Gulf War Illness - causes

[Joan Crawford]

I've done a thread:


I think the reason this has been "known for a while now" is because it is damn complicated! It's very easy for minimisers to minimise - and boy will they be trying right now.

The full paper is here: https://ehp.niehs.nih.gov/doi/10.1289/EHP9009
From my quick deep dive today, I initially thought the same, but Haley has spent years (decades) carefully establishing the pathological pathways, toxicology and epidemiology. This paper helps lock it into place. It's an impressive piece of work.

There's a commentary here: https://ehp.niehs.nih.gov/doi/10.1289/EHP11057

Thanks @Lucibee for posting the links.

I hope to have time this weekend to read over.

I have assessed in detail the symptoms and severity of functioning/dysfunction along with neuropsychological difficulties in veterans with GWI/GWS in my clinic. It is very similar to ME. All that I have worked with have PEM, debilitating fatigue and flu-like symptoms after any type of activity, sleep and cog issues, autonomic, gastro dysfunction and so forth.

Having listened to them a few things stick out to me:
1) If this is true, then where is the evidence that it impacted on the civilian population? Perhaps this has not been studied?
2) If this were true, how does it explain the high levels of GWI/GWS in veteran groups who were made 'battle ready' as in given vaccines, tablets and so forth - who were never deployed to the Gulf!
3) How does it explain the French troop paradox? They were not vaccinated in the same way, nor do I recall they were given the tablets to take either (apologises it has been a while since I read so bear with) - and their troops did not appear to develop GWI/GWS?

It may be part of the answer for some with GWI/GWS - but it can't really explain it all. Perhaps it can - I'll have a wee read. Any thoughts?

 

[Joan Crawford]

https://www.science.org/content/article/gulf-war-illness-linked-neurotoxins
And here's a 2004 article

I haven't been able to find a scientific paper to support the 2022 claims of certainty.

Interesting that you found this re Wessely:

"Wessely, like many researchers in the field, believes that Gulf War illness arose from a combination of the stress of war, the use of experimental vaccines, and possibly exposures to environmental hazards such as oil-well fires."

I'd put my money on the experimental vaccines and / or a mixture, interaction with the anti-nerve agents they took. The National Gulf Veterans and Families Association (NGVFA) told me that they have no sick veteran with GWI/GWS who was not vaccinated. I have not met or assessed an ill GW vet who was unvaccinated.

@dave30th

 

[Lucibee]

Any thoughts?

One of the issues I tried to address in the thread is that this study is being widely misreported as "finding the cause of GWI" and that sarin gas is it. It doesn't and it isn't.

As Haley says (in @Lou B Lou's previous post), “Studies using nonspecific definitions of Gulf War neurological syndrome are biased toward finding negative results."

That's why this study takes a particular, specific gene-environment interaction and concentrates just on that for the purposes of showing whether there may be a causal association. His previous papers have shown that this association is far from simple, and suggest that the preventive treatments (so-called "experimental vaccinations" - actually pyridostigmine bromide - not a vaccine as such) taken may also have played their part in the development of the illness (but are not necessarily the cause in and of themselves). However, without those treatments, the deleterious effects of a gas attack or exposure would have much worse - in much the same way that vaccination against infectious diseases is necessary in the majority, but may lead to serious adverse reactions in a very tiny minority. And just because everyone is "vaccinated" doesn't mean that the vaccine is the cause. All veterans would have received vaccines and other treatments before being sent to the Gulf, so of course there are no sick veterans who were not vaccinated.

In some ways, like Wessely, Haley agrees that there is no single Gulf War illness. The "syndrome" is an umbrella for a collection of different symptom presentations. However, unlike Wessely, he has done a lot of work to categorise these, and to suggest and investigate putative causal pathways for some of them in animal models. Not all will be due to sarin exposure. Different illness presentations may be due to different combinations of exposures and gene interactions, which, again, is why it is extremely difficult to identify definitive causal associations.

