A Lipkin study re tick-borne viruses & diseases - Virome analysis of Amblyomma americanum...

[anciendaze]

It would be much more convenient for ID specialists if all infectious pathogens had signed onto their rules about rapid reproduction/replication. Many have not. Nor is there any evidence that antibody titers correlate well with degree of infection in chronic infectious disease. You would think these MDs had slept through the classes which discussed the development of immune tolerance. This is nothing new; there were good reasons tests for TB based on response to tuberculin often did not work on people who were chronically ill. This can still happen if you do not identify the infection right at onset when immune response is strong and specific.

What they are actually saying is that diseases which don't obey their rules for acute disease are not serious problems. They are all convinced, for example, that EBV, HSV, CMV, etc. is in everybody, and doesn't cause problems, except in those rare cases where it may cause cancer, MS or fatal encephalitis. (This is a particular problem for those patients on this forum who have recurring EBV infections.) The diseases being denigrated are certainly inconvenient for ID specialists. They are also inconvenient for patients.

Settling the controversies over Lyme disease is not going to be easy. It was hard to begin with because all doctors had been ignoring all patients with such symptoms for a long time when a cluster of cases around Old Lyme CT caught researcher's attention. There is absolutely no evidence that this was due to introduction of a new pathogen. The distribution of b. burghdorferi indicates it has been around for centuries.

We now know the spirochete is pleomorphic and can form biofilms. Both characteristics enable it to evade detection by routine blood tests. We are still learning about related spirochetes infecting humans. Some appear to be essentially harmless. Treponema denticola is an example. Unfortunately, this has sometimes turned up in the brain during autopsies of patients who died with dementia. Dementia has become a major medical problem with serious economic implications, and people who don't die earlier of other causes have about 1 chance in 3 of suffering dementia.

The extreme cases of chronic infectious disease are tied to HERVs. Some of these represent retroviruses which infected human ancestors 100 million years ago. Most are quite thoroughly defective. This doesn't mean all are either ancient or inactive. Many which are normally inactive in healthy individuals become active in pathological states. HIV is known, for example to activate HERV K-111. This has even been proposed as a marker for infected cells.

Other examples are more controversial, breast cancer typically activates HERVs derived from beta retroviruses related to one which causes mammary tumors in mice. MS can actually produce replication-competent virions resembling a presumed progenitor of HERVs derived from gamma retroviruses. These are not convenient to handle in the laboratory because they are quite slow to replicate, and contamination is easy. If, however, you are looking for the cause of many chronic illnesses you should expect a human pathogen causing them, if such exists, to have a very long latent period to match the time from infancy, when people are easily infected, to sexual maturity, when they can pass the infection to a new generation. Pathogens which replicated as rapidly as those studied in mice would likely kill a human host before being passed on.

My position is unpopular and does not have official backing. I believe all humans are infected with a variety of infectious agents which are currently disregarded the way TB or poliovirus was disregarded for thousands of years. These only benefit the species in the sense of eliminating any individuals whose immune systems are not in top condition from breeding pools.

If you want to go back to nature, and nature's way of dealing with chronic disease, returning to a state in which infant mortality claims about 25% of all children before age 5 would eliminate many individuals who now spend way too much time in doctor's waiting rooms. If you want to deal with many degenerative diseases of unknown etiology, where it is virtually impossible to work backwards from a pathological state which has grown worse over a decade or more, you will need to do a better job of detecting changes that take place at the front end of the pathology, when doctors insist the patient should be healthy.

Unless the gulf between ID specialists and specialists in areas like cardiology, neurology, rheumatology and oncology is narrowed we are not going to make great strides in preventing those diseases which take more and more time from healthy adult life in populations which are largely free of acute infectious diseases.

added: rheumatology to list of medical specializations disconnected from ID.

 

[duncan]

Anciendaze, I always enjoy your posts. Sorry, this response has been delayed.

The Lyme problem is a fairly heavy-handed and overt representation of what can happen to medical science when a few individuals control the on/off switch for research, and for interpretation of studies which were defined with bias to begin with.

The Post-Treatment Lyme Disease Syndrome phenomenon is also emblematic, albeit a bit fuzzier around the edges when trying to define it. Actually, that's the point - no one is really trying to define it. There is one meaningful study built around PTLDS and it's been 20 years in the making, and it is suppose to characterize PTLDS patients, but I'm thinking maybe not so much.

I touch upon PTLDS here because the idea is this may be a compromise of sorts, as in Steere and company won't admit Bb still exists post doxy treatment, but they are open to the idea that an immune dysfunction triggered by Lyme may be behind continued symptoms. So, you would think they'd be looking for immune markers in their efforts to characterize PTLDS in this major and long-lasting study. Say, NK activity, or raised titers in viruses and other pathogens, or cytokine profiles, or specific proteins, etc. Only when I spoke with a leading Lyme "person" at a govt agency, that person told me the only thing they are looking for in PTLDS to characterize that population in that study is the normal Lyme suspects, e.g. Bb ELISA WB, C6, AI, PCR.

