Chronic Lyme Disease: a discussion of the epidemiological data

One issue I have with many of these studies is that they are specifically looking at PTLD and not necessarily at chronic Lyme disease - and the two are not necessarily the same thing, as I tried to get to the bottom of a few months ago in my blog: https://lucibee.wordpress.com/2019/...ottom-of-the-latest-chronic-lyme-controversy/

Here's the bit where Sandra Pearson was discussing just that:
So when people talk about “chronic Lyme” it can mean any number of things, and actually has ended up meaningless. We tend to use terms such as late-stage or persistent Lyme, as the word “chronic” carries too much baggage.

Basically, any “chronic Lyme” cohort will be heterogeneous and likely to consist of the following:
  1. Untreated late-stage Lyme patients
  2. Patients in whom Lyme disease has been confirmed who have received the recommended course of antibiotics, but remain symptomatic. This tends to be called PTLD (post-treatment Lyme disease) or PTLDS (post-treatment Lyme disease syndrome). Use of the term “PTLD” acknowledges that we don’t know the cause of continuing symptoms, but includes the possibility of continuing low-grade infection. “PTLDS” assumes that the active infection has been eradicated.
  3. Possible or unconfirmed cases of Lyme disease that may not meet threshold to be included in group 2 (e.g. seronegative cases).
  4. People whose chronic symptoms have been attributed to Lyme disease, but who are not true cases and who may have another condition with overlapping symptoms (i.e. ME, MS).
There is no test that can determine the cause of ongoing symptoms in any one patient, and no test that can reliably distinguish between these groups. There is also a fierce and polarised split in expert opinion. Mainstream medicine tends to view Lyme disease as an infection that is simple to diagnose and treat. Others will maintain that both diagnosis and treatment are challenging. If Lyme disease is diagnosed early (in the first few weeks or months), outcome studies report that the vast majority of patients will recover, but 25-50% of those diagnosed late (>6 months) can have continuing, debilitating symptoms.
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Some of the epidemiological studies will follow those with diagnosed-and-treated LD forward to see if they subsequently develop late effects, and it seems that very few do.
Some will try to look retrospectively, but without the ability to definitively diagnose LD without the original rash and/or serology, that's tricky too. To do both at once would be impossible. There is also the problem that although the rash is a definitive sign of LD, not everyone who is infected presents the rash. This can lead to late presentation, and if they are treated at all, late treatment is not as effective. There just seem to be multiple things that would make any epidemiological study fraught with pitfalls. If you are too strict, you will miss people, and if you are not strict enough, you will inevitably include people who have something else.
 
Dolphin said:
The most rare scores for the SF-36 are on a 20-point scale. If I recall correctly, 10-30. So subtract by 10 and multiply by 5 to get non-normalized scores.
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Yes, thank you. But I'm mostly confused by the scores. The text says "the Lyme group had lower global health status scores compared with controls." But the table gives a mean and standard deviation of 23.8 (15.2) for the Lyme disease group and 18 (15.6) for the control group. Maybe it's just a typo where they mixed up both groups. Anyway, not that important.

duncan said:
This can only be done if you look at all the epidemiological efforts, and do so chronologically.
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That's what I tried to do. I've tried to summarize what I found, with references so everyone can have a look. If someone thinks there are important studies missing that would change the overall conclusion, it might be best to point them out directly and bring them into the discussion.

Lucibee said:
One issue I have with many of these studies is that they are specifically looking at PTLD and not necessarily at chronic Lyme disease
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I don't see how that would make a difference cause if there is no evidence for PTLDS that would have the same consequences for chronic Lyme disease.

Lucibee said:
If you are too strict, you will miss people, and if you are not strict enough, you will inevitably include people who have something else.
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I share these methodological concerns but I would argue that the burden of proof is on those making diagnoses that suggests a connection between Lyme disease and long-term disability. If we don't have strong or reliable evidence for such a connection it seems inappropriate to do so. I don't like how a hypothesis about a causal explanation for symptoms is turned into a diagnosis.
 
Michiel Tack said:
That's what I tried to do. I've tried to summarize what I found, with references so everyone can have a look. If someone thinks there are important studies missing that would change the overall conclusion, it might be best to point them out directly and bring them into the discussion.
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Understood. I think I was not entirely clear. First. how can you map epimediologic efforts reliably after 1983 since definitionally what constitutes serious Lyme changed at that time, and not in a way that favored or even reflected patients' reports? Second, you need to look closely at earlier efforts, even prior to WB announcing a spirochete was behind the sickness. Third, and certainly every bit as important as the first two, you need to expose your review to non-IDSA researchers lest you find yourself in a closed loop. That loop may be right, yes, but it's best to review all the lit.

If I were to pick a key concern, it's tracking persistent Lyme AFTER 1983. With shifting symptom parameters announced, qualifying the disease by any given clinician would have been almost uncommon.

