Mythbusting

Lyme Disease is such a peculiar affair. In a recent radio chat pitching doctors did agree on one thing, acute (early) lyme & chronic lyme are two completely different entities. Ask a patient who just had a rash & was treated early & they’d say ah it was nothing, few weeks antibiotics & I was good to go. Those who skipped stage one or didn’t get a rash, or didn’t get an astute doctor making a quick diagnosis or didn’t the right kind of results on blood tests (even when it’s known that blood tests can give incorrect results) are the ones sadly being left behind. And it’s these folks who develop chronic symptoms. Chronic or late stage symptoms look NOTHING like early Lyme. A doctor will tell you it can’t be Lyme you have a negative result, or it can’t be Lyme you didn’t have a rash, it can’t be Lyme you have far too many symptoms (therefore you must be sick in the head right?) or it can’t be Lyme as it doesn’t exist here in Ireland (yes that’s still happening despite all our hard work)

So let’s look at some of the problems….

There’s no such thing as seronegative lyme

– (actually there’s no such thing as a 100% accurate test but that fact seems to be ignored)

First let’s take a look at the testing. Back in the 90’s a vaccine was being developed to prevent lyme disease. This was a great leap forward especially as lyme was outstripping cases of AIDS & is the fastest growing vector-borne disease in the Western Hemisphere. Also it can be a debilitating & longterm illness which puts a strain on the patient, the family & the welfare system. BUT there was a problem. Firstly they realised that anyone being tested for Lyme would automatically react to certain bands on the testing. Borrelia can produce outer surface proteins but so can the Lyme vaccine. So to prevent anyone being tested falsely positive for Lyme in the future they decided to restrict the banding & bands 31 & 34 were taken out. Then along came the vaccine. Conflicting reports ensued, the manufacturers of the vaccine said that Lymerix was withdrawn from market due to poor sales, other reports say that patients were finding themselves succumbing to the disease AFTER being vaccinated. Was this being caused by the vaccine itself? Some unfortunate folks with a certain gene type HLA-DR4 (see PDF) could also succumb to antibiotic refractory arthritis – FOR LIFE. Not good from a vaccine. Others with a latent infection could then have an acute infection triggered by the vaccine itself. So in any case the vaccine was withdrawn BUT the bands remained restricted.

Along came even more confusion, the CDC stated that for SURVEILLANCE CRITERIA only that for testing purposes the following 2 tier testing system should apply: (2 tier testing requires a positive or borderline ELISA followed by a positive WB using the newly restricted criteria).

For the purposes of surveillance, the definition of a qualified laboratory assay is

1. Positive Culture for B. burgdorferi, or
2. Two-tier testing interpreted using established criteria [1], where:

a. Positive IgM is sufficient only when ≤30 days from symptom onset*
b. Positive IgG is sufficient at any point during illness**

3. Single-tier IgG immunoblot seropositivity using established criteria [1-4].
4. CSF antibody positive for B. burgdorferi by Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA), when the titer is higher than it was in serum

*Postive IgM = 2 of the following 3 bands present: 24 kDa (OspC), 39 kDa (BmpA), and 41 kDa (Fla)

**Positive IgG = 5 of the following 10 bands are present: 18 kDa, 21 kDa (OspC), 28 kDa, 30 kDa, 39 kDa (BmpA), 41 kDa (Fla), 45 kDa, 58 kDa (not GroEL), 66 kDa, and 93 kDa

They also state that this surveillance case definition was developed for national reporting of Lyme disease; it is not intended to be used in clinical diagnosis, however despite the shortfalls in testing using this 2 tier method many doctors simply WILL NOT diagnose Lyme without a positive result. So what are the shortfalls in testing?

One is that both tests are reliant on the production of antibodies to specific strains. A person can have a different strain to that being tested (despite reports saying that other strains may be non pathogenic a few reports counter that some of the less commonly tested strains can in fact cause symptoms so we need to keep an open mind).

In fact in Ireland we have very high levels of strain VS116 – B. valaisiana (shown in 50% of infected ticks in one study). The studies below shows possible pathogenic* problems regarding this strain so we maybe missing many patients by not testing for it..

*Group VS116 was detected in two EM patients, and therefore this group has pathogenic potential. Mixed infections of B. afzelii and B. garinii, group VS116 or B. burgdorferi sensu stricto were found in three EM and three ACA patients.

*Indirect evidence suggests that B. valaisiana is involved in some chronic clinical manifestations. We report the genetic detection of B. valaisianain the CSF of a 61-year- old man with a history of spastic paraparesis, which is strong clinical evidence of advanced neuroborreliosis.

Antibiotics may abrogate immune response. In fact some say that patients may never seroconvert after antibiotics but still have an infection* and antibody response may vary per person aswell as during the course of the illness**

*Immunoblot seroconversion can only be documented in a follow-up sample, and, sometimes, even this option is blocked because antibiotic treatment may interfere with the development of the anti- Borrelia antibody response.

**With respect to the course of IR [immune response] after therapy, 21 of 61 (34%) patients did not show IgM seroconversion (constantly negative), whereas 12 (20%) were constantly positive. In the remaining 28 patients, different kinds of IgM seroconversion occurred. Nine patients (15%) seroconverted from positive to negative and 6 (11%) from negative to positive during the observation period. Seven seronegative patients (11%) seroconverted to positive and than back to seronegative during the 12 months. Six patients (10%) showed repeated seroconversions of IgM antibodies that presented as a switch of anti-23kD to anti-39 kD antibodies and vice versa or the dis-or reappearance of either anti-23 kD or anti-39kD antibodies.

Some say steroids can inhibit immune response – could this also affect testing?

Some co-infections carried by ticks can cause immune suppression possibly affecting test results.

The test kit states “The diagnosis of Lyme disease must be made based on history, signs (such as erythema migrans), symptoms, and other laboratory data, in addition to the presence of antibodies to B. burgdorferi.

*Negative results (either first- or second step) should not be used to exclude Lyme disease.*

Thus, (in their own words) “serological tests for antibodies to B. burgdorferi are known to have low sensitivity and specificity, and because of such inaccuracy, these test cannot be relied upon for establishing a diagnosis of Lyme disease”.

The other downfall with 2 tier testing is that the 2nd tier tends only to be offered after a positive first tier. If the 1st tier missed a patient due to problems listed above they will never be offered the 2nd test. What’s worse, if they do get a positive & do not produce enough BANDS in the 2nd test they still won’t get a positive (remember the restrictive bands mentioned in the first part? Well less bands available for testing = less bands available for reacting & so more false negatives will result.) For IgG testing for instance a person needs to obtain 5 out of 10 bands to be positive. So if lyme specific bands were taken out you can see why this makes no sense at all. An astute lyme doctor would request an Igenex WB for example & pick out the bands the patient reacted to & identify which are lyme specific. You have some lyme specific bands? Well then you most probably have lyme disease, it’s that simple. But the method currently used is you have less than 5 out of 10 bands, then you don’t have lyme disease. Where’s the logic in that? As Tom Grier mentioned in his article, children tested AFTER the testing band criteria were restricted are now more likely to be a negative. He states “under the old criteria, all of 66 pediatric patients with a history of a tick bite and Bull’s Eye rash who were symptomatic were accepted as positive under the old Western Blot interpretation. Under the newly proposed criteria, only 20 were now considered positive”. Would you want your child undiagnosed with an illness that can seriously affect the brain due to such hit & miss methodology?

Some studies showing problems with 2 tier testing in Europe:

Large differences between test strategies for the detection of anti-Borrelia antibodies are revealed by comparing eight ELISAs and five immunoblots.

http://www.ncbi.nlm.nih.gov/pubmed/21271270

Ang CW, Notermans DW, Hommes M, Simoons-Smit AM, Herremans T.
Eur J Clin Microbiol Infect Dis. 2011 Jan 27. [Epub ahead of print]

VUMC, Amsterdam, The Netherlands, w.ang@vumc.nl.

Comparison of immunoblots yielded large differences in inter-test agreement and showed, at best, a moderate agreement between tests. Remarkably, some immunoblots gave positive results in samples that had been tested negative by all eight ELISAs. The percentage of positive blots following a positive ELISA result depended heavily on the choice of ELISA-immunoblot combination. We conclude that the assays used to detect anti-Borrelia antibodies have widely divergent sensitivity and specificity. The choice of ELISA-immunoblot combination severely influences the number of positive results, making the exchange of test results between laboratories with different methodologies hazardous.

Serodiagnosis of Borreliosis: Indirect Immunofluorescence Assay, Enzyme-Linked Immunosorbent Assay and Immunoblotting.

http://www.ncbi.nlm.nih.gov/pubmed/21258869

Arch Immunol Ther Exp (Warsz). 2011 Jan 22. [Epub ahead of print]
Wojciechowska-Koszko I, Mączyńska I, Szych Z, Giedrys-Kalemba S.

Department of Microbiology and Immunology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111, Szczecin, Poland, IwonaKoszko@interia.pl.

