Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

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dlf
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Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Post by dlf » Wed 20 Apr 2016 5:47

At long last, a study that examines strain differences in the same genospecies. If they are ready to acknowledge differences in clinical features and inflammatory potential between European and American strains of Borrelia burgdorferi sensu stricto, hopefully the next avenue of research will look at strain differences in a single species located within a single continent.

I would love to see the full text for this one.

Emerg Infect Dis. 2016 May;22(5):818-27. doi: 10.3201/eid2205.151806.

Differences in Genotype, Clinical Features, and Inflammatory Potential of Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Cerar T, Strle F, Stupica D, Ruzic-Sabljic E, McHugh G, Steere AC, Strle K.

http://www.ncbi.nlm.nih.gov/pubmed/27088349
Abstract
Borrelia burgdorferi sensu stricto isolates from patients with erythema migrans in Europe and the United States were compared by genotype, clinical features of infection, and inflammatory potential. Analysis of outer surface protein C and multilocus sequence typing showed that strains from these 2 regions represent distinct genotypes. Clinical features of infection with B. burgdorferi in Slovenia were similar to infection with B. afzelii or B. garinii, the other 2 Borrelia spp. that cause disease in Europe, whereas B. burgdorferi strains from the United States were associated with more severe disease. Moreover, B. burgdorferi strains from the United States induced peripheral blood mononuclear cells to secrete higher levels of cytokines and chemokines associated with innate and Th1-adaptive immune responses, whereas strains from Europe induced greater Th17-associated responses. Thus, strains of the same B. burgdorferi species from Europe and the United States represent distinct clonal lineages that vary in virulence and inflammatory potential.


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ChronicLyme19
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Re: Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Post by ChronicLyme19 » Fri 22 Apr 2016 3:07

Important to note:
In a study of patients with Lyme borreliosis in the United States (Rhode Island and Connecticut), 91 B. burgdorferi isolates were cultured from erythema migrans lesions (10). One isolate had a mixed genotype and was not included in our study. All patients met the Centers for Disease Control and Prevention (Atlanta, GA, USA) criteria for erythema migrans.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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ChronicLyme19
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Re: Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Post by ChronicLyme19 » Fri 22 Apr 2016 13:24

Also interesting:
Consequently, strains defined as the same species might cause a spectrum of disease with different clinical features. Thus, species determination on the basis of genetically conserved regions of the genome might not adequately reflect the difference in virulence.
Thus, we believe that differences among Borrelia strains are the critical factor in explaining differences in clinical features of Lyme borreliosis on the 2 continents.
They didn't seem to address the possibility of those from the US that showed worse symptoms as potentially having at least one other co-infection that could trigger the stronger immune response that seemed to correlate with more severe symptoms in this study. I would like to see that addressed before concluding this.

They make the assumption that Lyme in the mid-west is generally not as bad as in the northeast. I wonder how the co-infection rates differ for the northeast to mid-west.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

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LHCTom
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Re: Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Post by LHCTom » Mon 25 Apr 2016 18:47

I believe it would be more important to review the wide range of genotypes of Borrelia that cause a Lyme like condition such as Borreliosis that would treated identically as common infections. Borrelia has a long history of migration across the world over millions of years with large barriers such as the Atlantic Ocean, Pacific Ocean, Rocky Mountains etc. blocking easy geographic movement via hosts. Birds are likely the most dominant host able to carry genotypes over wide oceans, the near arctic loops or tall mountain barriers. That is why Europe, the Americas and Asia all have different genotypes and even within a group like burgdorferi there are significant differences impacting antibody test design.

One would expect disparate genotypes with occasional lucky similarities to appear in Europe, Asia, North America's East Coast and North America's West Coast. And this is essentially what is seen by geneticists doing population studies. It’s one of the underlying reasons that when a test is developed for Europe, or Asia or North America's East Coast, its sensitivity is lower when used outside its intended target range of genotypes. The statistical nature of both the ELISA and Western Blot ratios contribute to this sensitivity effect. It’s also due to the surface proteins on which the ELISA and WB are based is sensitive to variations of amino acid sequences that end up being the dominant epitopes on which the test relies.

