Jun 20, 2015, 9:03:59 PM6/20/15
Some information to consider before any test is accepted. The tests are mainly about patenting.
It is important for the population in general to realize the limits of testing. I can't tell you how many times I have a friend, family member, acquaintance with probable Lyme disease that has said to me , "They tested me for Lyme. I was negative."
This is from the California Lyme Disease Symposium 1994;
"Regarding the PCR, Dr. Burrascano believes it is a technique which
looks promising but has serious limitations. One very important thing to
remember when considering antigen-capture tests in general, he stated, is
that 'the spirochetes of Lyme do not live in the liquid portions of the
body; they are deep tissue infections'. He stated that it is a very rare
occurence , especially in later Lyme, to find spirochetes in the spinal
fluid, in the urine or in the blood, and he feels that this is a big
limitation of the clinical usefulness of PCR testing which needs to be
studied further. "
"Dr. Nick Harris, president of IGeneX .......who spoke on laboratory
testing for Lyme disease, further emphasized the testing problem created by
low tissue densities of spirochetes, noting that serial sections of a
patient who had Lyme carditis revealed only one
spirochete................He stated that 'the PCR is a very sensitive tool,
but there are some pitfalls. The laboratory has to recover at least one
organism, or the DNA from at least one organism. A positive test says,
'yes, we've found the DNA of Borrelia.' aA negative says 'that sample is
"While the Lyme spirochetes grow to high densities in ticks.....in mammals
there is an extremely low density, probably less than one spirochete per
gram of tissue or blood. This fact plus the probable abitlity of the
spirochete to bind IgM antibody to itself are two reasons why it is so
difficult to test for the presence of Lyme disease."
This is information from 1994--
from: California Lyme Disease Symposium--Lyme Disease Resource Center of
California pg. 18
Reported by Jean Hubbard
"Dr. Burrascano also emphasized the complexity of Lyme disease, particularly
chronic disease, and he too recommended an article....by Kenneth Leigner in the
Journal of Clinical Microbiology, August 1993, 1961-1963 that deals with the
very basic questions that need to be addressed in diagnosing and treating Lyme
disease: the accuracy of the diagnostic tests, the accuracy of beliefs about
the existence of 'post-Lyme syndrome', and the accuracy of beliefs about
"He observed that he has a practice of patients who are really 'end-stage,
chronic Lyme patients, and therefore my view of things is biased'. He noted
that CNS symptoms can begin one day after EM and that experimental infection in
rodents shows that within 12 hours after their injection spirochetes can be
recovered from the CNS. He noted that there are studies in humans showing that
' At the time of otherwise asymptomatic EM you can find evidence of infection
in the CNS...........Treatment for early Lyme disease has to be designed to
penetrate the CNS, even if it is an asymptomatic person with EM,' especially
since the CNS disease can then become latent for long periods of time, up to 14
years. He sees patients who were not treated early and who present sometimes
14 years later with encephalopathy, headache, irritability, stroke, persistent
neurogenic Lyme. 'The best correlation of this with other illnesses, of
course, is syphilis, and we all know about the Tuskegee study where syphilis
was purposely not treated to to see what would happen. Patients who are not
treated or who are given minimal treatment may go on to progress. The bottom
line,' he says, 'is not just how does the patient feel next week, or does the
treatment make the patient feel well, or is the joint better. The better
question is: Is the whole person better? How long do we follow these people?
For a month? Three months? Six months? I basically recommend that until we
have more technology to tell whether the patient is infectious, they be
followed for life.'
"With regard to diagnosis, Dr. Burrascano emphasized that serologies are not
reliable, and that several groups have been able to culture Borrelia
burgdorferi spirochetes in the CSF of patients who had negative serologies both
on blood and CSF. Lyme disease is not diagnosed with a blood test; it is
diagnosed with the whole clinical picture, the background of the patient, the
exposures, the symptoms, the evolution of symptoms over time, ....taking the
whole picture into account.'