In order to detect the antibodies against Borrelia sensu lato three kinds of serological tests were used: indirect immunofluorescence assay (IIFA), enzyme-linked immunosorbent assay (ELISA), and immunoblot. The IIFA and immunoblot tests conducted on 45 patients (100%) produced positive results for both the IgM and IgG antibody types. In the case of ELISA, positive or borderline results were observed in only 24 patients (53.3%)..The IIFA screening test used for diagnosing Lyme borreliosis produced the highest percentage of positive results, which were then confirmed by immunoblot, but not by ELISA. Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable.

Another reason for seronegativity can be down to antibodies sequestered in immune complexes. As evidenced by these studies…

Diagnosis of Lyme Borreliosis

Aguero-rosenfeld, Maria E Wang, Guiqing Schwartz, Ira Wormser, Gary P, Clin Microbiol Rev. 2005 July; 18(3): 484–509.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1195970/

The enzyme-linked IgM capture IC [immune complex] biotinylated antigen assay was found to be more sensitive and specific than the aforementioned tests and furthermore detected antibodies more consistently in those patients with clinical evidence of active disease. Potential utilities of this type of assay include detection of antibodies in seronegative patients during early disease and ascertainment of whether persistent seropositivity is due to ongoing infection, since IC are speculated to be present only in active infection.

Immune complexes from serum of patients with Lyme disease contain Borrelia burgdorferi antigen and antigen-specific antibodies: potential use for improved testing.

Brunner, M Sigal, L H, J Infect Dis. (2000) 182 (2): 534-539.

http://jid.oxfordjournals.org/content/182/2/534.full

Serum from a patient with Bannwarth syndrome (lymphocytic meningitis, cranial neuropathy, and radiculoneuritis) was seronegative by standard isotype-specific IgG ELISA and immunoblot and was positive by IgM ELISA. When the ICs [immune complexes]-and FAs [free antibodies] were used at equal concentrations of IgM, more Bb antigens were bound by IC derived IgM than by FA IgM, including the 23-, 30/31-, and 66-kDa bands of the Centers for Disease Control and Prevention interpretation criteria. Thus, specific IgM was sequestered within ICs.

Binding to the 23-kDa protein was more intense in ICs than in the FA fraction;** FA immunoblot reactivity would have been classified as negative, according to the manufacturer’s instructions. **

We found OspA within ICs of some patients with later features of LD, which is analogous with the persisting infection in the mouse. These findings suggest that OspA may be expressed in long-term infection; the appearance of anti-OspA antibodies in later disease suggests that this antigen is present to elicit that humoral response

One potential explanation for the absence of serological reactivity with OspA in standard serological assays in many patients with later manifestations of LD may be that anti-OspA antibodies are sequestered within ICs.

Benjamin J. Luft, M.D. Professor, Chair (acting) Department of Medicine, State University of New York at Stony Brook says it all:

“Since Lyme disease is a clinical diagnosis, research must continue to improve diagnostic assays using recombinant proteins which are more sensitive and specific than the whole organism sonicate used for both ELISA and Western blots. Possible biological markers of chronic Lyme disease, such as positive Borrelial antigen, Borrelial DNA and pleocytosisin the CSF or synovial fluid, need to be assessed and validated. Elimination of biological markers in combination with sensitive indices of neuropsychological symptoms will be useful for the evaluation of treatment modalities.”

Those ‘other’ tests used abroad are not accredited

– (well depends on your definition of accredited!)

Of course what they mean is that they are not accredited for use in the 2 tier system & the 2 tier system is considered the ‘gold standard’ despite its set backs. Any others tests used are treated with suspicion, however saying they’re not accredited maybe pushing it slightly. For instance the test kit used for Elispot techniques is CE approved (a quality mark for use throughout Europe). Igenex testing in the States is heavily quality controlled & surpasses expectations. Remember there’s no test that’s a 100% BUT ignoring other tests just because it’s not in line with the 2 tier testing that A. follows RESTRICTED criteria (due to the vaccine issues mentioned above) & B. was only meant for SURVEILLANCE not diagnostic criteria, just makes no sense.

Elispot or LTT testing looks at immune responses in a different way, for instance looking at T cell activity against the lyme bacteria. According to this study it is entirely possible for patients to exhibit T-cell activity without showing positive antibodies: “We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay.

We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.

Igenex meanwhile do the 2nd tier test (Western Blot) but DO NOT use restrictive criteria. In other words they put back in bands 31 & 34 that were restricted during the Dearborn Convention. If you were testing your own children or family member wouldn’t you want the best? So why aren’t patients allowed the best too?

As Lyme disease has the potential to spread throughout the body (it doesn’t care whether it’s in tissue,the blood, organs, behind the eyes, in the heart, in joints or even in the brain) it can be a serious infection that’s difficult to treat. Why should patients go untreated just because someone somewhere says that overseas testing should be discredited even though they have the potential to pick up more cases?

If you had lyme you’d see a rash

– (or maybe not)

There is a familiar pattern going around the world. Patients, doctors & the public are repeatedly told that lyme will nearly always emit a bulls-eye shaped lesion days to weeks after a bite. Some studies I’ve seen suggest up to 90% of patients others as low as 50%. Another actually suggested as low as 9%* are typical bulls-eye (EM) lesions the rest are multiple EM rashes, uniform EM rashes in fact a whole manner of forms**. Rashes can appear by the bite, away from it, can repeatedly occur throughout the illness. According to a study at the Univ College Hospital they found “While twenty-two patients (71%) had a rash at presentation, only 43% of patients presented with EM rash“.

Results of our own surveys (word doc) found that the erythema migrans (EM) rash was only present in 44% of the patients at the start of the illness and 19% have multiple EM’s during the course of the illness. This shows that a rash is not always present or noticed during Stage One of the illness… Also differing strains can cause differing skin reactions so really it is hard to pin down an exact percentage. Just be known that a bulls-eye rash does not appear in everyone & those who do get a rash it may not be conforming to the normal picture portrayed. Some pics of differing rashes can be seen at: http://www.ticktalkireland.org/diagnosis.html

*[PDF]The EM lesion has been classically described as erythematous with central clearing, the so-named “bull’s eye” appearance (Figure 3) (4). However, in a study of 118 cases of EM, in which Borrelia burgdorferi infection was confirmed by culture or polymerase chain reaction, the lesion was homogeneous in 59%, had central erythema in 32% (Figure 4), and was a “bull’s eye” with central clearing in only 9%.

**In another study that contains pics of various rashes” While 80% of EM in the United States are uniformly red, only 19% have the stereotypical bull’s eye appearance [5].

While typically circular or oval, it can also be triangular, rectangular or distorted in other ways when occurring in areas such as the neck [6]. Atypical features may include erythema with central induration, urticarial like lesions, confluent red-blue lesions mimicking ecchymosis, vesicles mimicking shingles, and central necrosis mimicking spider bites”

Lyme does not exist here in Ireland

– (yes this is still being said despite the reverse being true & has been untrue for many years)

This comment riles me. The internet is so full of information that there is no excuse NOT to realise that Lyme exists in Ireland. Prof Gray from the 90’s had tons of papers identifying high risk areas & the disease that ticks may carry. If a doctor mentions this to you then they haven’t spent the time learning. You can’t treat a patient for something you don’t think exist. Learning is key for all of us – ignorance is not. For some of the Irish related studies go to https://ticktalkireland.wordpress.com/lyme-links/irish-related-articles/

Lyme does not become chronic, in fact a few weeks antibiotics should see you right

– (not so according to many studies even by IDSA guideline authors themselves..)

Well anyone in the Lyme world, doctor or patient knows how frustrating this topic can be. First as a patient you have to jump through the hoop of diagnosis (did anyone recognise the symptoms?) then the testing (did you manage to get a positive or did you manage to get overseas test taken seriously?) If you’re eventually offered treatment after being years without a diagnosis you may find that nothing happens! Why? Because you may have been treated too little too late. Don’t get me wrong, I don’t advocate endless years of treatment to the point where the patient becomes so toxic they can’t function at all BUT I think lack of treatment or too little treatment after years of waiting for a diagnosis is an insult. Anyone who has lived a day in the life of a chronically ill Lyme patient knows how awful it is. Remember how crap you feel during a bout of flu? Well a lyme patient suffers from that sometimes on a weekly basis, the chills, weakness, muscles ache, joint pains, severe headaches, pains behind the eyes, sore throats, swollen glands – it ain’t pretty. Throw in a few heart palpitations or a racing heart, some numbness & tingling, swellings in unusual places, chronic bladder pain, back troubles, stiff neck & knees & you’d be welcoming treatment with open arms wouldn’t you? But what happens when they refuse to treat you. Hold on, there’s no lyme in ireland, you didn’t have a rash, your tests were negative (any positive ones from overseas? Let’s ignore those) & the 3 weeks antibiotics I gave you would have killed it anyway so proof you didn’t have Lyme in the first place. Heard all these before?