In the case of the CDC 2T test Western Blot confirmation test, it relies on 10 antigens in the IgG ratio of 5/10. If one or two of the 10 antigens have changes that impact either the ELISA or Western Blot, the test will fail. This is why the Europeans and Asian researchers developed their own tests based on the local situation. I contend the Rocky Mountains is as significant a barrier to genotype movement as either ocean, the arctic loops (via Iceland-Greenland or Alaska-Siberia).

Evolution, lateral gene flow and other mechanisms slowly alter the surface antigen amino acid sequences plus the gene expression of these target surface antigens for a particular infection varies under the control of other genes that have evolved interworking with the host’s immune system and the ease or hostility it encounters while disseminating. So to design a test with high sensitivity and specificity across all its application geography usage, it must take into account nearly all the genotypes in the geographic range and their impact on surface antigen expression. Designers should do large, complete and exhaustive actual human with infections genotype studies in not only the East Coast but most importantly the West Coast. This must be true for any cases likely encountered by physicians who don't have the time or depth to understand the issues. If a CDC 2T comes back negative at the ELISA or Western Blot, the medical record is marked as negative and Lyme is eliminated. This is happening on the West Coast over and over.

If that patient had B. bissettii, B miyamotoi or a burgdorferi genotype (or other) infection that was unique, that Lyme sufferer will go years fighting an uphill battle and probably will encounter a whole range of physician competence. The supposedly best IDSA physicians are pushing ill patients into the hands of possible quacks and then complaining about their treatment strategies. These are ill patients and too many IDSA doctors look at test report black and white and ignore the patient reality. Too many physicians diagnose based on 80/20 (works on 80% and ignore the 20%) designed or even faulty tests. That’s called questionable ethics.

Among the most obvious example cases is the US East Coast versus West Coast. The original 1994 CDC 2T design was based on a genotype with its heritage in the US Northeast. But California has identified Borrelia miyamotoi as being approximately 1/4 of the Borrelia genotype found in North Coast Counties. This implies a physician in a San Francisco North Coast County would see and test 1 Borrelia miyamotoi patients per 3 Borrelia burgdorferi. Ignoring the fact that these 3 Bb in CA may have sufficiently evolved to have lower sensitivity in California, there is no reliable Borrelia miyamotoi test available leaving at least one out of four Lyme patients in CA, doomed to a missed diagnosis and a long uphill battle to overcome that one failed test. The real number may be as 1/3 when one takes the other genotypes into account plus the patient’s immune system response and its effect on the test temporally.

In a recent April 13 2016 publication:

http://www.ncbi.nlm.nih.gov/pubmed/27076681

“Borrelia miyamotoi is a relapsing fever spirochete in Ixodes ticks that has been recently identified as a human pathogen causing hard tick-borne relapsing fever (HTBRF) across the Northern Hemisphere. No validated serologic test exists, and current serologic assays have low sensitivity in early HTBRF.” There is no reliable antibody test for late disseminated Borrelia miyamotoi either. There is no high caliber antibody test that is FDA approved nor reliably validated across all Borrelia miyamotoi genotypes from Europe to Asia to the US West Coast to the US East Coast. An upcoming paper will show that a Borrelia miyamotoi spirochete found in a tick in Sonoma has dramatic differences from its East Coast cousin.

