is Igenex the ONLY reliable lab?

[Eeyore]

Is it a good thing to be identifying more people who are suffering from Lyme? Obviously, if they all really are, then yes, it is... but false positives aren't doing anyone any good.

The problem is that we don't really have anything perfect to calibrate against. For many infections, the WB is considered the gold standard, which just means it's the best we have, and everything else is compared to it. However, if it's giving false negatives and positives, then it's not very useful.

With HIV testing they use an ELISA to screen as it has a high sensitivity (but not very high specificity). It usually has a reflex to a WB, because the blot has a higher specificity, but lower sensitivity. That way you don't miss very many in the initial screen, and the reflex to blot means you won't report a whole bunch of false positives.

It the blot and elisa disagree, maybe that just has to be taken as equivocal.

Obviously a positive culture has just about 100% specificity, although sensitivity isn't usually that high on cultures.

I'm concerned with the chronic lyme hypothesis that people who don't have an active infection, but do have a real disease, are trying to find a test that gives them the answer they've decided on in advance. I've had a lot of hypotheses over the years - but when the tests show the opposite, back to the drawing board I go... The scientific method is hypothesis, test, accept or reject based on test results. I'm concerned these less well known labs are just helping people to get false positives even though they are not really positive for lyme, and in the process throwing the patients and doctors off the trail of the real illness.

There are so many mechanisms that seem much more plausible than seronegative chronic active lyme infection. If the tests are all negative, and you are still sick, and still believe you have Lyme - then I'd ask what it would take to convince you that you don't, and that instead, you have something else? Early in my illness I had to entertain the Lyme possibility too - and my doc was big on it, but test after test after test all came back negative. Different tests, repeated over and over - all negative. Then the doc treated me with high dose doxy for a couple months, and it didn't help at all. So after all that, the only thing that made sense is that I didn't have Lyme. I suppose the tests could have all been wrong, but I don't see why that would be the "Occam's Razor" solution to the problem.

I wouldn't be surprised if lyme is often responsible for triggering ME - the evidence is pretty strong that it is not one single infection. Epidemic ME looks like it may begin with an enterovirus based on Dr. Hyde's thinking regarding incubation periods. My suspicion is that most infections that trigger ME are neurotropic to some degree - but I don't believe there is a chronic infection, not decades later, and especially not bacterial (like Lyme). Dr. Hyde claims they isolated an enterovirus similar to echovirus-25 by PCR from a substantial number of patients as late as 3 yrs post infection, but never after that. Still, not all patients were positive, and not all patients exposed to that virus ended up with ME.

 

[valentinelynx]

test after test after test all came back negative

I'm puzzled. If your tests were all negative, why the concern about false positives? I think it was reasonable that you consider Lyme as a possible of cause of your illness, and reasonable that you try treatment, and also reasonable that you decide you no longer wish to entertain that hypothesis as the cause of your illness due to lack of evidence.

However, if you have a high pre-test probability, e.g. tick bite, rash, endemic area, and your labs show evidence of infection (even if it doesn't meet the flawed CDC criteria) then I would put more weight on the likelihood of Lyme and pursue that more assiduously.

 

[duncan]

Eeyore, you've asked some fair questions. I will try to add to valentinelynx' response..

Yes, we are agreed, it is a good thing to be revealing Lyme in individuals who may have otherwise been told they don't have it, but obviously only if they, in fact, do. You seem concerned about the possibility for false positives; again we are agreed. An issue here is that the bigger problem may rest with the risk of false negatives - bigger both in terms of numbers, and bigger, too, in terms of health ramifications. If someone gets Lyme & Company, and is not treated quickly, the disease can disseminate and worsen, leaving many without any hope of recovery.

Here's the point of that last paragraph: Because of the nature of the current crop of diagnostics, many experts believe the risks associated with false negatives far outweigh those of false positives. How many people are being told they don't have Lyme when they do? How many are simply being told that their tests were "negative", without ever being made aware of the flaws or limitations associated with those tests?