But can lyme really persist? These folks seem to think so:

Survival of Borrelia burgdorferi in antibiotically treated patients with 
Lyme borreliosis. 

http://www.ncbi.nlm.nih.gov/pubmed/2613324
 
Preac‐Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. 
Neurologische Klinik Grosshadern, München, FR Germany. 

Abstract 

Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients. B. burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B. burgdorferi. We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi.

Spirochetes in the spleen of a patient with chronic Lyme disease. 

http://www.ncbi.nlm.nih.gov/pubmed/2910019

Cimmino MA, Azzolini A, Tobia F, Pesce CM. 
Istituto Scientifico di Medicina Interna, Università di Genova, Italy. 

Abstract 

A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year’s duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.

Chronic neurologic manifestations of Lyme disease. 

http://www.ncbi.nlm.nih.gov/pubmed/2172819 

Logigian EL, Kaplan RF, Steere AC. 
Department of Neurology, Tufts University School of Medicine, Boston, MA 02111. 

Abstract 

BACKGROUND AND METHODS: To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients (age range, 25 to 72 years) with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection.  

Clinical implications of delayed growth of the Lyme borreliosis spirochete, 
Borrelia burgdorferi. 

http://www.ncbi.nlm.nih.gov/pubmed/1980573
 
MacDonald AB, Berger BW, Schwan TG. 
Department of Pathology, Southampton Hospital, New York 11968.
 
Abstract 

The latency and relapse phenomena suggest that the Lyme disease spirochete is capable of survival in the host for prolonged periods of time. We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations. Some patients with Lyme borreliosis may require more than the currently recommended two to three week course of antibiotic therapy to eradicate strains of the spirochete which grow slowly.

Electron microscopy and the polymerase chain reaction of spirochetes from 
the blood of patients with Lyme disease. 

http://www.ncbi.nlm.nih.gov/pubmed/8004045

Hulínská D, Krausová M, Janovská D, Rohácová H, Hancil J, Mailer H. 
Department of Electron Microscopy, National Institute of Public Health, Prague, Czech Republic. 

Abstract 

Results of studies using direct antigen detection suggest that seronegative Lyme borreliosis is not rare and support the hypothesis that Borrelia antigens can persist in humans.
 
Lyme borreliosis‐‐a review of the late stages and treatment of four cases. 

http://www.ncbi.nlm.nih.gov/pubmed/9701852

Petrovic M, Vogelaers D, Van Renterghem L, Carton D, De Reuck J, Afschrift M. 
Department of Internal Medicine, University Hospital Ghent, Belgium. 

Abstract 

Difficulties in diagnosis of late stages of Lyme disease include low sensitivity of serological testing and late inclusion of Lyme disease in the differential diagnosis. Longer treatment modalities may have to be considered in order to improve clinical outcome of late disease stages. The different clinical cases illustrate several aspects of late borreliosis: false negative serology due to narrow antigen composition of the used ELISA format, the need for prolonged antibiotic treatment in chronic or recurrent forms and typical presentations of late Lyme disease, such as lymphocytic meningo-encephalitis and polyradiculoneuritis.

Treatment of late Lyme borreliosis.

http://www.ncbi.nlm.nih.gov/pubmed/7884218 

Wahlberg P, Granlund H, Nyman D, Panelius J, Seppälä I.
Department of Medicine, Aland Central Hospital, Mariehamn, Finland.

[From the abstract:] “Short periods of treatment were not generally effective.”

[From the article:] “Symptoms and signs often improve temporarily shortly after treatment but reappear within weeks or months. …To conclude, we have shown that long-term treatments beginning with intraveous ceftriaxone and continuing with amoxycillin plus probenecid or with cephadroxil were useful in the treatment of late Lyme borreliosis.” (pp. 260-1)

First isolation of Borrelia burgdorferi from an iris biopsy.

http://www.ncbi.nlm.nih.gov/pubmed/8106639

Preac‐Mursic V, Pfister HW, Spiegel H, Burk R, Wilske B, Reinhardt S, Böhmer R.
Max v. Pettenkofer Institut für Hygiene u. Medizinische Mikrobiologie, LM‐Universität München,
Germany.

Abstract

The persistence of Borrelia burgdorferi in six patients is described. Borrelia burgdorferi has been cultivated from iris biopsy, skin biopsy, and cerebrospinal fluid also after antibiotic therapy for Lyme borreliosis. Lyme Serology: IgG antibodies to B. burgdorferi were positive, IgM negative in four patients; in two patients both IgM and IgG were negative. Antibiotic therapy may abrogate the antibody response to the infection as shown by our results. Patients may have subclinical or clinical disease without diagnostic antibody titers. Persistence of B. burgdorferi cannot be excluded when the serum is negative for antibodies against it.

So where to go from here.

Let’s stop restrictive practises, restrictive banding on testing, restrictive guidelines (thou’ must not treat long term) & restrictive attitudes. Only then can we move on. As Stella Huyshe-Shires eloquently put it in a recent hearing ‘To us in the UK there seem to be two principal aspects to the Lyme disease problem: politics and the uncertainties of the science. The first is preventing recognition of the second. Politics, prestige and defence of positions should not obstruct patient care and should not hamper the search for understanding’. Stella Huyshe-Shires: Chairman, Lyme Disease Action, UK.

And all these lyme patients are feeling neglected. We won’t go away, not because we don’t want to, it’s because we can’t.

“The controversy in Lyme disease research is a shameful affair” says Willy Burgdorfer

I’d like to finish off with this quote from an interview with Willy Burdgorfer himself (the scientists who identified the bacteria causing lyme disease)

Dr. Burgdorfer: “The controversy in Lyme disease research is a shameful affair. And I say that because the whole thing is politically tainted. Money goes to people who have, for the past 30 years, produced the same thing—nothing. Serology has to be started from scratch with people who don’t know beforehand the results of their research. There are lots of physicians around who wouldn’t touch a Lyme disease patient. They tell the nurse, “You tell the guy to get out of here. I don’t want to see him.” That is shameful. So [this] shame includes physicians who don’t even have the courage to tell a patient, “You have Lyme disease and I don’t know anything about it.”

Some useful posts:

Myths about Lyme Disease
Blood testing
WB comparison (excel)
Persistence & seronegativity (PDF)
A look at patents (word doc)
Video clip from Dr Shor explaining the problems evident in the Lyme world
A doctor’s dilemma by Dr. McNeil
Our useful links page – Lyme & MS, Lyme & ME, rashes, chronic lyme etc.

Read Full Post »

Spring 2012 news!

Welcome to our news updates for Spring 2012!

The weather is warming, the ticks are stirring, time to take precautions!!

No need to fear nature but knowing what lurks out there can make all the difference. Knowledge is power. To learn how to protect yourself from ticks check out our site at: Preventing Tick Bites

Remember, A Tick in Time Saves Lyme!

Tick Bite Prevention Week

BADA-UK have kick started their Tick Bite Prevention Week (runs from 26th March – 1st April 2012. For great tips on how to protect yourself, children & pets head on down to: Tick Bite Prevention Week

Surveys

Spot any ticks this Spring or Summer? Why not fill in our survey showing ticks being spotted across Ireland? This will help to highlight high risk areas. For links to our previous results plus links to complete new surveys go to:

New Surveys
Results from past Surveys

Education

Do you like to walk, camp, hunt, spend time in the country? Are you a farmer, hunter or scout leader. Or maybe a scientist, medical professional, herbalist, vet surgeon, vet nurse or politician? Perhaps you’re a confirmed or suspected Lyme disease patient. Would you like to learn more about Lyme disease, ie how to prevent lyme, how to spot high risk areas, find out about tick-borne infection in animals, hear about testing, traditional, alternative & suportive remedies & ways to tackle chronic infection? Why not come down to our lyme disease conference to find out more? Tickets available at 20 euro for half day Tuesday 5th June & 40 euro for full day Wednesday 6th June. (A reduced rate of 50 euro is available for both days). Early bird prices are valid until March 31st. To learn more about our conference including details on agenda, speakers profiles, bookings & local accomodation check out our site at: Lyme Disease Conference

NB: Please note that CPD (continuinig professional development credits) have been approved for biologists, GP’s, vets & veterinary nurses..CPD Accreditation

Fundraising

May is International lyme awarness month

We’re currently looking for folks willing to undertake small projects across the country for fundriasing & raising awareness. Maybe hold a green theme Friday, everyone at work or school have to wear green clothes. Or maybe buy a selection of awareness ribbons & sell them at work. Anyone daring enough to die their hair green in aid of Lyme sufferers? Perhaps persuade your local street to Go Green for Lyme with posters, flyers & leaflets. Maybe a sponsored stroll, coffee morning or local showing of our lyme awareness presentation (not available online but can mail a copy on request).

Note for fundraisers remember to take photos for our web page!

Also wanted..

