): 1383-1387.

Authors: Alan J. Magill, M. D.; Max Grogl, Ph. D.; Robert A. Gasser Jr., M. D.; Wellington Sun,
M. D.; Charles N. Oster, M. D. 49_
49 Page 50 51
marrow aspiration (seven patients) or lymph-node
biopsy (one patient). Six isolates were identified as
L. tropica, which usually causes only cutaneous
disease. Of the six patients treated with sodium
stibogluconate, five improved and one remained
symptomatic.

No patient had lesions that suggested cutaneous
leishmaniasis according to his history or physical
examination. In the six patients in whom the
infecting species could be differentiated, the
leishmania were characterized as L. tropica. This
organism has been reported to cause cutaneous
leishmaniasis, but has rarely been reported to
produce systemic illness. Six of the patients were
otherwise healthy and immunocompetent. No
other diagnosis was confirmed in these six patients
despite extensive evaluations, and five of them
responded to specific therapy for leishmaniasis.
Patient Seven, who was HIV infected, had a
nonspecific illness associated with HIV
seroconversion. He was examined for
leishmaniasis because of the high index of
suspicion and an elevated titer. In Patient Eight,
the localized renal-cell carcinoma was an
unexpected finding during an exhaustive
evaluation. Acute retroviral seroconversion and
renal-cell carcinoma could explain the illnesses
seen in these two patients, and the authors could
not conclude that their clinical presentations were
due solely to leishmaniasis. Visceral leishmaniasis
was included in the differential diagnosis of
systemically ill soldiers because it is one of the
endemic infectious diseases of Saudi Arabia.

Discussion
The most severe clinical manifestation of visceral
infection caused by leishmania is kala-azar, caused
by L. donovani. L. tropica can produce visceral
infection that can cause unexplained systemic

illness in persons returning from areas where this
organism is endemic. The finding of visceral
illness due to Leishmania in returning troops
raised at least two important clinical issues: late
presentation due to prolonged incubation and
activation of latent infection in immunosuppressed
persons.

Leishmanial illnesses similar to those described
here may not be recognized as such when they
occur in populations in which they are endemic,
because of their protean clinical manifestations,
insensitive diagnostic tests, and infrequent
examination of bone marrow for amastigotes.
Another possibility is that nearly universal
infection in childhood leads to resistance to
disease in adult life. The exposure of more than
500,000 nonimmune adults during Operation
Desert Storm may therefore have revealed more of
the clinical spectrum of infection caused by L.
tropica.

The authors describe a systemic illness caused by
L. tropica. This illness is called "viscerotropic"
leishmaniasis to distinguish it from "visceral"
leishmaniasis. The natural history of this illness is
not yet defined and the prevalence of infection
among returning troops is not known. Diagnosis
still requires an invasive procedure, such as a bone
marrow aspiration or a lymph-node biopsy, and
specialized laboratory support that is not widely
available. This disorder should be included in the
differential diagnosis of unexplained systemic
illness in patients who have returned from areas of
the world where leishmaniasis is endemic.

A Guide to Gulf War Veterans' Health 50_
50 Page 51 52
Background
In November 1994, the U. S. Department of
Veterans Affairs (VA), the Department of Defense
(DoD), and the Pennsylvania Department of
Health requested that CDC investigate a report of
unexplained illnesses among members of an Air
National Guard (ANG) unit in south-central
Pennsylvania (Unit A) who were veterans of the
Gulf War (August 1990� June 1991). These
veterans had been evaluated at a local VA medical
center for symptoms that included recurrent rash,
diarrhea, and fatigue.

A three-stage investigation was planned to:
1. verify and characterize signs and symptoms in
GW veterans attending the VA medical center;

2. determine whether the prevalence of
symptoms was higher among members of Unit
A than among members of other units
deployed to the Gulf War and, if so, whether
the increased prevalence was associated with
GW deployment; and

3. characterize the illness and identify associated
risk factors. This report presented preliminary
findings from stages one and two (stage three
is in progress).

Stage One
In December 1994, a team of CDC medical
epidemiologists visited the VA medical center,
conducted standardized interviews and performed
standardized physical examinations of 59 GW
veterans reported to be asymptomatic, and
reviewed medical records. Of the 59 veterans,
26 were selected from the health registry that had
been established for GW veterans who reported
symptoms believed to be related to service in the

Gulf War, and 14 were selected as typical cases by
the physician who reported the illnesses to VA; the
remaining 19 were listed on the registry but had
not yet been evaluated at the VA medical center to
determine whether they were eligible to be on the
registry. In addition, 40 primary care physicians
and 16 regional hospitals in south-central
Pennsylvania were surveyed; the survey did not
identify additional GW veterans with any health
complaints.

The median age of the 59 persons was 39 years
(range: 23-59 years), and 53 (90%) were male. All
were enlisted personnel: 30 (51%) had been
assigned to Unit A during the Gulf War and the
remainder were in other Air Force units and
military branches; 48 (81%) had been in the
military for 10 or more years; 16 (27%) had served
for five or more years on active duty; and 19
(32%) had been deployed for 2 or more tours to
the GW theater. At the time of the survey, 89%
were employed in addition to their ANG work.

The most frequently reported symptoms
considered "moderate" or "severe" were fatigue
(61%), joint pain (51%), nasal or sinus congestion
(51%), diarrhea (44%), joint stiffness (44%),
unrefreshing sleep (42%), excessive gas (i. e.
flatulence, bloating, and gastrointestinal distress)
(41%), "difficulty remembering" (41%), muscle
pains (41%), headaches (39%), abdominal pain
(36%), general weakness (34%), and impaired
concentration (34%). The two symptoms identified
as "most bothersome" were fatigue (27%) and
diarrhea (14%). Patients reported that their
symptoms began during or two to three months
after departure from the Persian Gulf, and all
reported that several symptoms persisted for six or
more months. No consistent abnormalities were
identified among the participants on standardized
physical examination or by review of medical

A Guide to Gulf War Veterans' Health
5E: Unexplained Illness/ Symptoms
Reference: Unexplained Illness Among Persian Gulf War Veterans in an Air National Guard Unit:
Preliminary Report August 1990� March 1995
Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report.
1995 Jun 16; 44( 23): 443-447. 51_
51 Page 52 53
records and accompanying laboratory tests
performed at the VA medical center. After the war,
one participant had viscerotropic leishmaniasis
diagnosed and treated.

Stage Two
From January through March 1995, members of
Unit A and three comparison units (units B, C, and
D) were surveyed to determine the prevalence of
selected symptoms identified in stage one and to
examine the relation between reported symptoms
and GW service. Comparison units were chosen
for similarity in mission responsibility to Unit A
and were located in Pennsylvania and another
state. Units B and C (both reserve units) were
surveyed during routine monthly training sessions,
and Unit D (an active duty unit) was surveyed
immediately after the Unit C survey. All personnel
on each base at the time of the survey were asked
to participate, regardless of health status or
participation in the Gulf War, by anonymously
completing a questionnaire describing the
frequency, duration, and severity of 35 symptoms
most commonly mentioned during the stage one
investigation and a general health history. In
addition, personnel who had been deployed to the
Persian Gulf were asked about possible exposures
(e. g. geography [location of service], duties
[combat or support], medical and other procedures
[e. g. vaccinations, dental work], outdoor activities
[sports, recreation, mission-related], and food and
water sources).

A total of 3,927 personnel participated in the
survey. Response rates varied by unit: 63% (677 of
1,083) in Unit A, 36% (540 of 1,520) in Unit B,
74% (843 of 1,141) in Unit C, and 78% (1,867 of
2,407) in Unit D. The distribution of demographic
characteristics and deployment status of these
study participants was similar to the distribution of
these variables in the population of each unit.

In all units, the prevalence of each of 13 chronic
(lasting six or more months) symptoms was
significantly greater (p < 0.05) among persons
deployed to the Gulf War than among those not
deployed. The prevalence of five symptom
categories� chronic diarrhea, other gastrointestinal

complaints (gas, bloating, cramps, or abdominal
pain), difficulty remembering or concentrating,
"trouble finding words," and fatigue� were
significantly greater (p < 0.03) among deployed
personnel from Unit A than among deployed
personnel from each of the other units. Prevalence
of symptoms among non-deployed personnel were
similar in all units.

Editorial Note
The preliminary findings of this investigation are
subject to at least two limitations. First, the stage
two data on symptom prevalence reflect self-reported
information that was not evaluated by
physical examination and laboratory tests.
However, standardized physical examinations and
review of VA laboratory test results from patients
in stage one did not reveal consistent
abnormalities. Second, participation rates for the
stage two survey varied widely because persons
with symptoms may have been more likely to
participate; therefore, the prevalence of reported
health conditions may have been over-estimated.

The preliminary findings presented in this report
indicate that some chronic symptoms were
reported more commonly by GW veterans than by
nondeployed Gulf War-era service personnel.
Potential explanations for the higher prevalence of
symptoms among deployed personnel� and the
increased prevalence among deployed personnel
from Unit A� may include factors specific to the
Persian Gulf region (e. g., environmental, toxic,
and infectious exposures); factors related to
military service and combat (e. g., exposure to
toxic agents and combat-related disorders, age-related
effects, or other poorly defined chronic
illnesses); and factors especially specific to Unit A
(e. g., increased local concern and media attention
about illnesses related to GW service when
compared with other units). The stage three case-control
study in progress will assess risk factors in
ill and healthy GW veterans from Unit A.

Mechanisms have been established to rapidly
identify and treat GW veterans with health
problems. All GW veterans with health problems
are encouraged to obtain an evaluation at their

A Guide to Gulf War Veterans' Health 52_
52 Page 53 54
local VA medical center or military treatment
facility. Veterans can be referred for further
evaluation at specialized referral centers
established by VA and DoD.

GW veterans and their eligible family members
can register for medical examination and treatment
by calling toll-free telephone numbers (VA: 1-800-
749-8387; DoD: 1-800-796-9699). DoD has
established a separate toll-free number
(1-800-472-6719) for GW veterans to report
details of incidents they believe may be associated

with a medical problem experienced since
returning from the Persian Gulf and for healthcare
providers with questions about illnesses possibly
related to service in the Gulf War.

A Guide to Gulf War Veterans' Health 53_
53 Page 54 55
Introduction
Although psychiatric casualties were low during
Operations Desert Shield/ Desert Storm, service
members were exposed to the traumas of war
either directly through combat operations or
indirectly through exposure to the aftermath of
combat. These service members represented
potential mental health casualties. The purpose of
this study was to assess the general physical,
psychological, and psychosocial health and
adjustment (including risk for development of post
traumatic stress disorder [PTSD]) of veterans in
Pennsylvania and Hawaii who either deployed or
did not deploy to determine the need, if any, for
additional resources by the Department of Veterans
Affairs to resolve any potential readjustment
problems resulting from service in Southwest Asia
during the Gulf War.