As Sarah Williams said about her press release (here: https://www.utsouthwestern.edu/newsroom/articles/year-2022/sarin-nerve-gas-gulf-war-illness.html), "The important thing here, he [Haley] emphasized many times to me, is not that they showed an association between sarin exposure and GWI. Instead, they showed that a gene affecting how sarin is processed in the body mediated that interaction."

 

[Hutan]

Good questions

1) If this is true, then where is the evidence that it impacted on the civilian population? Perhaps this has not been studied?

This 2011 paper is interesting:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159173/
Health Effects Associated With Geographical Area of Residence During the 1991 Gulf War: A Comparative Health Study of Iraqi Soldiers and Civilians

To the best of our knowledge, this is the first epidemiological study of the health of Iraqi Soldiers being part of the GW operations in 1991, Moreover, we have assessed Iraqi civilians using well-validated measures. We applied a theoretical dose-response exposure-effect model, based on the distance from Kuwait.

Briefly, they asked men who had been Iraqi soldiers around Kuwait during the Gulf War and male citizens who had also been around Kuwait during the Gulf War about their health. Soldiers only were less than 100 km from Kuwait and are assumed to have the most exposure; there were both soldiers and citizens 100 to 200 km from Kuwait and it is assumed that the soldiers in this zone had more exposure than the citizens because of their activities; and then there are soldiers and citizens over 200 km up to 300 km from Kuwait, regarded as the reference group.

742 veterans of the Gulf War(Soldiers) and 413 civilians

Among the Soldiers, 168 (22.6%) had been deployed to zone1, the Kuwait war zone; 253 (34.1%) to zone2; and 321 (43.4%) to zone3, the reference zone. Among the 413 civilians, 147 (35.6% of all civilians) had resided in zone2 and 266 (64.4%) in zone3during the war.

There are arguably issues with selection but people didn't volunteer to be involved in the survey so it's not too bad.
There are big differences in a lot of health issues, with people in zone 1 definitely suffering more than people in zone 3.

For example, 30% of people (all soldiers) in Zone 1 reported 'chronic fatigue'
7% of people (soldiers and civilians) in Zone 2 reported 'chronic fatigue', and
just 0.3% of people (soldiers and civilians) in Zone 3 reported 'chronic fatigue'.

'Musculoskeletal disorder ' Zone 1 53%; Zone 2 20%; Zone 3 21%
'Ear/Nose/Throat disorder' Zone 1 96%; Zone 2 7%; Zone 3 15%
'Headaches' ....................Zone 1 55%; Zone 2 18%; Zone 3 25%

And so on. It looks pretty compelling.

The Iraqi soldiers didn't have protective gear, weren't vaccinated and weren't given pyridostigmine. They were exposed to sarin nerve gas and to the burning oil.

There is also no compensation schemes available to Iraqi Soldiers as compared to US and UK Soldiers.

In terms of exposure, Iraqi Soldiers and civilians, by most accounts, were exposed to higher dose of war-related environmental factors, and for a considerably longer period of time. Thus, there are numerous reasons why there is a need for long-term follow up health studies of Iraqis, regardless of whether they were deployed during the Gulf War or not.

The odds ratios for a number of somatic disorders were elevated for Soldiers as compared to civilians, including cardiac disease, headaches, respiratory disease, chronic fatigue syndrome, allergies, and skin disorders. This held true even after adjusting for possible confounders such as age, smoking status, and years of education. A number of studies of Allied forces also report an increase in mental disorders, including depression and anxiety, and chronic fatigue syndrome.6,11,19,23 Studies of Allied forces have also reported an increased prevalence of skin disorders31 and respiratory symptoms, including bronchitis and asthma.29 The increased risk for respiratory disease in this study of 1.94 (95% CI, 1.22–3.09) is similar to that reported by Iowa Persian Gulf Study Group.36 Our study confirms prior findings of GW veterans that psychosomatic disorders, including headaches and fatigue, appear to be the most systematically increased somatic and psychosomatic disorders.

 

[Lucibee]

Just to add - you might know pyridostigmine bromide by another name - Mestinon.