Runners for the Flora Marathon
Folks willing to Parachute Jump in aid of Tick Talk
Raffle prizes for our June Conference
Folks willing to distribute conference flyers
Folks to distribute Lyme in Ireland leaflets to vets, doctors, medical centres, hospitals, national parks & librairies – Contact Us with your mailing address

Letter of Concern

March 2012 Tick Tak Ireland lodged a letter of concern regarding issues faced by Lyme Disease Patients Uk & Ireland. This was sent to the Minister of Health & Children Dr James Reilly, Dr Paul McKeown of the Health & Protection Surveillance Centre & the Director of the European Centre for Disease Prevention & Control. David Cameron PM for the UK will also received a copy in due course.

For a look at our concerns covering recognition, testing, persistence, co-infections (see appendix), transmission & guidelines click on the following links below:

Letter of Concern
Coinfections UK & Ireland

Testing is so confusing!

Tick Talk has put together a Western Blot comparison xls. This highlights differences between the CDC criteria (US) to Igenex labs to Scottish Labs & from German MiQ 12 2000 criteria to rest of Europe MiQ 12 2000.

Types of bands & number of bands required for a positive are all different. This highlights exactly why tests are so confusing! Remember, the test kit manufacturers themselves say a negative does not rule out a diagnosis of Lyme Disease.

Trinity Biotech test kit states “The diagnosis of Lyme disease must be made based on history, signs (such as erythema migrans), symptoms, and other laboratory data, in addition to the presence of antibodies to B. burgdorferi.

*Negative results (either first- or second step*) should not be used to exclude Lyme disease.*

*NB first step – Elisa, 2nd step – Western Blot..

Some reasons for the possible pitfalls with Elisa testing per the kit manufacturer’s notes include the following…

*B. burgdorferi is antigenically complex with strains that vary considerably.

*Early antibody responses often are to flagellin, which has cross-reactive components.

*Patients in early stages of infection may not produce detectable levels of antibody.

*Early antibiotic therapy after EM may diminish or abrogate good antibody response.

Thus, (in their own words) “serological tests for antibodies to B. burgdorferi are known to have low sensitivity and specificity, and because of such inaccuracy, these test cannot be relied upon for establishing a diagnosis of Lyme disease”.

Lyme is a clinical diagnosis & according to the CDC the 2 tier testing is only meant for surveillance criteria & it is not intended to be used in clinical diagnosis..

Time to Listen

Isn’t it time we looked at ways to improve the lives of patients?

I’d like to quote from a 2003 article “The Lyme Wars: Time to Listen” by Raphael B Stricker† & Andrew Lautin

†Department of Medicine, California Pacific Medical Center, San Francisco, CA, USA

“Lyme disease remains a public health threat of major proportions. Continued trivialisation of this complex spirochetal illness only serves to augment the threat by legitimising ignorance of Lyme disease and neglect of Lyme disease patients. Until this trend is reversed, we will continue to see thousands of patients suffering at the hands of the medical establishment and desperately seeking care from the few providers who will listen. As modern medicine rockets into the 21st Century, this ostracism of suffering patients and persecution of dissenting healthcare providers can no longer be tolerated. For their part, Lyme disease patients and their providers must learn from the AIDS experience, where activism brought change when it was perceived that nobody was listening. And as more people listen, the ‘Lyme Wars’ may finally reach an end.”

Let’s hope through dialogue & research changes can be made soon!

For details on persistence & seronegativity check out our blog post: Persistence & Seronegativity

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Lyme Disease Conference in Ireland

Clontarf Castle, Dublin. 5/6 June 2012

WHEN:

Half day Tuesday 5th June – protection & prevention tips, plus tick-borne infections in animals

Full day Wednesday 6th June – lyme disease in humans including testing, treatment & research

WHERE:

Clontarf Castle, Dublin (close to the airport, city centre, motorways & ferry terminals)

WHO:

The conference will be suited to the following audience:

Tuesday session – members of the public who enjoy walking, camping or hunting, pet owners, farmers, park rangers & vets

Wednesday session – patients of diagnosed or suspected tick-borne diseases, doctors, nurses & interested scientists

TOPICS OF PRESENTATIONS:

Afternoon Tuesday 5th June:

Jenny O’Dea: Lyme Disease in the UK & Ireland – results of our tick studies & plus methods of protection
Dr Healy: The Factors Influencing the Density and Distribution in Space and Time of the Tick Ixodes ricinus
Dr Paul Nolan (GP, Ireland): Prevention is better than no cure
Jyotsna Shah (Igenex, USA): A comprehensive approach for diagnosis of Lyme and associated Diseases
Mícheál Casey (Head of Regional Vet Labs): An overview of tick-borne disease in Irish farm animals

All day Wednesday 6th June:

Dr Joseph Jemsek: – Dawn of a New Paradigm in Chronic Illness – The role & relevance of Lyme Borreliosis Complex
Dr Eva Sapi: – Killing Borrelia – is it possible?
Dr Armin Schwarzbach: Staging processes in the laboratory diagnosis of Lyme and co-infections by indirect laboratory tests
Dr Jean Monro – Supportive therapies for the Nervous System
Kate Bloor: An online survey of Lyme patient’s experience of health care in the UK and Eire
Nicola Darrell: Herbal Treatments for Lyme Disease – a look at treatment for lyme & management of post lyme symptoms

Please note that space will be allocated to allow for questions & answers

For details on registration & conference starting times please click here and for information on places to stay please click here. Cheap Flights are available through Ryanair or Aerlingus.

To reserve your ticket for the Lyme Conference go to:Conference Reservation

We also welcome exhibitors & sponsors, more information available on the link above.

Notes:

Conference Bookings:

Please note to avail of the early bird special (a saving of 5 euros per person) bookings must be received by 31st March 2012

Half Day Tuesday 5th June: registration begins at 1pm, conference runs from 1.30 to 5pm = 20.00 Euro (*price will rise to 25.00 from 1st April) – coffees are included in the price

Full Day Wednesday 6th June: registration begins at 9am, conference runs from 9.30 to 5pm = 40.00 Euro (*price will rise to 45.00 from 1st April) – coffees & buffet lunch are included in the price

Both Days (afternoon 5th June / all day 6th June): registration & conference times above are applicable = 50.00 Euro (*price will rise to 55.00 from 1st April) – coffees both days & buffet lunch on Wednesday are included in the price

For payments by cheque or money order please contact us for address details.

*Please retain your paypal receipt to show on arrival*

Hotel Accommodation:

Clontarf Castle has offered a rate of 109 per room (single) & 119 per room (double). To obtain this rate please quote the ref code: TICK TALK IRELAND – Valid until 4th March (now extended until March 18th) 2012 (for more choices on accommodation please click here)

Exhibitors:

Price includes 4ft table, coffee & wed buffet lunch (where applicable). Max 2 per table booked. 50% deposit payable now, remainder due 31st March 2012.

Please click here to download exhibitor’s booking form, more details are included on the form.

Coming from the UK? Here’s some tips on how to get to Ireland:

By Air:

Cheap flights are available through Ryanair or Aerlingus.

Euroline coaches:

Travel to Ireland with Eurolines is easy, we provide a range of services to over 40 destinations with prices starting from just £42 return to Dublin (price includes transfer by ferry)

Services operate from most major cites in Britain including Birmingham, Bradford, Bristol, Cardiff, Leeds, London and Manchester arriving at city centre locations saving on the need for expensive airport transfers.

http://www.eurolines.co.uk/coach/Destinations/Ireland/Ireland-index.aspx

Sail/Rail:

Why not combine the convenience of rail travel with your ferry crossing? Prices start from £32 per person each way.

http://www.irishferries.com/gb/fares-offers-ireland-from-britain.asp?tab=fares-sail

Irish Ferries:

Save up to 25% Car plus 1 from £79 one way. From £79 online fare for you and your car is valid for midweek travel (Mon – Thurs) on all cruise ferry services up to 30 June 2012. Must be booked a min of 7 days in advance of travel date and by the 27 Feb 2012.

http://www.irishferries.com/gb/fares-offers-ireland-from-britain.asp?tab=fares-sail

Stena Line:

Travel by ferry to Ireland with the Irish Sea’s leading ferry company from only £79 single for a car plus driver. Speed across the Irish Sea from Holyhead to Dun Laoghaire on our fastcraft or cruise over to Dublin City onboard one of our stylish Superferries.

http://www.stenaline.co.uk/ferry/ferries-to-ireland/

NB: Please note that Dublin Port & Dun Laoghaire are 2 seperate ports of entry to Dublin. Important to note when looking at directions to the hotel 😉

Wheelchair friendly hotels:

http://www.accessibleireland.com/search_by_county.php?county_id=1&facility_id=1

Wheelchair friendly B & B’s:

http://irelandbnb.com/dublin-bed-breakfast-wheelchair-access.html

Other B & B’s in the area:

http://irelandbnb.com/clontarf-bed-breakfast-dublin.html

Hotel Accommodation:

Clontarf Castle has offered a rate of 109 per room (single) & 119 per room (double). To obtain this rate please quote the ref code: TICK TALK IRELAND – Valid until 4th March 2012.