I was incredulous. BTW, when speaking about my symptoms, this same executive when discussing my relentless exhaustion, said that for ME/CFS only one therapy has been proven to work, and that is exercise. I was told to cure my Lyme/PTLDS/MECFS with exercise and better habits to induce better sleep patterns. I'm pretty sure my jaw made a loud thump as it slammed onto the floor.

 

[anciendaze]

@duncan

There was, of course, a study of the proteome found in cerebrospinal fluid (CSF) of both ME/CSF patients and PTLDS patients which showed large numbers of proteins in both not found in healthy people. This seemed to demonstrate that there are distinct infections of the CNS in both cases, though no specific infectious agent was identified.

Such studies are expensive, though the cost should be coming down. There were also issues caused by the need to pool samples to get enough material for analysis. The result was that people like the administrator you spoke with could go on saying "the science isn't there", while implicitly ensuring that the science will not be there because they have no intention of following up such leads. Dr. Lipkin's study of the microbiome, to be funded by contributions from patients, is a preferred response. Arguments about scarce funding make it pretty clear what funding is available will be used for internal political purposes aimed at perpetuating a status quo these individuals find satisfactory. (If only those damned patients would go away.) My interpretation of "Pathways to Prevention" is that they are more concerned about preventing disability claims and internal change than disease -- classic behavior for any self-perpetuating bureaucracy.

On the subject of your comments about exercise, I can report that I was telling doctors I was, in modern technical language, exercise intolerant, and that I suffered prolonged reductions in capacity for exercise following either an exercise challenge or a metabolic challenge like a GTT (or drinking alcohol), long before the term Chronic Fatigue Syndrome existed. This was either ignored or redefined to mean something quite different. I was literally told I had to force myself to exercise to get better. This continued up to the point where I was hospitalized after more than a year of "pushing myself" simply to hold a job. ("Well, obviously, we didn't mean you should push yourself into collapse." This ignores the problem that I can't easily tell the difference between acceptable levels of "pushing" and those that cause relapses. This is then classified as a psychological problem, because "everybody knows" when they are making a strenuous effort.)

For those who are new to this subject I include links to two studies showing that some patients do show prolonged reductions in capacity for aerobic exercise following an exercise challenge: Snell, Keller. These were far from the first indications that PEM/PENE was real, only the most rigorous. Official response to this has been a study in evasion. Criticism of the control arm, possibly on the grounds that the healthy people were not sufficiently deconditioned, ignores the fact that a search of prior literature shows no minor conditions at all which produce substantial drops in anaerobic threshold. If you go far enough back you can find studies of healthy volunteers who were as completely deconditioned as possible in an effort to predict what would happen to astronauts after prolonged exposure to microgravity ("weightlessness"). (While I was preparing this I ran across a paper on the use of IV saline on astronauts suffering from orthostatic intolerance, another condition I have long been reporting. In connection with ME/CFS, this is routinely dismissed as quackery used to placate neurotic patients. Neurotics like Neil Armstrong?)

You aren't going to find rigorous research on the effects of vigorous exercise on people with major conditions like heart failure for the simple reason that every doctor knows this would be unethical because it might kill them.

By redefining the patient population to include people with psychological problems unrelated to exercise tolerance you can get the preferred answer: most patients will get better if they exercise. Ignoring those whose condition declines until they end up in the emergency department (Been there, done that.) is essential to exhortation for the patient to solve the problem by his or her self without bothering the doctor or administrator who has "real important stuff" to deal with.

 

[duncan]

Yes, I know about the Natelson/Coyle/Shuster(? he used to be with Rutgers) study. You'd think that the NIH would have jumped all over that. I would take that study with a grain of salt, because I am not a fan of at least one of its authors. Regardless, it IS a susbstantive and seemingly relevant effort, and to differentiate the two is a potentially (or was) seminal opportunity.

So, why didn't the Lyme group at the NIH expand efforts into this area? As in its PTLDS body of work? Looking at proteins etc? They have not, as far as I am aware. They have a study - 20 years old and still operational - that is dedicated to PTLDS, so why not embrace this sort of stepping stone and take it to the next level? The question, naturally, and sadly, is rhetorical.

I brought into the discussion the comment about exercise to demonstrate the woeful state of knowledge at that agency. Everyone knows so many Lyme patients get diagnosed with ME/CFS. Wouldn't you think those following Lyme would understand about exercise and PEM, and want to help differentiate between, at the very least, post treatment Lyme for ME/CFS - or prove one is causal of the other - at even better, Lyme and all its sustaining symptomology?

