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Lyme Disease Lab Testing17 min read

Lyme disease can be difficult to diagnose. Sadly, recent data shows more than 85% of Lyme disease patients were not diagnosed until after four months of illness and over 70% saw four or more doctors before receiving a diagnosis.[1]

There are several reasons for this difficulty, including the fact that many people don’t remember a tick bite, EM rash isn’t always present, Lyme symptoms mimic so many other conditions, and current FDA-approved/CDC-recommended testing fails to accurately diagnose in 60-70% of cases.[2]

When an expanding EM rash is present, however, especially if you’re from or have traveled to a Lyme-endemic area, a diagnosis is given without laboratory testing, and treatment is started immediately.

In all other suspected cases of Lyme disease, your physician will assess your symptoms, medical history, any past diagnostic tests, and run new laboratory tests.

What Tests Are Available to Diagnose Lyme Disease?

If you have every sign and symptom of Lyme disease, but your lab tests are negative, you are not alone.

Unfortunately, many doctors still rely on one or two lab tests to give a Lyme diagnosis. Since early diagnosis and treatment are critical in Lyme disease, a delay resulting from a false-negative lab test can have detrimental, long-term consequences on your health.

At Brio Medical, we make use of more than the standard testing discussed here. We rely on cutting-edge diagnostics from labs who specialize in Lyme and its coinfections.

What is the Standard Two-Tiered Testing for Lyme Disease?

Standard testing for Lyme disease involves indirect, two-tiered serological testing that helps rule out or confirm a Lyme diagnosis. These tests are indirect because they detect the immune system’s response to certain Borrelia species through the presence of antibodies rather than testing for the bacteria directly.

Traditionally, an enzyme-linked immunosorbent assay (ELISA or EIA) test is run first. Since the ELISA is quite sensitive, you may receive a positive result even if you don’t have Lyme disease. That’s why all positive or inconclusive ELISA tests are followed up with a second test called a Western Blot. If your ELISA test was negative, you can be fairly sure you don’t have Lyme.

The Western Blot test is very specific and is usually only positive if you’re truly infected with Lyme. If you receive a negative, it’s likely that your positive ELISA result was a false positive.

If you’ve had symptoms for less than 30 days, you’ll have an IgM and IgG Western Blot, which tests for two different types of antibodies. For symptoms over 30 days, only an IgG is necessary.

IgM antibodies are produced before IgG antibodies and usually indicate a recent or active infection. The body makes IgG antibodies later. They can be found even when there’s no longer an active infection.

Typically, if you test positive for IgM antibodies but not IgG antibodies, the test will be run again a few weeks later. If you’ve been sick longer than 30 days and have a positive IgM but a negative IgG, you most likely do not have Lyme disease.

On the other hand, if you received a positive IgG but a negative IgM, you were exposed to Borrelia at some point in the past and have antibodies, but your infection is not new or active.

Both tests must be positive for a Lyme disease diagnosis. Results usually take one to two weeks, which can delay treatment in the early stages of Lyme. In 2019, the FDA approved a modified two-tiered test that uses only concurrent or sequential EIA tests instead of the Western blot, which significantly speeds up diagnosis.[3]

What Are The Problems With Standard Two-Tiered Testing for Lyme Disease?

There are several problems with the standard two-tiered protocol. To begin, it can take the immune system up to two months after initial infection to develop enough Borrelia antibodies for a positive test.

Tick saliva, which is able to suppress the immune response, is thought to be the cause of this delay,[4] leading to false negatives in early Lyme cases 50-65% of the time.[5]

Some tests may not be sensitive enough to detect antibodies, especially if you’ve already started antibiotics. Or you may even be seronegative, meaning you don’t produce antibodies at all.

Additionally, once you carry Borrelia antibodies, they can remain in your body for years, even if you were successfully treated. It’s impossible to know if a positive test means you have a recent, active infection or were infected at some point in the past.