Methods
The population samples consisted of over 16,000
active duty personnel assigned to units in Hawaii
and Pennsylvania. From this population, the
deployer sample consisted of 715 active duty
veterans and 766 reserve veterans. The non-deployer
sample consisted of 1,576 active duty and
948 reserve veterans. All participants anonymously
completed a questionnaire that consisted of self-reported
information on demographics,
psychological and psychosocial health
symptomatology, presence of symptoms
specifically related to deployment and life in a
combat theater, physical health symptomatology,
perceived sources of past and current
psychological stress (i. e., environmental demands
exceeding the individual's ability to cope),
perceived levels of current psychological stress,

causal attributions of present problems, unit
cohesion, social support, and the perceived impact
of deployment.

Results
Those veterans who deployed to the Persian Gulf
area were asked a series of questions about any
stressors they may have experienced while
deployed and how stressful they found each to be.
The first set of stressors consisted of apprehension,
anxiety, and, in a number of cases, exposure to
possible traumatic events of combat. Directly
experienced traumatic events were stressors for a
large minority of deployed veterans. The most
widely shared stressor for deployed veterans was
the period of waiting for deployment. The major
source of chronic stress within the combat theater
were those related to conditions of life and work.
A final source of stressors consisted of issues
involving family and home.

The most widely cited problems for both deployers
and non-deployers were financial matters, the way
things are usually done in their ship/ unit, career
and chances for promotion, and personal future
and the meaning of life. With few exceptions,
these problems were of greater concern for
deployers than non-deployers.

Data on psychological health were gathered with
the Brief Symptom Inventory (BSI) which
includes nine symptom dimensions or subscales.
Both deployers and non-deployers differed
markedly in comparison to civilian non-patient
norm reference groups. Deployers scored
significantly higher than "normal" as defined by
the civilian non-patient norms. Although the non-deployer
scores were in the high range, they were

A Guide to Gulf War Veterans' Health
5F: Psychological Health
Reference: Psychological Health of Gulf War-era Military
Military Medicine. 1996 May; 161( 5): 257-261.

Authors: LTC Robert H. Stretch, MSC USAR; CPT Paul D. Bliese, MSC USA;
David H. Marlowe, Ph. D.; Kathleen M. Wright Ph. D.;
LTC Kathryn H. Knudson, MSC USA; Charles H. Hoover, B. A. 54_
54 Page 55 56
not significantly different statistically from the
civilian non-patient norms. In addition, the BSI
mean scores for the active duty deployers were
significantly higher than those of the non-deployers
across all subscales.

The gross results suggested that deployers and
non-deployers had modest, but real, differences in
psychological outcomes as measured by the BSI.
The findings, however, are tempered by the fact
that the deployed and non-deployed groups tended
to differ on a number of demographic variables
that might explain the differences as well as, or
better than, deployment.

Discussion
The results of this study demonstrated that those
veterans who deployed to the Persian Gulf in
support of Operations Desert Shield/ Desert Storm
experienced significant levels of stress. The results
also demonstrated that stress remains a current
daily fact of life for those who deployed. The data
on general psychological health taken from
respondents' BSI scores also demonstrated that
caution must be used when interpreting these
scores. Compared to civilian non-patients, the
deployed veterans' scores were significantly higher
on most subscales. Compared to other active duty
and reserve soldiers who did not deploy to the
Persian Gulf, the deployed veterans' BSI scores
were essentially identical.

A problem with the comparison of BSI scores is
that the "norms" for participants in a military
subculture may not be the same as those for a
civilian cohort. Thus, a "normal" military sample
may not look the same as "normal" civilian non-patients.
This could be the result of exposure to
military-specific events (such as deployments,
training experiences, etc.), the result of self-selection
in that individuals with certain
psychological traits may be drawn to the military,
and the consequences of participation in the
special subculture of the military.

Overall, findings from this study supported the
conclusion that deployment did not result in any
significant increases in psychological distress (as
measured by the BSI) relative to other military

personnel who did not deploy to the Persian Gulf.
However, the deployers in the current study do
remain significantly different from the non-deployers
in terms of higher BSI scores, which
was not the case with deployers contrasted to non-deployers
in the authors' previous studies of post-Operation
Desert Shield/ Desert Storm Army
veterans. This would indicate that, although the
overall levels of psychological distress for those
individuals in the current study (both deployers
and non-deployers) may be lower than those of
other samples previously studied, there are still
differences within the present sample based on
deployment.

Although there are differences between BSI scores
of deployers and non-deployers, deployment status
plays only a minor role in the ability to predict
respondents' scores. With demographic differences
and smoking/ drinking behavior accounted for,
deployers have BSI scores that are, at most, 4%
higher than the scores of non-deployers. Although
small, these differences cannot be dismissed as
trivial. Even 4% may constitute a significant
difference in the context of 400,000 personnel
deployed to the Persian Gulf. It may well indicate
that a subset of the population is experiencing
significantly more psychological distress than its
members would have if they had not deployed.

As the military continues to draw-down in
response to the end of the Cold War, the likelihood
of deployments into limited warfare and
peacekeeping scenarios throughout the world
increases. These deployments will present U. S.
forces with ongoing and new stresses. Pre-deployment
baseline assessments of units most
likely to deploy should be made, otherwise
attempts to try to explain the stress patterns and
readjustment needs of returning veterans will
continue to be made post hoc. To facilitate these
assessments, a need exists for military-normed
assessment instruments.

A Guide to Gulf War Veterans' Health 55_
55 Page 56 57
Background
Recent studies show that disaster rescue workers
and military personnel assigned duties of
recovering and identifying human remains have
been traumatized by their experiences. The
psychological effects of exposure to mass death
have also been demonstrated in workers who were
close to, but not necessarily directly involved with,
recovery and identification. These studies point to
traumatization among rescue workers assigned
duties of recovering and identifying human
remains in a disaster situation. The psychological
impact of such duties among war zone troops has
not been explored. In this report, the authors
hypothesized that war zone troops exposed to
human remains as part of their duty assignment,
though not help-seeking or designated by patient
status, would exhibit evidence of psychological
distress, specifically negative mood states such as
symptoms of depression, anxiety and anger,
heightened concerns for bodily functioning,
symptoms of post-traumatic stress disorder
(PTSD) and, in some cases, sufficient
psychopathology to warrant diagnostic labeling of
clinical disorders, specifically PTSD.

Methods
Participants were 24 troops of a 35-member Army
Reserve Quartermaster Company who were
assigned graves registration duties and mobilized
to military action in Saudi Arabia. A
comprehensive psychological and psychiatric
evaluation protocol was devised to assess variables
thought to be pertinent to understanding war
trauma events and their potential impact on
psychological functioning and possible mental
disorders. Respondents were also asked to

complete a short questionnaire requesting personal
demographic and history information.

The measurement scale for severity of war zone
stress and its perceived critical elements reflected
perception of injury and death, unpreparedness for
deployment and combat, sense of unit
cohesiveness, harshness of physical environment,
perceived level of national support for the war, and
stress attributable to nonmilitary events.
Symptoms of psychological and physical
discomfort were categorized as negative mood
states such as anxiety, anger, and depression;
somatic discomfort and physical concerns; and
features considered specific to PTSD. Diagnosis of
mental disorders were assigned when threshold
criteria were met, and frequencies were
determined for each disorder, including PTSD
related specifically to participation in Operation
Desert Storm.

Results
Content analysis of one of the instruments used in
this study yielded four major themes of stress
exposure: human casualties, suffering, and death;
separation from home, family, and friends; loss of
control, uncertainty and fear of the unknown; and
austere physical environment and inadequate
living conditions. Written replies in addition to
statements made during clinical interviews showed
that all of the sample troops were exposed to threat
to life during war zone duty and to the
gruesomeness of identifying and processing
human remains.

Troops endorsed symptoms of negative mood
states and psychological distress on measures of
depression, anxiety, anger, and health discomfort.

A Guide to Gulf War Veterans' Health
5F: Psychological Health
Reference: Psychological Symptoms and Psychiatric Diagnoses in Operation Desert Storm Troops
Serving Graves Registration Duty
Journal of Traumatic Stress. 1994 Apr; 7( 2): 159-171.

Authors: Patricia B. Sutker, VAMC New Orleans; Madeline Uddo, VAMC New Orleans;
Kevin Brailey, VAMC New Orleans; Albert N. Allain, VAMC New Orleans;
Paul Errera, VAMC Washington D. C. 56_
56 Page 57 58
Symptoms suggestive of trauma-related
psychopathology, or symptoms of PTSD, were
prevalent. The most common endorsements
outlined were avoidance of thoughts or feelings
associated with traumatic events, exaggerated
startle response, recurrent intrusive recollections of
traumatic events, loss of interest in usual activities,
irritability, and anger outbursts. Also salient were
avoidance of activities or situations arousing
recollections of traumatic events, intense
psychological stress upon exposure to trauma-related
events, concentration difficulties, sleep
disturbance, hypervigilance, and interpersonal
distancing.

Data showed that one-half (12) of the troops met
criteria for at least one current psychiatric
diagnosis, whereas the other 12 soldiers did not
evidence symptoms warranting current diagnosis.
Forty-six percent of the sample were assigned
current diagnoses of PTSD that was related to
Operation Desert Storm. A high prevalence of
comorbid psychopathology was associated with
current PTSD diagnoses. Other prevalence rates
were 25% for major depression, 17% for alcohol
abuse/ dependence, 8% for depressive disorder, and
4% for simple phobia. Review of the distributions
of negative mood state and physical distress data
suggested that there may be a bimodal clustering
of extreme scores such that troops manifesting
current PTSD, for example, endorsed depressive
features and other negative symptoms in greater
frequency and intensity than troops who were not
labeled by PTSD.

Discussion
These descriptive findings suggested that
symptoms of psychological distress and physical
discomfort, as well as diagnosable
psychopathology, may develop among individuals
with no preexisting psychopathology subsequent
to service in a war zone, particularly involving
performance of duties that demand contact,
recovery, and identification of human remains. The
results revealed that half of the men and women
reported symptoms and psychological discomfort
sufficient for labeling by current psychiatric
diagnosis. Forty-six percent of the troops were

judged to suffer frank PTSD, and there was
evidence of relatively high rates of disorder
comorbidity, particularly associations between
depressive and substance abuse disorders and
PTSD. Many of the troops reported indications of
psychological and physical distress, although these
symptoms tended to be more frequent and more
intense among troops assigned PTSD diagnoses.
Roughly one-third admitted feeling nervous and
fatigued and having problems with concentration,
general aches and pains, and headaches. Data
derived from this study demonstrated the need to
explore more carefully the psychological and
physical symptom constellations common among
GW returnees and the relationships between
psychiatric disorder, specifically PTSD, and
exaggerated somatic concerns.