ETA: By the way, this is a very impressive piece of work.
 
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Michiel Tack said:
Ok. Are there any epidemiological studies from before 1983 I should take a look at
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Alan Steere will be the guy. But he got a lot wrong. In fact, he was fairly certain he was dealing with a virus since abx therapy left so many of his patients sick.

It's wacky in a way, right? how do you do such an epi study without first identifying the disease? But we do that now with ME/CFS. But, the irony is that they announce it's a spirochete in '82, and then they make an epi study less reliable by changing the definitional parameters, at least in terms of major/minor symptoms. Anyway, most of the people that were doing epi studies back in the 80's would have subscribed to the new rules as layed out in 83, which, for people like me, renders those results suspect.

The CDC 2-tier test standardization protocol would make matters even worse a decade later.
 
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Michiel Tack said:
The main question I wanted to answer is whether there is an increased incidence of chronic debilitating symptoms such as fatigue, pain and cognitive difficulties following Lyme disease compared to a control group that didn’t experience Lyme disease.

In my view, if the answer to this question is no, all other discussions on the etiology and treatment of chronic Lyme disease become redundant as the diagnosis might not be the correct one.
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One must but say, the evaluation of data, both clincial and biomedical ones, is difficult here, for two reasons:

  • the symptoms are unspecific, i.e can arise from several causes, known and unknown ones
  • biomedical diagnostic tools for borrelia are not reliable
If both parameters for an association are still uncertain (and here the first ever will stay so, I guess), then the association will stay questionable. This does not mean that there is no sense in investigating the issue (causal relation of ticks on symptoms). If there is a plethora of single causes, and they were distributed equally, it would not suggest to stop any investigation and any try of treatment.

More likely though is, I think, that there is not a single cause (for such unspecific symptoms). It may be true that in this case it´s not appropriate to speak about -"Lyme disease" (i.e. about a disease with a single cause). But nevertheless the impact of such a parameter needs to be investigated.


Here is a new finding which pretty fine fits in, my bold:

Anti-lysoganglioside and other autoantibodies in post-treatment lyme disease ...
Fallon et al 2020

from the intro
We report here the results of the first study examining the hypothesis that the serum of patients with Lyme disease have a greater frequency of specific anti-neuronal autoantibodies and functional neuronal activation compared to community controls without a history of Lyme disease.
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After all, a greater frequency of specific anti-neuronal autoantibodies may rather mean a greater risk to display such unspecific enough symptoms.

This does neither say that there are less ppl affected with symptoms in the generel or also, if you want, non-lyme population, nor does it exclude other causal agents.
 
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New study: A retrospective observational study of Lyme neuroborreliosis in the southwest of England by Petridou et al.

They retrospectively followed up on 72 patients with Lyme neuroborreliosis (selection criteria weren't very strict). The long-term outcomes were reported as follows:
The outcomes for patients treated for Lyme neuroborreliosis in the UK were very good and although some people reported ongoing subjective symptoms these rarely interfered with people 's day to day lives
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Although 16 (22%) patients reported ongoing, subjective symptoms, only 2 (3%) felt that these significantly affected their activities of daily living. Such nonspecific symptoms are common in the general population, and studies comparing the rate of these between sufferers of Lyme disease and the general population show no significant difference
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Michiel Tack said:
New study: A retrospective observational study of Lyme neuroborreliosis in the southwest of England by Petridou et al.
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A couple of quick, unsolicited observations, if no one minds too much:

First, I'm always wary of retrospectives. They seem to me to be more susceptible to bias. Not always, of course, but enough to make them for me troublesome.

Second, these patients appeared to have all been treated in the acute or early disseminated phases. I, at least, could not find anything which suggested any were late stage when they received treatment. This matters. It matters a lot. It seems to follow the US old convention of mostly referring treatment efficacy studies to acute cases, where treatment success is more robust and consistent. This focus, if deliberate, concerns me.

Third, it does not appear that any of these was CDC 2-tier compliant. Less than 20% even had a lumbar puncture.

Fourth, this dismissiveness of some of the symptoms vs others smacks of the almost 40-year old study which arbitrarily bifurcated symptoms into Major vs Minor - even though it was often the collective impact of so-called Minor symptoms that resulted in sustained disability. Moreover, more than 25% of this "cohort" reported persistent symptoms. To refer to those symptoms as pretty much what the healthy population can experience...again, this is right out of the old conventional Lyme practitioners play book. Does the phrase "aches and pains of every day life" ring a bell?

Fifth, boy, I'd like to see the wording of that patient questionnaire. I'd also like to go back and re-interview all those 72 now.
 
