Study of Insect-borne Infections in ME patients planned

[halcyon]

This is sort of the point of the CFS construct. Group together people with roughly the same clinical syndrome and then study them. If this study finds a percentage of people with Borrelia infections OK great, remove them from the CFS pool their correct diagnosis is Lyme borreliosis. If it finds people with Bartonella their correct diagnosis is bartonellosis, etc. It doesn't make sense to continue to study these patients generically as CFS patients if they have a more specific diagnosis. Would you want to give these people rituximab for example if they test positive for an active infection with a vector borne pathogen? Probably not. What we learn then is what all a CFS patient should be tested for upon presenting with the symptoms of the syndrome so that they can receive an accurate diagnosis right away and get appropriate treatment instead of rotting away in a catch-all syndrome that has no treatments available.

 

[duncan]

@halcyon , you may be jumping to conclusions.

You going to disqualify any of these qualified ME/CFS samples for testing positive for the flu or for cancer?

 

[halcyon]

You going to disqualify any of these qualified ME/CFS samples for testing positive for the flu or for cancer?

I'm not aware of any studies that have associated the influenza virus with ME or CFS and it's not a virus that can persist in the body like the others that have been associated with the disease.

Are you saying that someone with cancer should just be given a CFS diagnosis and left to die? This is my point, if someone is sick with a missed infection that could plausibly explain the symptoms, that infection should be caught and treated appropriately.

 

[duncan]

Agreed, but by the same token, you should not assume that if they find Borrelia or EBV or an enterovirus or Bartonella in the ME/CFS samples, that these samples are not from legitimate PWME.

Any PWME can have any of the diseases Knox is looking at on top of their ME/CFS - or potentially as the cause of their ME/CFS.

We also don't know how deep she will delve, i.e. evidence of exposure, or titers sufficient for a diagnosis. Regardless, several relationships need to be considered.

 

[SOC]

This is sort of the point of the CFS construct. Group together people with roughly the same clinical syndrome and then study them. If this study finds a percentage of people with Borrelia infections OK great, remove them from the CFS pool their correct diagnosis is Lyme borreliosis. If it finds people with Bartonella their correct diagnosis is bartonellosis, etc. It doesn't make sense to continue to study these patients generically as CFS patients if they have a more specific diagnosis. Would you want to give these people rituximab for example if they test positive for an active infection with a vector borne pathogen? Probably not. What we learn then is what all a CFS patient should be tested for upon presenting with the symptoms of the syndrome so that they can receive an accurate diagnosis right away and get appropriate treatment instead of rotting away in a catch-all syndrome that has no treatments available.

All true, but we have to be careful not to throw people out of ME diagnosis if treatment for the given pathogen/condition does not clear up all the ME symptoms.

Case in point 1: Pure dysautonomia looks a lot like ME to the less-than-expert. Exercise intolerance is often mistaken for PEM. Pure dysautonomia is a separate condition from ME, BUT many people with ME also have dysautonomia as a symptom. You should not throw all patients with dysautonomia out of the ME diagnosis just because they have dysautonomia, a condition which can be distinct from ME

Case in point 2: Hypothyroid is often misdiagnosed as CFS. When treated properly, CFS-like symptoms disappear. In those cases, the patient should not have an ME diagnosis because treatment for hypothyroid eliminated all CFS-like symptoms. However, many PWME are hypothyroid. Treatment improves hypothyroid symptoms, but does not clear up all ME symptoms. Those people should not be taken out of the ME patient cohort just because they have hypothyroid.

Case in point 3: Lyme Disease can be a distinct entity from ME. However, Lyme Disease patients do not have PEM. In cases where Lyme Disease is "properly" treated and symptoms persist, especially PEM, something beyond pure Lyme Disease is going on. Patients who have been treated for Lyme Disease, but still have hallmark symptoms of ME still belong in the ME patient cohort.

Exclusionary conditions for a disease are generally considered exclusionary if treatment for the exclusionary condition alleviates the identifying symptoms of the disease. The other case where exclusionary conditions exist is when the two conditions are mutually exclusive -- having one means you can't possibly have the other.

