Applicability of Two-Tier CDC testing to various Borrelia strains

[Valentijn]

One argument against the reliability of the CDC two-tier Lyme testing system is that it is designed only to test for a single strain, Borrelia Burgdorferi. Some claim that as a result of that, it will miss other strains of Borrelia.

Lyme disease is strictly defined as only resulting from a few strains, yet a dozen strains of Borrelia are known to infect humans. Will the serology (IgG & IgM) and/or Western Blot give a positive or partial positive result for these other infections?

 

[duncan]

Well, let's see. The species the CDC's two-tier testing was designed or intended for was Bb sensu stricto. The strain used was G39/40, but the lab kit most use when they are tested is the B31 strain.

I suppose that doesn't help much.

Some strains don't share the all of same proteins as others. For instance, supposedly strain N40 doesn't have the C6. Strain 49736 doesn't have one of the Osp's, I think, but it's a mutant.

So there are differences in the way different strains present. Not sure of the implications to WB testing, though.

I suppose I can do some sleuthing...

 

[duncan]

btw, I know that strain/species are sometimes used interchangeably. Confuses the crap out of me on a basic level. I mean, I know by the name vs number thing what a given researcher is looking at, but, geez, sometime I feel like a dolt because I've superimposed my own cheat-sheet approach, and it isn't always applicable.

Check out "Validity of Interpretation Criteria for Standardized Western Blots for Serodiagnosis of Lyme Borreliosis Based on Sera Collected throughout Europe", Hauser et al., J Clin Microbiol, July 1999.

Is suggests sensitivity levels to WB varies by garinii vs afzelii.

 

[anciendaze]

@duncan,

The whole idea of species defined by reproductive isolation is questionable with bacteria, which can exchange DNA even with very different species. A bacterial species is a more closely analogous to a eukaryotic genus.

 

[duncan]

Ok, but that should make cross-elasticities between species - in terms of diagnostics - more doable. Or no?

My brain is stumbling over itself at this point, @anciendaze ; what are the implications of your observation?

Diagnostically speaking, what is the import of the irrelevance of reproductive isolation with bacteria?

I read the abstract you provided a link for. One or two other people - who I also respect deeply - have spoken about this greater applicability of describing Bb at the genus level, that species distinctions may not apply.

I have to study this abstract some more. I do know that this suggests that symptomatic manifestations of Bb may not be that different after all, which is what I've argued, too. Or not.

Please tell me I am on the right track here...

eta: I think I'm guilty of oversimplifying the abstract's takeaway.

 

[anciendaze]

@duncan,

First, a reference to evidence of lateral exchange of genes among Lyme spirochetes. Second, evidence that a common spirochete also exchanges genes with very different bacteria in biofilms.

There is not much question at present that b. burgdorferi does form biofilms, and we are still at the early stages of figuring out which other species can participate. Chronic disease states are more likely to have long-term associations of multiple human pathogens, with potential for gene exchange.

The implications for pathology are that a species considered relatively harmless can become quite pathogenic in a short evolutionary time by acquiring a plasmid from another strain or species. Speculatively, this seems a likely origin of modern treponema pallidum from common spirochetes present in most humans, at the time of Columbus. We really don't want another such pathogen.

In diagnostic terms, we have a different problem. Unless the sequences and proteins you are testing for are fundamental to pathogenicity you may be missing dangerous infections, and getting false positives from harmless ones. Our present ignorance about what is essential and what is irrelevant in a number of borrelia species makes it impossible to say exactly what we are accomplishing with current tests.

There was a time when we did not think b. miyamotoi infected humans. Then there was a time when we did not think this took place in the U.S. These were false assumptions. Since it is widespread in wildlife, there is no problem finding natural reservoirs for similar spirochetes.

Even if our current tests were reliable, we would still need an on-going surveillance program to spot the emergence of new infectious diseases which might be as long-term and devastating as syphilis. Assumptions about extremely rare events, and limits of transmission, no longer apply when you are dealing with a single connected human population of 7 billion, and common travel between continents. The current situation is completely outside historical comparisons.

 

[duncan]

@anciendaze , understood. Thank you for the detailed and fascinating explanation.

I noticed the paper on lateral transfer of OspD was dated 1994 - they could have known all this at the Dearborn conference, arguably sooner.

It would be interesting if someone could date the transfer of OspD to sensu stricto from garinii and afzelii.

The issue then, if I understand correctly, may be not which strain or species, but which Borrelia has the right genetic mixture of plasmids to cause damage. That could be subsets -- or over-arching umbrella groups -- of what we currently define by species/strains labels.

 

[alex3619]

First, a reference to evidence of lateral exchange of genes among Lyme spirochetes. Second, evidence that a common spirochete also exchanges genes with very different bacteria in biofilms.

Most bacteria can exchange genes with most other bacteria. Its a big issue, and one that has doctors worried about antibiotic resistance. An innocuous antibiotic resistant bacteria from chickens, for example, could pass that to a human pathogenic bacteria. In hospitals there is risk of resistance transferring to different pathogenic bacteria that were never resistant before, which is why hospitals have such strict rules about medical waste, even more than they used to.

Bacteria do not, to my (possibly outdated) understanding, transfer genes wholesale. Its a few at a time. They have small strings of genes called plasmids that transfer. This does however happen differently with millions of bacteria, so that even a colony of bacteria will have considerable variation over time if other bacteria are there also.