"He warned that in his opinion it is the patients who are much more ill who
remain seronegative or only weakly seropositive for years ......His experience
suggests that these patients also in general respond much more poorly to
therapy, and he is concerned that they are not studied at all by groups which
limit their patient poplulation to CDC-defined cases of Lyme disease, which
"Dr. Burrascano noted that there is controversy related to how long someone is
supposed to be treated. Articles often state that treatment should consist of
two to three or sometimes four weeks of antibiotics, but he asserted that this
is an arbitrary time period, that...'Never in the entire history of this
illness has there ever been a single study that has proven by any scientific
method whatsoever that x number of weeks was enough to kill the spirochete. If
you look at the the science of this, there are many studies of failures of
four weeks or less of treatment, proven by positive antigen capture and culture
and so forth.' He said that this is particularly true for late stage Lyme. He
stated that if treatment is stopped when patients are still sick, they are
still going to be sick, and that the hard part for the clinician to decide is
when the patient is over the active infection. ' There is no test for a cure,
' he said, 'and there probably will not be one, because of the nature of the
So what you have to try to do is discover, from close work with the patient,
what the symptoms are that are indicative of an ongoing, active infection, as
opposed to some permanent damage or autoimmune phenomena that may or may not be
occurring .' For example,'some ongoing low grade fevers or night sweats, with
the low-grade fevers often occurring in the late afternoon at about 4 o'clock,
are a sign if you exclude other sources of fever. Patients who have migratory
polyarthritis or polyarthralgia, when it's in the elbow for two weeks and then
it moves to the knee and it moves to the wrist, something is moving around in
there, and that is a sign of ongoing infection.' Dr. Burrascano finds that if
patients have such signs, and treatment is stopped, 'either they are never
going to go completely back to normal, or they will relapse fully after they
have been treated, and this is what makes the treatment of Lyme so difficult.'
Some patients in his practice, he observed, have had Lyme disease for over five
years, undiagnosed and untreated, and have had one month of amoxicillin and
were absolutely fine, and in five to ten years of followup never have been sick
again. On the other hand, other patients in his practice have been on
antibiotics for more than three years and have been found by objective cultures
or by electron microscopy to harbor living spirochetes.
"Dr. Burrascano discussed some of the means by which the spirochete might
resist both detection and antibiotic therapy. These include dormancy or
latency, residence within intracellular structures, residence within certain
organisms of the body which are resistant to both immunologic defenses and
antibiotics, and the ability of the spirochete, as described by Dr. Dorward, to
coat itself with a gel-like substance including immunoglobulins which may well
insulate it from detection by the immune system and from the effects of
"With respect to dormancy/latency, he reported a study done in 1991 by McDonald
which cultured spirochetes from EM lesions and found that, in the same medium
and using the same techniques. some spirochetes grew for a month or two, some
spirochetes did not appear to grow until several more months went by, and one
culture lay dormant for over 10 months before it started to regrow. This
correlates with observations on latent periods and relapses in human
symptomatology, and Dr. Burascanno noted that if the laboratory findings hold
true in human systems, this is very important in as much as antibiotic therapy
kills spirochetes only in their growth phase.
"With respect to intracellular residence, he noted that several different
scientists have found the spirochetes inside the cells of the body, inside
fibroblasts and inside macrophages. If spirochetes actually take up residence
in these intracellular structures for more than a transient passing through,
he observed, then they will be resistant to drugs like cephalosporins, which
don't penetrate cells. He also reported that in New Jersey a well-known
opthalmologist is the field of Lyme disease has shown electron micrographs of
spirochetes that have been cultured from the inside of the eyes. The eye is
well known as an immunologically favored site and can serve as a persistent
locus of spirochetes that can keep a person infected, or can reinfect them when
antibiotics are stopped....."
from: The American Journal of Medicine April 24, 1995 Volume 98 (suppl 4 A)
Andrew Pachner: "The problem with PCR is that it detects spirochetes in the
tissue where there are problems. PCR in blood is almost universally
unhelpful, AND IT IS GOING TO CONTINUE TO BE UNHELPFUL--unless there is an
acute viral syndrome with fever, and you think there are spirochetes in the
blood. But animal studies as well as our experience show that THIS ORGANISM
DOES NOT LIKE TO BE IN THE BLOOD FOR VERY LONG."