An excellent example is major depressive disorder (MDD) which can present with some symptoms similar to CFS. For that reason, some ignorant doctors misdiagnose MDD as ME/CFS or vice versa. We all know that ME and MDD are NOT the same illness. But they are not mutually exclusive. Having MDD does not protect you from having ME, nor does ME does protect you from having MDD. It's possible to have both. If you are treated for MDD and you no longer have the identifying symptoms of ME, then you don't have ME, you have MDD alone. If you're treated for MDD and you still have identifying symptoms of ME (PEM, in particular) then you still have ME, regardless of the state of your MDD. MDD and ME are not mutually exclusive conditions, therefore MDD by is not exclusionary for ME. It is only exclusionary if MDD treatment clears up all ME-like symptoms.

You cannot remove everyone with Borreliosis from the ME patient cohort. You can only remove those who don't have the identifying features of ME after (or before) treatment. True PEM (not exercise intolerance which is a symptom of a number of different conditions) still identifies ME, regardless of any other conditions you may have. This is why unique identifying characteristics are critical in a good disease definition while exclusionary conditions are not.

PWME can have many symptoms and illnesses in common with other conditions. That does not mean they don't have ME. The tricky business is to separate out those who have symptoms/conditions in common with ME, but not the identifying characteristics of ME. This is no easy task. Treatment for individual symptoms/conditions that leads to alleviation of all ME symptoms is one way to eliminate those who do not have ME. This is probably easy with with uncomplicated hypothyroid or POTS. Not so much with other confounding conditions. Finding a way to clearly identify what we call PEM would give us another way to separate out non-PWME. Unfortunately very few people are currently knowledgeable enough to distinguish PEM from exercise intolerance or exercise-related problems, and we don't have a non-destructive test.

Bottom line: Positive tests for any individual pathogen is not sufficient to eliminate an ME diagnosis. Many pathogens may be a part of an ME presentation given our immune abnormalities. Only eliminating all ME symptoms with treatment for another condition, or establishing that the patient definitely doesn't have PEM (good luck with that) can truly eliminate someone with ME-like symptoms from an ME diagnosis.

Side note: My daughter hasn't had a clear PEM episode in 2+ years while living a relatively normal life -- working full time (and more), socializing mildly, day hiking in the mountains, touristing major cities. She is still taking AVs to keep EBV and HHV6 under control, thyroid medications, treatment for OI, high dose CoQ10 and a number of other things. Does she still have ME? There's no question that she had it for 10 years or so. Is it gone because she's largely asymptomatic with treatment? Do we have to send her on a 10 mile run to see if she gets PEM to prove that she does (or does not) still have ME? At the moment we are considering ME a life-long condition that in her case is well managed. But is that true? Should ME be removed from her diagnosis list now? Nobody really knows.

Without a completely reliable testable biomarker, we really can't say for certain who has ME and who doesn't. We could certainly do a much better job of removing the diagnosis from people who clearly don't have ME, but there's still going to be a fair bit of grey area. Chronic Lyme Disease is in that grey area at the moment. Simple chronic fatigue (the symptom) is not.

 

[halcyon]

We also don't know how deep she will delve, i.e. evidence of exposure, or titers sufficient for a diagnosis. Regardless, several relationships need to be considered.

It's not clear is it. I assumed that it would involve looking for direct evidence of infection rather than qualitative evidence of antibodies. If the latter then it will be less interesting and they'll need a sufficient control population to study etc.

 

[Research 1st]

CFS will always be a dead duck as long as it's based on Fukuda CFS.
ME will always be a lame horse as long as the forward slash '/' plagues it (ME/CFS CFS/ME - all BS non science).
ME will never exist encapsulated in concrete via SEID (No inflammation necessary with SEID, thus not ME then).

By making CFS a diagnosis of exclusion, inclusionary signs of ME prevent ME from being researched.
This is only achieved by refusing have inclusion based signs of ME refused as part of the CFS criteria as was designed in the agreement below:

Here is Reeves in his own words.

Maybe, we would have been smarter to have suggested that model to begin with rather than easing through CFS
hypothesis as a default pathway for a failed viral hypothesis. So be it.

I commend you again on your efforts to forge an international consensus that has scientific merit and is politically acceptable.

Dr Stephen Straus (DHHS) writing to Fukuda.

Analogy:
If you think of ME as a face, and CFS as a mask, then you can never guess who is behind the mask, if the government refuse the face to be seen first.

The face is the disease, and the mask if CFS research criteria the government (in denial of ME) created
in response to an outbreak of infection which was 'researched' by people who said it didn't exist (researcher bias anyone?) and who wanted a good political conclusion from the failure to find the cause.

This state sponsored bias cannot be overcome irrespective if you look for Lyme or a retrovirus if you stick to the rules of the CDC - which just happen to be research criteria. (The way to defeat this corruption of science, is to change the CFS case definition to ME-ICC type medical disease not based on fatigue. Hence the cast iron refusal to do just that).

