LTT for Borrelia Detects Active Lyme Borreliosis

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
RitaA
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Joined: Thu 1 Jul 2010 8:33

LTT for Borrelia Detects Active Lyme Borreliosis

Post by RitaA » Sat 13 Oct 2012 4:45

http://www.benthamscience.com/open/tone ... TONEUJ.pdf
The Open Neurology Journal, 2012, 6, 104-112

Open Access

The Lymphocyte Transformation Test for Borrelia Detects Active Lyme Borreliosis and Verifies Effective Antibiotic Treatment

Volker von Baehr 1, Cornelia Doebis 1, Hans-Dieter Volk 2, Rüdiger von Baehr 1,*

1 Institute for Medical Diagnostics, Immunology Department, Nicolaistrasse 22, 12247 Berlin

2 Institute for Medical Immunology, Charité University Medicine Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin

Abstract: Borrelia-specific antibodies are not detectable until several weeks after infection and even if they are present, they are no proof of an active infection. Since the sensitivity of culture and PCR for the diagnosis or exclusion of borreliosis is too low, a method is required that detects an active Borrelia infection as early as possible. For this purpose, a lymphocyte transformation test (LTT) using lysate antigens of Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii and recombinant OspC was developed and validated through investigations of seronegative and seropositive healthy individuals as well as of seropositive patients with clinically manifested borreliosis. The sensitivity of the LTT in clinical borreliosis before antibiotic treatment was determined as 89,4% while the specificity was 98,7%. In 1480 patients with clinically suspected borreliosis, results from serology and LTT were comparable in 79.8% of cases. 18% were serologically positive and LTT-negative. These were mainly patients with borreliosis after antibiotic therapy. 2.2% showed a negative serology and a positive LTT result. Half of them had an early erythema migrans. Following antibiotic treatment, the LTT became negative or borderline in patients with early manifestations of borreliosis, whereas in patients with late symptoms, it showed a regression while still remaining positive. Therefore, we propose the follow-up monitoring of disseminated Borrelia infections as the main indication for the Borrelia-LTT.

Keywords: Borrelia serology, borreliosis, diagnostics, immune response, lymphocyte transformation test, T cells.

[The complete article follows]

ChuckG
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Location: Berkeley

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by ChuckG » Sun 14 Oct 2012 1:33

I only skimmed the paper. On page 10.
A Borrelia-LTT test that has become negative is not evidence, however, that a Borrelia infection has been cured. This was demonstrated in follow-up studies over a one year period in patients with late borreliosis. Borrelia that persist in spite of antibiotic treatment, which have been described multiple times [27, 28, 29, 30], are very likely responsible for this phenomenon. After reactivation of the infection with renewed antigen presence, apparently Borrelia-specific T cells are rapidly mobilized from the lymphoid organs. The clinical symptoms and the course of the LTT reactions suggest that these patients could suffer from persistent or latent borreliosis with phases of reactivation. For this reason doubts are arising about the prevailing opinion that a single, con- cerning dose and duration appropriate, antibiotic treatment is sufficient to eliminate the Borrelia completely.
Need Henry.

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by RitaA » Sun 14 Oct 2012 2:27

ChuckG wrote:I only skimmed the paper. On page 10.
A Borrelia-LTT test that has become negative is not evidence, however, that a Borrelia infection has been cured. This was demonstrated in follow-up studies over a one year period in patients with late borreliosis. Borrelia that persist in spite of antibiotic treatment, which have been described multiple times [27, 28, 29, 30], are very likely responsible for this phenomenon. After reactivation of the infection with renewed antigen presence, apparently Borrelia-specific T cells are rapidly mobilized from the lymphoid organs. The clinical symptoms and the course of the LTT reactions suggest that these patients could suffer from persistent or latent borreliosis with phases of reactivation. For this reason doubts are arising about the prevailing opinion that a single, con- cerning dose and duration appropriate, antibiotic treatment is sufficient to eliminate the Borrelia completely.
Need Henry.
I agree. I miss his input.

X-member
Posts: 5146
Joined: Mon 30 Jul 2007 18:18

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by X-member » Sun 14 Oct 2012 16:28

Thank you for posting this very interesting information, Rita!