Other hotels in the area:

for more choices on accommodation please click here! 🙂

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Dispelling the Myths

Dispelling the myths by Tom Grier (microbiologist) adapted by Jenny O’Dea

Seek & You Shall Find!

[NB: My notes have been placed inside brackets in italic bold!]

(Full article “Lyme on the Brain” with references can be found at): http://madisonarealymesupportgroup.wordpress.com/2010/08/09/tom-grier-lyme-lecture-outline/

Myth One: Length of Tick Attachment: A tick must be attached for at least 36-48 hours. WOW! How could you ever make that conclusion on the sparse veterinary and human data we have? In fact the data suggests this is not true. Studies that looked at improper removal of a tick showed much shorter attachments are possible.

What happens when a tick attaches?

This is the essence of the pathogenisis of Lyme disease: if you understand this concept of infection, you begin to understand why the conservative viewpoint of Lyme is causing latent morbidity and mortality.

In several mammal studies in the late 1980s, it was shown in many species including dogs that within hours of tick attachment that the Lyme organism is with every beat of the heart circulating through the entire body. The spirochete’s motility allows it to position itself into the cracks and folds of a blood vessel wall. Borrelia burgdorferi has a tropism or an attraction to attach to the endothelial cells lining blood vessels. Once the bacteria has attached it traps tissue plasminogen that converts to plasmin and this begins the process of inflammation.

The net result is within 24-48 hours we can measure the breakdown of the blood-brain- barrier in dogs that peaks at 48 hours and lasts for up to 14 days! So are we really going to say that a tick has to be attached 48 hours? This animal model suggests that the infection is potentially already established within the brain. This study was done by tagging normal blood albumin with radioactive Iodine and tracking it into the CSF of the dogs. (1989 Immunological Methods of Borreliosis Cold Spring Harbor)

Why is there such an absolute dictatorship in our guidelines when we have direct animal studies since 1989 that suggest that not only does Borrelia bacteria penetrate blood vessels and enter the brain, but once the blood-brain-barrier closes up 10-14 days after initial infection; the sequestered bacterial infection within the brain is undetectable by serology tests.

Myth Two: Elisa & Western Blot Tests are the gold standard for testing Lyme Disease

Short-comings of the current antibody based Lyme serology tests:

To create these tests we need a representative source of the wild bacteria as a source for specific antigens that can be used to detect the specific antibodies that patients produce as a result of an infection from their local area.

Since Borrelia bacteria are genetically equipped to change their antigenic appearance (strain variation) it is important to use tests that are designed using the best representation of the bacteria that is found in the local area. There can be tremendous variation in Borrelia isolates even those found within close proximity to each other. There are well over 1000 Borrelia isolates of Borrelia burgdorferi that are strain variations in the USA alone. This is not even counting the greater variation that we see if we look at other related geno-species such as Borrelia lonestarrii in Missouri, or Relapsing Fever Borrelia in the SW USA, or the genospecies Borrelia garinii and Borrelia afzelii found in Europe, or the dozens of other related bacteria in the world that cause Lyme-like or Relapsing-Fever-Like diseases caused by various variant strains of Borrelia bacteria.

[Benjamin Luft, M.D., Professor of Medicine, Stony Brook University Medical Center, and a team of medical researchers have determined the genetic blueprint of 13 strains of the bacteria that cause Lyme disease. Dr. Luft and colleagues point out in the study that improved diagnostics are needed because the best clinical sign of Lyme disease, the erythema migrans skin rash, does not always occur in patients. In addition, diagnostic assays and vaccines developed before their blueprint of the entire genome of B. burdorferi have had less than satisfactory results. http://www.physorg.com/news/2010-10-genetic-blueprint-bacteria-lyme-disease.html]

Once you see this global picture you can never look at Lyme as an isolated disease ever again. It is part of a global-pandemic called Borreliosis. But the tests that have been chosen for us, and dictated that we use are not based on any Borrelia found in nature! Why? Since Borrelia identity changes quickly by inserting variant plasmid genes into its larger linear chromosome, the bacteria will always have built in variation unless you eliminate plasmids. (Borrelia burgdorferi has about 31 circular or linear plasmid-chromosomes that facilitate genetic variation, it is estimated that over 60 genes can insert in at least three different chromosome loci resulting in over sixty to the 3rd power variations in the bacteria or potentially over 200,000 possible variations that could be predicted based on what we currently know.) This creates an economic and practical dilemma for manufactures of Lyme serology tests who want consistency and reproducibility without the expense of isolating local bacteria from local ticks and growing them in the lab which is very difficult, time consuming, inconsistent and expensive. For this reason manufacturers use a strain that was developed in a lab that resists variation.

Strain B-31 that was originally isolated from the NE USA ticks, and was created through high-passage selection until it remained consistent from division to division.

B-31 is never found in nature, and when B-31 tests were compared and tested by independent researchers in Madison WI, France, Austria, and United Kingdom, B-31 had short comings and never had the essential antibody detection that the tests developed from local wild-strains produced. One can make an argument for B-31 consistency, but never for its local strain selectivity.

What makes this discussion about what strain we use to make Lyme serology tests completely moot; is the one fact that we completely ignore in the United States:

Once Borrelia bacteria breach the brain’s defenses, absolutely no Lyme serology test short of an autopsy can rule out infection within the human brain!

The nearly arbitrary decision to eliminate species specific antibody-bands from the reporting of the Western Blot tests definitely made the Western-Blot test less accurate. This change in accuracy did not come about from changing the actual test but rather by enforcing a reporting-bureaucracy that made the test less sensitive. Make no mistake the labs that do this test still see the positive bands that are banned from reporting, but are legally unable to report them. Then to further cloud the already muddy waters of accuracy it was decided that all laboratories across the USA have to report all Western Blots as either positive or negative and not report the essential bands.

Not reporting significant Western Blot Band is to a scientist, tantamount to saying: There are no contaminates in your drinking water, so please don’t waste your time testing the well water, and if you do test the waters and find something that we haven’t reported, we have already deemed that the contaminates are unimportant and benign.

Well the contaminates (bands 31, and 34) aren’t as benign as we are told. Let’s look at the old Western Blot reporting criteria on 66 kids with a tick-bite and bull’s-eye rash compared with the new reporting criteria. This is the same test and same patients, but we are now using the Dearborn MI “Dressler” criteria for Western Blot reporting.

Western Blot and False Negatives in Children:

1995 Rheumatology Symposia Abstract # 1254 Dr. Paul Fawcett et al. This abstract showed that under the old criteria, all of 66 pediatric patients with a history of a tick bite and, Bull’s Eye rash who were symptomatic, were accepted as positive under the old Western Blot interpretation. Under the newly proposed criteria only 20 were now considered positive. That means 46 children who were all symptomatic, would probably under the previously mention YALE Criteria be denied treatment! That’s a success rate of only 31 %.

[The Elisa test which is used as a 1st tier test (meaning do not use Western Blot unless Elisa is positive) can also be hit & miss: Department of Microbiology and Immunology, Pomeranian Medical University, Poland:The serological tests for borrelia routinely done in laboratories often produce ambiguous results, which makes a proper diagnosis rather complicated and thus delays the implementation of an appropriate treatment regimen. Thirty-seven outpatients and eight inpatients with suspected borreliosis diagnosis hospitalized at the Clinics of the Pomeranian Medical University (Szczecin, Poland), participated in the study. In order to detect the antibodies against Borrelia sensu lato three kinds of serological tests were used: indirect immunofluorescence assay (IIFA), enzyme-linked immunosorbent assay (ELISA), and immunoblot. The IIFA and immunoblot tests conducted on 45 patients (100%) produced positive results for both the IgM and IgG antibody types. In the case of ELISA, positive or borderline results were observed in only 24 patients. (53.3%). Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable. http://www.ncbi.nlm.nih.gov/pubmed/21258869]

[Interestingly the Scottish labs recently changed their Western Blot criteria to make it more sensitive: This study reviews the Lyme borreliosis Western blot interpretation process, including what bands are classed as specific, the number of bands needed for a positive result, the role of band intensity and the use of clinical information. New interpretation criteria and a testing algorithm were developed. The revised criteria changed the results in 109/3688 (3%) patients and produced significantly more Western blot-positive and weak-positive patients than with the current criteria (485 vs. 442, P<0.0001). In total, 76 patients who were negative/equivocal became positive, which may have led to a change in their management. http://www.bjbs-online.org/article.asp?id=438]

See http://www.lymeneteurope.org/info/the-complexities-of-lyme-disease for more information on Lyme Testing

Myth Three: Now consider this: Recently a Lyme disease expert stated nationally that there is no evidence of transplacental transfer of active infection from mother to fetus. We have actually observed in culture Borrelia burgdorferi penetrating umbilical vein. We also have nine case histories 1987-1989 that confirmed by either culture or direct tissue staining that in fact Borrelia burgdorferi does cross the placenta, and has caused still-births including infections within the fetal brain. [For references please go to: http://madisonarealymesupportgroup.files.wordpress.com/2010/08/part-5-references-corrected-lyme-on-the-brain-by-tom-grier-9-1-10.docx (word doc) & type in fetal or gestational for more information]

Myth Four: Absolute treatment: Two weeks of doxycycline is adequate despite persisting symptoms: I am curious: Has two weeks of tetracycline ever cured a case of acne??? [For an interesting look at other infections that require long term antibiotic treatment including acne, rosacea, reactive arthritis & crohn’s disease go to: http://www.campother.blogspot.co.uk/2011/05/report-lyme-disease-antibiotics-more.html

How antibiotics work:

In most cases bacterial lethal exposure occurs only during cell division. For a spirochete like Borrelia that is a slow divider (24 hours under good conditions) to get the same lethal exposure during cell-wall synthesis as say treating strep bacteria, you would have to treat for one year and five months. Using the old microbiology formulas for tuberculosis from the 1950s, we would expect both TB and Lyme disease to require in many cases over one year of antibiotics including combination therapy. Well we learned our lesson with Tuberculosis but not yet with Lyme disease.