Add to that the fact that these blood tests aren’t able to identify antibodies of every Borrelia species that cause Lyme. Finally, the test may come back positive even if you don’t have Lyme, as it may not be specific enough to distinguish Borrelia antibodies from other antibodies.

What is the C6 Lyme Enzyme Immunoassay Test for Lyme Disease?

The C6 Lyme Enzyme Immunoassay (EIA) is a single-tier FDA-approved serologic test that measures IgG antibodies to a specific protein of Borrelia burgdorferi, the C6 peptide of the variable major protein-like sequence-expressed (VlsE).

The VlsE lipoprotein creates a strong immune response throughout all stages of  Lyme disease. Since it’s unique to B. burgdorferi, the presence of antibodies to C6 indicates infection. The debate remains as to whether the C6 ELISA is superior to the standard ELISA.

One study did indicate using the C6 Elisa resulted in 82 fewer false positives out of 2208 control sera, which produced a 77% reduction in immunoblot testing, a possible cost-saving benefit.[6]

What is the Cerebrospinal Fluid Test for Lyme Disease?

The Cerebrospinal Fluid (CSF) test for Lyme disease is similar to serological testing, but it looks for Borrelia antibodies in your cerebrospinal fluid rather than your blood.

If your physician suspects the bacteria that causes Lyme disease has spread to your central nervous system, you may have a spinal tap or lumbar puncture to confirm.

Lyme disease affects the central nervous system in nearly 15% of cases. It’s called Lyme neuroborreliosis (LNB), and evidence suggests its cause is the inflammatory response that occurs when Borrelia contacts nerve cells,[7]  leading to symptoms that may include:

  • Headache
  • Deafness
  • Bladder dysfunction
  • Painful nerve inflammation
  • Facial paralysis (Bell’s Palsy)
  • Infection of brain and spinal cord tissues (Meningitis)
  • Chronic Fatigue Syndrome (Myalgic Encephalomyelitis)
  • Chronic skin disorder (Acrodermatitis Chronica Atrophicans) – European Lyme

If test results for Borrelia antibodies in the CSF are higher than in your blood, your CSF white blood cell count is high, and the protein concentration in your CSF is between 200 and 300 milligrams per deciliter, you’ll probably be diagnosed with Lyme disease of the central nervous system.

What Is Immunofluorescence Assay Testing for Lyme Disease?

Immunofluorescence assay (IFA) is an indirect serology test. It was the first serology test used to confirm Lyme disease in the early 1980s.

Many laboratories still use it, but it requires skilled technicians to interpret results. It works by indirectly detecting Borrelia burgdorferi antibodies attached to spirochetes that are incubated with human serum on a glass microscope slide.

The antibodies are confirmed when nonhuman antibodies labeled with fluorescein isothiocyanate are added to the slide and incubated. A fluorescence microscope is used to visualize the binding of these second antibodies, which indirectly confirms Borrelia is present.[8]

What is a Urine Antigen Test for Lyme Disease?

The Urine Antigen Test is a direct test, meaning it detects the Lyme antigen, B. burgdorferi, directly rather than detecting the presence of Borrelia antibodies.

The test detects the shedding of outer surface protein A (OspA), a protein expressed on Borrelia burgdorferi spirochete surfaces in a tick before it feeds.

With only a urine sample, it’s able to measure OspA in urine at all stages of infection. Urine antigen tests are especially accurate in patients with an EM rash, making them helpful in detecting early-stage Lyme disease.

Urine antigen testing is also beneficial when assessing treatment effectiveness, as it measures how much treatment has changed OsPA levels.

What is Live Culture Testing for Lyme Disease?

A live culture test is a direct test derived from samples of tissue, blood, or cerebrospinal fluid, and is the gold standard for confirmation of Lyme or any infection.