Michiel Tack said:
Which seems rather inappropriate - it's not like they have any data for or against this hypothesis...
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They actually do have data that chronic Lyme , or persistent Lyme, or late stage Lyme, all can survive antibiotic protocols. They have it in several animal studies e.g. Tulane University's Monica Embers, where it's routine to autopsy, and they have it in specific human case studies where they've autopsied patients, e.g. Vicky Logan, or even survivors of Lyme carditis, e.g. Neil Spector at Duke University.
 
duncan said:
And b garinii. I also think bb is now in Europe as well, if I recall correctly. Bb sensu lato vs Bb sensu stricto, where the former includes all three species, while the latter is just Bb.
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Is it not unhelpful to be doing epidemiological studies referring to Bb sensu lato, when it appears to be recognised that the B afzelii and B garinii seem to cause a different range of symptoms? Would it be fair to say that afzelii is more associated with EM and garinii with neuroboreliosis? https://doi.org/10.1086/506936

In that Retrospective Study linked to in an above post, would the figure of 36% reporting EM tend to indicate a likelihood of involvement of B garinii rather than B afzelii or B burgdorferi. I seem to recall that WB suggested a figure of 90% of patients reporting EM, and I have seen elsewhere a figure of 60-80%. 36% seems very low.

My first inclination was to be critical of the lack of specificity, but reflection suggested that, as it was retrospective study, the authors could only try and make the best of the data they had available.
 
chrisb said:
Is it not unhelpful to be doing epidemiological studies referring to Bb sensu lato, when it appears to be recognised that the B afzelii and B garinii seem to cause a different range of symptoms?
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Perhaps. That may or may not be accurate. History of Borrelia can be suspect. History is written by...whom, when it comes to Borrelia?

chrisb said:
Would it be fair to say that afzelii is more associated with EM and garinii with neuroboreliosis? https://doi.org/10.1086/506936
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Maybe. I'm not sure I buy into it, but, sure, maybe. If different strains can cause different symptoms/manifestations, then that seems plausible on a species level. Obvously, not all Borrelial species appear to even cause disease in humans. I'm just not sold on where we stand today, and part of that is a lack of confidence in some historical endeavors.

chrisb said:
In that Retrospective Study linked to in an above post, would the figure of 36% reporting EM tend to indicate a likelihood of involvement of B garinii rather than B afzelii or B burgdorferi. I seem to recall that WB suggested a figure of 90% of patients reporting EM, and I have seen elsewhere a figure of 60-80%. 36% seems very low.
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Yeah, it's all kinda weird.

chrisb said:
My first inclination was to be critical of the lack of specificity, but reflection suggested that, as it was retrospective study, the authors could only try and make the best of the data they had available.
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I think you are being kind. You may be right. Still, in theory, it's not all that difficult in the world of Lyme to find whatever you may be looking for. This is an argument that speaks to the fact that, in some regards, we need to start from scratch.
 
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On reflection that figure of 36% showing EM seems closer to the figure of 18%, which Newby quoted in Bitten for the early Connecticut cases, than to the post Bb discovery figure of 90%.

If that figure of 36% is representative for distinct groups it does leave the way open for a lot of misdiagnosis if the tests are not to be relied on.
 
EM rates are all over the place, @chrisb . Factor in odd things like so-called STARI that presents with an EM like rash, but supposedly is not Lyme, or that EMs can frequently be irregular in shape and size and appear like spider or insect bites - and it gets even more bizarre.

I wish they would create a genus test, ie, one for Borrelia. Period. Get that done, preferably a direct test, none of this indirect crap. THEN parse down into species'-level tests, and then farther with strain-specific. That might resolve a lot of the nonsense that hounds the world's diagnostic efforts relative to Lyme and its cousins. No more questions about the US Midwest and Lone Star ticks. No more mystery in Australia. No more dispute that at the very least someone is infected with a spirochete.
 
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Michiel Tack said:
The protocol was been published here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466793/
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Another acute study. Generally speaking, acute and/or early disseminated cases - that are promptly treated - are not the issue. Late stage is. Persistent Lyme. What few potential Late stage patients they recruit appear to me as not having been even confirmed.

This is not complicated.

Find Late stage patients. It's really not hard. See if there is ANY Borrelia antibodies in their serum and CSF and tissue. Start autopsying brains in patient deaths where Lyme may be a contributing factor. If spirochetes are found, then you know you've got a story.

Edit to Add: Think about syphilis, also a spirochetal disease. What if almost every study only examined the first or second stage of syphilis? That would be pretty meaningless to tertiary syphilis, the one with dementia and death. And it was believed for years, that to treat syphilis, you had to get it early; once it reached the fourth stage, treatments were pretty much useless.

Well, there is an endless string of acute Lyme, ie, early Lyme, studies coming out. There have been, especially in the US, since around 1990. These studies are relevant to patients who have been diagnosed and treated early, but not so relevant for those in whom the spirochete has disseminated deep into protected areas of the body like tissue and brain etc.

This is where many, many, Lyme patients would like to see research dollars directed. They wonder that they are not. And they are concerned when they see the results of studies which target acute patients extrapolated out to apply to an entirely different disease phase: Late Stage Lyme.
 
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