Title:Interlaboratory comparison of test results for detection of Lyme disease
by 516 participants in the Wisconsin State Laboratory of Hygiene/College of
American Pathologists Proficiency Testing Program.
Authors:Bakken LL, Callister SM, Wand PJ, Schell RF
Source:J Clin Microbiol 1997 Mar;35(3):537-43
Organization:Department of Continuing and Vocational Education, University of
Wisconsin, Madison 53706, USA.
In 1991, we reported that 55% of laboratories participating in the Wisconsin
Proficiency Testing Program could not accurately identify serum samples from
Lyme disease patients containing antibody against Borrelia burgdorferi. The
purpose of this study was to determine whether the accuracy of Lyme disease
test results reported by approximately 500 participants in the Wisconsin State
Laboratory of Hygiene/College of American Pathologists Lyme Disease Survey had
improved. From 1992 through 1994, 50 serum samples were sent to participants of
the survey. Each laboratory received 28 serum samples from individuals with
Lyme disease according to the case definition of the Centers for Disease
Control and Prevention and 22 serum samples from healthy individuals.
Unfortunately, the serodiagnosis of Lyme disease by participants had not
improved. The specificity of the Lyme disease assays steadily decreased from
approximately 95% to approximately 81% during the 3-year period of the survey.
False-positive test results approached 55% with some of the serum samples from
healthy donors. A serum sample containing antibody against Treponema pallidum
was reported as positive by 70% of the participants. In addition, the
sensitivity fluctuated between 93 and 75%, depending upon the conjugate used by
the laboratories. These results suggest that stronger criteria must be applied
for approving and continuing to approve commercially available kits for the
serodiagnosis of Lyme disease.
Antibodies, Bacterial, BLOOD, Bacteriology, STATISTICS & NUMER DATA, STANDARDS,
Borrelia burgdorferi, IMMUNOLOGY, Comparative Study, Data Collection, False
Negative Reactions, False Positive Reactions, Human, IgG, BLOOD, IgM, BLOOD,
Laboratories, STANDARDS, Lyme Disease, DIAGNOSIS, IMMUNOLOGY, Quality Control,
Reference Standards, Sensitivity and Specificity, Serodiagnosis, STATISTICS &
NUMER DATA, STANDARDS, Wisconsin
Unique ID: 97193799
source: Lyme Disease 1991: Patient/Physician Perspective from the U.S. and
Lora Mermin, editor
More On Lyme Testing
James H. Katzel
Back in the January 1990 "ticked-off tract" we looked at why it is so hard to
diagnose Lyme borreliosis, as well as the methods and problems associated with
testing. In the March 1990 "ticked-off " we evaluated serologic testing (blood
tests) and urine antigen testing in terms of their predictive values at various
stages of the disease. Both of those articles confirmed the fact that Lyme
borreliosis (Lyme disease) was, and still is a clinical diagnosis rather than a
disease easily diagnosed by a lab test.
Some lab tests can help sometimes, or can point you in the right direction.
But the patient might still have Lyme despite having a negative lab test. At
times, a positive Lyme test might also be incorrect, leading to delayed
diagnosis of some unrelated disorder, while the patient or doctor thinks the
patient indeed has Lyme borreliosis.
Previous studies have shown that lab tests vary from lab to lab, or may vary
from day to day at the same lab, this being true even for some of the best
testing labs. To make things worse, there are now dozens of different "kits"
which may be used in a lab or office to try to make a laboratory diagnosis of
Lyme borreliosis. Some kits are quite simple, others more complex and time
consuming, but in general these kits are purchased from the manufacturers and
set up in a doctor's office, a hospital lab, a public health lab, a reference
lab, etc. The lab director buys the kit he or she thinks is the best. The
purchase of the kit is based on their knowledge (or lack of ) regarding Lyme
borreliosis, the cost of the kit, or possibly on the basis of how well the
sales representative wined and dined them. It is all pretty arbitrary. Most
labs that I surveyed used three or more different kits, one after the other,
trying to determine if results were accurate, or if they felt comfortable with
the kit. What does comfortable mean?