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by Lorima » Mon 15 Oct 2012 15:36

It's easy to know what Henry would say, just search the web for "LTT Lyme CDC". 
What comes up first is this: 
 
http://www.cdc.gov/lyme/diagnosistreatm ... /OtherLab/
Other Types of Laboratory Testing
Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. Unvalidated tests available as of 2011 include:

Capture assays for antigens in urine
Culture, immunofluorescence staining, or cell sorting of cell wall-deficient or cystic forms of B. burgdorferi
Lymphocyte transformation tests
Quantitative CD57 lymphocyte assays
“Reverse Western blots”
In-house criteria for interpretation of immunoblots
Measurements of antibodies in joint fluid (synovial fluid)
IgM or IgG tests without a previous ELISA/EIA/IFA
References
Notice to readers: caution regarding testing for Lyme disease. MMWR, CDC Surveillance Summary, 2005, 54:125.
Marques A, Brown MR, Fleisher TA: Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin Vaccine Immunol 2009, 16:1249–1250.
If we want more, click on the link in the references, and you get this: 
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5405a6.htm

Notice to Readers: Caution Regarding Testing for Lyme Disease

CDC and the Food and Drug Administration (FDA) have become aware of commercial laboratories that conduct testing for Lyme disease by using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall--deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. In addition, some laboratories perform polymerase chain reaction tests for B. burgdorferi DNA on inappropriate specimens such as blood and urine or interpret Western blots using criteria that have not been validated and published in peer-reviewed scientific literature. These inadequately validated tests and criteria also are being used to evaluate patients in Canada and Europe, according to reports from the National Microbiology Laboratory, Public Health Agency of Canada; the British Columbia Centres for Disease Control, Canada; the German National Reference Center for Borreliae; and the Health Protection Agency Lyme Borreliosis Unit of the United Kingdom.

In the United States, FDA has cleared 70 serologic assays to aid in the diagnosis of Lyme disease. Recommendations for the use and interpretation of serologic tests have been published previously (1). Initial testing should use an enzyme immunoassay (EIA) or immunofluorescent assay (IFA); specimens yielding positive or equivocal results should be tested further by using a standardized Western immunoblot assay. Specimens negative by a sensitive EIA or IFA do not need further testing. Similar assays and recommendations are used in Canada (2). In the European Union, a minimum standard for commercial diagnostic kits is provided by Conformité Européene (CE) marking; application and interpretation guidelines appropriate for Europe have been published (3,4).

Health-care providers are reminded that a diagnosis of Lyme disease should be made after evaluation of a patient's clinical presentation and risk for exposure to infected ticks, and, if indicated, after the use of validated laboratory tests. Patients are encouraged to ask their physicians whether their testing for Lyme disease was performed using validated methods and whether results were interpreted using appropriate guidelines.

References

CDC. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR 1995;44:590--1.
Consensus Conference on Lyme Disease. Can Dis Wkly Rep 1991; 17:63--70.
Wilske B, Zöller L, Brade V, et al. MIQ 12 Lyme-Borreliose. Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. Munich, Germany: Urban & Fischer Verlag; 2000;1--59. Guidelines available in English at http://nrz-borrelien.lmu.de/miq-lyme/index.html.
Robertson J, Guy E, Andrews N, et al. A European multicenter study of immunoblotting in serodiagnosis of Lyme borreliosis. J Clin Microbiol 2000;38:2097--102.
If we want it with attitude, that's a little more experimental. I got it on the second try, typing in "LTT Lyme Feder" (referring to Henry Feder, who often participates in Lyme establishment screeds against heterodoxy in prestigious journals). If that hadn't worked, I would have used McSweegan, Shapiro, etc.

http://www.hpa.org.uk/web/HPAweb&HPAweb ... 4013002855

This is a UK official site with an aggrieved tone seeping through. 
Says the same thing as above. 

Finally I tried "LTT Lyme ALDF" and got this article. It's good, if you want a summary of the IDSA-consistent position from Europe (or at least from Germany):

