Immunizations and Chronic Fatigue Syndrome in Gulf War Veterans

  

Immunizations and Chronic Fatigue Syndrome

in Gulf War Veterans

By:    Tiffany L. Hartzheim

Epidemiology 757 – Spring 2014

Prof. Kwangseong Ahn

April 26, 2014

 

 

Abstract

Chronic Fatigue Syndrome (CFS) is a symptom of veterans returning from the Persian Gulf War in February 1991.  The United States government did not know and was not prepared to comprehend or handle the symptomatic veterans.    Over immunization of soldiers preparing for deployment have been thought to be a cause for the CFS  and the Th1 to Th2 shift when the immunizations used with adjuvant cause an autoimmunity.  This combined with deployment stressors such as long hours, lack of sleep, environmental toxins and immunizations given during theater raise suspicion that the fatigue they experienced was an immunization – CFS relationship.   There is still much research on causal factors to link these two factors together and there has been much bias and lack of aetiological studies to prove otherwise.   Since this is still a controversial topic by using a survey and historical data I hope to find a correlation between immunizations and CFS.

 Introduction

The Persian Gulf War or Operation Desert Storm began on August 2, 1990 and ended on February 28, 1991.   The United States was one of many coalition countries, including Britain (UK) and Australia to neutralize the Iraqi invasion of Kuwait   President George H.W. Bush sent nearly 700,000 US troops overseas to Saudi Arabia, Kuwait and Iraq to support the effort.    In less than one year the war was over and veterans returned to United States after being exposed to multiple situations and factors they could not control and some they did not even know about.   The term Gulf War Syndrome (GWS) was labeled after veterans not only in the US returned, but also in the UK experienced multiple symptoms that could not be diagnosed by medical professionals as they did not have any previous experience with these types of symptoms of Chronic Fatigue Syndrome (CFS).  In 1993 U.S. Congress passed the Veterans Health Care Act establishing a registry of all Gulf War veterans.  The conclusion of the registries was that several Gulf War veterans had been misdiagnosed and were not regarded as disabled by their military headquarters (Oumeish ,2002).   Many epidemiological studies on environmental and physical  hazards, exposures, past history of war illnesses, and vaccinations have been completed.  There are many symptoms that comprise of GWS, such as chronic fatigue syndrome (CFS) and auto-immunity is a symptom that  is stated to possibly caused by vaccinations given to military personnel.  There is still controversy over the exact causal factor that links vaccinations to CFS or that CFS actually exists for veterans.

CFS is a disabling fatigue associated state acquired in armed services personnel during the Persian Gulf War – a disorder of unknown aetiology and no proven biologically plausible mechanism (Staines 2004).  The characteristics of CFS is chronic fatigue, memory and concentration disturbance, sensory disturbance and chemical sensitivity, muscoskeletal symptoms and general malaise.  The Department of Defense definition of CFS is similar to the Center for Disease Control definition in which CFS is clinically defined as illness in which fatigue is reported by the patient himself lasting for at least six months, no medical explanation for the symptoms can be found and the symptoms limit daily function (Soetekouw et al, 2000).   Epidemiological studies and medical studies have been completed to determine a  causal relationship between vaccinations given to service members combined with environmental and physical hazards to inner workings of the human body, pre-war preparations such as stress  and an adjuvant used for immunizations.

Many environmental and physical hazards were present during the Gulf War.  The climate was one of extremes from dry, windy, low humidity, high temperatures of 100°F to 120°F in the summer.   Exposures to smoke from burning oil wells, fumes of petroleum products, contact with radioactive substances, lead, mercury, nickel, tin, silver and natural and synthetic chemicals and poisons like pesticides and DDT.  Another hazard is war preparation in which included exhaustive training in chemical warfare and maneuvers and the possible negative effect of different immunizations with an adjuvant used in those immunizations (Oumeish et al. 2002).  The environmental hazards were difficult to assess or quantify due to low levels of radiation, chemicals, food additives, pesticides and pollution (Durodie 2006).

Vaccinations have an important role in preparing service members to be protected immunologically from potential  life endangering diseases, illness or chemical warfare.   In preparation for their deployment servicemen receive vaccinations dependent on their destination.  Possibly given vaccinations in anticipation of biological warfare such as anthrax and plague.

