+ Recommended for further review and research
- Unlikely to be of primary concern for long-term health consequences
* The exposure was either considered by the panel, but not highlighted, or was not considered by the panel.
The most important question about the health of Persian Gulf veterans is:
Are Persian Gulf veterans experiencing a greater prevalence of symptoms and illnesses in comparison with an appropriate control population?
From the answer to this question springs virtually all subsequent questions that may be addressed through research. For example, if there is an increased prevalence of certain symptoms among Persian Gulf veterans in comparison to controls, then what disease or diseases are being manifested by these symptoms, and what connection with service in the Persian Gulf might exist? Therefore, the first research question that needs to be addressed is:
RESEARCH QUESTION 1: What is the prevalence of symptoms/illnesses in the Persian Gulf veterans population? How does this prevalence compare to that in an appropriate control group?
Research Currently Underway
PROJECTS VA-2,4,5,6,18, DoD-1, HHS-1,2: Components of each of these projects will estimate the prevalence of symptoms in Persian Gulf veterans and compare this prevalence to control groups of non-deployed veterans. VA-18 is focusing on gastrointestinal symptoms. (NOTE: Project numbers associated with current research refer to projects contained in the Appendix.)
Additional Needed Studies
Casting the problem of Persian Gulf veterans' illnesses into an exposure-outcome framework helps to isolate two interconnected questions: (1) what was the nature and extent of possible exposures experienced by veterans while in the Persian Gulf?, and (2) what adverse health outcomes, if any, have occurred among Persian Gulf veterans, beyond what would be normally expected in such a large population? These two questions lead to a third, namely: (3) is there a relationship, or set of relationships, between exposure to the complex environment of the Persian Gulf theater, and any excess health outcomes that is consistent with established biological and toxicological principles, and with epidemiological data? This last question needs to be addressed by investigating both exposures and outcomes. Investigation of exposures can lead to hypotheses about expected health outcomes based on the nature and extent of the exposures, and investigations of health outcomes can lead to hypotheses about exposures.
Because of the inherent logical value of separating the problem into exposure and health outcome, this working plan separates research oriented primarily toward exposure from research directed primarily at evaluating health outcomes.
3.1 EXPOSURES
While deployed in the Persian Gulf theater, troops may have experienced a variety of exposures, both natural and environmental/occupational in origin, to a varied extent. Potential exposures of concern are: infectious agents (such as Leishmania Tropica); smoke from oil well fires; other petroleum products and their combustion products; other occupational exposures such as pesticides, chemical agents resistant coating (CARC) paint; CBW agents; vaccines; pyridostigmine bromide (PB); and psychophysiological stressors of war. The number of troops experiencing any one, or combination of, these exposures is not known at this time.
TABLE 1
Summary of Potential Exposures of Concern for Health Outcomes
+ Recommended for further review and research
- Unlikely to be of primary concern for long-term health consequences
* The exposure was either considered by the panel, but not highlighted, or was not considered by the panel.
Table 1 summarizes the findings of the DSB, NIH, and IOM panels with respect to these exposures. All three panels agreed that psychophysiological stressors of war and infectious agents required further review or research. Further research into exposure to other petroleum products, and pyridostigmine bromide was recommended by IOM and NIH, but DSB made no specific recommendation.
All three panels also agreed that it is unlikely that oil well fires or vaccines caused illnesses in Persian Gulf veterans. The NIH panel initially deferred making a finding about CBW until the DSB completed its deliberations. Both the DSB and the IOM subsequently reported lack of confirmation of exposure to CBW agents. Further research related to these potential exposures was not recommended by DSB and IOM.
Below is a discussion of each of the possible exposures. For each exposure a general background is provided. This is followed by specific research questions with statements of current research and any additional studies that are needed. Studies that pace other studies (i.e., studies that must be complete before others can proceed) or studies that are paced by other studies are identified.
3.1.1 Infectious Agents
Coalition troops were exposed to a number of infectious agents present in the Persian Gulf area. The most notable of these is the parasite Leishmania tropica. Only 12 cases of viscerotropic and 19 cases of cutaneous leishmaniasis have been diagnosed among Persian Gulf veterans to date (PGVCB, 1995), suggesting minimal exposure. Diagnosis of viscerotropic leishmaniasis, however, is difficult because there is no accurate serological test for the presence of the parasite. Thus, actual exposure and infection rates are difficult to obtain.
