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.
* 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.
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.
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.
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.
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