Exposure to death in the form of human remains
represents a significant stressor and may well
result in traumatization, even among
psychologically robust persons. The prevalence of
psychopathology judged to predate war zone
deployment was minimal; it is reasonable to
conclude that the psychological distress was
derived from military duty and its aftermath. These
and other findings underscore needs for adequate
military preparation for graves registration
assignment, skillful debriefing of war zone troops
after combat service, and systematic follow-up to
determine patterns of symptom expression and
chronicity. In the case of at least one-half of the
sample, and perhaps more, options for
psychotherapeutic interventions must also be
considered, particularly strategies for teaching
positive coping mechanisms and aids to managing
anger, depression, and anxiety, as well as
symptoms of PTSD.

A Guide to Gulf War Veterans' Health 57_
57 Page 58 59
Background
Research and clinical observations have indicated
that a predictable pattern of psychological
symptoms, labeled PTSD, may develop
subsequent to the experience of extraordinary or
life-threatening trauma, although not all outcomes
to severe or life-threatening stress are negative and
debilitating. In this study, the authors hypothesized
that response to war zone stress, whether adaptive
or marked by psychological distress, varies as a
function of variables classified in personal and
environmental resource domains, in addition to the
potent impact of stress severity and trauma
characteristics.

Methods
Participants were 775 troops deployed to combat
in the Gulf War. Two troop subsets were identified
for comparison: troops with self-reported PTSD
symptoms sufficient to warrant disorder diagnosis
(N = 97) and those reporting no evidence of PTSD
or other psychological distress measured in this
assessment (N = 484).

The authors conducted a series of stepwise
discriminant-function analyses to study
associations between personal and environmental
resource variables and psychological outcomes
subsequent to war zone stress. Within the category
for personal characteristics and resources, the
authors selected measures of personality hardiness,
coping strategies, and intellectual sophistication.
To reflect the environmental resources domain, the
measures of social and family support and
satisfaction were selected. Two measures of PTSD
and two measures of psychological distress were
used to identify and characterize the troop subsets
compared in this study.

Results
As a group, GW troops showed minimal
psychological distress on the instruments
administered. Troop subsets identified for this
study differed significantly on the personal and
environmental resource variables explored.
Univariate analyses of variance indicated that
PTSD-diagnosed troops showed more avoidance,
wishful thinking, and self-blame coping and less
problem-focused coping strategies than those who
reported no psychological distress, but the subsets
did not differ in social support coping. PTSD-diagnosed
troops produced lower scores on the
hardiness dimensions of commitment, control, and
challenge. Subsets did not differ in intellectual
sophistication. Troops assigned PTSD diagnosis
reported fewer and less satisfaction with social
supports and less perceived family cohesion and
expressiveness than their counterparts who had no
psychological distress.

Results showed that among troops exposed to war
zone stress, certain factors within the domains of
personal and environmental resources were
associated with stress-related symptoms, or
conversely, with their absence following war
participation. A combination of resource variables
distinguished troops categorized as PTSD-disordered
from those who lacked PTSD
symptomatology. Prediction on the basis of four
variables was relatively successful, yielding
correct assignment in 87% of the overall sample.

Discussion
Among the factors of interest in this study,
personal resource variables appeared to be more
strongly related to psychological vulnerability or
resistance to the negative impact of war zone duty

A Guide to Gulf War Veterans' Health
5F: Psychological Health
Reference: War Zone Stress, Personal Resources, and PTSD in Persian Gulf War Returnees
Journal of Abnormal Psychology. 1995 Aug; 104( 3): 44-452.

Authors: Patricia B. Sutker, VAMC New Orleans; J. Mark Davis, VAMC New Orleans and
University of Georgia; Madeline Uddo, VAMC New Orleans and Tulane University
School of Medicine; Shelly R. Ditta, VAMC New Orleans 58_
58 Page 59 60
than were the resources selected from the
environment domain. Personal resources
accounted for 35% of the variance in
discriminating troop subsets, whereas the
remaining variables accounted for 5%. Although
the commitment disposition of the hardiness
construct appeared to function as a relatively
strong resistance resource, there is also the
possibility that lower scores on hardiness measures
simply confirm the presence of PTSD as a
disorder. Compared to personal resources and
characteristics measured, demographic variables
did not contribute as significantly to group
prediction, even though troop subsets differed in
ethnicity, education, and rank. The role of family
and social support as agents to protect persons
from the potentially pathogenic influence of
stressful events was not as strongly related to
mental health outcomes among GW troops as
personal resource factors.

A combination of resource variables distinguished
troops categorized as PTSD-disordered from those
who lacked PTSD symptomatology. Personal
resource variables appeared to be more strongly
related to psychological vulnerability or resistance
to the negative impact of war zone duty than were
the resources selected from the environment
domain. Commitment disposition of the hardiness
construct appeared to function as a relatively
strong resistance resource, although there is also
the possibility that lower scores on hardiness
measures simply confirm the presence of PTSD as
a disorder. Results also revealed a significant
association between PTSD symptoms and
avoidance coping strategies, a finding of
relationship that, as was acknowledged for
hardiness results, did not convey information
about direction of the causal pathway.

Results of this study are consistent with the notion
of a diathesis-stress model of PTSD (i. e. stress
alone is not sufficient to evoke psychopathology

and some individuals are more inclined to mental
health stability than others). Resource variables
can be seen as possible moderators or conditions
that qualify the relationship between stressor
events and mental health outcomes. Because of
acquired or inherited vulnerabilities or
dispositions, some susceptible members of military
units were perhaps at greater risk than others for
developing PTSD when exposed to war zones.
Conversely, certain variables can be hypothesized
to moderate the relationship between stress and
psychological outcomes. Following this logic,
hardiness personality style and cohesive family
relationships, as examples, may have existed prior
to war zone duty and operated to protect the
asymptomatic group from developing symptoms
of PTSD and other psychopathology.

Without the use of a prospective design, it is
impossible to determine whether resource factors
existed differentially between groups prior to war
stress exposure. As such, differences in personal
and environmental resource factors after exposure
to war stress may reflect disrupted personality
dispositions and interpersonal relationships
symptomatic of stress-related psychopathology.
The present retrospective time frame permits only
associative links between variables identified as
effective in predicting war-related psycho-pathology.
Use of a discriminant function model
precludes testing possible causal pathways and the
relative contributions and potentially mediating
and moderating effects of variables on outcomes
of interest.

A Guide to Gulf War Veterans' Health 59_
59 Page 60 61
Background
Previous studies, particularly those involving
comparisons of men and women, lack sufficient
numbers of participants and suitable comparison
samples to allow meaningful conclusions.
Nevertheless, research has suggested that
psychological disturbances, and PTSD specifically,
may be greater among ethnic minority and women
veterans of military service. This study used data
collected by psychological assessment in a sample
of troops mobilized by Operation Desert Storm.
The hypothesis was that ethnic minority status and
female gender are associated with higher levels of
psychological distress, including negative mood
states, complaints of physical discomfort, and
PTSD symptoms, following war-zone duty.

Methods
Participants were 912 military personnel derived
from 1,423 troops mobilized for active duty during
the Gulf War who underwent psychological
debriefing and evaluation within one year of war-zone
return. They were divided into 653 war-zone-deployed
and 259 stateside-duty military
personnel. The sample reported an average age of
29 years and comprised white (63%), African-American
(28%) Hispanic (8%), and other (Asian-American
and Native American, 1%) troops.
Percentages of women and officers were 14% and
9%, respectively.

Participants were administered a battery of paper-and-
pencil psychological tests. Measures of
psychological distress focused on current feelings
and symptoms, reasoned to reflect post-war-zone
functioning rather than more stable characteristics

spanning a broader time frame, including prior to
war-zone duty. PTSD symptoms were measured
only among war-zone-deployed troops.

Results
Comparisons of troops deployed to the war zone
and those assigned duty stateside on measures of
psychological distress revealed significant
differences on two measures of depression, an
index of state anxiety, and somatic complaints.
Twenty-two percent of war-zone-deployed troops
reported at least mild levels of clinical depression.
GW troops also scored higher on depression and
anxiety scales and endorsed more somatic
discomfort and physical complaints than personnel
who remained stateside. Other frequently endorsed
items, although not significantly different,
included headaches, general aches and pains, and
sleep problems.

Minority troops reported more depression than
nonminority troops regardless of war-zone
assignment, and more minority than white troops
were classified as depressed. In addition, men and
women differed in reports of physical symptoms,
with women tending to endorse more physical and
somatic complaints than men, regardless of war-zone
assignment. Women more frequently
admitted headaches, lack of energy, and upset
stomach.

Comparisons of gender and ethnicity subsets on
measure of PTSD among military troops who
served in the Gulf War showed that ethnic
minorities reported more symptoms than whites.
The results also showed a tendency for minority,
particularly male minority, troops to report more

A Guide to Gulf War Veterans' Health
5F: Psychological Health
Reference: Assessment of Psychological Distress in Persian Gulf Troops: Ethnicity and
Gender Comparisons
Journal of Personality Assessment. 1995; 64( 3): 415-427.

Authors: Patricia B. Sutker, VAMC New Orleans; John Mark Davis, VAMC New Orleans;
Madeline Uddo, VAMC New Orleans; Shelly R. Ditta, VAMC New Orleans 60_
60 Page 61 62
psychological distress and PTSD symptoms,
although the conclusion could not be made that
minority troops, generally speaking, may have
been more negatively impacted by Gulf War
exposure. Further, minority troops tended to score
higher on measures of depression than their non-minority
counterparts, regardless of gender, and
this tendency toward pessimism or dysphoria may
account for the apparent increase in symptoms of
PTSD. Female GW veterans did not report greater
symptoms of psychological distress than their male
counterparts or score higher on measures of PTSD
symptomatology. Although women endorsed more
symptoms of physical discomfort and somatic
concerns regardless of war-zone duty, this
tendency was not increased by war-zone exposure.

Discussion
The results of this study suggest that the
experience of war-zone duty was associated with
higher levels of post-military-duty psychological
distress, specifically symptoms of depression,
anxiety, and physical discomfort, than was found
for troops who remained stateside, regardless of
gender and ethnicity characteristics. These
findings are noteworthy, because the study
compared sizeable samples of demographically
similar military troops who differed in war-zone
exposure. The finding that 22% of troops deployed
to the Gulf War reported at least mild levels of
depression compared to 9% of those who served
stateside within the first year of such military duty
is of clinical significance. Comparisons with
stateside troops were not available on measures of
PTSD, but 12% of war-zone-deployed troops met
criteria for PTSD diagnosis. Complaints regarding
physical distress and somatic discomfort were
higher among war-zone-deployed troops than
those who remained stateside, regardless of

ethnicity and gender. The one item that emerged as
statistically significant was that of lack of energy,
or fatigue, reported by war-zone troops in general.