Other infectious agents were also present in the Persian Gulf area that could cause chronic diseases, including schistosomiasis, Q fever and brucellosis (DeFraites, et al., 1992; Ferrante MA et al. 1993). Few cases of these diseases have been diagnosed among the U.S. troops who served in the Persian Gulf, and there is no indication that such infections are related to unexplained illnesses.
Acute infectious disease outcomes typical of cramped military living conditions, such as dysentery and respiratory tract infection, were actually lower than expected during the Persian Gulf conflict (DSB, 1994; Richards et al., 1993; Richards et al., 1991). Exposure to other infectious agents such as mycoplasmas, bacteria, viruses, and fungi probably occurred but there is not a strong case from clinical evaluations that supports these organisms as possible etiological factors. However, because of the possible role for leishmania in unexplained illnesses, all three scientific review panels recommended further research to develop a simple, sensitive and specific diagnostic test.
RESEARCH QUESTION 2: What was the overall exposure risk of troops to Leishmania tropica?
First, a sensitive and specific diagnostic screening test must be developed, if possible. Only then will it be possible to address the research question. Serum samples collected as a part of population-based epidemiologic studies of Persian Gulf veterans should be banked to facilitate testing once an appropriate test is available.
Research Currently Underway
PROJECT DoD-8: This project involves development of a reliable skin test (screening for past infection) and serologic assay (testing for active infections).
Additional Needed Studies
Work has recently been completed on an exposure model (USAEHA, 1994) for the oil well smoke plume. When the model output is expressed in a format compatible with the military geographic information system (GIS) for troop unit location (PROJECT VA-3), it should provide an approximation of the oil well plume exposure as a function of time for troop units. The GIS will prove to be very valuable for future spatial analyses. Based on the recommendations of the review panels, further oil well smoke exposure research beyond this model is not being pursued at this time.
3.1.3 Other Petroleum Products
During the war, many troops may have been exposed to petroleum vapors, solvents and combustion products during the war. Kerosene, diesel and leaded gasoline were used for heating, ground spraying to suppress sand dust, and incinerating both trash and human waste. As a result, some troops could have been exposed to benzene, toluene, ethylbenzene, xylene and other petroleum combustion products. Elevated levels of sulfur dioxide, nitrogen dioxide, nitric acid, acidic sulfates, carbon monoxide, lead, respirable particulates and other pollutants may be expected in tents using unvented heaters burning gasoline and diesel fuels. There were no measurements of any of these pollutants in tents. Concern that this type of exposure was high enough for significant health consequences prompted both the NIH and IOM panels to recommend a simulation of exposure in tents heated by diesel fuel with composition similar to that used in the Persian Gulf area. The IOM noted the presence of elevated blood lead levels derived from autopsy specimens from seven service members who died in the Persian Gulf theater (IOM, 1995). The pharmacokinetics of lead make meaningful follow-up difficult at best (EPA, 1986). In an ongoing clinical investigation at the Birmingham, Alabama VA medical center, investigators have not found any evidence of current elevated blood lead levels among Persian Gulf veterans (Roswell, 1995).
RESEARCH QUESTION 3: What were the exposure concentrations to various petroleum products, and their combustion products, in typical usage during the Persian Gulf conflict?
Research Currently Underway
PROJECT DoD-2: A component of this project involves the simulation of exposures to petroleum and petroleum combustion products in enclosed spaces.
Additional Needed Studies
3.1.4 Other Occupational Exposures
Other potential environmental hazards, including pesticides, microwaves, chemical agent resistant coating (CARC) paint fumes, depleted uranium (DU) and cleaning solvents were present in the Persian Gulf theater. Some of these chemicals, such as CARC paint and DU, are not likely to be the primary cause of unexplained illnesses among Persian Gulf veterans because only small numbers of troops were exposed (NIH, 1994). A full assessment of risk from exposure to these chemicals cannot be made in the absence of accurate exposure data.
RESEARCH QUESTION 4: What was the extent of exposure to specific occupational/environmental hazards known to be common in the Persian Gulf veteran's experience? Was this exposure different from that of an appropriate control group?
Research Currently Underway
PROJECT DoD-2: In addition to the petroleum and combustion products simulations listed above, simulations of exposure to other chemicals will also be conducted.
PROJECTS VA-2,4,5,6,13, DoD-1, HHS-1,2: Components of each of these epidemiology studies will collect self-reported exposure data using a variety of survey instruments. Results of exposure simulations may help to estimate the intensity of self-reported exposures.