Dr. Gary Green is the predominant Infectious Disease Physician in the California North Bay Counties. This is also the center of the Lyme and TBD infection occurrence in Northern CA and his positions drive both the largest Insurance Carrier “Kaiser Permanente” internal view with its 8 million CA members and his writing in local medical publications and seminars spreads his views to many Physicians in this area. In a recent publication by Gary Green and the California Department of Public health he said :

https://mydoctor.kaiserpermanente.org/n ... /garygreen

https://www.cdph.ca.gov/HealthInfo/disc ... nsinCA.pdf

The Article at:

http://www.nbcms.org/about-us/sonoma-co ... &tabid=747

Says:
“Borrelia miyamotoi is an emerging tick-borne spirochete pathogen in Europe and the East Coast, and it has been detected in almost 2% of the western black-legged ticks in California since 2000,12,13 but no human cases have yet been confirmed in the state. Other interesting pathogens, such as a Bartonella species, are not yet identified as tick-borne. Many patients and some physicians prematurely consider Bartonella as a tick-borne pathogen. There is little evidence that Bartonella species can replicate within ticks, and no definitive evidence of transmission by a tick to a vertebrate host.14” Gary Green fails to mention that a large percentage of ferl cats in Sonoma have Bartonella and a simple scrtach transmits the bacteria. It might not be a high probability TBD but its a very HIGH cat host vector disease in Sonoma. :idea:

His statement regarding finding B. miyamotoi in 2% of western black-legged ticks seems to give a misleading impression since its occurrence can be far higher in any one geographical area. It also gives the impression a “good test is available that they are using. He also claims this 2% (the long term 16 year average over many sets of ticks across the entire state and not the hotspots where patients live and play) has been monitored since 2000 ( 16 years) but no human cases have yet been confirmed in the state. That doesn’t meet the common sense test in that roughly ¼ of the North Coast infections in his very Santa Rosa Sonoma County clinic should have been B miyamotoi, B. bissettii and a few other local genotypes with test problems. That doesn’t sound good to me. It does sound cost effective for Kaiser Permanente and by bringing in the CDPH and educating many Physicians; he spreads the responsibility to the patients out to the CDPH and other Physicians. Maybe it was just a propagating error? Oh well. What do you think? The article is pack jammed with this kind of information seemingly minimizing the problem in almost every case. :twisted:

Given the earlier April 2016 publication plus the CDC openly states no current sensitive or reliable test for B. miyamotoi exists, how did Dr. Green and the CDPH authors draw this conclusion? What test does he use to prove no cases were found? None mentioned. Why would they mislead the North Coast Physicians rather than explain the situation refarding no FDA approved test. Odd ? Anyone following the problem knows there is no effective test for B miyamotoi that is FDA approved and commercially available. PCR testing is only effective during the early febrile pulses of spirochetemia when the blood is surging with spirochetes. Once it disseminates, it requires an effective antibody test and even our 25 year old CDC 2T is fraught with issues on the Bb genotypes it is effective against. Was the potential of patients tested with the CDC 2T serologic expected to be unrelaiblel? Sound like what happened in Europe after the US released the CDC 2T and it did so poorly in Europe. Oops. Another lesson learned and lost. :woohoo: :woohoo:

That was one simple example of how one dominant IDSA Physician in a position of direct diagnosis power over >166,000 Kaiser members in Sonoma plus indirect power over 8 million members in California and probably >300,000 in the greater North San Francisco Bay Area potentially misleads readers into believing there is a valid B miyamotoi test and not one human case has been found in California. That concerns me. I hope all the patients where the test failed didn't go on to PTLDS and a lifetime of possible suffering. This is all because of the poor design of antibody tests that are not effective against Lyme Borreliosis due to genotype variations.

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:woohoo: :woohoo:
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Lorima
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Re: Differences in Borrelia burgdorferi sensu stricto Strains from Europe and the United States.

Post by Lorima » Tue 26 Apr 2016 2:07

2T also doesn't work on the east coast or in the midwest US. It was developed using arthritis patients, who are likely a minority of late stage patients, and who are known to have exceptionally high Bb antibody levels. 2T is too insensitive to use for diagnosis. Maybe the CDC knew that in the past, which is why they kept emphasizing it was "for surveillance purposes only." But they suffered an institutional memory failure.
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