 

[Lucibee]

Just to add - you might know pyridostigmine bromide by another name - Mestinon.

Just a few more interesting points...

Here is Haley's first paper about PON1, pyridostigmine and sarin (from 1999): https://pubmed.ncbi.nlm.nih.gov/10373407/
in which the abstract says: "A history of advanced acute toxicity after taking pyridostigmine was also correlated with low PON1 type Q arylesterase activity."

Pyridostigmine is used in advance of chemical nerve agent attack because it blocks the pathways that the nerve agents use. However, if it is used too late, once a person has already been exposed to sublethal amounts of nerve agent, it can exacerbate the effects of the agent.

I'm wondering whether the reason it [Mestinon] doesn't work for some as a treatment for POTS is because of their particular PON1 subtype and/or activity?
Maybe there's also an interaction with pesticides too (pet flea treatments)?

 

[Joan Crawford]

Good questions

This 2011 paper is interesting:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159173/
Health Effects Associated With Geographical Area of Residence During the 1991 Gulf War: A Comparative Health Study of Iraqi Soldiers and Civilians




Briefly, they asked men who had been Iraqi soldiers around Kuwait during the Gulf War and male citizens who had also been around Kuwait during the Gulf War about their health. Soldiers only were less than 100 km from Kuwait and are assumed to have the most exposure; there were both soldiers and citizens 100 to 200 km from Kuwait and it is assumed that the soldiers in this zone had more exposure than the citizens because of their activities; and then there are soldiers and citizens over 200 km up to 300 km from Kuwait, regarded as the reference group.

742 veterans of the Gulf War(Soldiers) and 413 civilians


There are arguably issues with selection but people didn't volunteer to be involved in the survey so it's not too bad.
There are big differences in a lot of health issues, with people in zone 1 definitely suffering more than people in zone 3.

For example, 30% of people (all soldiers) in Zone 1 reported 'chronic fatigue'
7% of people (soldiers and civilians) in Zone 2 reported 'chronic fatigue', and
just 0.3% of people (soldiers and civilians) in Zone 3 reported 'chronic fatigue'.

'Musculoskeletal disorder ' Zone 1 53%; Zone 2 20%; Zone 3 21%
'Ear/Nose/Throat disorder' Zone 1 96%; Zone 2 7%; Zone 3 15%
'Headaches' ....................Zone 1 55%; Zone 2 18%; Zone 3 25%

And so on. It looks pretty compelling.

The Iraqi soldiers didn't have protective gear, weren't vaccinated and weren't given pyridostigmine. They were exposed to sarin nerve gas and to the burning oil.

Thanks for sharing this @Hutan. Really interesting.

 

[Joan Crawford]

Just a few more interesting points...

Here is Haley's first paper about PON1, pyridostigmine and sarin (from 1999): https://pubmed.ncbi.nlm.nih.gov/10373407/
in which the abstract says: "A history of advanced acute toxicity after taking pyridostigmine was also correlated with low PON1 type Q arylesterase activity."

Pyridostigmine is used in advance of chemical nerve agent attack because it blocks the pathways that the nerve agents use. However, if it is used too late, once a person has already been exposed to sublethal amounts of nerve agent, it can exacerbate the effects of the agent.

I'm wondering whether the reason it [Mestinon] doesn't work for some as a treatment for POTS is because of their particular PON1 subtype and/or activity?
Maybe there's also an interaction with pesticides too (pet flea treatments)?

My recall, which might be inaccurate, is that the troops took the pyridostigmine pre deployment to the Gulf AND during there time out there too.

Really interesting what you have shared here about this as it has been a while since I looked it up. Thanks for sharing.

 

[Joan Crawford]

One of the issues I tried to address in the thread is that this study is being widely misreported as "finding the cause of GWI" and that sarin gas is it. It doesn't and it isn't.

As Haley says (in @Lou B Lou's previous post), “All veterans would have received vaccines and other treatments before being sent to the Gulf, so of course there are no sick veterans who were not vaccinated." "

Not true that all veterans receive vaccines. Some veterans declined vaccines pre-deployment. Some were ordered to be vaccinated. Other parts of the military were more flexible. Some of the press teams too decline vaccination. Word got about regarding the experimental nature of some of the vaccines being used.