Accordingly, how many are not receiving treatment in the early stages of disease progression when it is more easily remedied, and before it progresses to a more challenging stage?

Still, since the tests aren't that good, there is a threat either way. The only way to remedy that is to build a better test. It's hard to do that when the world is being told, wrongly, that the current 2-tier mechanism is virtually flawless. Also, it helps to stifle competitive offerings when one group already has the ear of the press. Most importantly, it is devilishly difficult to get government funding when the spigot is manned by the same people who have an interest in keeping the current metrics in place.

I think many are under the assumption that some how mass migrations of people that truly have no Lyme are being told they have Lyme. Although I am sure this happens, the more likely reality is that people get tests that are negative via 1994 Dearborn MI criteria - i.e., at least five bands IgG positive, two bands IgM - but clinically are evaluated as Lyme, and have some lab results that support that diagnosis. Let me repeat that: They have received some lab results which strengthen a clinical diagnosis. Maybe they have only three bands IgG positive, or two, or four... or maybe they have two bands IgM positive even after three or more months of having the disease...yet the bands they do have are specific to Bb. For many clinicians that know how the Dearborn criteria were crafted, a Borrelia diagnosis becomes a reasonable hypothesis.

Are there more reasonable theories than seronegative Lyme? That depends on the case, but the short answer is yes, there can be. But if you can embrace that the current tests really are that bad, and you understand which elements have merit...and if you will concede there are some doctors with intelligence and integrity that appreciate the science and the split trail it leads to...then maybe you will agree that at least seronegative Lyme should be part of the differential diagnosis - and that sometimes, the result will be a Lyme diagnosis. Sometimes.

Sometimes it won't even enter the picture. My wife showed some symptoms. We live in a Lyme-endemic area. I had her get a WB and C6 and she showed nothing. Not only was she negative, but she showed no signs of ever being exposed. I was comfortable with her diagnosis of Lyme free. I cannot speak to your case, but maybe you had no signs whatsoever, too. For that, you can be thankful.

You - as well as most people- seem to get hung up on the seronegative verdict. The only way I can think that you can get around that obstacle is to read up on the history of how Lyme diagnostics evolved, and why, and how that evolution really is more similar to a guided, prodded assured outcome with a lot of money in play for only a few.

Or you can take my word for it.

The other thing to remember is that there are many similarities between Bb and Syphilis. Both are spirochetes. Both are easier to cure earlier in the disease progression. Both are notoriously difficult to culture. Indeed, for the first 10-15 years of efforts into characterizing Borrelia Burgdorferi, more often than not, that comparison was made to help explain diagnostic AND treatment failures.

As for your suggestion that maybe Lyme is a trigger mechanism for ME? Yes, maybe it is. That's one of the reasons I too am a member of this forum. My problem is that people charged with researching Lyme - at government agencies like the NIH and CDC and NHS - need to be following the Bb pathogen to see if that's where it leads. Why them? Because that's their job, and they work for me, and they work for you, and because if they do have a tiger by the tail, at least they know what it is. It seems to me, they are in as good a position to follow it as most, and to discover where it leads while they are serving their respective communities.

Only, that really isn't happening so much.

 

[Antares in NYC]

The only way I can think that you can get around that obstacle is to read up on the history of how Lyme diagnostics evolved, and why, and how that evolution really is more similar to a guided, prodded assured outcome with a lot of money in play for only a few.

That cannot be emphasized enough, Duncan. The way patents and money played into the equation is not only sickening, but one of the main reasons why we find ourselves in this bind. In a fair world, many of the researchers appointed as gatekeepers of all things Lyme should be investigated for corruption and fraud. You know the ones. The damage they have done with their greed just can't be measured.

In light of many recent peer-reviewed studies demonstrating the resistance of the spirochete to antibiotic treatment, the way this gang has circled the wagons against sound science makes it quite evident that, at this point, they are just defending their academic turf and their lucrative patents.