Among the strengths of this study are assessment
of psychological symptoms in sizeable samples of
mobilized troops and recruitment from the
community rather than from a treatment-seeking
population. There are, however, limitations in
study methods that suggest the need for caution in
interpretation of present findings:

1. data were collected by self-report measures;
2. measures of PTSD symptoms were
administered only among the war-zone-deployees
subset; and

3. responses were collected during the first year
subsequent to war-zone exposure.

Regardless of these study limitations and the need
for replication, results point to the potentially
negative psychological impact of war-zone
exposure among troops generally and suggest that
ethnic minorities may be more vulnerable to the
risk of negative psychological sequelae. The
possibility that women in military service may be
at no greater risk of war-zone stress exposure
sequelae than their male counterparts is
interesting, given the increased numbers of women
serving such duty. To what extend these findings
may be extended for women as their role in direct
combat and fighting is expanded has yet to be
determined.

A Guide to Gulf War Veterans' Health 61_
61 Page 62 63
Background
Despite the fact that the Gulf War was believed to
have few adverse consequences for military
personnel, anecdotal and clinical reports from
soldiers suggested that exposure to a number of
traditional and novel stressors occurred. Although
empirical work has demonstrated adequate
psychometric properties for a number of combat
exposure scales, some important methodological
issues still exist. For example:

1. as studies of PTSD evolve, more questions
have arisen about the need for specificity of
stressor characteristics to assess their
interaction with subject-level characteristics;

2. presently used scales may not be descriptive of
(or sensitive to) distinctive experiences of
female, ethnically diverse, married, and older
military personnel who represent rapidly
growing segments of the volunteer-based U. S.
Armed Forces; and

3. the time between self-reported stressor
exposure and stressor onset may be
confounded by the format and administration
of scales.

Method
The authors conducted a series of statistical
analyses to investigate the potential impact of
certain variables on psychological adjustment,
focusing particularly on the relationship of
traditional exposure measures as compared to the
relationship of newer scales developed or modified
following the Vietnam War. Because follow-up
phases of this longitudinal study are ongoing, the
authors provided data from the acute evaluation

phase, a period not typically explored in wartime
studies. These data depicted some critical effects
of wartime exposure on very early outcomes
following military deployment. The authors had
the following goals:

1. to review existing parameters in the traditional
measurement of war-zone exposure;

2. to consider conceptual and methodological
limitations in these approaches;

3. to present empirical data from a cohort of GW
veterans that support the utility of a broader
conceptualization of war trauma, and

4. to examine how gender may be differentially
associated with some dimensions of war-zone
stress and psychological outcome following
deployment.

The Ft. Devens Operation Desert Storm (ODS)
Reunion Survey was designed to investigate
dimensions of war stressors and their effects
following the conclusion of the Gulf War. The
ODS Reunion Survey consists of a series of
standardized measures and these were
administered to veterans within five days of their
return to this country before they rejoined their
families, thus offering some of the earliest
systematic data on soldiers' experiences during the
conflict. Based on findings from existing exposure
measures and feedback from veterans, the ODS
Reunion Survey chose to investigate three major
stressor categories: traditional wartime activities,
non-traditional wartime events, and nonwar-zone,
deployment-related experiences. All respondents
provided information on these three stressors in
three ways: a fixed format checklist (" traditional
Laufer combat") involving minor modifications of
previously validated combat exposure questions; a

A Guide to Gulf War Veterans' Health
5F: Psychological Health
Reference: Reassessing War Stress: Exposure and the Persian Gulf War
Journal of Social Issues. 1993; 49( 4): 15-31.

Authors: Jessica Wolfe; Pamela J. Brown; John M. Kelley, VA Medical Center, Boston 62_
62 Page 63 64
fixed format checklist expanded to reflect ODS
war-zone experiences (" ODS expanded
checklist"); and an open-ended format where
respondents described the single most distressing
incident during their deployment period (" self-generated
stressor categories").

Summary scores on the Laufer combat and ODS
exposure scales were developed as the sum of the
number of occurrences of all events. A more
qualitative analysis of soldiers' exposure to combat
and deployment (including domestic) stressors was
conducted using subjects' self-generated
descriptions of their single most stressful
deployment event. To assess initial psychological
outcome, measures of both PTSD and general
psychological distress were included.

Results
Using the traditional (Laufer) combat scale and a
five-level combat exposure classification scheme
based on the Vietnam experience, 56% of men and
58% of women in this sample scored in the lower
ranges for traditional combat activities. Only 3%
of male and 3% of female returnees would be
classified as having high levels of traditional
combat exposure according to this scale. No
significant differences were found between male
and female veterans. The more comprehensive
ODS expanded checklist yielded higher mean
scores and showed that the three most commonly
endorsed war-zone experiences for both genders
were similar: formal alert for chemical or
biological attack, receiving incoming fire from
large arms, and witnessing death and/ or
disfigurement of enemy troops.

The distribution of self-generated stressor
categories was significantly different for males and
females. Combat stressors were the most widely
selected and noncombat, war-zone stressors were
second in prevalence. Primacy of domestic
stressors were reported by approximately one-fourth
of the men and women; only a small
percentage reported no critical stressor. Although
the prevalence of presumptive PTSD was
relatively low, a substantial number of returnees
reported high levels of general psychological

distress. Examination of the behavioral checklist
of stress-related symptoms showed that individual
PTSD symptoms occurred at considerable rates
and were significantly different for males and
females.

Discussion
Results showed that Laufer combat and ODS
expanded exposure scores did not differ
significantly between men and women. Both
scores were associated with psychological and
PTSD outcome measures, a finding consistent with
prior research employing traditional combat scales.
Although the Laufer scale was a significant
predictor of outcome measures, components of the
expanded wartime measure were as significant. All
ODS checklist factors were significantly related to
outcome.

Considering the available background and combat
exposure variables, PTSD symptoms (as defined
by the PTSD checklist) were best predicted by
regression models, although models predicting
other outcome measures were significant as well.
This finding may reflect the low rates of formal
PTSD and other psychiatric disorders in the
sample as well as our choice of outcome measures.
Adjustment of women in the sample was
significantly affected by certain back-ground and
event-based characteristics. Prior wartime service
also was predictive of outcome for women, but not
for men. Age was also identified as a risk factor
and had an inverse relationship to outcome. Other
variables were not described.

Although the findings suggest that female
personnel were more symptomatic in response to
certain wartime stressors, at least during the initial
postdeployment phase, these results should be
interpreted cautiously. First, reporting style was
not assessed and social desirability in reporting
psychological states may differ considerably
between men and women. Second, some
potentially critical experiences, such as prior
sexual or criminal victimization which may
predispose to subsequent distress, were not
evaluated. In addition, one possible decisive
stressor--sexual harassment or assault during the

A Guide to Gulf War Veterans' Health 63_
63 Page 64 65
deployment--was not addressed in the initial
survey phase. Thus, stressor assessment as it
relates to gender-specific experiences should be
pursued in greater detail.

This project offered an unusual opportunity to
track the perceptions, experiences, and reactions of
a relatively diverse group of deployed individuals
after war. The data confirmed that a host of event,
social environment, and personal characteristics
should all be considered in the development of
more valid models of post-trauma outcome. The
current findings did not suggest that new exposure
scales are needed for all subsequent military
conflicts or catastrophic occurrences. Rather, the
results pointed to the conceptual and clinical utility

of evaluating stressors more precisely, in this case
in light of the changing composition of wartime
forces and military experiences. Overall, these data
served two purposes: to alert clinicians and
researchers alike to the importance of obtaining
early baseline data and the importance of
broadening identification and measurement of
components of exposure as population
demographics and types of trauma evolve over
time.

A Guide to Gulf War Veterans' Health 64_
64 Page 65 66
Background
This preliminary study examined the possible
harmful effects of three compounds (pyridostig-mine
bromide, permethrin and DEET) when used
individually and in combination. For this study,
conducted in rats, the critical questions were:

1. what levels of use would be lethal to
laboratory rats, and

2. whether or not the lethal effects would be
higher when these three compounds were
combined than would be expected by adding
up the effects of the three compounds
individually.

Definitions
1. Pyridostigmine bromide: an FDA-approved
compound for the treatment of myasthenia
gravis (a neurologic condition); used in the
Gulf War against the possible effects of
chemical weapons.

2. Permethrin: an EPA-approved insecticide used
in many household and agricultural products;
during the Gulf War, aerosol spray cans
received only limited distribution within
theater during the conflict.

3. DEET: an EPA-approved insect repellent that
was used in the Gulf War.

Overview
This study investigated the lethal interaction of
pyridostigmine bromide (PB), permethrin, and
DEET when given to adult male rats by gavage.
The study was separated into two phases. Phase I
determined the acute oral lethal dose-response
relationship of each compound with the vehicle,
propylene glycol. Phase II was divided into two
parts. The first part (positive control) was a dose-response
study using probit units obtained from
Phase I (LD 16, 30, 50, 70, and 84). Dosage
solutions for the second (interaction) part of Phase
II contained the calculated LD( 16) (additive
LD[ 32]) of two compounds while the
concentration of the third compound was varied.
Rats were fasted overnight, dosed, and observed
for 14 days. A significant increase in lethality
occurred when PB, permethrin, and DEET were
given concurrently when compared to additive
values. This information suggested that lethality in
this study was more than an additive effect.
Dosage levels of compounds used in this study
were sufficient to produce lethality following a
single dose and were far in excess of conceivable
human exposure levels. For example, in order for
an average 70 kg (155 lb) service member to
become exposed to the lowest doses used in this
study (PB = 46 mg/ kg, Permethrin = 279 mg/ kg,
DEET = 1,946 mg/ kg), this person would have to
simultaneously ingest 107 PB tablets (30 mg
each), 23 six-ounce cans of 0.5% permethrin

A Guide to Gulf War Veterans' Health
5G: Toxicology
Reference: Acute Oral Toxicity Study of Pyridostigmine Bromide, Permethrin and DEET in the
Laboratory Rat. Toxocological Study 75-48-2665
Toxicological Study 75-48-2665. Prepared for the U. S. Army Medical Research and
Materiel Command, Fort Detrick, Fredrick, Maryland by the Health Effects Research
Program, Directorate of Laboratory Science, U. S. Army Center for Health Promotion and
Prevention Medicine, 31 May 1995.

Principal Investigator: Wilfred C. McCain, Ph. D. 65_
65 Page 66 67
aerosol spray, and 6.6 two-ounce tubes of 33%
DEET. Human exposure, however, would most
likely occur at low levels over an extended period
of time and by differing routes.

Discussion
As designed, the study demonstrated that a
massive oral exposure of the three compounds
killed laboratory rats. This can occur whether the
compounds were administered individually or in
various combinations. When all three were used
together, the effects on laboratory rats were greater
than the additive effect, but the combination of
DEET and permethrin did not produce a greater
than additive effect.