Spirochetes are masters at morphing and changing forms. It helps them survive or another way of putting it; it contributes to relapses occurring even after aggressive antibiotic therapy.

[Study by Eva Sapi at el: Studies have suggested that resistance and recurrence of Lyme disease might be due to formation of different morphological forms of B. burgdorferi, namely round bodies (cysts) and biofilm-like colonies. Better understanding of the effect of antibiotics on all morphological forms of B. burgdorferi is therefore crucial to provide effective therapy for Lyme disease.http://www.dovepress.com/evaluation-of-in-vitro-antibiotic-susceptibility-of-different-morpholo-peer-reviewed-article-IDR]

Myth Five: Chronic Lyme doesn’t exist –

[for a look into ‘just some’ of the many studies on chronic Lyme please visit: https://ticktalkireland.wordpress.com/2010/07/28/persistence-seronegativity/ ]

• Chronic Lyme exists
• Long term inflammation in Lyme borreliosis
• Lyme Disease: Sensible pursuit of answers
• Why the controversy over testing & treating Lyme Disease?
• Chronic Lyme links

The Emperor’s New Clothes, Chronic Lyme Disease, and the Infectious Disease Society of America

Burton A Waisbren Sr. M.D. FACP, Founding Member and Fellow of the Infectious Disease Society of America

This essay will start with a definition of Chronic Lyme disease: Chronic Lyme disease is a syndrome that results when individuals who have been inoculated with multiple microorganisms by infected ticks and who have not responded to an initial course of doxycycline develop extreme fatigue, intermittent fever, joint pain, muscle pain, brain fog, concentration difficulties, skin rashes, and in many instances symptoms of autoimmune disease to the extent that they impinge upon their quality of life.

It’s a conundrum why a group of respected physicians who are members of the Infectious Disease Society of America have not recognized this and have, instead, written a guideline that essentially denies that the syndrome exists. This guideline has resulted in literally hundreds of patients unable to be treated for Chronic Lyme disease.

Sadly Dr Waisbren passed away & the website below has been closed – have kept here for reference only… http://www.waisbrenclinic.com/chronic-lyme-disease-idsa.html

An article on treatment of chronic lyme patients by Waisbren is available at: https://ticktalkireland.wordpress.com/2010/08/03/treatment-of-chronic-lyme-by-founding-idsa-member/
_________________________________________________________________________________________________________

Interestingly if you are a dog you may be lucky in getting sufficient treatment!

[The antibiotics must be given a minimum of 14 days, but 30 days is recommended. However, some preliminary studies show that some animals may not even clear the organism after 30 days and will relapse once the antibiotic is discontinued. In these cases, the animal may have to be on the antibiotic for much longer. http://www.peteducation.com/article.cfm?c=2+1556&aid=458 ]

I’d like to end by presenting a link to poem When will you see me?

Or more important, when will you listen to me.

We humble patients deserve to be tested, treated & taken seriously. Not turned away with false negative Elisa’s, not ridiculed for all our symptoms & told to take anti-depressants for a somatization disorder we don’t have & not be left under-treated for a condition that is far more serious & debilitating than acne. My challenge is can we achieve that?

Let’s hope so!

*Take care this Summer – if you see ticks here in Ireland please complete our survey to help us track them:

Tick Talking while you’re Walking Tick Survey

*Planning a trip to a national park or forest area this summer? – how about taking the survey to report if Lyme leaflets & notices are being presented, to warn the general public about Lyme disease:

Tick in Time Survey

*Do you or someone you know have Lyme & live in Ireland or (live abroad & contracted Lyme in Ireland) then why not fill in our survey regarding symptoms, treatment & testing? (This is completely anonymous to protect your privacy)..

Lyme in Ireland Survey

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Hilysen’s New Lab Test for Lyme

Some interesting developments are afoot in Europe. The Elisa test, long touted for insensitivity (thereby missing prompt diagnosis for many patients) needs to be improved. A consortium of partners has stepped up to the challenge & are embarking on a 2 year project to develop a new ‘lab on a chip’ technology. Designed to catch those who are recently infected as well as those who are chronically ill or who have received antimicrobial treatment (which can affect results in the current system of Elisa) the test should be easily performed by staff, quickly & effectively. This will be good news for patients who are often told they do not have Lyme disease when in fact the serology may not have detected the antibodies in an infected patient (resulting in a false negative test)!

Let’s hope we will see the way to improved methods in testing & ensure effective treatment for all those who suffer from this insidious disease..

BACKGROUND

The deer tick (Ixodes ricinus)

Lyme Disease is the most common tick‐borne infection in Europe and North America, and endemic in 63 countries all over the world including the EU27 countries. The illness is caused by the spiral‐shaped bacteria Borrelia burgdoferi which is transmitted by the bite of infected ticks. The World Health Organisation (WHO) estimates about 85,000 cases of LD annually in Europe but stresses that this number is largely underestimated and many infections go undiagnosed.

When detected and treated early, the infection and its symptoms are eliminated by antibiotics in most cases. Late, delayed, or inadequate treatment can lead to more serious symptoms, which can be disabling.

Borrelia is a pleomorphic bacterium with a complex life cycle that comprises multitude of forms including corkscrew shaped “parent” forms and “cyst” forms lacking a cell wall, among others. These wall-deficient forms are very difficult to detect by common imaging techniques such as light microscopy as well as by standard serological tests since they trigger a different immunological response than their walled counterparts. This fact together with their resistance to antibiotics that act on cell wall synthesis makes them truly difficult to diagnose and treat, so that they persist in the body over long time periods causing chronic diseases.

To date there is no available diagnostic tool able to detect in a sensitive and specific way the immunological response to the cell-wall deficient forms of Borrelia, thought to be responsible for borreliosis chronic severe symptoms. Traditional combination of ELISA and Western blot fails to detect up to 80% of the first stage cases and does not distinguish between acute and chronic infections. Similar sensitivity problems are encountered in the evaluation of cerebrospinal fluid where current serological tests only detect 10%‐30% of neuroborreliosis patients.

Due to the evident pitfalls of current laboratory methods, diagnosis has to be based on the clinical findings but since they are very diverse and may mimic those of many common diseases (arthritis, fibromyalgia, multiple sclerosis) patients suffering from symptoms of the chronic disease go through several months or years of repeated misdiagnosis and inadequate treatment. Besides, this represents a big economic burden for European Health Systems: Lyme Disease costs to society were estimated at €660 million with a cost per patient of €40,750 in 1993. Since then, the number of cases has more than doubled, so the current costs are well above €1000 million. Moreover, lack of diagnosis means underestimation of disease prevalence and health risks leading to critical delays in starting awareness and preventive policies.

Therefore there is a crucial need to develop a sensitive tool for laboratory diagnosis of Borrelia burgdoferi acute and chronic infections to provide novel treatment options for patients suffering from their harmful infestations. The action has to be taken at a European level, making sure that standard testing criteria are developed and disseminated so that effective control of this disease is achieved on time.

The solution

Based on the market needs, two main required features were clearly identified:

* In order to improve the current WB [Western Blot] technique which is very labour‐intensive, time consuming and difficult to standardise, the tool should be robust, easy‐to‐use and enable unambiguous interpretation of test results.
* To avoid the need of two different tests to get a diagnosis and allow chronic infections to be detected, new antigens, that have been reported in the literature in the last years but have not reach clinical use, should be included.

With these premises in mind and with the input of all the partners, the HILYSENS consortium came to the following solution:

A highly‐sensitive, specific and robust diagnostic tool for Lyme Disease, easy to use and interpret by frontline physicians and clinical laboratories that will become a standard detection tool, rising awareness of this disease among European clinicians and permitting accurate quantification of the increasing disease incidence in order to carry out prevention campaigns before the disease becomes epidemic.