Instead, the Lyme group to me seems intent on re-enforcing outdated dogma for both diseases.

 

[Research 1st]

@duncan
By redefining the patient population to include people with psychological problems unrelated to exercise tolerance you can get the preferred answer: most patients will get better if they exercise. Ignoring those whose condition declines until they end up in the emergency department (Been there, done that.) is essential to exhortation for the patient to solve the problem by his or her self without bothering the doctor or administrator who has "real important stuff" to deal with.

Very well explained anciendaze.

We can see the government health agencies defend their own agendas whilst making a mockery of science in the process, and it's most upsetting to see people's lives ruined in the process by capturing them within a pseudo illness definition, such as Fukuda CFS criteria.

Science now has now added to it's arsenal, repeat published exercise studies on abnormal 2-day VO2 max for CFS, and the CDC refuse to incorporate this a potential diagnostic tool, claiming exercise makes CFS patients better. .

2014 published Science says:

''Our work confirms that repeated CPETs warrant consideration as a clinical indicator for diagnosing ME/CFS. Furthermore, if based on only one CPET, functional impairment classification will be mis-identified in many ME/CFSparticipants''.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24755065

I have bolded this above, because the CDC's Dr Unger preferes 1-day VO2 max, rather than 2-day.

Over time, is this kind of rejection of science, indefensible negligence on the CDC's part and the people who 'run the show'? I think we all know the answer.

Why is it so taboo for people with potentially novel infections, (such as tick born), to get treated with medicine rather than superstition (psychiatry) just because they have a diagnosis of CFS?
Is it possible, that CFS all along was for many, a chronic infection, rather than a psychosomatic mal adaptive belief system?

I also think we will soon know the answer to that question also.

 

[anciendaze]

Just as another volley in my barrage concerning ID and exercise, here's more. There are some very well-known examples of infectious disease causing heart problems if patients are pushed to exercise when they have "flu-like symptoms", as I have been. (Any specialist dealing with myocarditis should be aware that this is dangerous. Fortunately, I did not have acute myocarditis, and survived.)

Rheumatic fever is the classic example, caused by infection with streptococcus pyogenes which typically presents as pharyngitis in children. This is known to cause massive damage to the left ventricle of the heart leading to death in severe cases. Less severe cases often result in lasting heart murmurs. You can also find a list of symptoms which are highly suggestive. (People with Lyme disease may be particularly interested in the characteristic rash with rheumatic fever, erythema marginatum, which is assumed to be caused by immune response, and forms rings.)

When I went looking for other examples in adults I ran across the case of Swedish competitors in the sport of orienteering who died of sudden unexpected heart problems. Autopsy reports showed damage very similar to rheumatic fever, which is quite unusual in adults. These were eventually traced to infection by bartonella quintana, known to cause trench fever, and usually transmitted by lice (which were not found). There are at least 8 species of bartonella involved in zoonotic epidemics affecting humans. I can scarcely emphasize enough that tracing this to a cause was difficult. As far as I know neither the natural reservoir from which this infection resulted nor the specific arthropod vector has ever been clearly identified.

Both these serious or fatal infectious causes of heart disease are identified because of the close association between infections and deaths. Asking what happens in less severe cases, where no pathologist gets to examine heart tissue, produces a bewildered response. How do I know there are such cases? The question of "how do you know no such marginal cases exist?" does not get asked. It would be astonishing if no such cases existed.

The most plausible answer to my question is that patients who escape death during the initial infection are over-represented among mysterious cases of unexplained heart failure at a later date when it is difficult to trace the cause to an infection. A brief look at statistics will show there are plenty of cases which might well fit in this category. This is a major health problem.

Added: if such chronic conditions do show up in patients, they should be expected to involve abnormal behavior of the left ventricle of the heart. Many patients with long-term ME/CFS do show a peculiar left-ventricle condition called diastolic dysfunction. If this were more severe you could predict death within 3 three years, just as with serious systolic dysfunction. Most ME/CFS patients have a less severe form which most cardiologists ignore.

 

[duncan]

I came at my illness from an ME/CFS vantage. Everything I learned, I learned first about ME/CFS. It was only years later when my borrelia titers shot past the five band threshold that I was diagnosed with Lyme.

At the time I had a WTF moment, and I knew now I had a pathogen I could track and treat and monitor and study and research - where before I had none, just whisps of possibilities that characterize ME/CFS research.