The Lyme testing kits are made by reputable major medical companies seiously
trying to produce a good test. They are also made by some dedicated companies
tying to cash in on the milion dollar business being created, for testing of
To try and put some order to all the chaos in Lyme testing, a conference was
held in November 1990, in Dearborn, Michigan. An objetive of the conference
was to evaluate the commercial Lyme test kits and to look at the nationwide
lack of standardization in Lyme disease testing. This "First National
Conference on Lyme Disease Testing" was sponsored by the Association of State
and Territorial Public Health Laboratory Directors (ASTPHLD), the Food and Drug
Administration(FDA), and The Centers for Disease Control (CDC). A goal of the
conference was to address this lack of standardization. It was expected that
certain kits would stand out as being superior in Lyme detection, thereby
standardizing Lyme disease testing worldwide. As seen, that did not exactly
The CDC used twenty kits. These kits tested blood or serum from thirty-six
(36) specimens, including thirteen (13) from patients who met the 1989 CDC case
definition for Lyme disease, three (3) from patients with syphilis, and twenty
(20) with no history of disease--so called negative controls from non-Lyme
endemic areas. The results of lab testing using the kits was compared with the
CDC's standard ELISA test using the B31 strain of Borrelia burgdorferi as the
antigen. Only seven (7) of the kits, 3 ELISA, 1 dot blot ELISA, and 3 IFA,
correlated with the CDC testing, using a statistical measure of agreement known
as Kappa statistics. With this kappa statistic system a value of
less than 0.4 was poor
a value of 0.4 to 0.7 was fair
and a value of 0.7 or greater was good.
Only seven (7) kits out of twenty (20) passed with values of 0.4 or greater.
These seven (7) kits that scored fair or good were then tested again in the
second phase of the CDC's evaluation.
The state public health labs in California, Minnesota, New York, and Wisconsin,
along with the main CDC lab, used the seven kits to blindly test 158 specimens.
Again, these specimens came from patients with early or late Lyme borreliosis,
syphilis, and negative controls. To me the results were dismal and showed a
large variation between the five labs and between the seven kits. The mean
agreement of testing results between the seven test kits was 0.16 to 0.06, no
better than fair results.
Using regular statistics, again the rather dismal results showed a mean
sensitivity for the kits ranging from 26% to 57%, and mean specificity for the
kits ranging from 12% to 50%. Not very good numbers in medical testing. Both
should be above 90%. The testing went on to try to identify which sub-set of
patients might be picked up with the kits. But, as the CDC finaly
stated,"..when the overall proportion of positive tests was used as the outcome
variable, donors who met the Lyme disease case definition were less likely to
be seropositive than were donors who did not meet the case definition. " I had
to read that twice too, folks, but you read it right!! The CDC went on to say
that when patients with erythema migrans were excluded from the numbers, there
was no association between the case definition and the overall seropositivity.
In fact, that was just about the only thing that was statistically significant,
that is, that there was no provable association between the tests and the
What the conference proved, was that none of the kits, and in fact no serology,
may be considered "the gold standard" for Lyme borreliosis testing. Before we
are able to say that one test is bad or that one test is good, we need to have
an acceptable standard that we can compare it to. The CDC goes on to say that
at present, the only "gold standard" for Lyme disease is isolation of B.
burgdorferi from clinical material such as biopsy of the erythema migrans, or
the culture of a body fluid such as blood, spinal fluid, or synovial fluid. It
was concluded that until such methods are established, "serologic testing for
Lyme disease will result in a high rate of misdiagnosis."**********
So, the only thing once again shown is that Lyme borreliosis continues to be a
diagnosis made by clinicians on clinical rather than laboratory evidence. It
is a clinical diagnosis.
source: Lyme Disease 1991:
Patient/Physician Perspective from the U.S. and
Lora Mermin, editor
author: John Drulle M.D.