This means that bacteria can evolve very very fast. Not as fast as viruses, but much faster than us. This is because the huge numbers and short reproduction cycles make the evolutionary process tick over faster.

 

[anciendaze]

@anciendaze , understood. Thank you for the detailed and fascinating explanation.

I noticed the paper on lateral transfer of OspD was dated 1994 - they could have known all this at the Dearborn conference, arguably sooner.

There was nothing surprising about that paper. This is the norm for bacteria.

It would be interesting if someone could date the transfer of OspD to sensu stricto from garinii and afzelii.

Borrelia species have been around for a long time. The "iceman", who died before the pyramids were built, tested positive for some such species. It appears that all three current "species" derive from a common ancestor, and it is not even clear that these species are completely distinct today. This is even true of some highly-pathological species of borrelia.

The issue then, if I understand correctly, may be not which strain or species, but which Borrelia has the right genetic mixture of plasmids to cause damage. That could be subsets -- or over-arching umbrella groups -- of what we currently define by species/strains labels.

Here's a detailed analysis which is somewhat overwhelming.

To a surprising extent, our ability to test for b. burghdorferi depends on unimpaired immune response, and our willingness to test specifically depends on clinical signs like the "bullseye rash" (erythema migrans) which are themselves local consequences of immune response to proteins in the outer membrane. A change in surface proteins, which sometimes happens in wild species moving to new hosts, could result in a stealth infection which would cause serious damage to CNS, heart, joints, etc. without ever provoking those initial clinical signs. We aren't even certain that this has not already taken place. Depending on immune response to detect an infectious disease which often impairs immune response involves circular reasoning.

Some patient's peripheral blood remains seronegative even though DNA and specific immune cells suggesting active spirochetes can be recovered from synovial fluid at joints, and possibly from CSF.

 

[duncan]

Thanks for the detailed analysis link. I read some of it, but it seemed to very quickly descend to characterizations promoted by mainstream interests. No surprise as one of the authors is Durland Fish.

I will try to delve deeper into it at another time.

 

[anciendaze]

To a large extent the problems with borrelia spp. are similar to problems with other infectious diseases. The difference comes when you talk about chronic infectious disease, which infectious disease specialists would rather not deal with. The whole range of chronic infectious diseases is inconvenient for clinical practice.

Where our current official response fails badly is in providing useful information and tools for clinicians who don't spend all their time reading research papers. You can question ordinary doctors about the prevalence of erythema migrans in Lyme disease just as an example. Many assume it is almost always present. You should then ask about the time from appearance of the rash to general seroconversion. Most do not know there is often a delay of weeks. Finally, you should ask about testing to see if the infection has been cleared after treatment. This is a real problem as people go on producing antibodies after infection.

Now imagine you live in a geographic region where the CDC has declared that Lyme is not present, but only STARI, which produces a similar rash. If a doctor does anything about a patient exhibiting such a rash, he/she will treat with a common antibiotic for a few weeks, then declare the medical problem solved. This is not done on the basis of objective evidence. Despite all this there are quite a number of confirmed cases of Lyme disease in patients from regions where STARI is said to be the only problem. (BTW: STARI is not a reportable disease.) Some of these patients have never been in an area where Lyme is endemic. Wild animals are under no such restriction, and some migratory birds carry borrelia.

We now know that STARI also appears in regions where Lyme is endemic. Thus a doctor getting a negative serological test is encouraged to ignore that initial clinical sign. If you can ignore clinical signs when you feel like it, and you don't understand when to test, and laboratory tests are unreliable, and there is no good way to tell if treatment has cleared the infection, what is the result?

This reminds me of a game show imagined by Firesign Theater: Beat the Reaper.

 

[duncan]

Right.

The STARI thing is one of the reasons I had to put down that paper you linked to. Conventional Lyme says Bb is only communicated by ixodes ticks. So a disease conveyed by say, the Lone Star tick, cannot be Lyme. Case in point: STARI.

Brings to mind the recent paper out of North Carolina that more or less said Lyme does not exist in NC at a significant level yet, despite documented reports of patients not only symptomatic, but registering 2T positives. So what did these researchers say? They said that the 2T positives registered in patients within a certain area in NC, reviewed retrospectively, had to have been false positives. In this case, that meant acknowledging an 80% error rate in the 2T in this area of NC.

80%.

eta: @msf provided a link to that study in a thread here not too long ago.

 

[anciendaze]

You seem to be assuming there is any logical consistency in papers on Lyme approved by HHS agencies. This is dangerous, unless you are talking politics. The official line is that Lyme disease is "mostly harmless" except in those few cases where it results in heart block causing death, CNS damage, or crippling arthritis. These exceptions must be rare because they are seldom reported as such.

(On the other hand, we have a wide range of heart problems, CNS problems, peripheral neurological problems and arthritis now considered "of unknown etiology".)

That paper you did not read is almost guaranteed to prevent practicing clinicians from delving into details. This supports official obfuscation which leaves everyone dependent on authority. This is much preferable in certain quarters to admitting "we don't know what is going on, or what to do about it."

 

[duncan]

Yeah, one cannot have a meaningful conversation about Lyme - or most other TBDs, for that matter - without confronting the absolutely stark paucity of logical consistency, embracing and becoming proficient in Bb politics, and forever finding yourself rubbing your eyes in disbelief.