The results of this study indicated that a significant
increase in lethality occurs when PB, permethrin,
and DEET are given concurrently to male rats by
gavage. Furthermore, solutions containing PB and
permethrin or PB and DEET also caused a
significant increase in lethality when compared to
expected additive values. This information
suggested that lethality in this study was more than
an additive effect. The study also provided new
information on the lethal effects of permethrin
when used in conjunction with the vehicle,
propylene glycol.

There are at least two possible mechanisms which,
by concurrent oral exposure to compounds used in
this study, could increase lethality. For instance,
PB, which has a steep dose-response curve, is
poorly absorbed by the gut. It is possible,
therefore, that an increase in the bioavailability of
PB could cause the increased lethality seen in this
study. DEET, which has been used as a
transdermal carrier molecule for the delivery of
drugs and other agents, may enhance the uptake of
PB from the gut. This would increase the levels of
PB in circulation and decrease the activity of
esterases. Another possible mechanism is the
inhibition of detoxification systems. For instance,
esterase inhibition by PB could also inhibit the

degradation of permethrin, an ester. Hydrolysis of
the ester bond in permethrin is mediated by non-specific
esterases. Inhibition of this class of
enzymes would effectively increase the residence
time of permethrin in the body and may explain
the increased lethality when these compounds are
given simultaneously. Carbamates and pyrethroids
are also degraded by cytochrome P-450 in the
liver. This detoxification system may become
overloaded with an increase in circulating levels of
this toxicants. This would decrease the
effectiveness of this enzyme system.

Conclusions
The study concluded that these substances may
become more toxic when used in combination than
when used separately. This study, however, was
performed in rats that were given large doses of
the three chemicals. Soldiers in the Persian Gulf
were exposed to much smaller doses.

This study also used only one route of exposure in
order to produce a quantifiable effect. The most
likely human exposure scenario would be dermal
exposure to permethrin and DEET and oral
exposure to pyridostigmine. Mechanisms which
caused increased lethality in this study may be
partitioned if different routes of administration are
used. Furthermore, dosage levels of compounds
used in this study were sufficient to produce
lethality following a single dose. As noted, human
exposure would most likely occur at low levels
over an extended period of time.

Another factor considered was the assumption of
concurrent use. For instance, less than 5% of the
deployed units had distributional access to
permethrin for uniform impregnation.
Furthermore, entomologists assigned in the Gulf
during the conflict indicated a very low usage of
personal repellents, including DEET, even at times
and in areas where mosquitoes were present and
biting. Also, the cool seasonal climate conditions
which prevailed at the time of the war resulted in

A Guide to Gulf War Veterans' Health 66_
66 Page 67 68
the near absence of biting insects. In addition, PB
was taken for about two weeks at the start of the
air war and for a briefer period at the start of the
ground war� a time when insect biting rates were
extremely low. These factors indicate that the
concurrent use of PB, permethrin, and DEET by
service personnel was probably very low.

However, because several questions were not
answered by this study, the suggestion was made
that further research was indicated to determine
whether these substances are among the causes of
GW veterans' illness. Biopharmaceutic and
pharmacokinetic studies would identify increases
in blood levels of PB and decreases in esterase
activity as well as alterations in clearance rates for
compounds and metabolites.

Neuropharmacological, neuropathological and
neurobehavioral assessment is also necessary in
order to determine if nonlethal endpoints are
neurological in nature. Another possible study
could examine various routes of administration
associated with the use of these compounds. The
Department of Defense announced their intent to
fund proposals from scientists across the country
to address these questions.

A Guide to Gulf War Veterans' Health 67_
67 Page 68 69
Background
During the Gulf War, service personnel were
concurrently exposed to biological, chemical, and
psychological environments. Potential exposure
was to fumes and smoke from military operations,
oil well fires, diesel exhaust, toxic paints,
pesticides, fire sand, depleted uranium,
chemoprophylactic agents, and multiple
immunization. The reported chemical exposure
included DEET and permethrin to protect against
insect-born disease and pyridostigmine bromide
(PB) to protect against possible nerve gas attack.
Although these chemicals differ in many aspects
such as chemical structure, use, mechanisms of
action, and metabolic pathways, the major site of
toxicity for all three is the nervous system.

Materials and Methods
This study investigated neurotoxicity produced in
hens by individual or simultaneous exposure to
these agents. The adult, leghorn, laying hens were
considered specific-pathogen-free and medication-free
without abnormalities of gait; they were
vaccinated against common chicken diseases. The
adult hen was chosen for the test animal because
of its known susceptibility to anticholinesterase
compounds and to allow direct comparison with
ongoing studies of organophosphorus compounds
in the laboratory.

Individual test compound studies were performed
using the following dosages over the test period:
PB, 5 mg/ kg/ d in water, po; DEET, 500 mg/ kg/ d,
neat, sc; and permethrin, 500 mg/ kg/ d in corn oil,
sc. A group of five hens was used as an untreated
control group. Four groups of hens were given the
following combinations: PB/ DEET,
PB/ permethrin, DEET/ permethrin, and
PB/ DEET/ permethrin.

Spinal cord and sciatic nerve were excised
immediately after sacrifice. Tissues were assessed
with a step-down approach by first comparing
sections from control and triple treatment groups,
then double and single treatment groups were
subsequently examined for any evidence of
alterations observed in the triple treatment groups.
Twenty-four hours following administration of the
last dose, treated and control hens were
anesthetized and decapitated; the brains were
removed. Cholinesterase activities in plasma and
brain homogenates were determined.
Neurotoxicity was quantified by ranking control
and treated hens according to severity scores.

Results
Animals treated with PB developed transient mild
signs of cholinergic toxicity characterized by
decreased activity and slight diarrhea. Animals
treated with DEET developed rapid shallow
breathing and tendency toward inactivity shortly
after dosing, but recovered within 24 hours after
dosing. Animals treated with permethrin did not
exhibit any clinical signs. Only DEET-treated hens
had significantly less weight at termination. All
birds treated with single compounds survived the
experiment. Neuropathological examinations of
tissues revealed no difference between controls
and PB-treated animals. Some animals treated with
permethrin or DEET exhibited minor
neuropathological changes.

Of the five animals treated with PB/ permethrin,
one developed a reluctance to walk and mild gait
disturbance; another developed a fine body tremor.
Animals treated with DEET/ permethrin or
PB/ DEET exhibited transient hyperexcitability
between one and four weeks of dosing. In addition
to clinical signs observed in animals treated with

A Guide to Gulf War Veterans' Health
5G: Toxicology
Reference: Neurotoxicity Resulting from Coexposure to Pyridostigmine Bromide, DEET and
Permethrin: Implications of Gulf War Chemical Exposures
Journal of Toxicology and Environmental Health. 1996; 48: 35-56.

Authors: M. B. Abou-Donia, K. R. Wilmarth, K. F. Jensen, F. W. Oehme, T. L. Kurt 68_
68 Page 69 70
the single compounds, animals treated with
DEET/ permethrin developed a transient leg
weakness 9-14 days after the beginning of dosing.
Animals treated with PB/ DEET also exhibited
intermittent diarrhea, marked shallow breathing,
and decreased locomotor activity. Microscopic
examination of spinal cord and sciatic nerve did
not reveal any differences between control animals
and those treated with PB/ permethrin. Mild
neuropathological alterations were observed in two
of the animals treated with DEET/ permethrin;
middle to moderate alterations were observed in
all animals treated with PB/ DEET.

Concurrent treatment with PB/ DEET/ permethrin
caused severe diarrhea, shallow rapid breathing,
and moderate inactivity within 15 minutes of
dosing starting on the first day. At termination,
hens from this group significantly lost weight. All
animals developed a gait disturbance and exhibited
body tremors after dosing. Animals treated with
the three compounds exhibited neuropathological
changes that ranged from mild to severe. A total of
four of the five treated hens did not survive the
experimental period.

In this study, the mean rank value was used to
quantify and compare the neurotoxic effects of
various treatments. The mean rank value for the
control group was significantly less than the values
for all treated groups except for hens treated with
permethrin alone. Hens treated with two
compounds (PB/ DEET, PB/ permethrin, or
DEET/ permethrin) had mean rank values
significantly higher than for single treatments
except for PB/ permethrin which was not
significantly different from DEET alone.
Treatments with the three compounds had a mean
rank value that was significantly higher than
single-and two-compound treatments.

Clinical signs that developed shortly after dosing
with test compounds were:

1. reluctance to walk and decreased activity in
cage;

2. diarrhea; and/ or
3. shortness of breath.

Persistent signs of neurotoxicity were categorized
into two classes: locomotor dysfunctions and
whole-body tremor. The results demonstrated that
PB significantly increased the neurotoxic effect
when combined with individual chemicals. For
comparison of the permethrin/ DEET/ PB group
with the permethrin/ DEET group, the difference
in the mean ranks was significantly higher in the
permethrin/ DEET/ PB group. For the PB/ DEET
versus DEET comparison, the mean rank was
significantly higher with PB/ DEET; this appeared
to be associated with an increase in locomotor
dysfunction and changes in the spinal cord. Mean
rank for PB/ permethrin was also significantly
greater than that for permethrin. The combined
results also show the significant increase in
neurotoxicity of the triple-compound treatment
over the individual and binary treatments.

Discussion
This study demonstrated that concurrent
administration of any two compounds of PB,
DEET, and permethrin results in neurotoxicity that
is markedly greater than that resulting from
treatment with any individual compound.
Additionally, neurotoxicity is further enhanced
following concurrent administration of all three
agents. Because combined treatments increased
neurological deficits characterized by both
peripheral nervous system and central nervous
system injury, one might assume that this
neurotoxicity resulted primarily from the direct
action of DEET and permethrin, with PB playing
an indirect role as it does not cross the blood-brain
barrier. Inhibition of plasma BuChE enzymatic
activity is consistent with the mode of action of the
test compounds.

The authors hypothesized that competition for
liver and plasma esterases by these compounds led
to their decreased breakdown and increased
transport of the parent compound to nervous
tissues. Thus, carbamylation of peripheral
esterases by PB reduced the hydrolysis of DEET
and permethrin and increased their availability to
the nervous system. In effect, PB "pumped" more

A Guide to Gulf War Veterans' Health 69_
69 Page 70 71
DEET and permethrin into the central nervous
system. Consistent with this hypothesis, hens
exposed to the combination of the three agents
exhibited neuropathological lesions with several
characteristics similar to those previously reported
in studies of near-lethal doses of DEET and
permethrin. If this hypothesis is correct, then blood
and liver esterases played an important "buffering"
role in protecting against neurotoxicity in the
population at large. It also suggested that
individuals with low plasma esterase activity may
be predisposed to neurologic deficits produced by
exposure to certain chemical mixtures.

The variety of symptoms reported by veterans
make it unlikely that a single etiologic cause was
responsible for Gulf War illnesses. Although this

study was not intended to simulate actual exposure
conditions that may have existed during the Gulf
War (nor designed as a dose-response study), an
hypothesis can be formulated as to why
coexposure to test compounds may have
contributed to GW veterans' illnesses.