'Studying' CFS patients for a consensus agreement on pathogens is always futile, the second you find correlation you just role out the weak case definition in patients without the signs of ME and you won't find it.

Anyway, severe ME is likely a prion infection that disables mitochondria in case no one realised. (Test your blood PrPC with severe ME and you won't find hardly any in your blood!!!!). That is very bad news if you're only 20 or 30. PrpC is meant to last you for life, it's needed. And yes I made sure to get some controls, and yes they had normal levels thus proving the test works.

Activated HERV research is needed now in Lyme patients (and ME) and not on people with Chronic Fatigue with no tests. What could possibly go wrong trying to find an AIDS like disease? Answer = everything.

The whole thing is designed to fail until you insist the patients you look at have the classic signs of ME and only draw blood from these people in research studies. The state won't do that, they'll continue looking at self reported chronic fatigue and wait for the hype machine to big up up the negative findings, in unison.

This is how they deny Chronic Lyme. Place the patients with the disease inside CFS at all costs. That has been achieved. And thus Chronic Lyme, doesn't exist, as the patients are never researched, or out of desperation latch onto CFS hoping someone will help them.

Who ever planned all this, is sick in the head.

 

[Art Vandelay]

@ukxmrv , that Australian effort is curious considering the official stance there on Lyme disease (although there are other TBDs, to be sure).

I dare say that the only reason the Sydney Uni study is taking place is because it's being funded by the Karl McManus Foundation (a Lyme charity and lobby group). They are also funding research at a few other unis.

 

[sarah darwins]

Case in point 3: Lyme Disease can be a distinct entity from ME. However, Lyme Disease patients do not have PEM. In cases where Lyme Disease is "properly" treated and symptoms persist, especially PEM, something beyond pure Lyme Disease is going on. Patients who have been treated for Lyme Disease, but still have hallmark symptoms of ME still belong in the ME patient cohort.

Absolutely. That's the "lyme flavoured ME" on my Venn diagram (which wasn't entirely flippant!).

 

[Valentijn]

I'm not sure the idea of ME clusters caused by outdoor insects (or arthropods) flies very well. The clusters we know about tend to be focused on social groups collected in indoor areas -- hospitals, schools, concert halls. It's more workgroup-related than geographical. IIRC, the groupings of the cluster were less family groups (as would be expected with outdoor activity exposure) and more work/school groups.

This is a good point. But what if the relevant pathogens occasionally find a different way to be distributed? Into an experimental vaccine at the LA Hospital outbreak, or into the new closed air circulation system at the Truckee high school, etc? The clusters are extremely rare after all ... the sporadic cases are the norm.

 

[Valentijn]

But some of the ME criteria say that other primary causes of fatigue should be ruled out, don't they?

I haven't even had MS ruled out But I also very clearly have PEM, so I'm not sure exclusions are actually necessary, except with doctors or patients who have no idea what PEM is.

Lyme doesn't come with PEM. Typical LLMDs and Lyme patients have no idea what PEM is, and think it's a great idea for everyone diagnosed with Lyme to engage in mild exercise.

Because I have PEM, I have ME. And because I had a Borrelia infection, I had Lyme too. The Lyme has been treated, and I still have ME, though at least some of my symptoms are gone as a result of treatment.

Oh, and I don't think fatigue is a particularly important symptom in Lyme either. The entire focus on "other causes of fatigue" is just ridiculous for soooo many reasons. They might as well say "do a normal differential diagnosis like a normal doctor would do for any normal sick patient." As someone else mentioned recently, some form of a fatigue is part of pretty much every illness known to mankind.

 

[Valentijn]

This is sort of the point of the CFS construct. Group together people with roughly the same clinical syndrome and then study them. If this study finds a percentage of people with Borrelia infections OK great, remove them from the CFS pool their correct diagnosis is Lyme borreliosis.

Wonderful! I had Borrelia, so I'm out of the ME group. But it's been treated now and thus far I still have PEM.

How about we just toss out the people who don't have the symptoms required for an ME diagnosis? Since Lyme doesn't come with PEM (unless it progresses to ME), it doesn't make sense to throw out Lyme+ME patients any more than it would make sense to throw out people who have ME/CFS triggered by EBV, Ross-River Virus, Q-fever, or enterovirus. Or the people with chronically reactivating viruses.