Table 1. Vaccines Routinely Given to U.S. Military Personnel at   the Time of Gulf War (Brinns et al 2008)
Vaccine Personnel Directed to   Receive Vaccine Schedule
Adenovirus all recruits 1 oral dose
Influenza all recruits and active   duty annual shot
Measles all recruits and active   duty 1 shot
Meningococcal all recruits, active duty   as required 1st shot, then booster ev   3-5yrs
Plague all Marines; Army and   Navy special 5 shots over 12 months,   then
forces, others in at-risk   occupations every 1-2 years
deploying to high risk   areas
Polio all recruits 1 oral dose
Rabies special forces; at-risk   occupations 3 shot series
Rubella all recruits 1 shot
Smallpox vaccine or booster to new   recruits 1 dose
through the late 1980’s
Tetanus-diphtheria all recruits, active   duty, & reserve booster every 10 years
Typhoid Army & Air Force   alert forces and for 2 doses in 2 months, then
deployment to high risk   areas booster every 3 years
Yellow Fever all branches alert forces   and for 1st shot then booster
deployment to high risk   areas every 10 years
Table 2.   Vaccines Given to U.S. Military Personnel Specifically for Gulf War   Deployment (Brinns et al 2008)
Vaccine/ U.S .Personnel Recommended Proportion of  Veterans
Prophylactic Recommended to Schedule Reporting (US Survey)
Measure Receive Vaccine for Gulf War Received the Vaccine
Anthrax fixed units, rear   deployed 2 shots, 2 weeks apart 41%
Botulinum   toxoid fixed units, forward   deployed 2 shots, 2 weeks apart 12%
3rd shot 10 weeks later
Immune   globulin all troops, dose varied   by 1 dose (some recvd 60%
branch & length of deployment 2nd dose)
Meningococcal all Army; other personnel   who 1 shot 14%
had not received it in 5   yrs &
would have close contact   with
locals
Typhoid all Army; other personnel   who 2 initial doses or 1   booster 59%
had not received it in 3   years
Yellow Fever all Marines, Navy, Air   Force; 1 shot    only U.K. received
Army special forces

Immunizations with adjuvant have raised been as a possible contributing factor for CFS.  In general, Th1 responses are more effective against viruses and bacteria that are inside host cells, where Th2 responses are more effective against parasites and toxins.  Th2 inducing stimuli can be identified because Gulf War veterans were given multiple Th2 inducing immunizations.  The likelihood that immunizations used caused a systemic Th1 to Th2 switch is increased by four features of the vaccination protocol (Rook and Zumla 1997).  The four features that Rook and Zumla stated were 1.) Pertussis was used as an adjuvant and its adjunvanticity is potently Th2  2.) a large antigen load tends to drive the response toward Th2  3.) The immunizations were given after deployment in the war zone, at a time when the soldiers would have been under a good deal of stress 4.) The troops were exposed to carbamate and organic phosphate insecticides which inhibit interkeukin-2 driven events.   CFS was described in 4-8% of soldiers who participated in the Gulf War and symptoms ranged from impaired cognition, fatigue, joint and muscle pain and this was related to chronic Th2 biased immune response (Appel, Chapman and Shoenfeld 2007).   Appel, Chapman and Shoenfeld also state that immunizations raises suspicion that they are given in order to trigger an immunological defense reaction that may cause an aberrant reaction expressed as CFS.     Further studies need to be carried out and suspicion should be raised because the possibility of immunization induced CFS is reasonable in view of the ability of immunizations that cause Th2 dominant response (Appel, Chapman and Shoenfeld 2007).   There is little to no information available on studies or monitoring programs that quantifies short or long term adverse effects resulting from specific combinations of immunizations or large number of immunizations given concurrently (Brinns et al 2008).    Surveying the complaints of the veterans and those associated with CFS and looking at the Th1 to Th2 switch through the immunizations they received associated with the stressors of deployment, there should be a correlation.  However, Appel, Chapman and Shoenfeld researched an association between immunizations and CFS and it is much less documented.  A working group of the Laboratory Center for Disease Contol (LCDC) of the Canadian National Health & Welfare was to examine the suspected association between immunization and CFS.  After testing cases after a period time, they stated that immunizations did not exacerbate their symptoms of CFS.

The type of vaccine, the efficacy of the vaccine and the combination with stressful circumstances and short period within the vaccinations were administered contributed to some development of GWS/CFS (Soetekouw 2000).  A common feature of the syndrome is the perception of damage to the so-called immune system resulting from vaccinations, toxins or radiation (Martin 1994).   The over vaccination or multiple vaccinations administered  prior or during deployment could have caused a change in T helper (Th-1, Th-2) balance.  Individuals with GWS/CFS had an increase in Th-2 cells and could have been caused by vaccinations received due to increased physical effort, depression, lack of sleep, food shortages, giving rise to brain chemical changes, all which depends on the individual and their reactions to environment and individual Th-2 profile could lead to symptoms  (Soetekouw 2000).     Veteran’s showed cases in which Th-2 inducing stimuli can be identified as they were given multiple Th-2 inducing vaccinations (Rook, Zumla 1997).