PROJECT VA-14: This project is monitoring the retention kinetics and the health status of veterans who have embedded depleted uranium fragments.
Additional Needed Studies
3.1.5 Chemical and Biological Warfare Agents
Both the DSB and IOM panels concluded that reports of the possible use of CBW agents cannot be confirmed and that bombing of Iraqi storage areas did not cause CBW agent exposure. While awaiting assessment of the DSB, the NIH panel drew no conclusions about the presence or absence of CBW. The IOM panel stated that claims of exposure to chemical or biological warfare agents should not be made or given credence in the absence of reliable substantiating data. Although continued DoD investigations of individual exposure reports may be necessary, further research is unwarranted unless creditable data establish that exposure to CBW agents actually occurred.
3.1.6 Vaccines
Troops who served in the Persian Gulf conflict were vaccinated against common infectious diseases with vaccines frequently used in the general population without significant side-effects. In addition, approximately 150,000 troops received at least one dose of anthrax vaccine and about 8,000 received at least one dose of botulinum toxoid. Both vaccines have been used for many years without adverse effects. All three review panels stated that no long-term adverse effects have been documented or would be expected. Further study of the potential adverse effects of vaccines in this population is not recommended by any of the three panels, nor is it endorsed in this plan.
3.1.7 Pyridostigmine Bromide
Pyridostigmine bromide (PB) is a cholinesterase inhibitor (ACHE) that was supplied to troops for use as prophylaxis against exposure to nerve agents. PB was distributed to troops in blister packs of 21 tablets of 30 mg each. PB tablets were taken on order when it was believed a gas attack was imminent. The recommended dosage was one tablet every 8 hours. PB has been in use for decades (at much higher dosages) in the treatment of patients with myasthenia gravis. Short-term side effects are well known -- e.g., nausea, vomiting, diarrhea, abdominal cramps, increased salivation, miosis, headache and dizziness. There have been no documented long-term side effects of this drug.
The simultaneous or sequential administration of neurotropic compounds (for example, PB and the insect repellent DEET) conceivably could interact to produce an additive or synergistic effect. However, previous research has indicated that PB does not persist in the body and, therefore, is unlikely to cause any long-term effects. DoD investigators have conducted a study of the acute interactions of PB, DEET, and permethrin when administered orally to rats (DoD-10). The endpoint studied was lethality at very high doses. They found synergism of effect when PB was combined with DEET and permethrin. The relevance of high dose acute oral toxicity studies to the potential for chronic effects from acute low-level exposures is unknown. The IOM panel concluded that PB is a well-studied medication belonging to a class of drugs about which extensive knowledge exists and that PB could interact with other compounds to cause acute and short-term problems, but was unlikely to cause chronic effects. Nonetheless, the IOM panel recommended that the possibility of chronic neurotoxic effects needs to be tested in appropriate animal models (IOM, 1995; see Section 3.2, Health Outcomes).
RESEARCH QUESTION 5: What was the prevalence of PB use among Persian Gulf troops?
Research Currently Underway
PROJECTS VA-2,4,5,6, DoD-1, HHS-1,2: Components of each of these epidemiological studies collects self-reported PB use data for Persian Gulf veterans using a variety of instruments.
Additional Needed Studies
3.1.8 Psychophysiological Stressors of War
Psychiatric morbidity among U.S. troops deployed to the Persian Gulf area was predicted even though the war was of short duration, resulted in relatively low numbers of casualties, and positive support for the war prevailed at home. Persian Gulf veterans were exposed to many psychophysiological stressors besides direct combat, such as sudden mobilization for military service (especially among members of reserve and National Guard units), exposure to dramatic oil well fires, the constant threat of CBW agents, and fear of combat in general. A wide range of somatic and psychological responses could be expected from individuals deployed to the Persian Gulf area from stress associated with deployment (Wolfe, 1993). All three review panels recognized the possible role of psychophysiological stressors associated with deployment and the possibility of a psychophysiological response among Persian Gulf veterans. All three panels encouraged further scientific research
RESEARCH QUESTION 6: What was the prevalence of various psychophysiological stressors among Persian Gulf veterans? Is the prevalence different from that of an appropriate comparison population?