Lyme Disease: The Pitfalls of Laboratory Testing
"...........Currently available commercial tests for Lyme diseae provide
indirect evidence of exposure to the Lyme bacteria. When someone is infected
with the Lyme bacteria, the immune system responds by making specific proteins,
called antibodies, whose role is to seek out the Lyme bacteria, attach to them
and initiate the process of destruction . In most patients, these antibodies
are unable to destroy the Lyme bacteria, which by methods which are not
completely understood, may remain alive in the human body for many years, in
spite of high "titers" or concentrations of antibodies. Detectable levels of
these antibodies may not be found until 3 to 8 weeks after exposure.
Significant illness may be present before the test is positive. Most people
who present with the characteristic EM (erythema migrans ) rash of Lyme disease
test negative at that time. A number of patients clearly do not develop
measurable antibodies. This is usually due to antibiotics given early in the
infection for Lyme or non-Lyme infections. There is a significant strain
variability in Lyme bacteria isolated in different geographic areas, and since
commercial tests have been developed from certain isolates, they may be
incapable of detecting antibodies to a different strain of Lyme bacteria. It
is also possible that some people's immune systems do not recognize the Lyme
bacteria as an invader and do not produce specific antibody .* When there is
an excess of Lyme bacteria and their fragments, they may combine with all the
circulating Lyme specific antibodies.
Current commercial antibody tests for Lyme can only detect free circulating
antibodies, and are incapable of detecting those bound up in immune complexes.
Ivestigational tests have been developed to free these sequestered antibodies
and render them measurable by the standard tests. There is wide variability
between tests of commercial laboratories, and it is not unusual to have a serum
sample test positive in one lab and negative in another.
"....Some people who appear to be in good health and have no Lyme related
symptoms may test positive. This may indicate past exposure to the Lyme
bacteria, with spontaneous recovery, or it may represent a dormant infection
which may activate at some future date and cause clinical disease. This has
been well documented in the European literature.
"The Western Blot is now commercially available for Lyme disease. Here
various sized Lyme antibodies are allowed to migrate on a strip of filter
paper. They separate into distinct bands, and serve as a 'fingerprint' for
Lyme disease. This technique is wrongly thought to be a 'confirmatory test'
for Lyme disease, which it is in AIDS. It may be useful to sort out false
positive tests and in cases where the antibody titer is 'borderline'. Since
its results depend on the presence of Lyme specific antibodies, the same
factors which can cause a negative test may cause a negative 'Western Blot'.
"The Cell Mediated Immunity Test (CMI) or T-Lymphocyte Stimulation Test,
has also been used to make a laboratory diagnosis of Lyme disease. It attempts
to determine if one's immune system has 'memory' of exposure to Lyme bacteria.
It is currently done by StonyBrook University and several other research
laboratoies. It costs more that $300.00 to do and is very labor intensive. It
also has a high rate of false positive and false negative results.
"The most common errors made by physicians in interpreting these previously
mentioned tests are: 1) A negative test excludes the diagnosis of Lyme.
2) A NEGATIVE TEST IN SOMEONE WHO PREVIOUSLY TESTED POSITIVE AND RECEIVED
ANTIBIOTIC TREATMENT IMPLIES 'CURE'.
"It must be stressed that these tests do not correlate with symptoms and
activity of the Lyme bacteria once antibiotics are initiated. THERE IS NO
CURRENTLY AVAILABLE TEST FOR CURE. Physicians who monitor Lyme titers
(concentration of antibodies) during and after antibiotic therapy , and
pronounce their patients 'cured' when their test becomes negative, do not
understand what they are measuring and are wasting the patient's money and
doing them a disservice.
".....The laboratory tests may be a useful adjunct in making the diagnosis
, but negative results do not rule out the possibility of the disease."
Ticked offTract--June 1991