I'm unsure if those declining vaccines would have taken or not the pyridostigmine.

 

[Joan Crawford]

[QUOTE="As Sarah Williams said about her press release (here: https://www.utsouthwestern.edu/newsroom/articles/year-2022/sarin-nerve-gas-gulf-war-illness.html), "The important thing here, he [Haley] emphasized many times to me, is not that they showed an association between sarin exposure and GWI. Instead, they showed that a gene affecting how sarin is processed in the body mediated that interaction."[/QUOTE]

Would it not make sense to state that a gene affecting how sarin is processed in the body mediated that interaction - along with how anti sarin medication, such as pyridostigmine, also is processed and interacts?

 

[Wonko]

It strikes me as a blame deflection exercise;

They seem to be saying that GWI is caused by a combination of genetics (not the militaries fault) and the presence of sarin in weapons dumps (not the militaries fault - the fault of a dead guy).

So in no way is 'our' military responsible, even if they did know that the weapons dumps contained sarin, and chose to order them blown up.

and of course, if they aren't responsible, then they owe no compensation, to anyone, in any form.

It's all the fault of the nasty dead rotter.

Much the same as the radiation exposure caused by ordering people to stand in a circle around nuclear tests wasn't their fault. They couldn't be expected to know that it might be dangerous, standing around watching a nuke go off, to see what happens.

Someone else's fault, but not the people who gave the orders.

 

[Hutan]

I don't think this report has been posted yet, sorry if it has.
https://www.govinfo.gov/content/pkg/CRPT-105hrpt388/html/CRPT-105hrpt388.htm
The second report by the committee on Government reform and oversight
Gulf War veterans' illnesses: VA, DOD continue to resist strong evidence linking toxic causes to chronic health effects
1997

It's absolutely scathing.
Summary (just bits of it here, it's worth reading in full)

Responding to requests by veterans, the subcommittee in March 1996 initiated a far-reaching oversight investigation into the status of efforts to understand the clusters ofsymptoms and debilitating maladies known collectively as ``Gulf
War Syndrome.'' We sought to ensure sick Gulf War veterans were being diagnosed accurately, treated effectively and compensatedfairly for service-connected disabilities, despite official denials and scientific uncertainty regarding the exact causes of their ailments. We also sought to determine whether the Gulf War research agenda was properly focused on the most likely, not just the most convenient, hypotheses to explain Gulf War veterans' illnesses.

After 19 months of investigation and hearings, the subcommittee finds the status of efforts on Gulf War issues by the Department of Veterans Affairs [VA], the Department of Defense [DOD], the Central Intelligence Agency [CIA] and the
Food and Drug Administration [FDA] to be irreparably flawed. We find those efforts hobbled by institutional inertia that
mistakes motion for progress. We find those efforts plagued by arrogant incuriosity and a pervasive myopia that sees a lack of evidence as proof. As a result, we find current approaches to research, diagnosis and treatment unlikely to yield answers to veterans' life-or-death questions in the foreseeable, or even far distant, future.

We do not come to these conclusions lightly. Nor do we discount all that has been done to care for, cure and compensate Gulf War veterans. But lives have been lost, and many more lives are at stake.

Our hearings convinced us the journey from cause to cure for Gulf War veterans runs through the pools, clouds and plumes of toxins in which they lived and fought. It is a journey VA and DOD might never have taken but for persistent pressure from this subcommittee, and other House and Senate panels, that forced the Pentagon to acknowledge a ``watershed event''--the probable exposure of United States troops to chemical weapons fallout at Khamisiyah, Iraq.

Before Khamisiyah, voluminous and compelling, albeit circumstantial, evidence regarding neurotoxic exposures had
been ignored, denied or discredited, while far less abundant evidence and far less plausible psychological theories of
causation were pursued with vigor. As a result, diagnostic protocols were insensitive to exposure effects, treatments were limited and vital research was delayed.