Research Currently Underway
PROJECTS VA-2,4,5,6,7,12, DoD-1,4,5,6, HHS-1,2: Components of these studies are acquiring self-reported data on exposure to psychophysiological stressors among Persian Gulf veterans and appropriate control populations.
Additional Needed Studies
3.1.9 Troop Locations
One of the most important variables in considering any exposure is determining the location in the Persian Gulf theater of individual service members as a function of time. Information about troop location down to the individual service member was not recorded. However, unit diaries (where a unit consists of approximately 100 troops) were maintained on a daily basis for all units. Matches between units and individuals can be made. The U.S. Army and Joint Services Environmental Support Staff Group (ESG) is currently in the process of computerizing troop unit locations (PROJECT VA-3). At the current work level, computerized records are expected to be complete for the Air Force, Navy, and Marines by the end of 1995. Eighty percent of the records will be completed for the Army by the end of 1995, with all records complete by 1996. Because the results from this project are needed for several epidemiological investigations, this project is of vital importance.
There are no further research questions or suggestion of need for additional studies.
3.2 HEALTH OUTCOMES
The most frequently cited health outcomes and concerns related to service in the Persian Gulf are:
Table 2 provides a summary of the DSB, NIH, and IOM findings on health outcomes. When the potential for long-term health consequences was considered, all panels agreed that further research into psychological outcomes, non-specific symptom complexes, and leishmaniasis was needed. In addition, the IOM and NIH panels recommended research on neurological and neuropsychological outcomes. The remaining potential health outcomes were each considered significant by only one panel. In such cases, though, the other two panels had no comment. This latter observation must be treated with caution since concern about some potential health outcomes have been raised only recently.
TABLE 2
Summary of Reported Health Outcomes
+ Recommended for further review and research
- Unlikely to be of primary concern for long-term health consequences
* The outcome was either considered by the panel, but not highlighted, or was not considered by the panel.
** Including Chronic Fatigue Syndrome (CFS), chemical sensitivities, and fibromyalgia
Below, each health outcome is considered individually. For each health outcome a general background is provided. This is followed by specific research questions with statements of current research and any additional studies that are needed.
3.2.1 Non-Specific Symptoms/Symptom Complexes
Within any population the size of the Persian Gulf veterans cohort (approximately 700,000), individuals will experience various health complaints and may become ill at some time. Some of these symptoms and illnesses may not be fully explained despite intensive clinical work-ups. It is possible that some of these symptoms may fall into unique complexes that can be categorized.
RESEARCH QUESTION 7: Are Persian Gulf veterans more likely than appropriate controls to experience non-specific symptoms and symptom complexes?
Research Currently Underway
PROJECTS VA-2,4,5,6,18, DoD-1, HHS-1,2: Components of each of these studies are acquiring data on self-reported non-specific symptoms. Some (see below) are also investigating the presence of identifiable symptom complexes
PROJECT VA-2, HHS-2: This study includes a physical examination to validate the self-reported symptoms on a subset of the survey study population.
PROJECTS VA-4,5,6, HHS-1,2: Components of these studies are directed specifically at hypotheses that unexplained illnesses are associated with symptom complexes identified as CFS, fibromyalgia, or chemical sensitivities. At a minimum they should provide information on the prevalence of these complexes.
Additional Needed Studies
3.2.2 Immune Function
Suggestions have been made that Persian Gulf veterans have experienced an alteration in immune function or host defense. One hypothesis is that aromatic hydrocarbons, and other related compounds, may cause suppression of immune function through activation of the aromatic hydrocarbon receptor (AhR) on cell lymphocytes and subsequently induce lymphocyte death thereby suppressing immune function.
RESEARCH QUESTION 8: Do Persian Gulf veterans have a greater prevalence of altered immune function or host defense when compared with an appropriate control group?
Research Currently Underway
PROJECTS VA-4,5,6,17: Virtually all of these studies are collecting standard, clinical immune function data. VA-4 will conduct research on a model for the upregulation of the AhR. VA-5 will study peripheral blood polymorphonuclear leukocytes for chemokine expression. VA-5 will also examine blood mononuclear cells for reactivation for EBV, CMV, herpes 6 and herpes 7.
Additional Needed Studies
3.2.3 Reproductive Health Outcomes
Adverse pregnancy and birth outcomes associated with Persian Gulf area deployment have been a major concern among the Persian Gulf veterans. An investigation was conducted by the Mississippi Department of Health in collaboration with CDC of birth defects in children of Persian Gulf veterans from a Mississippi national guard unit (CDC, 1994). Birth defects were identified and the diagnoses verified. The results were compared to expected values. The number of birth defects was not higher than expected for that population. The IOM panel has recommended that reproductive outcomes be included among the health endpoints in surveillance programs and that population-based studies of these outcomes be conducted.