Imagine my shock when I found that even with a pathogen gripped in my fist I would be turned away. That a named pathogen associated with my symptom cluster could not just be under researched, but dismissed as phantomlike, even somatoform. And that as it was dismissed, so too was meaningful research into its most devastated population, those with Late Stage Lyme, and in particular, Late Stage Lyme NB. That the same sort of posturing that has defined ME/CFS research historically was being repeated on a different stage. A stage where even a recognized disease could be dismissed out of hand, and research smothered, and an entire population of patients set adrift without any means of redress.

It was like an epiphany. If they could do this with a universally recognized infectious disease, and castigate those stricken with the disease, and stop meaningful research into the ramifications of a Lyme epidemic...If they could do that and simultaneously redirect the world's attention towards avenues that suited their purposes and coffers, i.e. acute diagnostics and PTLDS....Well, how could anyone ever stop such a thing from continuing in the ME/CFS world that didn't even have a pathogen identified and characterized, and yes, embraced?

 

[Dufresne]

They've really got to do something about the testing for these infections. I'm forced to rely on online pharmacies and go it unsupervised up here in Canada because, as I was told by an infectious disease specialist just last week, "these infections cannot persist in a chronic, smouldering state." When I asked him about the likelihood of an accidental positive FISH test for babesia, the guy actually suggested Igenex was turning out false positives to make money. I'd originally imagined this might be the case but then I thought to myself that it would be so easy to expose this sort of thing; all one would have to do is take five samples from a single patient and send them in individually under different names for a borrelia and co-infections panel, then compare the results. Wouldn't the deniers have done this already if they really had a case?

Here's a little followup regarding this IDS for anyone interested.

I was at my GP's office the other day and I asked him if he'd received any of the lab work from the IDS I'd asked to be referred to. He looked at my file and right on top found a letter from said specialist. He glanced at it, smiled, and said, "you're going to want to have a copy of this for your scrapbook." So he left his office and returned a minute later with a photocopy. It reads as follows (names excluded), his bolding.

Dear Dr XXXXXXX

The above 40 year old, who carries a diagnosis of chronic fatigue syndrome since -2005, was seen at our XXXXXXXXXXXXX today for evaluation of results found by IGenex testing.

Assessment /Plan

This patient most likely has an over-valued idea (that he is infested with babesia) or has delusions of parasitosis. An actual parasitic infection or Lyme disease is not suspected presently. The differential diagnosis includes symptoms related to drug abuse given his “experimentation” with GHB and frequent purchase of anti-parasitic and other agents over the Internet. Igenex testing for babesia is not standardized and testing, itself, is only one part of the diagnosis of this condition. A giemsa smear has been offered along with testing for signs of of hemolysis; we will inquire as to whether PCR testing is available here but I’m not convinced the patient would accept a negative result even if it were reliable. Furthermore, treatment for babesiosis is not recommended even for symptomatic patients if their smears/PCR are negative. If this is the case, these difficult-to-manage conditions fall more under the care of Psychiatry which affected patients are often reluctant to accept.

Thank you for referring this patient in consultation.

Dr XXXXXXXX

For the record I never said I believed I was infested with babesia. I actually told him I thought my problem was due to a reaction to a toxin the pathogen was producing. I conceded I normally didn't suffer the typical babesia symptom of sweating, which is associated with damage done by the pathogen itself. I also informed him I was a teetotaller, seeing as alcoholics have an apparent inability to control infections such as babesia and bartonella, but that I had used baclofen and GHB medicinally in the past. Furthermore it was my suggestion that a smear be done, not his.

He'd originally agreed to see me based on the Igenex results I'd faxed him. He said he couldn't treat the ME/CFS but that he would the Lyme, which surprised the hell out of me. My only intention was to try to prove the babesia infection and maybe get access to atovaquone. I now suspect all he wanted to do was swipe my card and get paid. He even offered a followup appointment, which I immediately cancelled, and asked that the lab results be sent to my GP. Even months later we haven't received these. I believe I'll call his office and see if they aren't available. You never know, maybe there is something there.

I understand this guy was trying to do his job. Frankly, his thoughts and tone don't discourage me in any way (I actually got a kick out them, as did my doctor). But to be so convinced of the science around Lyme and co-infection testing to suggest a chronically ill person testing positive by CDC criteria for borrelia, and actual observation of babesia duncani by staining, should be treated by a psychiatrist is incredibly narrow-minded and goes a bit far, in my opinion. He actually seemed somewhat sympathetic in person, suggesting maybe Igenex was legit and ahead of things; and that he sees more and more patients such as myself who are suffering, and something needs to be done, etc. But then he turns around and writes this crap to my MD. I don't respect his action and I think he lacks the curiosity to educate himself on the other side of the argument concerning his "specialty."

 

[duncan]

Hubris, but a sneaky skulking form of the arrogance where doctors act one way in person, another in what they communicate with their peers.

Racial prejudice can manifest in similar fashion.