An adjuvant is an aid commonly used in medicine to boost an immune response to treatments such as vaccination.  Adjuvant increase innate immune responses to enhance the immune response triggered by the vaccine.  They also increase the local reaction to antigens (ie. at the site of the infection) and subsequently the release of cytokines and chemokines from T-helper and mast cells (Stines, 2004).   The most common adjuvant used is aluminum hydroxide and the only Anthrax and botulinum toxoid were the most significant vaccines received in preparation for the Gulf War.   Anthrax is given in a series of 6 injections over an 18 month period with annual boosters.  Adequate supplies were not available to protect all deploying troops with the 6 shot regimen, nor to fully immunize troops in the form expected war (Brinnes et al 2008).  Many adverse effects to vaccinations are usually local at the site of the injection, but systemic flu-like reaction and allergy may occur.  GWS/CFS was described in 4-8% of soldiers who participated in the Gulf War and a few months to years later suffered from illness that included impaired cognition, fatigue, joint and muscle pain (Appel et al, 2007).   The aluminum hydroxide is known to induce a shift of the immune response toward a Th-2 profile reaction.  The persistent elevated levels of the Th-2 cytokines induce systemic symptoms of chronic fatigue, muscle and joint pain (Appel et al, 2007).   A specific correlation between multiple vaccinations given during deployment and later ill health was not seen, however multiple vaccines combined with “stress” of deployment may be associated with adverse health outcomes (Buskila et al, 2008).   With the 6 series shots of anthrax,  timeframe for vaccination and the shortage of available vaccine, some troops received some vaccinations in theater, in a stressful environment, among environmental and other physical hazards (Brinns et al 2008).   There were 310,680 dose of anthrax vaccine delivered in theater and 150,000 troops received one or more anthrax shots (Brinns et al 2008).

                                                                                Hypothesis

The Null Hypothesis – “There is no known or proven association between the immunizations received in deployment for the Gulf War and Chronic Fatigue Syndrome.”  The alternative is that there is known or there is proven association between the immunizations received in deployment for the Gulf War and Chronic Fatigue Syndrome.

METHOD

The participants were the soldiers who were deployed to serve in the Persian Gulf War from August 1990 until February 1991.  Kang (2000) stated in their study that with the nearly 700,000 soldiers deployed there were 7 percent female and 93 percent male with the mean age of all soldiers was 28.4 years and 83.3 percent as regular active-duty units.    For the purpose of the Kang (2000) study no particular group or population was separated out from the total deployed soldiers as all received immunizations prior or during deployment.  I completed an independent survey of four soldiers who were not involved in the military during the Gulf War but have been deployed to different parts of the world and to Iraq.  I emailed the following questions to four males aged 37-44 years old, three white and one Hispanic and they were asked about their military  experiences with immunizations and deployment.    I wanted to see if they had any personal opinion of immunizations they received, if they experienced any side effects from their immunizations from their deployment.  I also wanted to see if there is a correlation between these soldiers who received similar immunizations and were in similar deployment experiences and if had any CFS effects.

See the following questions.

1.) Please state your rank, branch, and what dates did you serve? Active or reserve?   In theater?

2.)   What vaccinations/immunizations did you receive for your deployment?  Did you receive them all at once in the states or given in theater?

3.)  Did you have any illness or adverse effects from those vaccines, whether right away or after time had passed while in theater?

4.)   If so, what were they?

5.)  After the vaccinations/immunization, do you feel that the stress of deployment/being in theater contributed to those illnesses?

6.)  Even if you did not have any adverse effects from vaccinations of any kind, do you think there is an association between the vaccinations and Chronic Fatigue Syndrome (CFS)/autoimmunity?

7.)  Do you feel that the military over vaccinates?

8.)   Do you have any comments or want to add anything freely?

9.)  Did you have any health issues prior to enlisting with the military?  If so what was it?  (i.e.  allergies food or environmental, seasonal flu, seasonal colds, asthma)

10.)  If you had prior health issues as state above, did those get worse or stay the same after receiving the vaccinations you received in the military/duration of service?

11.)  If you didn’t have any prior health issues (as in question #1), did you develop any health issues (as in question #9  after receiving vaccinations/duration of service?

Research was done through Scientific Journals and Papers to find the definition, symptoms and causes and associations of Chronic Fatigue Syndrome (CFS) and Gulf War Syndrome(GWS) immunizations.  CFS is a disabling fatigue associated state and has characteristics of fatigueability, concentration disturbance, sensory disturbance and chemical sensitivity and Th1/Th2 shift and attributed to stress, immunizations and their adjuvant, exposure to neurotoxin substances and biological warfare agents.   Gulf War Syndrome has multiple causes and immunizations is names as one of them.