The solution lays on the lab‐on‐a‐chip technology to permit robust and automatic sample processing and detection in a single step, combined with very specific antigenic proteins and peptides that will be detected by fluorescent nanoparticles due to its excellent properties in terms of enhanced signal to background detection and performance in multiplexed assays. The marriage of both technologies is highly innovative and will provide outstanding features in terms of sensitivity and assay robustness addressing therefore the gaps of existing assays.

Impact

HILYSENS will solve the major problem faced by health professionals when treating Lyme Disease patients: the lack of a reliable and standardised diagnostic test. HILYSENS will be the first lab‐on‐a‐chip tool that will allow specific and sensitive detection of acute, chronic and autoimmunity associated Lyme Disease infections and will ensure non‐invasive, fast, specific and easy diagnosing, prognosis and monitoring. Specific and sensitive detection of immunologic profiles will allow better point of care treatment and intervention of the disease. Moreover, acquired knowledge on the pleomorphic forms arising from the project, will permit future implementation of novel treatment options that will be offered to patients suffering from acute and chronic harmful infestations contributing, in all, to improve quality of life EU‐wide.

If not treated in the early stages Lyme Disease can progress to chronic stages of more serious symptoms even interfering with patients daily activities and causing inability to attend school or work. All of these make the long‐term cost of Lyme Disease to families, school systems and health care systems astounding. Autoimmune and chronic conditions represent immense costs for European Health systems and their economic impact goes beyond the costs of healthcare treatments. Indirect costs, such as those from lost productivity, can match or sometimes exceed the direct costs.

Earlier detection and treatment of Lyme Disease will thus greatly reduce the associated costs of the treatment and management of the illnesses, as well as increase the possibility of the patient making a full recovery and going on to live an active life as a contributor to society and the economy.

Summary

One tick bite can cause many diseases. Lyme Disease is the most prevalent tick-borne infection in Europe and North America. Patients with acute Lyme disease need prompt diagnosis to prevent the development of chronic infections. Current commercial laboratory methods fail to detect a huge amount of cases. As consequence, patients receive delayed or inadequate treatment, leading to more serious symptoms which can be disabling.

HILYSENS will be the first lab-on-a-chip tool allowing specific and sensitive detection of acute, chronic and autoimmunity associated Lyme Disease and ensuring non-invasive, fast, specific and easy diagnosing, prognosis and monitoring. Optimisation of resources, reduction of the associated costs and an increase in the quality of care are some of the potential impacts of HILYSENS .

HILYSENS is a 2 year R+D project funded by the European Commission’s Seventh Framework Programme (FP7) under Research for the Benefit of the SMEs. The project officially started on November 1st 2010. The Kick-off Meeting was held in Barcelona on November 8th and was hosted by AROMICS at the PCB.

To learn more about the project go to: http://www.hilysens.eu/index

Patient support groups estimate that about 500,000 to 600,000 people in Germany only are already chronically infected with Lyme disease, with yearly increases of > 50,000 (estimate of the Bavarian State Department for Health and Food Safety). If the Lyme disease is not recognized early enough, the infection can cause severe pain (e.g. chronic joint ailments) and loss of power (up to incapacity).

In contrast to the tick-borne Encephalitis (a virus, TBE) it is not yet possible to get vaccinated against Lyme disease. This is the reason why it is so important to identify the disease early enough. Every sixth to tenth tick bite leads to such a bacteria disease. Every sixth to tenth tick bite leads to such an infection.

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The problem with Elisa!

Serodiagnosis of Borreliosis: Indirect Immunofluorescence Assay, Enzyme-Linked Immunosorbent Assay and Immunoblotting.

Arch Immunol Ther Exp (Warsz). 2011 Jan 22. [Epub ahead of print]

Wojciechowska-Koszko I, Mączyńska I, Szych Z, Giedrys-Kalemba S.

Department of Microbiology and Immunology, Pomeranian Medical University, Powstańców Wielkopolskich 72, 70-111, Szczecin, Poland, IwonaKoszko@interia.pl.

‘using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable’

Abstract

Lyme disease is an infectious, multi-system, tick-borne disease caused by genospecies of Borrelia burgdorferi bacteria sensu lato, characterized by remarkable heterogeneity. In this situation choosing an optimal antigen array for diagnostic tests seems problematic.

The serological tests for borrelia routinely done in laboratories often produce ambiguous results, which makes a proper diagnosis rather complicated and thus delays the implementation of an appropriate treatment regimen. Thirty-seven outpatients and eight inpatients with suspected borreliosis diagnosis hospitalized at the Clinics of the Pomeranian Medical University (Szczecin, Poland), participated in the study. In order to detect the antibodies against Borrelia sensu lato three kinds of serological tests were used: indirect immunofluorescence assay (IIFA), enzyme-linked immunosorbent assay (ELISA), and immunoblot.

The IIFA and immunoblot tests conducted on 45 patients (100%) produced positive results for both the IgM and IgG antibody types. In the case of ELISA, positive or borderline results were observed in only 24 patients (53.3%). The immunoblot test for IgM most frequently detected antibodies against the outer surface protein C (OspC) antigen (p25), and, in the case of IgG, against the recombinant variable surface antigen (VlsE).

The IIFA screening test used for diagnosing Lyme borreliosis produced the highest percentage of positive results, which were then confirmed by immunoblot, but not by ELISA. Therefore using only ELISA as a screening test or for diagnosing Lyme borreliosis seems debatable.

PMID: 21258869 [PubMed – as supplied by publisher]

For more articles on testing check out the following:-

Will there ever be an accurate test for Lyme Disease? by Tom Grier

Reasons for Lyme seronegativity by Dr Robert Bransfiield

Persistence & seronegativity – a compendium of peer reviewed articles

Where to obtain private testing in Europe

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Will there ever be an accurate test for Lyme?

Will there ever be an accurate test for Lyme?

Tom Grier examines all the problems with testing including Elisa, WB, DNA/PCR & microscopic examination. At the bottom is a summary on key words.

ELISA Recap:

* The ELISA test is useless within the first four weeks of a tick bite.

* The ELISA may not detect late infection because the bacteria can find immune privileged sites in which to hide.

* The ELISA test is not a standardized test. The design of the test can vary greatly from lab to lab.

* The choice of antigens used in the test is derived from a laboratory strain B-31 instead of the naturally occurring wild strains. The B-31 strain is proving to be highly variable and changing. Using a high passage lab strain may be cheap and convenient, but not an accurate representation of the various strains of Borrelia found in nature.

* The accuracy of the test varies even on identical samples, meaning that even the labs themselves introduce a variable of inaccuracy by poor procedure, interpretation, or quality control.

Western Blot:

The Western Blot antibody test has only two slight advantages over the ELISA test. First, it is slightly more sensitive, probably due to the inclusion of more bacterial antigens. Second, it tells us which bacterial proteins are eliciting an antibody response in that patient. However, in the end, the Western Blot still suffers from all the same downfalls as the ELISA.

* Note: A misconception about Western Blots and ELISA tests is that they have as many false positives as false negatives. This is not true. False positives are rare. Negative serologies despite a rash or a positive culture is routine. Remember words like sensitivity, specificity, and accuracy DO NOT MEAN DIAGNOSTICALLY ACCURATE to determine if a patient has an infection. A NEGATIVE TEST CANNOT RULE OUT AN INFECTION THAT HAS ESCAPED THE BLOODSTREAM.

The biggest misunderstanding physicians have about Lyme antibody tests is thinking that a high titer of antibody in a patient means that the patient is more ill than a patient with a low titer of antibodies. What these tests are really measuring is the body’s natural immunity against the bacteria. A patient who is able to mount a strong antibody defense against this pathogen is far better off than a patient who makes little or no antibody. It only stands to reason that a patient with a high infection load and no antibodies is going to be more symptomatic than a patient with a high natural immunity. Unfortunately, most physicians look at higher titers and assume those patients are the most ill, but their reasoning is backwards. Low titers in a highly symptomatic Lyme patient is a very bad thing.

DNA Amplification or PCR (Polymerase Chain Reaction) Tests:

In Lyme disease, the PCR test really has limited value. The main problem is that doctors and labs like to use blood, urine, and spinal fluid to test simply because of the ease of collection. In the case of Lyme disease, however, the borrelia spirochete does not like the blood stream, and PCR tests of fluids are frequently negative while the same PCR tests of skin biopsies in the same patient are positive. This indicates that finding a sample with the bacterium’s DNA is a bit like finding a needle in a haystack.

PCR Recap:

No single sample from a patient can be diagnostic for Lyme disease using PCR as the test. Even the University of Minnesota reported a mere 18% success rate in early Lyme when skin biopsies were obtained from culture positive bull’s-eye rashes.

Patent disputes often result in poor PCR tests being marketed with little or no sharing of technology between competitors. This competition often leads to over-hyped performance and over hyped accuracy claims by manufacturers.

