Performance of United States Serologic Assays in the Diagnosis of Lyme Borreliosis Acquired in Europe
John A. Branda1,
Mary Jane Ferraro1,2, and
Allen C. Steere2,4
+ Author Affiliations
1Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
2Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
3Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
4Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Send correspondence to: Dr. John A. Branda, Clinical Microbiology Laboratory, GRB 526, Massachusetts General Hospital, Boston, MA 02114, Phone: 617-726-3611, Fax: 617-726-5957, E-mail: branda.***@****
Background. American physicians sometimes need to evaluate a patient for suspected Lyme borreliosis (LB) who may have acquired the infection in Europe. Using serum samples from European LB patients, we compared the performance of European and U.S. serodiagnostic tests, including newer-generation assays containing VlsE or its C6 peptide.
Methods. The sensitivity of each assay was determined using 64 serum samples from LB patients with early or late disease manifestations who acquired the infection in Europe. Specificity was measured using 100 sera from healthy subjects from a non-endemic area.
Results. For the detection of European-acquired infection, conventional 2-tiered testing (ELISA followed by immunoblotting) using U.S. assays had an overall sensitivity and specificity of 52% and 100% compared with 81% (P=0.0007) and 99% (P=1.0) using analogous European tests. The sensitivity of a U.S. C6 ELISA used as a stand-alone test (88% overall) was statistically comparable to that of conventional 2-tiered testing using European tests (P=0.47) and was 100% specific. Similarly, an alternative 2-tiered algorithm using a standard U.S. ELISA followed by a C6 ELISA was comparably sensitive (84% overall) compared with conventional 2-tiered testing using European assays (P=0.82), and specificity remained 100%.
Conclusions. European assays outperformed analogous U.S. assays in a conventional 2-tiered testing algorithm. However, a C6 ELISA used as a stand-alone test or in the second-tier of a 2-tiered algorithm performed comparably to conventional 2-tiered testing using European assays, and can be used for evaluation of any patient, regardless of travel history.
Received December 18, 2012.
Accepted March 4, 2013.
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However, a C6 ELISA used as a stand-alone test or in the second-tier of a 2-tiered algorithm performed comparably to conventional 2-tiered testing using European assays, and can be used for evaluation of any patient, regardless of travel history.
The conclusion says:
"a C6 ELISA used as a stand-alone test .....can be used for evaluation of any patient"
Which is garbage, I think we all know that no ELISA can be used as a stand alone test.
When they refer to "european tests" I think they are referring to those devised by Infectolab in germany (There's no other lab that devises lyme tests here as far as I know) and they themselves are most emphatic that ELISA is not to be relied on as a stand alone. They actually DO NOT offer Elisa alone to their patients.
So basically their whole assertions are garbage. They know that the C6 ELISA isn't a very good test, and yet here they are saying it's good as a stand alone test! I hate to say it, but this isn't the first time Steere or his ilk have said things like this before. They say something is okay despite ample evidence that it's not.
The only useful info in there for me is that the US tests only found the European species/strains 52% of the time. This is according to their own methodology, which says that the US tests find it 90-something percent of the time.
Since at least half a dozen other studies in the US found the CDC two tier testing finds Lyme only a little more than half the time, we should assume the same for finding European Lyme. That would put the REAL percentage somewhere around 30%.
I should print this out and send it to the docs at the hospital who insisted I couldn't have Lyme because of my negative tests. From what I've heard from Australia (where I got mine), the US based tests find only a small percentage of cases. One doctor wrote that only 2 of 30 of his patients who got tested at IGeneX were CDC positive on the WB, but both were negative on the ELISA, which means a protocol-following lab wouldn't have run the WB on those two.
I am amazed that Steere et.al. were actually willing to check out the US test kits against European strains. Now, will they publicize this to doctors? Want to take any bets on that? Or do you think it'll just collect dust in PubMed?
I am very curious....anybody know how the UK does its Lyme testing? I've only heard it's pretty much useless. I am curious if they use U.S. based test kits or if they use a European made test kit.
Clearly the Europeans need to come up with their own interpretation. With no other way to absolutely confirm Lyme Disease without culturing a rash, I don't know how they'll do it. Will the strains that cause Lyme without a rash look the same on the tests??
Infectolab does 5 tests whenever they test for lyme activity.
Their tests react to the US strains of lyme and the European ones.
In the ILADS conference (2011 I think) they presented their test methods to some labs in the US which found that European strains of Lyme are remarkably common in America, to teh extent they shoujld be called "various strains" of lyme as they cannot be considered specifically European variants.
Anyway, one of their tests is called ELISPOT LTT, which is an extra sensitised version of ELISA (I've seen online that elispot as a superior version of ELISA is not only done for lyme but exists for other illnesses too).
They do this test 3 times. Testing for:
Together with this they also do an immunoblot, their version of a Western blot. They do this twice, one complete western blot for IGM antibodies and one for IGG antibodies.
The blurb about their LTT test says the following:
This method detects an antigen (Borrelia, Chlamydia, Ehrlichia, EBV, Yersinia) induced
release of interferon gamma by reactive lymphocytes. In the Elispot-LTT the T lymphocytes
are stimulated by bacterial or viral antigens. Antigen specific release of
IFN gamma is detected by a standardized ELISA colour technique in form of “spots”.
The number of spots is resulted in form of a stimulation-index (SI) in comparison with a
negative control (reference range: 2 SI (positive) mean a specific response of the T lymphocytes
regarding the different antigens in the Elispot-LTT. The higher the result of
the SI, the stronger is the T-cellular immune-response in general.
If anyone wants a further explanation of what all this means, don't ask me - your guess is as good as mine!!!
Thanks, Youve. That's very interesting ... the science and medicine are in terrible disarray, as one might expect in an emerging disease. But the biggest barrier imho? The human factor exemplified in IDSA. Sigh.
Sounds interesting. And ILADS held a meeting there in 2011, so they must feel it would be 'friendly' to long term abx.
But they also offer alternative methods only----- which gives a patient a choice.
"The articles mentioned above are supposed to show that classic medical approach with a long-term antibiosis is the primary therapy approach. This is supported in terms of holistic approach to therapy with accompanying treatments.
On behalf of the German Borreliosis Society, the BCA-clinic arranges workshops and training sessions for interested physicians. These workshops or training sessions are supposed to give physicians, who are still in doubt, a better understanding of the diagnosis and treatment of chronic Lyme disease and co-infections."
Here is their web site which probably tells about the treatments offered. (I've only skimmed it)
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