I do feel the tide is turning, though. You can only push against overwhelming evidence for so long. More research is needed, but all recent studies point to a clear conclusion. Even the CDC last year had to unceremoniously upgrade the number of annual reported cases from 30,000 to 300,000. That's ten-fold. I think they have failed the public in containing this epidemic by using inadequate and out-of-date diagnostic methodology, which they still endorse.

 

[Eeyore]

"However, if you have a high pre-test probability, e.g. tick bite, rash, endemic area, and your labs show evidence of infection (even if it doesn't meet the flawed CDC criteria) then I would put more weight on the likelihood of Lyme and pursue that more assiduously. "

Absolutely agree with that.

My concern is that tests are being judged on how many positives they return, regardless of whether they are really positive. I'd like an objective standard to compare it to, which we lack really - there is no perfect test. Igenex might be better - I'm just not so sure that it is better, or that we have a way to show that it is (or is not).

I'm also concerned that people do contract Lyme, are appropriately treated, clear the infection, and are left with residual symptoms NOT caused by active infection, but rather triggered by previous infection and a resulting general immune dysregulation and/or induced autoimmunity of some sort. When that happens, patients don't get better because researchers are tilting at windmills.

 

[duncan]

Fair, only, the reality is there aren't too many researchers going down that path. Aucott at Johns Hopkins, even Steere as it relates to arthritic knees, and you've the Texas A&M team, I think.

The thing is, most research is directed at acute diagnostics. Little is looking at late stage, or post-treatment. And that's just on the diagnostic side. There is no research being conducted by the NIH that I am aware of at this moment relative to treatments, with the only exception I can think of being Zhang and Lewis with their persister study and follow-up efforts at isolating an abx protocol that is effective against those persisters.

Research efforts, more or less, in the TBD arena can be summed up as maintain the status quo, and don't rock the boat.

What progress is being realized is being legislated in.

 

[Eeyore]

@duncan -

Yes, I think if test results are ambiguous or conflicting, and one has clinical symptoms of Lyme and/or other reasons for high pre-test probability, it is reasonable to keep it in the differential and treat empirically.

I don't necessarily agree that false negatives are worse than false positives. I think that is true in an asymptomatic population. In a symptomatic population, false positives can prevent discovery of the true cause of underlying illness as one is focused on Lyme disease and stops looking for anything else, and treatments are ineffective as a result.

Furthermore, there are reasons to believe that treatments that are effective for Lyme disease could be detrimental to ME patients. So a false Lyme positive diagnosis might actually make patients worse.

Regarding the various bands on Lyme blots, I don't know the exact criteria they use. A single band won't really be specific enough to diagnose an illness w/o a lot of false positives (it's just protein electrophoresis, and many things will move at similar rates through agarose gels). That's why you need multiple bands. However, it also seems likely that certain individuals, depending on their particular HLA's, might fail to make antibodies to all of the epitopes that generate the various bands. I think it would be interesting to study HLA types and the various epitopes / bands that would result or not result from each. Generally epitopes are chosen based on the population having a very high chance of making antibodies to them as well as for their relative specificity, such that it would be very unlikely to fail to make antibodies to all of them or even a substantial percentage of them.

I would agree that some blots should be reported as inconclusive or ambiguous though - although the exact numbers of bands required would have to be studied statistically. If compared to HLA typing (which isn't nearly as hard as it used to be, nor as expensive, especially if you are only talking serotypes and not sequencing), that could increase accuracy substantially. e.g. Say we know that people who are HLA-A2/A2 don't make band X, then that could be accounted for.

I would have no objection to tests that reported a probability someone has an immune response to bb rather than a +/-.

No diagnostic test is perfect, and of course, we should always strive to improve them. My concern is people who consistently show no evidence of Lyme and insist they have it, because I don't think patients are malingering, I think they can get fixated on an idea and ignore evidence. I don't think a test should only be judged based on sensitivity, w/o regard to specificity. I can see high sensitivity / low specificity tests playing a role when used in conjunction with high specificity / low sensitivity tests. Most people, hopefully, fall into the same category on both, and then can be treated appropriately. If one has differing results, then you have ambiguity, and a method should be devised to resolve that better. (Again, my suggestion would be a blot that correlates HLA's with bands.)