Often the best tissues for PCR tests are tissue biopsies, which are rarely done because of costs, risk, and inconvenience. In truth, PCR tests are best used in the post-mortem exam on tissues such as the brain, bladder, and heart. As a diagnostic tool, it can be useful when positive, but tells us nothing when negative. I see few patients lining up for a brain biopsy.

Microscopic observation of the organism:

Using a microscope to find the Lyme bacteria is quite literally like looking for a needle in a haystack. The Borrelia burgdorferi organism is found in such low numbers in fluids and tissue that it requires hours and hours of lab time to do an adequate search of just a few millimeters of tissue. As a research tool biopsy and stain is useful, but to use microscopy to diagnose Lyme is too slow, too costly, and quite unreliable.

Conclusion:

One of the biggest misconceptions about Lyme disease antibody tests, which has led to years of unnecessary morbidity and mortality for Lyme disease patients, is the insistence that the absence of Lyme antibodies means the absence of active infection. You cannot equate the absence of antibodies with the absence of infection, nor can you use antibody serologies as an endpoint in treatment studies to determine the effectiveness of any treatment regimen. It isn’t just a bad idea – it is just plain bad science.

Will there ever be a Lyme test that can be used dependably to diagnose Lyme disease? I don’t believe such a test is within our current technology, and until such a test exists denying patients treatment using our current tests is bad medicine.

Key words and concepts used in this article:

Systemic: Borrelia burgdorferi and other spirochetes in the tick-borne relapsing fever family of bacteria circulate through the blood stream to the entire body. They can find passage through blood vessel walls and invade other tissues and organs, including known target tissues such as skin, tendons, joints, heart, nerves, and brain.

Sequestered: The Lyme spirochete can find haven in areas of the body that are poorly protected by the immune system (the brain), have poor areas of blood circulation (tendons), or where the bacteria can lay metabolically inactive for lengths of time and resist antibiotic penetration (the skin and the brain).

Multi-systemic: The bacteria has affected more than one system of the body, such as: Peripheral nervous system, skin, joints and connective tissues, cardiovascular system and circulatory system, eyes, muscles, liver and spleen, and central nervous system.

Blood Brain Barrier (BBB): The network of capillaries surrounding the brain that selectively let things in and out of the brain. A healthy BBB prevents infections, white blood cells, and many medicines from entering the brain. A breakdown of the BBB is not a good thing, and occurs very early in most animal models of Lyme disease.

Antigen: A protein usually on the surface of the bacteria that stimulates the immune system to make antibodies against that protein. Antigens can also stimulate other immune responses, such as T-cell and macrophage responses.

Serologies: Using the centrifuged serum extracted from blood to look for antibodies against the Lyme bacterium.

Titer: A measurement of antibody content in the serum. Titers are usually reported as dilution series. The higher the dilution of serum where antibodies are still detectable means there are more antibodies present in that patient’s serum. The cut off for reporting a positive is a bit arbitrary and varies from lab to lab. Institutions conservative on the diagnosis of Lyme have raised their cutoffs from 1:256 to 1:1024 Which is rare to see in most Lyme patients.

Infection Load: The actual number of bacteria in a host. If the bacteria remain in the bloodstream, the number of bacteria per unit of blood can be calculated, but this number is meaningless if the infection has moved beyond the bloodstream. In Lyme disease, there is no accurate way of determining true infection load. If the bacteria out pace antibody production then there is no FREE ANTIBODY only ANTIBODY COMPLEXES.

For a detailed view hop along to:

http://owndoc.com/pdf/when-accurate-lyme-tests.pdf

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Blood Tests for Lyme

NB: Tick Talk Ireland has no ties with or recommend any particular option – we have listed alternative labs for information only. As always it is best to work with your own GP with any health concerns you may have.

Disclaimer, please note that mainstream consultants may ‘not’ accept overseas tests as they are encouraged to use only UK & Irish 2 tier tests (Elisa & Western Blot). Therefore the details posted below are for your information only.

There are many types of testing for Lyme inc the following:

1: The general Elisa test through your GP. Word of warning – this has a low sensitivity rate and can produce false negatives. Although I suggest this as a first line of testing I do recommend to people that a negative result may not necessarily mean you don’t have Lyme.

Per the guidelines from the test kit manufacturer (PDF) https://ticktalkireland.files.wordpress.com/2013/02/elisa-trinity-vise.pdf

“The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease. High Complexity Test. Patients in the early stage of disease and a portion of patients with late manifestations may not have detectable antibodies. Serologic tests have been shown to have low sensitivity and specificity and, therefore, cannot be relied upon for establishing a diagnosis of Lyme disease.”

For a look at problems with testing check out our new article: Issues with Testing
or see our Newcomers Guide for more info..

A secondary test should be offered after a positive or borderline Elisa which is considered more specific, however this second test known as Western Blot or Immunoblot is often not offered if the first test is inconclusive. Strains of bacteria, length of time since the tick bite, plus early antimicrobial treatment as well as a hampered immune system can all affect results.

So, if Elisa is insensitive what other methods can you try? There are some labs. in the U.S. such as Igenex Labs who test for Lyme. I have listed below three labs. in Germany as the courier fees are much cheaper to send to Europe. Details as follows:

P.S.For those seeking in-depth knowledge on Western Blots we have a spreadsheet comparing lab test criteria across various labs (Igenex, CDC, European MiQ 12 2000 + current testing methods at Porton Down UK) – results can depend on types of band & number of bands being allowed before the cut off.

NB: Elisa v WB is covered also in our main site below at:
http://www.ticktalkireland.org/elisavswb.html

2: Melisa LTT (this test is for antigens not antibodies and considered far more accurate, particularly with regards to an active ongoing infection). They have a UK office who will send a test kit out to you, plus an application form. You would need to arrange for the bloods to be drawn at your local GP office early in the week and arrange for fedex to courier them for you. The London office will give you the fedex account number to use and details of how to arrange for fedex pickup. (To ensure your package is sent promptly, it may be worth dropping it directly at a fedex depot and write “Urgent – next day delivery” on it!) Melisa will then bill you for the test and courier fees and will give you results within 10 days. The website for more information is as follows:

Melisa Labs
MELISA Diagnostics Ltd 6 Heatherdene Mansions Cambridge Road Twickenham TW1 2HR UK Phone +44 20 8133 5166 Fax +44 20 8711 5958
Email info@melisatest.com

3: BCA/Infectolab – another lab. in Germany which does an amazing array of different tests regarding Lyme and its various co-infections. An important test to consider is the CD57 test which is a test developed to show immune suppression in chronic Lyme cases. For instance, results of over 100 (using the German Lab criteria) is considered a healthy immune system, results below this show immunity problems caused by Lyme and possibly other co-infections, and treatment should be continued until this normalises to prevent relapse.

BCA-labs
B-C-A Betriebs GmbH & Co. KG Morellstraße 33 · 86159 Augsburg, Germany. Phone + 49 821 4550740 Fax + 49 821 4550741
Email info@bca-lab.de

NB: Low CD57 results are more indicative of chronic Lyme and would not be considered suitable for a more recent infection. Please note, it is not specific to Lyme disease & cannot be considered diagnostic as a standalone test but may be useful in combination with other tests being performed.

*Added May 2015 –

4: Armin Labs – this is a new lab created by Armin Schwarzbach (who previously worked with BCA Germany). Similar to Infectolabs, this lab can test for borreliosis using a combination of Western Blot (antibody tests), Elispot (T cell tests) & CD57 NK markers. Also tests for multiple tick-borne co-infections.

http://www.arminlabs.com/en
Armin Labs Zirbelstraße 58, 2nd floor 86154 Augsburg, Germany. Phone +49 821 218 2879 Fax +49 821 218 3081
Email service@arminlabs.com

P.S Both Arminlabs & BCA Labs can offer patients a co-infection check list for those who feel that other infections may be at play (treatment may differ depending on which infection you may have). The co-infection check list can help rank which tests to go for based on your symptoms..

To learn more about co-infections go to: https://ticktalkireland.wordpress.com/lyme-links/co-infections/

5: Lastly, some people opt to use Lyme literate doctors for their testing in the UK. You would have someone check you over, ask questions about your history and then suggest further testing for you. One place to try is the Breakspear Hospital

Another ‘maybe’ is to see if you react to antibiotics. If your doctor is willing to try you on high dose doxycycline per Joseph Burrascano (recommended dose is 400mg – see guide below for more details) and you worsen this may be a sign of bacterial die off, which could show that your health problems are indicative of bacterial, rather than the post viral problems often associated with ME.

Some more useful links:

Is it Lyme or ME?
Suspect Lyme?
Newcomer’s Guide
Issues on Testing PDF
Articles on testing (in depth)
Reasons for Lyme seronegativity
Burrascano’s guide on treating and diagnosing Lyme
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Some future developments – a 2 year EU funded project to design a novel ‘lab on a chip’ test called Hilysens*.

For more details go to: http://www.hilysens.eu/index

Updated Nov 2015

*Pls Note: Hilysens ”II’ project is now under way (details & a video available at):

http://hilysensproject.eu/common_page.php?id=project

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