Culturing spirochetes is difficult, however, as they require a host to survive, so a special media and technical expertise is required for incubation. B. burgdorferi replicates slowly, so a long incubation period is necessary. Specimens are kept up to 12 weeks before considered negative.[9]

Due to its difficulty, a live culture test is best reserved for certain cases, including seronegative patients, a newborn with Lyme antibodies possibly received from the mother, the immunosuppressed, those with concurrent infections, past Lyme patients with a new tick bite, and post-treatment patients who remain symptomatic. Post-treatment, a positive culture means there’s an ongoing infection.

What is Direct Observation Testing for Lyme Disease?

Direct observation testing uses a microscope to search for Lyme spirochetes. It’s not a very efficient method, as there are so few Borrelia spirochetes in fluid and tissue samples.

here are a few ways to see spirochetes in the microscope. The use of silver stain is traditionally most common.

Nucleic acids in the spirochete’s membrane absorb the stain, making the spirochete appear black under a light microscope. The fluorescent stain is now also used and stains the antibodies that attach to the spirochete.

The bacteria are easily seen as brightly-colored spirals under a fluorescence microscope. Labs can also ultracentrifuge a bodily fluid, add a drop of orange dye, and view the sample under a light microscope.

Direct observation is timely and therefore costly. It’s also not possible to find out what species of Borrelia bacteria is present based on this method alone. Most experts agree direct observation is best reserved for post-mortem biopsies.

What is the Polymerase Chain Reaction Test for Lyme Disease?

The Polymerase Chain Reaction (PCR) test for Lyme disease is a direct test that detects the presence of certain Borrelia DNA. By amplifying the cloning of targeted sections of a DNA sequence, creating billions of copies, technicians are able to better study your sample to see if Borrelia DNA is present. Urine, blood, cerebrospinal fluid, synovial fluid, or other tissue can be used for the PCR test.[10]

For early or acute infection, direct testing with PCR can confirm Lyme disease before antibodies are developed. PCR testing is very specific, which is especially helpful in confirming chronic Lyme disease.

Because there are few Borrelia bacteria present in infected tissues, however, there’s a greater chance of a false negative, especially if antibiotic treatment has already started.

PCR tests require expensive equipment and advanced technical skills, so there are very few trusted labs able to run PCR tests. For that reason, in most clinical settings, PCR is used only to confirm Lyme after serologic testing is completed.

The Brio Medical Center is one of the few alternative medical treatment centers that regularly order PCR tests, providing you with a definitive diagnosis of Lyme or coinfections.

What Laboratories Are Used for Lyme Disease Tests?

There are several leading laboratories that specialize in the research and development of tests that detect Lyme disease and other tick-borne illnesses.

We work with you to determine the best tests at the best lab for your situation, taking into consideration your current condition, medical history, insurance coverage, and copays. Our goal is to diagnose and treat as efficiently and affordably as possible.

What Is IGeneX Lab?

IGeneX is a lab that’s been on the forefront of comprehensive testing for tick-borne illnesses for 25 years. IGeneX has developed several tests that are more sensitive and specific than others on the market.

They were the first to identify Borrelia burgdorferi in ticks in California and Babesia microti in New York, Switzerland, and Australia with their patented Fluorescent In-Situ Hybridization (FISH) assay.

They were also first to produce a Tick-Borne Relapsing Fever (TBRF) Western Blot test. Relapsing Fever mimics many Lyme disease symptoms. IGeneX is the only lab that accurately provides the correct diagnosis by distinguishing Borrelia that causes Lyme disease from Borrelia that causes TBRF.

Other cutting-edge IGeneX tests include the Lyme ImmunoBlot IgM and IgG , which is one of the best tests available for Lyme disease with 98% specificity for IgM and 98.7% for IgG. The sensitivity of the Lyme ImmunoBlot is 90.9% with well-defined samples. It’s able to detect antibodies to major Borrelia burgdorferi sensu lato specific antigens from North America and Europe, specifically B. burgdorferi B31, B. burgdorferi 297, B. californiensis, B. mayonii, B. afzelii, B. garinii, B. spielmanii, and B. valaisiana.[11]

When the ImmunoBlot is paired with the IGeneX PCR assay, immunofluorescence (IFA) assay, and enzyme-linked immunospot (ELISPOT), the full spectrum of a patient’s immune response to infection as well as the disease stage is determined.