Those denials and delays are symptomatic of a system content to presume the Gulf War produced no delayed casualties, and determined to shift the burden of proof onto sick veterans to overcome that presumption. That task has been made difficult, if not impossible, because most of the medical records needed to prove toxic causation are missing or destroyed. Nevertheless, VA and DOD insist upon reaping the benefit of any doubts created by the absence of those records.

The subcommittee believes the current presumptions about neurotoxic causes and effects should be reversed and the benefit of any doubt should inure to the sick veteran.

Finally, we reluctantly conclude that responsibility for Gulf War illnesses, especially the research agenda, must be
placed in a more responsive agency, independent of the DOD and the VA.

 

[Joan Crawford]

I don't think this report has been posted yet, sorry if it has.
https://www.govinfo.gov/content/pkg/CRPT-105hrpt388/html/CRPT-105hrpt388.htm
The second report by the committee on Government reform and oversight
Gulf War veterans' illnesses: VA, DOD continue to resist strong evidence linking toxic causes to chronic health effects

It's absolutely scathing.
Summary (just bits of it here, it's worth reading in full)

Responding to requests by veterans, the subcommittee in March 1996 initiated a far-reaching oversight investigation into the status of efforts to understand the clusters ofsymptoms and debilitating maladies known collectively as ``Gulf
War Syndrome.'' We sought to ensure sick Gulf War veterans were being diagnosed accurately, treated effectively and compensatedfairly for service-connected disabilities, despite official denials and scientific uncertainty regarding the exact causes of their ailments. We also sought to determine whether the Gulf War research agenda was properly focused on the most likely, not just the most convenient, hypotheses to explain Gulf War veterans' illnesses.

After 19 months of investigation and hearings, the subcommittee finds the status of efforts on Gulf War issues by the Department of Veterans Affairs [VA], the Department of Defense [DOD], the Central Intelligence Agency [CIA] and the
Food and Drug Administration [FDA] to be irreparably flawed. We find those efforts hobbled by institutional inertia that
mistakes motion for progress. We find those efforts plagued by arrogant incuriosity and a pervasive myopia that sees a lack of evidence as proof. As a result, we find current approaches to research, diagnosis and treatment unlikely to yield answers to veterans' life-or-death questions in the foreseeable, or even far distant, future.

We do not come to these conclusions lightly. Nor do we discount all that has been done to care for, cure and compensate Gulf War veterans. But lives have been lost, and many more lives are at stake.

Our hearings convinced us the journey from cause to cure for Gulf War veterans runs through the pools, clouds and plumes of toxins in which they lived and fought. It is a journey VA and DOD might never have taken but for persistent pressure from this subcommittee, and other House and Senate panels, that forced the Pentagon to acknowledge a ``watershed event''--the probable exposure of United States troops to chemical weapons fallout at Khamisiyah, Iraq.

Before Khamisiyah, voluminous and compelling, albeit circumstantial, evidence regarding neurotoxic exposures had
been ignored, denied or discredited, while far less abundant evidence and far less plausible psychological theories of
causation were pursued with vigor. As a result, diagnostic protocols were insensitive to exposure effects, treatments were limited and vital research was delayed.

Those denials and delays are symptomatic of a system content to presume the Gulf War produced no delayed casualties, and determined to shift the burden of proof onto sick veterans to overcome that presumption. That task has been made difficult, if not impossible, because most of the medical records needed to prove toxic causation are missing or destroyed. Nevertheless, VA and DOD insist upon reaping the benefit of any doubts created by the absence of those records.

The subcommittee believes the current presumptions about neurotoxic causes and effects should be reversed and the benefit of any doubt should inure to the sick veteran.

Finally, we reluctantly conclude that responsibility for Gulf War illnesses, especially the research agenda, must be
placed in a more responsive agency, independent of the DOD and the VA.

Shocking and sad. The impact on the veterans that I worked with was profound.