You'll almost never get any argument from me that we need more NIH funding. Many diseases and patients are underserved, and that is one thing that likely unites everyone on this forum who is ill.

 

[Eeyore]

Arthritic knees? Can you send me a link on that? That made me think of something else that relates to ME pathology.

 

[duncan]

Um, all you have to do is google Allan Steere and Lyme and that's all you will see.

Seriously, I suck at links. I am hopeless. Google Steere and autoimmune response in post-treatment Lyme. He is always trying to explain away treatment refractory Lyme arthritis - and to borrow Occam's Razor, he is ignoring what is right in front of him: Persistent unresolved infection.

 

[valentinelynx]

At risk of bringing down the wroth of the alternative medicine crowd (and I have nothing against alternative medicine per se...) another group that raises my hackles is the so-called and self-proclaimed medical practitioners who use flaky, scientifically absurd or unreproducible methods to "diagnose" illness, including Lyme, other infections and sensitivities.

Because Lyme disease is difficult to diagnose and treat, there are many afflicted people desperate for help, many of whom do not have the background to know when a diagnostic method or treatment is likely to be bogus. They are willing to take a chance, which is fine, except that those with a more skeptical bent see this, and say, "See, those chronic Lyme people are all nuts."

Those who promote methods of cure that defy logic and physics are not helping the cause of those trying to point out the real, solid research that shows that Lyme is a tricky illness to diagnose and treat.

End of rant.

 

[WillowJ]

Simple question: have you had a known tick bite? Had a suspicious rash? Neither is necessary for a Lyme disease diagnosis, but certainly raises the pre-test probability. Especially if the bite occurred in an area where Lyme disease is quite common. If either of these are true for you, then I would definitely pursue the possibility of Lyme disease. If they are not, it's something to consider if nothing else is working for you.

I agree with this all except I would take "endemic area" with a grain of salt.

"Endemic" means lots of cases have been reported there.

Lyme cases are reported pretty much everywhere, but fewer in areas where they are not expected. Is this because there really are fewer in the other areas, because the CDC-approved test doesn't pick up other strains of Borrelia, or because doctors don't even think to test for something they don't expect, unless the presentation is very, unusually, clear?

 

[SOC]

I agree with this all except I would take "endemic area" with a grain of salt.

"Endemic" means lots of cases have been reported there.

Lyme cases are reported pretty much everywhere, but fewer in areas where they are not expected. Is this because there really are fewer in the other areas, because the CDC-approved test doesn't pick up other strains of Borrelia, or because doctors don't even think to test for something they don't expect, unless the presentation is very, unusually, clear?

I'm skeptical of the excessive emphasis on whether a person lives in a "Lyme endemic area". Besides the very good points WillowJ makes above, I have to wonder about the idea that where one currently lives matters so much. This is the 21st folks! People travel. They go on vacation in Lyme endemic areas. They live in multiple places throughout their lives. People who lived in or visited Lyme endemic areas and are exposed can go home and get bitten by ticks who can transmit TBDs to other people in the non-endemic area. This isn't the turn of the century where most people spend all their lives within 20 miles of where they were born. Yeah, the odds of getting Lyme are higher if you live in certain areas, but that doesn't justify "You can't have Lyme because you don't live in a Lyme area".

I also wonder why people get so bent out of shape about false positives. Yes, we want to keep them to a minimum. We'd love to have a better test with fewer false results either way. But we don't. Where does that leave us? Going with a test with more false positives, or one with more false negatives. What's worse, someone getting a false positive, receiving (not especially dangerous) treatment and finding it doesn't do anything (ho hum), or someone getting a false negative and not getting treatment for a potentially serious illness? Sure, no one wants to take a treatment they don't need, but it's all a game of chance to some degree. No tests or treatments come with 100% guarantees. We do the best we can, which involves taking some risks. When the risks are relatively small, why deny people potentially life-changing treatments because the test result might be a false positive?