http://www.aldf.com/pdf/German_Review_o ... ssease.pdf
PubMed ref: 
Dtsch Arztebl Int. 2009 Jan;106(5):72-81; quiz 82, I. Epub 2009 Jan 30.
Lyme disease--current state of knowledge.
Nau R, Christen HJ, Eiffert H.
Source
Geriatrisches Zentrum, Evangelisches Krankenhaus Göttingen-Weende, Abteilung für Neurologie, Universitätsklinikum Göttingen, Göttingen, Germany. rnau@gwdg.de
Abstract
BACKGROUND:
Lyme disease is the most frequent tick-borne infectious disease in Europe. The discovery of the causative pathogen Borrelia burgdorferi in 1982 opened the way for the firm diagnosis of diseases in several clinical disciplines and for causal antibiotic therapy. At the same time, speculation regarding links between Borrelia infection and a variety of nonspecific symptoms and disorders resulted in overdiagnosis and overtreatment of suspected Lyme disease.
METHOD:
The authors conducted a selective review of the literature, including various national and international guidelines.
RESULTS:
The spirochete Borrelia burgdorferi sensu lato is present in approximately 5% to 35% of sheep ticks (Ixodes ricinus) in Germany, depending on the region. In contrast to North America, different genospecies are found in Europe. The most frequent clinical manifestation of Borrelia infection is erythema migrans, followed by neuroborreliosis, arthritis, acrodermatitis chronica atrophicans, and lymphocytosis benigna cutis. Diagnosis is made on the basis of the clinical symptoms, and in stages II and III by detection of Borrelia-specific antibodies. In adults erythema migrans is treated with doxycycline, in children with amoxicillin. The standard treatment of neuroborreliosis is third-generation cephalosporins.
CONCLUSIONS:
After appropriate antibiotic therapy, the outcome is favorable. In approximately 95% of cases neuroborreliosis is cured without long-term sequelae. When chronic borreliosis is suspected, other potential causes of the clinical syndrome must be painstakingly excluded.
Comment in
Different Symptoms. [Dtsch Arztebl Int. 2009]
Higher dosage at later stages. [Dtsch Arztebl Int. 2009]
Veterinary medical research. [Dtsch Arztebl Int. 2009]
PMID: 19562015 [PubMed - indexed for MEDLINE] PMCID: PMC2695290 Free PMC Article
Here's what it says about LTT: 
Neither antigen testing of body fluids nor PCR on urine samples is recommended, as these techniques have not been clinically validated. The same holds for the lymphocyte transformation test, which, in principle, should be able to detect very early Lyme disease and to distinguish active from no longer active infection. This method is particularly subject to false-positive results and is therefore not suitable for diagnostic use in its current stage of development (6, 15).
We could go on like this, but I guess this is thorough enough ;)

Best regards, 
Lorima

PS: It occurred to me that what might be wanted is a simple, authoritative statement with a scientific ring to it. I'm routinely suspicious of that sort of thing, but one could easily be generated from the paragraph quoted just above. Cutting and pasting, I get:
The lymphocyte transformation test, in principle, should be able to detect very early Lyme disease and to distinguish active from no longer active infection. However, this method has not been clinically validated. LTT is particularly subject to false-positive results, and is therefore not suitable for diagnostic use in its current stage of development.
Anybody want to tinker with it?
"I have to understand the world, you see."
Richard Feynman

TicksSuck
Posts: 100
Joined: Thu 31 May 2012 20:25

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by TicksSuck » Mon 15 Oct 2012 18:23

Can we trust publications in this journal?

http://scholarlykitchen.sspnet.org/2009 ... r-dollars/

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by Lorima » Mon 15 Oct 2012 21:58

Hard to say. Considering what the prestige journals have given us regarding Lyme in the last few decades, we might have to stop relying on shortcuts altogether. We could actually read papers and think about the data, ourselves. We could even discuss them on the internet. 
"I have to understand the world, you see."
Richard Feynman

Camp Other
Posts: 996
Joined: Wed 2 Mar 2011 4:32
Contact:

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by Camp Other » Mon 15 Oct 2012 22:44

Lorima wrote:Hard to say. Considering what the prestige journals have given us regarding Lyme in the last few decades, we might have to stop relying on shortcuts altogether. We could actually read papers and think about the data, ourselves. We could even discuss them on the internet. 
Good one.

X-member
Posts: 5146
Joined: Mon 30 Jul 2007 18:18

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by X-member » Tue 16 Oct 2012 15:48

I have now read the very interesting study that Rita posted.

I recommend people to do this too, and this can actually be something that Henry need?

Edit to add:

A quote (from the link in the first post):
The results of our study differ in part from some published data which show a low specificity of the Borrelia-LTT [24, 25]. This is very likely due to methodology.

X-member
Posts: 5146
Joined: Mon 30 Jul 2007 18:18

Re: LTT for Borrelia Detects Active Lyme Borreliosis

Post by X-member » Tue 16 Oct 2012 16:43

And if it (what they found in the study) is correct, I actually have nothing more to say in this forum. 8-)

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