A Guide to Gulf War Veterans' Health 70_
70 Page 71 72
62
A Guide to Gulf War Veterans' Health 71_
71 Page 72 73
Veterans began reporting suspected exposures to
chemical warfare agents shortly after returning
from Operations Desert Storm and Desert Shield.
VA carefully listened to veterans who expressed
concern about exposure to chemical warfare agents
in the Gulf War. VA's public statements have
always made clear that all exposures, including
neurotoxic exposures to low level chemical
warfare agents, were being investigated. In 1995,
VA began including questions about possible
exposure to chemical warfare agents as part of the
revised Registry examination exposure
questionnaires.

In 1996, VA learned that GW participants who
were involved in the demolition of an Iraqi
ammunition storage facility known as Khamisiyah
in southern Iraq in March 1991, may have been
exposed to the nerve agents sarin and cyclosarin.
In July 1997, DoD reported that a CIA computer
model revealed that although no U. S. personnel
experienced noticeable health effects from the
release of these chemical agents, about 98,900
U. S. troops may have been exposed to very low
levels of the agents.

Unfortunately, there is no valid biomarker to
identify chemical warfare agent exposure that
occurred years ago. Although computer models
estimate the number of GW veterans and level of
nerve agent exposure at Khamisiyah, no objective
measurement of exposure exists. Research is
continuing, and has been expanded in recent
months, on the possible toxicity of low level
chemical warfare exposures.

While long-term health effects due to very low-level
(asymptomatic) exposures to
organophosphate nerve agents are felt to be
unlikely, GW veterans with health problems which
they believe may possibly be related to chemical
exposures are provided needed care, without
charge to them, at VA medical centers across the
Nation.

The Armed Forces Epidemiology Board reviewed
the existing literature on the potential health
consequences of exposure to low level chemical
warfare agents. The summary analysis follows.

A Guide to Gulf War Veterans' Health
Chapter Six: Chemical Warfare Agents
Introduction 72_
72 Page 73 74
Background
Recent evidence by the Department of Defense
Persian Gulf Investigation Team suggested that
one bunker in Kamisiyah Ammunition Storage
Depot in South Iraq may have held chemical
weapons. U. S. soldiers from the 37th Engineer
Battalion destroyed bunkers at this site in early
March of 1991. Despite the complete lack of
confirmatory evidence, this information
highlighted the possible, though unsupported,
concern regarding exposure to U. S. troops to
chemical agents during Desert Storm. As a result,
the Armed Forces Epidemiological Board (AFEB)
was asked to conduct a literature review and to
critique and comment on the following question:
Are there observable long-term effects associated
with exposure to Sarin (GB) and mustard at
concentrations below that needed to cause acute
signs, symptoms, or injury?

Findings
Most of this report provides information about
Sarin (GB) and mustard (HD) based on a literature
review and discussions with outside consultants
knowledgeable in chemical weapons and/ or
toxicology. A summary of the findings follows:

Sarin (GB): Evidence indicates that GB does not
have carcinogenic, mutagenic or teratogenic
properties. Therefore, no increases in birth defects
or cancer would be expected from low dose,
subclinical exposure to GB. Follow-up of a cohort
of men exposed to GB found no increase in
hospitalizations, reported health problems,
mortality, or other measured end points.

Some information in humans and animals
suggested that repeated low-dose exposures to GB
could result in subtle, but measurable (based on
spectral analysis) changes in the EEG of exposed
animals and men. It was unclear whether the doses
used resulted in "no" or "few" minor symptoms in
animals, but the men reported minor effects

consistent with GB exposure. The type of EEG
changes were similar in the two groups; an
increase in the relative amount of beta voltage was
found up to one year post-exposure in animals.
The exposed group of men had significantly more
beta voltage, relative to other voltage classes, than
those who were not exposed to GB. The exposures
were unintentional and occurred up to six years
prior to the evaluation.

Neither the animal nor human studies regarding
EEG changes directly addressed the exact
question. The similarity in findings between
human and animal studies suggested that this may
be a true effect. Whether the effect occurs in
humans exposed to levels lower than that needed
to cause acute signs or symptoms was unclear.
Also uncertain was the clinical significance of this
finding, if real, to the soldier. This area deserves
continued study, but the data are simply
insufficient to recommend any additional action at
this time.

Mustard (HD): This vesicating agent is well
known to have carcinogenic potential, as it is a
strong alkylating agent of DNA and RNA. This
agent causes a variety of genetic lesions in many
types of mammalian cells in a dose-response
fashion. There is clear epidemiologic and
toxicologic evidence that exposures to mustard
(high enough to cause acute symptoms either on
the battlefield or in test chambers) are associated
with an increased risk of respiratory and skin
cancers and perhaps leukemia. This estimate is of
unknown precision since exact exposure
information is not available.

The risk of cancer related to mustard at dosages
less than that necessary to cause any acute effects
is much less clear. Carcinogenesis is a dose-response
phenomenon and very low exposures
would have a very low risk associated with it.
Additionally, the number of individuals exposed in
any scenario of the Persian Gulf would be
relatively few, making it unlikely that a

A Guide to Gulf War Veterans' Health
Reference: Long-term Health Effects Associated with Subclinical Exposures to GB and Mustard
Environment Committee, Armed Forces Epidemiological Board, 18 July 1996.

Authors: Dennis M. Perotta, PhD, CIC, Chair, Environment Committee, AFEB 73_
73 Page 74 75
measurable increase in cancers could be detected.
Finally, the length of exposure in these scenarios
was extremely limited as compared to the standard
decades of daily exposures that are used in
carcinogenic risk assessment.

Using standard cancer risk assessment
methodology, an estimate for cancer risk was
calculated. In 1991, the U. S. Environmental
Protection Agency derived a unit risk of 8.5 x10
(to the negative power of 2) per microgram/ m3 for
mustard. Considering a single 5 minute exposure
to HD at a concentration of 0.05 mg/ m3 (chosen to
approximate a level 10% of a dose that might
cause minimal signs and symptoms), the cancer
risk was estimated as 5.8x10( to the negative power
of 7). This essentially means that for every 10
million persons exposed under these
circumstances, 6 additional cancer cases would be
expected to arise from this exposure. Since no
Desert Storm scenario included more that a few
hundred to few thousand men at any one time,
there would be no detectable additional cancer
cases arising from this hypothetical scenario. It
must be understood that changes in any of the
assumptions of exposure will impact the final
estimate and that this estimate was calculated with
the understanding that no substantial evidence in
support of exposure to HD during Desert Storm
was found.

While animal experiments indicate that mustard is
a reproductive toxin at high doses, there is little
human information available to evaluate this risk
in humans at high or low dose exposures. The
scarce amount of information located for this
review suggested that HD was not teratogenic.

There is ample evidence to suggest that severe
exposure of skin to HD is related to a variety of
long-term skin ailments such as pigmentary
disorders, skin ulcers, and cutaneous cancers.
There is insufficient information to judge if
exposures lower than that necessary to produce an
acute effect will have a long-term adverse health
result.

There is evidence that severe exposure of the eye
to HD, with concomitant acute injury, is related to
adverse long-term ocular conditions. No evidence

of such an effect was found for exposures lower
than that necessary to cause an acute injury. The
data were very limited in this area and insufficient
for definite conclusions.

Exposure to high levels of HD causes significant
damage to respiratory tissue and results in a
variety of non-cancer respiratory conditions. There
is no evidence that suggests short-term exposure to
very low levels (less than necessary to cause any
symptoms) of mustard is related to long-term
health problems of the respiratory system. The
data are very limited and the theoretical possibility
of long-term effects without acute injury can not
be eliminated totally.

Immune function can be depressed or altered as a
result of high dose exposure to HD. No convincing
evidence was found that such alterations occur
over the long-term as a result of exposure to
concentrations less than that which causes acute
signs or symptoms.

While a thorough literature search was not
conducted on psychological aspects of chemical
agent exposure, one reference had potential use for
addressing the question. Psychological dysfunction
was related to the circumstances surrounding
exposures to mustard in test chambers and field
trials. These circumstances may parallel those
experienced by soldiers in selected areas of Desert
Storm; however, no conclusion is reached in this
report.

Conclusions
No scientific data was located that directly applied
to the question at hand and little that directly
addressed the fundamental question. All the human
studies found and reviewed dealt with persons
exposed (intentionally or unintentionally) who
reported signs, symptoms, or frank injury. In most
of the reviewed studies, the definition of
"exposed" was the presence of clinical effects of
any degree.

Although the AFEB found several health effects
for the two chemical agents that were related to
high level exposure, there was no useful
methodology found that could be used to

A Guide to Gulf War Veterans' Health 74_
74 Page 75 76
66
A Guide to Gulf War Veterans' Health
adequately extrapolate to the very low
concentrations proposed in the question. The
exceptions to that observation were those studies
that were adequate to judge no effect at high doses.
The results of the review showed that the long-term
effects of limited exposures to sub-clinical
doses of GB and HD are unclear, but the data
suggested that health effects would not be
detectable.

Note: A copy of this article is available in
Library Service at VA medical centers.
Please ask for "A Guide to Gulf War
Veterans' Health: 1997 Continuing
Medical Education Program." 75_
75 Page 76 77
U. S. service members potentially were exposed to
a wide range of risk factors during the Gulf War. A
number of individuals and groups have proposed
theories regarding the health consequences of such
exposures to veterans. Independent oversight
groups including the Presidential Advisory
Committee on Gulf War Veterans' Illnesses, The
National Academy of Science's Institute of
Medicine (IOM) and the National Institute of
Health Technology Assessment Workshop have
performed comprehensive reviews of these issues.
From their analysis of the information available to
them, they have determined that these theories do
not meet rigorous the scientific standards
necessary to support an association with GW
veterans' illnesses.

GW veterans are interested in the proposed
theories and frequently ask healthcare providers to
explain how the exposures are relevant to their

present and future health. Therefore, it is
important that healthcare providers be aware of
these theories and can provide informed
counseling to GW veterans regarding their
concerns. In response to Public Law 102-585, the
Institute of Medicine of the National Academy of
Science appointed a committee to review the
"Health Consequences of Service During the Gulf
War" The committee completed its review and
published a report in September 1996. Its report is
the most comprehensive published report on the
hypotheses about causes of the unexplained GW
illnesses. The information provided in this chapter
is a summary of the IOM's review of alternative
hypotheses for GW veterans illnesses.

A Guide to Gulf War Veterans' Health
Chapter Seven: Some Hypotheses Regarding Illnesses in Gulf War Veterans
Introduction 76_
76 Page 77 78
Background
In Chapter Five, many of the hypotheses
encountered by the committee as it attempted to
comprehensively investigate the health-related
consequences of service in the Gulf War area are
discussed. The hypotheses suggested a wide
variety of associations among agents and
exposures, circumstances that existed in the Gulf,
and adverse clinical outcomes. These hypotheses
had various degrees of plausibility and supporting
research. The investigations and putative causal
associations evaluated by the Committee
demonstrated the vexing nature of the medical
problem referred to by some as a "Gulf War
Syndrome" and by the Committee as "unexplained
illnesses."