Identifying a potential triggering agent for particular cases of ME/CFS does not negate the diagnosis of ME/CFS. It just wouldn't make any sense.

 

[Bob]

Here's an interesting short blog that I've just come across:

The Heartland virus may occur across the eastern U.S.
18 September 2015
http://news.sciencemag.org/health/2015/09/heartland-virus-may-occur-across-eastern-u-s

And here's a description of the life-cycle of a tick:
http://www.health.state.mn.us/divs/idepc/dtopics/tickborne/ticks.html

Interesting that a tick nymph can be as small a a speck of dirt. I wonder if they can ever get into a water supply?

 

[duncan]

The clusters have always thrown me a bit. They are one of the reasons I like the concept behind this study.

You can explain them with enteroviruses or any sort of contagion that can be transmitted through touch or can be aerosolized - but only to a certain extent. It seems the clusters remain the exception rather than the rule, at least for me.

So, there is a certain appeal in examining vector-borne pathogens which seem resistant to the process of clustering. Maybe something is happening that is not yet understood, in the sense that the transmission, or the level of infectiousness, morphs.

I'm not sure this is the right vehicle, using old blood samples as a platform. Also, we don't know their protocol, e.g., will they only require evidence of exposure to a virus of parasite or bacteria for inferences (which would get my vote)?

But the concept is curious and has possibilities.

 

[duncan]

Bob, deer ticks are really tiny. Hard to see, hard to remove once embedded because it's difficult to get a grip on them. And they are next to impossible to kill. We were taught heat/burning. I've had a couple hundred embedded on me over the last 20 or so years.

Could they get into the water supply? Maybe so. I've never heard of drowning a tick. What would happen if a bunch of infected ticks decayed in a local water supply (like a water cooler or water collector or a well)? Or if someone swallowed an infected tick?

I don't know. Interesting idea, though.

 

[sarah darwins]

Interesting that a tick nymph can be as small a a speck of dirt. I wonder if they can ever get into a water supply?

Whenever I can I like to sit out on the back step of our rural house and enjoy the view. This summer I noticed over several days a large number of tiny 'spiders' that were hatching and emerging from a crack in the wall and crawling over the step. It took me days to realise that they weren't spiders but ticks.

Eventually I trapped one on a piece of paper and brought it inside and took a photo with a macro lens. No question, ticks. Of course, even entomologists often have trouble identifying species, and I didn't ever try, so chances are it wasn't a disease carrying variety. But it brought home to me that a) ticks are very small and b) you don't have to venture out into the back woods to find them. Most of the country around our house is agricultural and wild, coastal grassland.

Next door's cat, which is a fairly wild kitty who is always outdoors, often sleeps on our back step at night and I wondered if a female tick dropped off the cat and crawled into the nearest dark space to lay eggs.

Incidentally, I stopped sitting on the step and put a chair out there!

 

[Valentijn]

@sarah darwins - Do you still have the tick photo?

 

[MeSci]

other primary causes of fatigue SHOULD be ruled out, but we all know they are often, dare I say usually not ruled out?
No GP has ever wondered if I might have a vector borne disease and I was working as a gardener immediately before I became seriously ill. The point is these infections are so often missed and are much more prevalent than first thought. My concern is that M.E patients are hardly ever fully investigated to have other causes ruled out. Perhaps we all remember Julia Newtons Newcastle clinics figure of misdiagnosis - either 30 or 40% cant remember which, but both are way too high.

I used to go to a forestry plantation every weekend collecting wood for the fire. I don't recall seeing ticks there but there were hordes of flies sometimes, and I had to tie veils round my face to keep them off me, and sometimes fled as they swarmed round me and tried to get on my skin. At other times I walked across country, crawling through fences and hedges, etc. But I didn't even have to leave home to see a tick - my cats sometimes had them, and I removed them, sometimes taking a period of days, as I didn't know it was important to remove them quickly.

 

[MeSci]

Just skimming the list, it does looks like many outbreaks are associated with work groups and/or indoor environments -- hospitals, schools, convents, group living quarters. One mentions spread from a hospital to staff children to the children's teachers. Those cases look like person-to-person transmission, although some other environmental factor could be at play as in Legionnaire's Disease.

Remember when newspapers had articles on 'sick building syndrome'? That seems to have fizzled out.

 

[Bob]

I used to go to a forestry plantation every weekend collecting wood for the fire. […] At other times I walked across country, crawling through fences and hedges, etc.

You're making me feel nostalgic. *Long Nostalgic Sigh*