RESEARCH QUESTION 9: Is there is a greater prevalence of birth defects in the offspring of Persian Gulf veterans than in an appropriate control population?
Current Research Underway
PROJECTS VA-2, DoD-1, HHS-1,2: Components of each of these epidemiological studies will identify through survey questionnaires birth defects in offspring of Persian Gulf veterans and in those of appropriate controls.
Additional Needed Studies
RESEARCH QUESTION 10: Have Persian Gulf veterans experienced lower reproductive success than an appropriate control population?
Research Currently Underway
PROJECTS DoD-1 and HHS-1: Components of these studies will investigate the prevalence of failure to conceive and miscarriage, and compare the prevalence to that of an appropriate control population.
PROJECTS VA-2, DoD-1, HHS-1,2: Components of these studies will determine the prevalence of miscarriage, spontaneous abortion, and stillbirth and compare the prevalence to that of an appropriate control population.
Additional Needed Studies
3.2.4 Genitourinary Disorders
There have been only individual reports of sexual dysfunction among Persian Gulf veterans. There have been infrequent reports of these phenomena in both the VA and DoD surveillance systems.
RESEARCH QUESTION 11: Is the prevalence of sexual dysfunction greater among Persian Gulf veterans than among an appropriate comparison population?
Research Currently Underway
PROJECTS VA-2, DoD-1, HHS-1: Components of these epidemiology studies will determine, through survey questionnaires, the prevalence of various manifestations of sexual dysfunction in Persian Gulf veterans (or in the veterans' partners) compared to that in an appropriate comparison population.
Additional Needed Studies
3.2.5 Pulmonary Function Abnormality
Some troops may have been exposed to potentially significant amounts of petroleum vapors, combustion products and sand dust. Depending on exposure concentration and absorbed dose, repeated and chronic exposure to these chemicals and substances could possibly result in impairment of pulmonary function. The NIH panel recommended a retrospective cohort study to investigate pulmonary function related to petroleum combustion products.
RESEARCH QUESTION 12: Do Persian Gulf veterans report more pulmonary symptoms or diagnoses than persons in appropriate control populations?
Research Currently Underway
PROJECTS VA-2,4,5,6, DoD-1, HHS-1: Components of these studies are using surveys to ascertain the prevalence of pulmonary diagnoses (e.g., asthma, bronchitis, etc.) among Persian Gulf veterans compared to an appropriate control population. Exposure-outcome relationships will be explored.
Additional Needed Studies
RESEARCH QUESTION 13: Do Persian Gulf veterans have a smaller baseline lung function in comparison to an appropriate control group. Do Persian Gulf veterans have a greater degree of non-specific airway reactivity in comparison to an appropriate control group?
Research Currently Underway
PROJECT VA-4: A component of this project is conducting a random cohort study to determine whether there are any differences in pulmonary function and airways reactivity between Persian Gulf veterans and Persian Gulf era veterans.
PROJECTS DoD-2,3: Components of these projects involve exposures of laboratory animals to a variety of inhaled pollutants. Pathophysiologic effects that may provide information on potential human health outcomes will be studied.
Additional Needed Studies
3.2.6 Neuropsychological and Neurological Outcomes
The subjective reports of generalized fatigue and cognitive impairment in Persian Gulf veterans enrolled in the VA and DoD registries suggest the possibility of a neurological component to their health problems. The self-reported exposures of troops to chemicals with potential neurological effects (such as PB, many of the pesticides, and the repellents DEET and permethrin) also suggest that neurological and neuropsychological outcomes should be investigated. DoD investigators have conducted a study of the acute interactions of PB, DEET, and permethrin when administered orally to rats (DoD-10). The endpoint studied was lethality at very high doses. They found synergism of effect when PB was combined with DEET and permethrin. The relevance of high dose acute oral toxicity studies to the potential for chronic effects from acute low-level exposures is unknown. Neither the IOM nor the NIH panel concluded that any of these exposures by themselves could be responsible for the reported health problems. Both panels expressed concern, however, that the possible interactive effects of these chemicals, especially when accompanied by other unusual stressors, not be overlooked.