Hypotheses
Hypotheses with supporting evidence presented to
the Committee as a cause for veterans' unexplained
illnesses are provided in this chapter. These
include:

1. Chronic fatigue syndrome (CFS). This
syndrome is of unknown etiology, occurs
worldwide, and results in significant disability
for the patient. There is a growing consensus
that CFS may be a valid diagnosis. The
classification of CFS is made when the criteria
for severity of fatigue, the main CFS
symptom, are met and four or more of eight
symptoms are concurrently present or
recurring for six or more months of illness not
predating fatigue.

2. Multiple chemical sensitivity (MCS). Gulf
War veterans who are experiencing multiple
symptoms had their disease "induced" by one
or more exposures in the Gulf. These include
pesticides, solvents, drugs, or virtually any of

the other agents encountered there;
"triggering" of disease occurs after low-level
exposures to similar noxious substances, likely
becoming manifest after the return home of the
affected troops. Four major views about the
etiology of MCS are provided.

3. Oxidative phosphorylation disorder.
Unexplained illnesses are caused by a disorder
of the mitochondrial metabolism leading to
encephalomyelopathy and is presumed to be
linked etiologically with poor nutrition
combined with increased metabolic demand.

4. Dental amalgams. Unexplained symptoms
may be related to mercury toxicity occurring
as a result of the installation of dental
amalgams just prior to, or immediately after,
service which results in clinically evident
elemental mercury toxicity that continues as
patients have ongoing exposure to mercury.

5. Bacterial illness. Persistent streptococcal or
other bacteremia have been suggested as a
cause of unexplained illnesses; the suspected
bacteremia is proposed to resemble that
encountered after dental procedures and is
claimed to be diagnosable by using unique
microscopic evaluation of the urine which
streptococci enter from the blood via the
kidney.

6. Mycoplasma and chronic fatigue. A subset of
soldiers with unexplained illness of a type
considered similar to CFS have mycoplasma
infections that can be diagnosed if appropriate
laboratory tests are available; no source of
mycoplasma infection has been documented
although mention has been made of the
potential immunosuppressive effects of
inhaled fine sand particulates present in the
Gulf region.

A Guide to Gulf War Veterans' Health
Reference: Health Consequences of Service During the Persian Gulf War: Recommendations for
Research and Information Systems.
Washington, DC: National Academy Press, 1996: 117-127.

Author: U. S. Institute of Medicine. Committee to Review the Health Consequences of Service
During the Persian Gulf War 77_
77 Page 78 79
7. Skeletal muscle bioenergetics. May share
some similarity with disorders of oxidative
phosphorylation; the investigative findings
were suggested to potentially contribute to
understanding the pathophysiology of fatigue;
no cause for this fatigue was suggested.

8. Sarcoidosis and lingual abnormalities. The
etiology of sarcoidosis is unknown and further
research might be indicated, particularly since
there has been some suggestion that
sarcoidosis is exposure related. Some veterans
were noted to have multiple linear inflamed
areas along the cheek and occasionally along
the dorsolateral surface of the tongue. These
initial signs suggest that the patient is suffering
multisystem effects of toxic exposures.

9. Brainstem dysregulation syndrome. This
hypothesis suggests that two "insults" to the
brainstem--one early in life and one later (e. g.
while in the Gulf region)--could produce a
polysymptomatic illness.

10. Microsporidia infection. Stool of GW veterans
was examined to search for protozoal
infections and the investigator suggested that
microsporidia infection might be related to
service in the Gulf War; an intensive follow-up
examination of these findings identified no
microsporidia.

11. Organophosphate-induced delayed
neurotoxicity. Unpublished reports of the
results of a study indicate that there may be
some evidence of delayed neurotoxicity
associated with symptoms in veterans; the
report was been peer-reviewed, however, and
the study has significant problems.

12. Chemically induced porphyria. This
hypothesis indicates a concern that pesticide
exposures in the Gulf region may have caused
unexplained symptoms. These findings are
similar to those for individuals who are
reported to have MCS syndrome.

13. Fibromyalgia. Diagnosis is based on
symptoms presented by the patient and one
symptom-related physical finding: namely, at
any of multiple sites of the body, pinching or
pressure by a probing finger induces
unexpected withdrawal or exclamations of
pain. Patients often have symptoms that
overlap those described for MCS and CFS. No
definite exposure or experience has yet been
linked to this entity.

14. Somatization disorder. An essential feature of
this disorder is a pattern of recurring multiple
somatic complaints that cannot be fully
explained by any known general condition or
by the result of exposure to any known
substance. Physical complaints are in excess of
those expected from evaluation of the patient.
Individuals usually describe their complaints
in colorful, exaggerated terms, but factual
information is often lacking.

Conclusions
The committee reached several conclusions based
on these descriptions of ongoing work.

1. Their diverse nature provided additional
compelling evidence that no one disease entity
will likely be adequate to resolve the
understanding of all unexplained illnesses in
Gulf War veterans.

2. These ideas, hypotheses, and investigations
served as testimony to the efforts of many
health professionals who strive to find
avenues, overlooked by others, that might lead
to new understandings of these illnesses and
result in amelioration of the suffering that has
occurred and continues to be reported.

3. Although these approaches have varying merit
and the investigators are dedicated to solving
the problem, the Committee was not optimistic
that they are sufficiently well-substantiated to

A Guide to Gulf War Veterans' Health 78_
78 Page 79 80
70
A Guide to Gulf War Veterans' Health
offer much hope of important answers or relief
for significant numbers of ailing American
veterans.

4. Although the Committee has not identified an
explanation for the unexplained illnesses in
Persian Gulf veterans, it does not doubt that
many individuals who report such illnesses are
seriously affected.

Note: A copy of this article is available in
Library Service at VA medical centers.
Please ask for "A Guide to Gulf War
Veterans' Health: 1997 Continuing
Medical Education Program." 79_
79 Page 80 81
A precedent among governmental agencies has been established that should continue
after Persian Gulf health issues are resolved.
During Operations Desert Shield and Desert
Storm, the United States deployed 697,000
military personnel to the Persian Gulf. Although
morbidity and mortality rates were much lower
than in previous wars, some veterans of the Gulf
War have developed unexplained illnesses since
returning home in 1991. 1� 3 Both VA and DoD have
developed comprehensive clinical evaluation and
treatment programs to care for Persian Gulf
veterans (Table 1). 3,4 HHS has not been
responsible for the health care of Persian Gulf
veterans but has been involved, along with VA and
DoD, in extensive research efforts to study the
nature and etiology of their illnesses (Table II). 5,6
Consequently, all three departments� VA, DoD,
and HHS� have developed complementary
programs to deal with Persian Gulf veterans'
health issues.

Because of the need to provide additional
coordination for these related government
activities, the Persian Gulf Veterans Coordinating
Board was established on January 21, 1994. The
Secretaries of VA, DoD, and HHS head the
Coordinating Board, which was established under
authority of Title 31 of the United States Code,
Section 1535.

Mission
The mission of the Coordinating Board is to
provide direction and coordination on health issues
related to the Persian Gulf War within the
executive branch of the federal government.
Establishment of a secretary-level board to provide
interdepartmental coordination is unique but was

considered necessary to ensure that the three
departments share a common understanding of the
issues, to effectively allocate all available
resources, and to provide a means of disseminating
information.

A Guide to Gulf War Veterans' Health
Supplemental Reading
Coordinating Federal Efforts on Persian Gulf War Veterans.
Federal Practitioner 1995 December; 9-15

Peter Beach, Ph. D.; MG Ronald R. Blanck, D. O., MC, USA; Timothy Gerrity, Ph. D.;
CAPT Kenneth Craig Hyams, M. D., M. P. H., MC, USN; Susan Mather, M. D., M. P. H.;
John F. Mazzuchi, Ph. D.; Frances Murphy, M. D., M. P. H.; Robert Roswell, M. D.; and
Raymond L. Sphar, M. D., M. P. H.

Reprinted by permission of Federal Practitioner: December 1995; 9� 15

VA programs*
� Persian Gulf Registry Health Examination
Program

� Specialized referral centers for complex and
difficult-to-diagnose patients

Washington VAMC, DC
Houston VAMC, TX
West Los Angeles VAMC, CA
Birmingham VAMC, AL

� Special medical programs
Depleted Uranium Surveillance Program at
Baltimore VAMC, MD
Neurocognitive Pilot Clinical Program at
Birmingham VAMC, AL

DoD programs*
� Comprehensive Clinical Evaluation Program
� Specialized care centers
Walter Reed Army Medical Center,
Washington, DC
Wilford Hall Medical Center,
San Antonio, TX

*Veteran information concerning VA and DoD
clinical programs is provided by two hotline
numbers: for VA call 1-800-PGW-VETS and for
DoD call 1-800-796-9699. Persian Gulf veterans
with health concerns possibly related to the Persian
Gulf War are encouraged to call on of these hotline
numbers. 80_
80 Page 81 82
72
A Guide to Gulf War Veterans' Health
The Coordinating Board has established three
primary mission objectives:

� To provide all veterans the complete range
of health care services necessary for
medical problems that may be related to
deployment in Operations Desert Shield
and Desert Storm. This objective was
aided substantially by passage of Public
Law 103-210, which provides priority care
at VAMCs for health problems possibly
related to exposures during Persian Gulf
service.

� To develop a research program that will
result in the most accurate and complete
understanding of the types of health
problems being experienced by Persian
Gulf veterans and the factors that have
contributed to these problems.

� To develop clear and
consistent guidelines for the
evaluation and compensation
of disabilities related to
Persian Gulf service.

Organization
The three Secretaries who head the
Persian Gulf Veterans Coordinating
Board are assisted by a permanent staff
and three working groups. The staff
includes five health specialists: an
executive director, two health
administrators provided by VA, and
two officers provided by DoD. The
staff has dedicated office space in
Washington, DC; administrative and
clerical support is shared responsibility
among the three involved departments.

The staff assists in all functions of the
Coordinating Board, including daily
operations of the Board,
implementation of recommendations
by the working groups, and rapid
dissemination of relevant information.
The primary liaison between
Coordinating Board staff and the three

departments is provided by: VA's Office of Public
Health and Environmental Hazards, Washington,
DC; DoD's Office of Health Affairs� Clinical
Services, the Pentagon; and HHS' s Office of
Veterans Affairs and Military Liaison, Washington,
DC.