 

[Lucibee]

Would it not make sense to state that a gene affecting how sarin is processed in the body mediated that interaction - along with how anti sarin medication, such as pyridostigmine, also is processed and interacts?

Yes - that's what he did in his 1999 paper. I think the point of the current paper is to look specifically at the gene-environment interaction in the context of gas attack warnings (recall thereof). Precise recall of when and whether pyridostigmine was taken on each occasion (it's short-lived) is probably beyond the scope of any investigation 30 years after the fact.

I wonder why they would take pyridostigmine pre-deployment though? Maybe it was to check whether anyone was going to have a bad reaction?

 

[Joan Crawford]

[QUOTE="I wonder why they would take pyridostigmine pre-deployment though? Maybe it was to check whether anyone was going to have a bad reaction?[/QUOTE]

I think it was more to get them into the habit of taking them. Which is curious as evidence already existed that taking pyridostigmine could make some people sick. But then again, troops were readied in short order and deployed. Instructions and information probably got mangled in the process. And the threat of chemical attack was very real / prominent as Saddam had a history of using chemical weapons.

 

[Lucibee]

Another couple of reports:

Haley's 1997 JAMA paper - Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms - https://pubmed.ncbi.nlm.nih.gov/9005271/

and a report in the LA Times from 1994 - https://www.latimes.com/archives/la-xpm-1994-10-21-mn-53035-story.html

No single substance or organism has been identified as the cause of the health problems suffered by Desert Storm veterans. But many of the troops were exposed to a variety of potentially toxic chemicals, such as fumes and smoke from oil well fires, diesel fumes, toxic paints, pesticides and depleted uranium used in munitions and armor. They were also given three drugs, including one to prevent the effects of chemical warfare, which many have blamed on their health problems.

The drugs given soldiers included pyridostigmine bromide, a drug to protect against chemical warfare, which has known gastrointestinal side effects and which is licensed only for the treatment of myasthenia gravis, a chronic muscle weakness disorder; an as yet unapproved vaccine to combat botulism, and a licensed vaccine to protect against anthrax.

In their letter to The Lancet in 2009, Wessely et al. make the point that pyridostigmine was also used in Iraq in 2003, and yet no GWS-like cases were reported as a result of that conflict.

And in their 1999 paper, Unwin et al. (Wessely is a co-author) do concede that "A specific mechanism may link vaccination against biological warfare agents and later ill health..."
although in later reports, they back away from that somewhat.

 

[Joan Crawford]

[QUOTE="In their letter to The Lancet in 2009, Wessely et al. make the point that pyridostigmine was also used in Iraq in 2003, and yet no GWS-like cases were reported as a result of that conflict.[/QUOTE]

Thanks for posting this information. It may well be that in 2003 pyridostigmine was 'used' (according to Wessely at al., ) however, having learned perhaps more about 'how' it should be taken, or taken appropriately, perhaps this was given out, distributed but not necessarily taken, if that makes sense? So in essence 'used' as in used up, not the the store anymore, but not necessarily ingested - although Wessely at al., do say it was 'taken' by 73%, but who is to know what actually occurred on the ground. Perhaps the instructions regarding when/how to take pyridostigmine were quite different the 2nd time around.

 

[rvallee]

Early in the history of Gulf War illness research, around 1993, a decision was made in the government to the effect that “there is no Gulf War syndrome,”

Won't somebody rid me of these meddlesome soldiers?

First prize is a knighthood.

Interesting to see the strategy of botching up case definitions on purpose, same as they did with us. Of course it's probably consistent with their beliefs that all illness is basically psychological, or whatever. The obsession with psychology needing to always be the most important factor has guaranteed this failure. Now they basically can't think outside of this fully-shielded enclosed box.

 

[Jaybee00]

Merged thread

 

[borko2100]

If Sarin is indeed the cause of GWI, then I guess we need to figure out how Sarin exposure leads to a permanent CFS-like state. I'm guessing it is likely damage to a certain part of the brain. After all post concussion syndrome is quite similar to GWI and CFS. The bad news though is, if it is indeed brain damage, then I don't see how we could possibly cure it.