We work with you to order the proper collection kits from IGeneX and determine which tests IGeneX will conduct with your sample. Unfortunately, IGenex doesn’t bill insurance accept Medicare Part B, so you will probably have to pay out of pocket.

What Is Armin Labs?

Armin Labs offers laboratory testing for chronic infections caused by tick-borne diseases. Armin specializes in T-cellular tests (EliSpot), B-cellular tests (IgA, IgM, and IgG-antibodies), and NK cell tests (CD57, CD56).

The Elispot is designed to eliminate the problems associated with monitoring the effectiveness of treatment. By measuring the activation of T-lymphocytes, the cellular immune response to Borrelia infections, the test provides the current activity of both chronic and recent infections.

The test is so sensitive that it’s able to detect a single Borrelia burgdorferi-reactive T-cell. It’s 20 to 200 times more sensitive than a standard ELISA with detection levels as low as one cell in 100,000. This level of sensitivity is similar to PCR, but it detects a secreted protein and not the messenger RNA (mRNA). For those reasons, EliSpot should become negative four to eight weeks after successful therapy.

Armin Labs also offers the TickPlex assay, which contains a new antigen for round bodies, known persister forms of Borrelia. With a high sensitivity of around 95% and a 98% specificity, TickPlex is superior to comparable immunofluorescence assay (IFA) tests and can be used at all stages of the disease.

TickPlex Plus allows for testing of IgG and IgM antibodies for Lyme and several coinfections at the same time while TickPlex Basic only tests for Borrelia burgdorferi.

What Is Vibrant Wellness?

Vibrant Wellness is a leading science and technology company providing laboratory services through their proprietary silicon microarray platform that enables multiplex testing at an affordable cost. Vibrant’s Tickborne Diseases panel includes direct (DNA) and indirect (antibody) testing for Lyme and its coinfections. The panel includes two tests.

The Vibrant Immunochip test is a qualitative and semiquantitative assay that tests human serum for IgG and IgM antibodies to Anaplasma, Babesia, Bartonella, Borrelia, Ehrlichia, and Rickettsia species. The Immunochip is made from proteins of several Borrelia burgdorferi species, not only B31, which is used by most other Western Blot tests. The second is a real-time Polymerase Chain Reaction (PCR) test that qualitatively detects infectious bacterial DNA of Borrelia and the other coinfections.

Clinical support for both patients and practitioners is included with vibrant testing. You can connect with their team of functionally-trained registered dieticians to help interpret your labs, set health and wellness goals, and make the diet and lifestyle changes recommended by Brio’s Lyme team that are necessary for your healing. Vibrant provides the opportunity for the ongoing screening of the microbiome with their Vibrant Gut Zoomer and Pathogens test, which is helpful if you’re taking antibiotics for Lyme disease.

What Other Tests Are Used to Diagnose Lyme Disease?

Beyond the laboratory, practitioners use several other diagnostic tests and tools to diagnose Lyme disease. Of course, a thorough evaluation of your medical history, a physical examination, and an assessment of past and current symptoms contribute to the diagnosis, but further testing may be helpful to decipher the complexity of Lyme and its coinfections, especially once it has become chronic.

What Neurocognitive Tests Are Used to Diagnose Lyme Disease?

Neurocognitive tests objectively measure cognitive function at a specific point in time, pretreatment and posttreatment, for example. Since difficulties with concentration, memory, communication, and other neurological and psychological symptoms are often reported but don’t always match up with objective data, neurocognitive tests provide quantitative results that are used to monitor changes.

There are many available test options that measure general intellectual function, attention, concentration, verbal fluency, virtual learning, fine and gross motor function, even depression and anxiety.