There have been media reports of research conducted by an investigator at Duke University (AP, 1995) which indicate the potential for synergistic interactions between PB and other compounds such as DEET, permethrin, and organophosphate pesticides. Full assessment of these findings awaits complete data analysis by the investigator, and peer-review of the research.
RESEARCH QUESTION 14: Is there a greater prevalence of organic neuropsychological and neurological deficits in Persian Gulf veterans compared to appropriate control populations?
Research Currently Underway
PROJECTS VA-2,4,5,6, DoD-1, HHS-1: Prevalence of symptoms associated with neuropsychological and neurological deficits will be estimated, compared to an appropriate control population, and assessed in relation to significant subgroups of the veteran population including those self-reporting specific exposures.
PROJECTS VA-4,5,6,9,10,11,13: Components of these projects administer specific neuropsychological and neurological tests to groups of Persian Gulf veterans and Persian Gulf era veterans. In addition, a pilot clinical program at the Birmingham, Alabama VA medical center (VA, 1995) is conducting neuropsychological tests on veterans from the VA Persian Gulf Registry who self-report exposure to environmental hazards.
PROJECTS DoD-7: This project will utilize a rat model to investigate the potential effects of depleted uranium on the nervous system.
Additional Needed Studies
RESEARCH QUESTION 15: Can short-term, low-level exposures to pyridostigmine bromide, and the insect repellents DEET and permethrin, alone or in combination, cause short-term and/or long-term neurological effects?
Research Currently Underway
PROJECT DoD-10: This project is an animal study of the high-dose toxic effects (lethality) of these compounds separately and in combination.
PROJECT DoD-11: This project investigates male/female differential tolerance to PB.
PROJECT VA-5: A component of this project is investigating the interactive effects of pyridostigmine bromide and 3-methylcholanthrene on the stress-response of laboratory animals.
PROJECT VA-6: A component of this project is investigating in-vitro the combined neural effects of hydrocarbon solvents and pyridostigmine bromide.
PROJECTS VA-4,5,6: Components of these projects are examining a variety of neurological and neuropsychological endpoints on selected cohorts of Persian Gulf veterans and Persian Gulf era veterans. Endpoints being examined range from nerve conduction velocity studies, to olfactory evoked potentials, to performance on computerized neurobehavioral test batteries. Results will be related to potential self-reported exposures to neurotropic compounds.
Additional Needed Studies
3.2.7 Psychological/Psychiatric Outcomes
A variety of symptoms have been reported by Persian Gulf veterans. Some symptoms may be related to post-traumatic stress disorder (PTSD). Published findings (Sutker et al., 1993; Sutker et al., 1994a,b; and Wolfe et al., 1993) suggest an increased prevalence of PTSD and other psychiatric diagnoses, such as depression, in some Persian Gulf veterans. Although the prevalence of these disorders was found to be lower than that found among Vietnam veterans, it is evident that stressors during the Persian Gulf conflict were sufficient to cause significant psychiatric morbidity. Because of the low level of combat experienced by many troops in the Persian Gulf conflict, the presence of psychiatric problems among some returnees suggests the importance of stress other than actual combat as a precipitating factor. All three review panels (DSB, NIH, and IOM) recognized unusual stressors (e.g., sudden deployment, crowded living conditions, threat of CBW, combat) associated with the deployment and the possibility of their effects on mental health. Additionally, the potential effect of psychological stress on the immune system needs to be considered.
RESEARCH QUESTION 16: Do Persian Gulf veterans have a significantly higher prevalence of psychological symptoms and/or diagnoses than do members of an appropriate control group?
Research Currently Underway
PROJECTS VA-2,4,5,6,7,8,12, DoD-1,5,6, HHS-1,2: Components of these projects are collecting survey questionnaire data from which extensive questioning will allow development of prevalence estimates of psychological symptoms and diagnoses in comparison to an appropriate control.
PROJECTS VA-4,5,6: Components of these projects are examining the relationship between symptoms/symptom complexes (such as chronic fatigue syndrome) and the presence of any psychological symptoms and/or diagnoses.
PROJECT VA-4,5: Components of these projects will investigate the immunological status among different symptomatic groups of Persian Gulf veterans.