The three working groups established by the
Coordinating Board address specific issues related
to medical care, research, and compensation and
then provide recommendations to the three
secretaries who comprise the Coordinating Board.
Working group membership is drawn from
administrative, clinical, and research specialists in
VA, DoD, and HHS. The chair of each working
group was selected by the three secretaries heading
the Coordinating Board, and working groups meet
at the discretion of the chairs (usually monthly, but

Table II. Major research efforts in VA, DoD, and HHS.
Epidemiologic research*
� VA's national, randomized mail/ telephone survey of 15,000 Gulf
War and 15,000 non-deployed Gulf-era veterans

� DoD's survey of Seabees and evaluation of active-duty
hospitalization records

� HHS's survey of military personnel from Iowa
� CDC's case-control study of Pennsylvania National
Guard/ reserve personnel

Environmental hazards research
� Establishment of three research centers at VAMCs:

East Orange VAMC, NJ
Boston VAMC, MA
Portland VAMC, OR
� DoD research at Wright Patterson Air Force Base, Dayton, OH

Other research efforts
� The health effects of depleted uranium
� Possible synergistic effects of chemicals found in the Persian
Gulf

� Development of improved diagnostic tests for leishmania
infection

� The psychological consequences of Gulf War-related stress

*The epidemiologic research conducted is focused on determining
the prevalence and potential risk factors of illnesses and adverse
birth outcomes 81_
81 Page 82 83
more frequently when necessary). the specific
functions of the three working groups are
described below.

Clinical working group
The clinical working group provides direction and
coordination for clinical efforts
on behalf of Persian Gulf
veterans. Oversight functions
include coordination of VA and
DoD Persian Gulf health
registries and provision of
comparable clinical assessment
questionnaires and comparable
laboratory examination
protocols
(Table I). 4,7

The clinical working group
ensures that the two clinical
registries are clearly defined as
a means for identifying and
reporting illnesses among
Persian Gulf War veterans. the
group also develops educational
tools and programs, publishes
medical articles that assist
clinicians caring for Persian Gulf veterans, and
helps educate patients and the public about
relevant health issues. 3

Research working group
This working group provides guidance and
coordination for VA, DoD, and HHS research
activities related to the Persian Gulf deployment
(Table II). Because of the President's designation
of VA as the lead agency for research efforts in this
area, VA's chief for research and development
chairs this working group. A representative of the
EPA also serves on this working group to advise
on toxicologic issues possibly related to Persian
Gulf service.

The research working group coordinates all studies
conducted or sponsored by VA, DoD, and HHS to
prevent unnecessary duplication and to ensure that
resources are directed toward high-priority

research questions. Specifically, this working
group assesses the state and direction of research,
reviews government research concepts as they are
developed, identifies gaps in factual knowledge
and conceptual understanding, recommends
research directions, and collects and disseminates
peer-reviewed research information.

Along with monitoring
relevant new data and making
it accessible, the research
working group generates
periodic reports to federal
oversight authorities. 6 In
addition, the research working
group coordinates the
development of a Persian Gulf
research plan. This plan is one
aspect of a dynamic
assessment process that is
reviewed at least yearly by the
Coordinating Board. As part of
this process, the research
working group analyzes
suggestions of
review/ oversight committees
and makes recommendations to
the Secretaries concerning
appropriate research goals. 8� 10

The research working group serves as a forum for
research data exchange among the three
departments. A database of VA, DoD, and HHS
research activities and accomplishments has been
established in the VA Office of Research and
Development, Washington, DC, to assist in
information exchange, the generation of reports,
and updating the research plan. The research
database also includes copies of Persian Gulf
research publications and abstracts that have
resulted from government-funded studies. VA,
DoD, and HHS share in the responsibility for
tracking research projects and updating the
research database.

Disabilities and compensation working group
This working group is responsible for assisting in
the establishment of fair, clear, and consistent

A Guide to Gulf War Veterans' Health 82_
82 Page 83 84
guidelines for VA and DoD disability
determinations and for compensation. Working
group coordination was particularly important
after December 8, 1994, when VA published new
rules to provide compensation for certain
disabilities due to undiagnosed illnesses among
Persian Gulf veterans (pursuant to Public Law
103-446, known as "The Persian Gulf War
Veterans Benefits Act").

Accomplishments
Although the Persian Gulf Veterans Coordinating
Board is a novel concept that has been in operation
only for a short period of time, it has been able to
accomplish several objectives that have aided
Persian Gulf veterans. One of the specific
accomplishments of the Coordinating Board has
been to ensure that the clinical evaluations
conducted by VA and DoD are comparable and
will generate complementary data.
Accomplishment of this objective has required
numerous meetings and much hard work due to the
differences in patient populations, the differences
in eligibility for medical care, and the difficulties
inherent in providing uniform clinical assessments
in numerous medical facilities, which are scattered
in every state and in foreign countries.

Another accomplishment of the Coordinating
Board has been to provide guidance to
governmental researchers who are evaluating
morbidity, mortality, and risk factors of disease
among Persian Gulf veterans. This coordination
will ensure that the major epidemiologic studies
and investigations of potential environmental
hazards avoid unnecessary duplication and provide
comparable data. Additionally, new research
findings are being rapidly disseminated among
researchers via the centralized research database
maintained by VA, DoD, and HHS. Furthermore,
because of continuous oversight by the research
working group, new and promising research
directions are being identified.

In addition to these specific accomplishments, the
Coordinating Board has been responsible for
rapidly disseminating relevant clinical and
research information on potential health risks,
research findings, and health outcomes. Also, the
Board has helped VA, DoD, and HHS coordinate
preparations for Congressional briefings and
hearings; the development of administration
legislative proposals and positions; and more
comprehensive responses to inquiries from
Congress , review bodies, and the public.
Importantly, the Coordinating Board has provided
a forum for the exchange of ideas within the
government and for the development of
interdepartmental relationships, which have
fostered treater understanding and cooperation.

Conclusion
The Persian Gulf Veterans Coordinating Board has
been an effective mechanism for bringing together
three separate government departments to work
toward a common goal of serving the needs of
Persian Gulf veterans. Because the Coordinating
Board's mission is to assist three government
departments rather than to supplant responsible
agencies and programs, its work is not well known
outside of VA, DoD, and HHS. Nevertheless, the
Coordinating Board has been able to accomplish
much for Persian Gulf veterans by helping ensure
uniform clinical evaluations, appropriate health
care, relevant research activities, specific and
uniform guidelines for disability/ compensation
determinations, and cooperation withing the
government. The Persian Gulf Veterans
Coordinating Board has established a precedent of
cooperation and effective government that should
continue even after current Persian Gulf health
issues are resolved. For VA and DoD� who share
responsibility for the health care of a common
patient population� future coordination is vital to
answering questions related to health risks,
medical records, and compensation.

A Guide to Gulf War Veterans' Health 83_
83 Page 84 85
References
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fatalities during Desert Storm. Mil Med. 1992; 157: A7

2. Helmkamp JC. United States military casualty
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3. Persian Gulf Veterans Coordinating Board. Unexplained
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4. Roy MJ, Chung RCY, Huntley DE, Blanck RR.
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6. Department of Veterans Affairs. Federal Activities
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7. Department of Defense. Clinical Evaluation Program
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Authors
Peter Beach, PhD, is director of the Office of Veterans
Affairs and Military Liaison, Immediate Office of the
Secretary at the Department of Health and Human Services,
Washington, DC.

MG Ronald R. Blanck, DO, MC, USA, is the commanding
officer of the Walter Reed Army Medical Center, Washington,
DC.

Timothy Gerrity, PhD, is deputy director of Medical
Research Services at the Department of Veterans Affairs,
Washington, DC.

CAPT Kenneth Craig Hyams, MD, MPH, MC, USN, is
medical director of the Persian Gulf Veterans Coordinating
Board, Washington, DC.

Susan Mather, MD, MPH, is assistant chief medical director
of Public Health and Environmental Hazards at the
Department of Veterans Affairs, Washington, DC.

John F. Mazzuchi, PhD, is deputy assistant secretary of
defense, Health Affairs-Clinical Services at the Department of
Defense, the Pentagon, Arlington, VA.

Frances Murphy, MD, MPH, is director of Environmental
Agents Service at the Department of Veterans Affairs,
Washington, DC.

Robert Roswell, MD, is executive director of the Persian
Gulf Veterans Coordinating Board, Washington, DC.

Raymond L. Sphar, MD, MPH, is acting chief of Research
and Development at the Department of Veterans Affairs,
Washington, DC.

A Guide to Gulf War Veterans' Health 84_
84 Page 85 86
76
A Guide to Gulf War Veterans' Health 85_
85 Page 86 87
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3. Centers for Disease Control. (1995).
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5. Cowan, D. N., DeFraites, R. F., Gray, G.,
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6. Gray, G. C., Coate, B. D., Anderson, C. M.,
Kang, H. K., Berg, S. W., Wignall, F. S., Knoke,
J. D., Barrett-Connor, E. (1996). The postwar
hospitalization experience of U. S. veterans of
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7. Hyams, K. C., Hanson, K., Wignall, F. S.,
Escamilla, J. & Oldfield, E. C. (1995). The
impact of infectious diseases on the health of
U. S. troops deployed to the Persian Gulf
during Operations Desert Shield and Desert
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1504.

8. Joseph, S. C. and the Comprehensive Clinical
Evaluation Program Evaluation Team. (1997).
A comprehensive clinical evaluation of 20,000
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162, 149-155.

9. Kang, H. K. and Bulman, T. A. (1996).
Mortality among U. S. veterans of the Persian
Gulf War. New England Journal of Medicine.
335, 1498-1504.

10. Magill, A. J., Grogl, M., Gasser, R. A., Sun, W.
& Oster, C. N. (1993). Visceral infection
caused by leishmania tropica in veterans of
Operation Desert Storm. The New England
Journal of Medicine, 328, 1383-1387.

11. Perotta, D. M. (1996). Long-term health effects
associated with subclinical exposures to GB
and mustard. Environmental Committee,
Armed Forces Epidemiological Board.

12. Stretch, R. H., Bliese, P. D., Marlowe, D. H.,
Wright, K. M., Knudson, K. H. & Hoover, C. H.
(1996). Psychological health of Gulf War-era
military personnel. Military Medicine, 161,
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13. Sutker, P., Uddo, M., Brailey, K., Allain, A. &
Errera, P. (1994). Psychological symptoms and
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14. Sutker, P., Uddo, M., Davis, J. & Ditta, S.
(1995). War zone stress, personal resources,
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15. Sutker, P., Davis, M., Uddo, M. & Ditta, S.
(1995. Assessment of psychological distress in
Persian Gulf troops: ethnicity and gender
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427.

16. Institute of Medicine. Committee to Review
the Health Consequences of Service During
the Persian Gulf War. (1995). Some
hypotheses regarding illnesses in Persian Gulf
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Washington, DC: National Academy Press,
117-127.

17. Wolfe, J., Brown, P. & Kelley, J. (1993).
Reassessing war stress: exposure and the Gulf
War. Journal of Social Issues, 49, 15-31.

A Guide to Gulf War Veterans' Health 87_

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