In adults with Lyme disease, verbal fluency, verbal memory, and mental processing speed are the most common neurocognitive deficits. The Controlled Oral Word Association Test is used to assess verbal fluency while the Buschke Selective Reminding Test and California Verbal Learning Test are often used for verbal memory. Processing speed is measured through a variety of timed tests, such as the Digit Symbol Substitution Test.

Unfortunately, many chronic Lyme patients have been accused of fabricating neurocognitive symptoms, or they’ve been brushed off as purely psychological. PET and SPECT brain function scans challenge those accusations by demonstrating physiological dysfunction.

How Are Brain Imaging Tests Used to Diagnose Lyme Disease?

Several brain imaging techniques are used to help diagnose Lyme disease, including magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computerized tomography (SPECT). In addition to their diagnostic utility, these tests, which show brain structure or function, have benefits for patients and families.

Observing real-time biological dysfunction increases understanding that Lyme disease is not, in fact, a psychological issue. These scans can also show treatment effectiveness, as improvement or resolution of abnormalities is visible post-treatment.

Magnetic resonance imaging (MRI) provides a picture of the physical structure of the brain. For nearly 40% of adults with Lyme disease, MRI captures hyperintensities on the white matter that point to inflammation and areas of demyelination.[12] These white matter hyperintensities are referred to as unidentified bright objects (UBOs), which may disappear or diminish after treatment.

Positron emission tomography (PET) is a brain imaging technique that uses radiopharmaceuticals to measure brain function. PET scans are able to detect widespread inflammation in the brain in those with Post-Treatment Lyme Disease Syndrome,[13]making it valuable in chronic cases of Lyme.

Single-photon emission computerized tomography (SPECT) measures healthy activity in the brain by capturing blood flow, revealing how the brain is functioning. SPECT scans are abnormal in most people with chronic Lyme disease. In one study, 75% of patients had abnormal perfusion to the frontal, temporal, and parietal lobes as well as other parts of the brain.[14]

What Peripheral Nerve Tests Are Used to Diagnose Lyme Disease?

Muscle weakness, spasms, and paralysis are common symptoms in Lyme disease as is tingling or numbness in the face and extremities. Lyme-related peripheral neuropathy is confirmed with peripheral nerve testing.

Nerve conduction studies and electromyography (EMG) are tests that measure the electrical activity of nerves and muscle function. Electrical signals sent out by nerves cause your muscles to respond in specific ways. Muscle response is then measured to determine proper function.

The EMG test measures muscle signals at rest and while in use. A nerve conduction study tests how fast and appropriately the body’s electrical signals travel through your nerves, assessing damage or disease.

To learn more about Lyme Disease treatment in Scottsdale, Arizona at Brio-medical, sign up for a free treatment consultation today with a patient care coordinator.

References:

[1] https://www.lymedisease.org/2019-mylymedata-highlights.pdf

[2]https://www.healio.com/news/rheumatology/20160307/study-early-lyme-disease-diagnosis-difficult-treatment-improvements-needed

[3]https://www.fda.gov/news-events/press-announcements/fda-clears-new-indications-existing-lyme-disease-tests-may-help-streamline-diagnoses

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938952/

[5] https://www.columbia-lyme.org/diagnosis

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052829/

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025284/

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327992/

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441761/

[10] https://pubmed.ncbi.nlm.nih.gov/23745373/

[11]https://igenex.com/press-release/igenex-inc-introduces-new-diagnostic-tests-for-lyme-disease-and-tick-borne-relapsing-fever/

[12] https://www.columbia-lyme.org/diagnosis

[13] https://www.radiologybusiness.com/topics/care-delivery/pet-imaging-technique-brain-inflammation-after-lyme-disease

[14]https://journals.lww.com/nuclearmed/Fulltext/2012/09000/SPECT_Brain_Imaging_in_Chronic_Lyme_Disease.33.aspx#:~:text=Brain%20SPECT

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