When looking at government research and the actual association between immunizations received and CFS, there is research that shows an association but there is not solid proof that the immunizations that cause a Th1 to Th2 switch cause the CFS to occur.   From my independent study 1 out of the 4 state that he experienced fatigue from being deployed but is unsure if it caused by the immunizations and not just the rigors of wartime.

Through the readings and the uncertainty that seems to cast a shadow to see the correlation between immunizations and CFS, more research needs to be completed.    I would take a sampling of 1000 veterans from deployed troops in theater and 1000 veterans active in the rear detachment (or not deployed) at the same time period of service.  Since they have been veterans for 23 years to date, symptoms should be able to distinguish and gather.   Did either group develop CFS through the same immunizations they received or a Th1 to Th2 shift for CFS?    Evaluate the immunizations that were given to the veterans along with the CFS symptoms and if there is a correlation between which immunization vaccine that was given had a causal effect to the CFS.     Since veterans were exposed to a number of environmental, physical and mental factors as described earlier in this paper, look at veterans who were in theater and veterans stateside given the same immunizations, are there differences in the symptoms of CFS if at all?      These analysis questions could continue to go on, but it comes down to the government recognizing that veterans who have symptoms of CFS were caused by over immunizations and to assist in their healthcare, or they say there is no causal relationship or it is unknown pending more research.  Those questions that I posed previously is just the tip of the problem that the government has spent many hours and money on researching.

In conclusion, after dealing with my husband and lasting injuries he sustained from the military, I believe there is a correlation between immunizations and CFS, however, the government research and findings state the facts of CFS and immunizations not to be substantiated.   They contribute the CFS to other environmental factors that they were exposed to and also to long deployment hours and stressors as being in a combat zone fearing for your life, lack of sleep, food and toxic or biological environment.   There are many issues that Gulf War veterans came back home with that the government didn’t know what they were and by putting the generic label of Gulf War Syndrome, and not know exactly a causal association, there is not enough evidence to substantiate the null hypothesis to be voided.

References

Appel, Shmuel, Chapman, Joab, & Shoenfeld, Yehuda (2007). Infection and vaccination in chronic fatigue syndrome: Myth or reality?. Autoimmunity, 40(1), 48-53. Retrieved from informa healthcare database.

Devanur, L.D., & Kerr, J.R., (2006).  Chronic fatigue syndrome. Journal of Clinical Virology, 37, 139-150. Retrieved from Elsevier database.

Durodie, Bill (2006). Risk and the social construction of ‘Gulf War Syndrome’. Philosophical Transactions of The Royal Society, 361. Retrieved from Biological Sciences database.

Gray, Gregory C., Kang, Han K. (2006). Healthcare utilization and mortality among veterans of the Gulf War. Philosophical Transactions of The Royal Society, 361.  Retrieved from Biological Sciences database.

Jones, Edgar (2006).  Historical approaches to post-combat disorders. Philosophical Transactions of The Royal Society, 361.  Retrieved from Biological Sciences database.

Mahoney, David B., (2001). A normative construction of gulf war syndrome. Perspectives in Biology and Medicine, 44, 4, 575-583.  Retrieved from Perspectives database.

Oumeish, Youssef Oumeish, MD., Ousmeish, Isam, MD., & Parish, Jennifer L., MD. (2002).  Gulf War Syndrome. Clinics in Dermatology, 20, 401-412.

Research Advisory Committee on Gulf War Veteran’s Illnesses (2008). Gulf War Illness and the Health of Gulf War Veterans: Scientific Findings and Recommendation.  U.S. Government Printing office.

Rook, Graham A.W., Zumla, Allmuddin (1997).  Gulf War syndrome: Is It due to a systemic shift in cytokine balance towards a Th2 profile?. The Lancet, 349, 1831-1833.

Sartin, Jeffrey, MD., (2006). Gulf War Syndrome: The Final Chapter?.  Mayo Clinic Proceedings, 81(11), 1425-1426.

Shaheen, Seif (2000). Shots in the desert and Gulf War Syndrome. British Medical Journal, 320, 1351-1352.

Shoenfeld, Yehuda, & Agmon-Levin, Nancy (2010).  ‘ASIA’ – Autoimmune/inflammatory syndrome induced by adjuvants.  Journal of Autoimmunity,  36, 4-8.  Retrieved from the Elsevier database.

Soetekouw, P.M.M.B., de Vries, M., van Bergen, L., Galama, J.M.D., Keyser, A. , Bleijenberg, G., & van der Meer, J.W.M. (2000). Somatic hypotheses of war syndromes. European Journal of Clinical Investigation, 30, 630-641.

Staines, Donald  (2004).  Is gulf war syndrome an autoimmune disorder. Medical Hypothesis, 62, 658-664.  Retrieved from Elsevier database.