Additional Needed Studies
3.2.8 Infection
Unlike veterans with less well-defined illnesses, all but one of 12 veterans diagnosed with viscerotropic leishmaniasis had objective signs of disease, including high fever, lymphadenopathy and hepatosplenomegally. Nevertheless, because of the possibility of subclinical infection and the late presentation of the disease due to the prolonged incubation period, all three review bodies recommended further studies on detection and treatment of leishmaniasis. The IOM Committee recommended that when a serological test or other easy-to-use screening test(s) becomes available, an epidemiological and seroepidemiological study of leishmaniasis in Persian Gulf veterans should be conducted with appropriate controls.
Other infectious agents, such as mycoplasmas, bacteria, viruses, and fungi, cannot be entirely ruled out. Therefore, in spite of the absence of a strong case from clinical evaluations to support infectious agents as possible etiological factors, targets of opportunity for collecting serological data should be exploited.
RESEARCH QUESTION 17: What is the prevalence of leishmaniasis or other infectious diseases in the Persian Gulf veteran population?
Research Currently Underway
PROJECT VA-5: In a component of this project blood mononuclear cells from Persian Gulf veterans (from existing study populations) will be tested for reactivation for Epstein-Barr Virus, Cytomegalovirus, herpes-6, and herpes-7. Comparisons with appropriate control populations will be made.
PROJECT VA-15,16: These projects are directed at treatment and prevention of leishmaniasis.
PROJECT DoD-9: This project is attempting to identify the gene in humans that controls for tropism of L. tropica with the hope of determining which Persian Gulf veterans, with latent L. tropica infection, are at risk for developing an active case of viscerotropic leishmaniasis in the event of future immune suppression.
PROJECT DoD-12: This project is examining dogs that were in the Persian Gulf theater to determine if they have any infections of importance to humans.
Additional Needed Studies
The occurrence of some cancers among Persian Gulf veterans, although infrequent, has elevated concern over the possibility that these cancers may be linked to service in the Persian Gulf. The DSB, in examining the VA Persian Gulf Registry data, found no discernible demographic, military, or pathological pattern to the distribution of cancer cases (DSB, 1994). However, the DSB points out that any conclusions based on the Persian Gulf Registry must be made with caution because it is a self-selected group of veterans. The DSB also pointed out that because of the long latency period associated with cancer originating from environmental causes, it is too early to evaluate cancer risk in Persian Gulf veterans.
RESEARCH QUESTION 18: Do Persian Gulf veterans have a greater risk of developing cancers of any type when compared with an appropriate control population?
Research Currently Underway
PROJECT VA-4: A component of this project involves establishing the basis for a cancer surveillance system among Persian Gulf veterans in the state of Massachusetts.
PROJECT VA-1: The mortality follow-up of Persian Gulf veterans that is underway will examine cause-specific mortality.
PROJECT DoD-1: A component of this project will analyze hospital records of over 1.2 million service members.
PROJECT VA-14: This project will longitudinally follow the health of Persian Gulf veterans who have embedded depleted uranium fragments.
PROJECT DoD-7: This project uses a rat animal model to investigate the carcinogenic potential of embedded depleted uranium fragments.
PROJECT HHS-3: This project is examining immunological markers in Persian Gulf veterans exposed to oil fire smoke. These markers may be used to indicate changes in DNA due to oil fire smoke exposure.
Additional Needed Studies
Postservice increases in mortality due to external causes have been previously documented (Boyle et al., 1987). Recently, the VA has compared the overall mortality rates of Persian Gulf veterans with the U.S. general population up to September 1993 (Han Kang, 1993). This preliminary investigation did not show an increased mortality rate for the time period considered. The DoD recently completed a study (Writer et al., 1995) comparing the one year, in-service mortality experience of service members who served in Operations Desert Shield/Desert Storm to that of service members who served during the same time period but were not deployed to Southwest Asia. No difference in mortality over that period was found. The latter two investigations have only examined mortality rates over narrow time frames, and cannot be used to draw any conclusions about Persian Gulf veterans' mortality over longer periods of observation time.
RESEARCH QUESTION 19: Are Persian Gulf veterans experiencing a mortality rate that is greater than that of an appropriate control population? Are specific causes of death related to service in the Persian Gulf?
Research Currently Underway
PROJECT VA-1: This study examines the post-deployment mortality experience of all Persian Gulf veterans compared to Persian Gulf era veterans. It also examines cause-specific mortality, as recorded on a death certificate, between these two groups to ascertain whether any particular underlying causes of death are more prevalent among Persian Gulf veterans.
Additional Needed Studies