Madison Area Lyme Support Group

An Introduction to Lab Testing

Lyme disease tests can serve as valuable resources for the diagnosis and treatment of tick-borne disease. But it’s important not to get too hung up on the results.

The problem of chronic Lyme disease, can’t be solved exclusively by looking at lab results, which is something I know from personal experience. In fact, becoming overly obsessed with lab results can hinder the recovery process.

Lab work provides a snapshot of what’s going on inside your body. But multiple other factors — including your symptoms, the length of time you’ve had them, and clinical presentation, as well as the environments in which you live, work, and travel — all factor into making an accurate diagnosis.

Furthermore, the human body is an immensely complex biological machine, with millions of different biochemical functions happening simultaneously. Lab tests provide an ever-so-small glimpse at certain key functions of different systems in the body. From those indicators, determinations can be made about how well the body is functioning and whether illness is present.

Laboratory assessment, however, is far from absolute. Because the human body is so complex, the ability of lab testing to predict a specific chronic illness, such as one from a tick-borne disease, is often limited. All labs are subject to variability and different interpretations.

There are literally thousands of different lab tests that can be performed, but only a fraction of them are well understood. Many should be left for research purposes only. Problems arise when doctors order obscure tests that are still poorly understood. Before you have labs drawn, ask your doctor to explain the purpose of each test and why they would be helpful in addressing your health situation.

The information provided by labs is only valuable if it is put to good use. Millions of dollars are wasted every year on labs, with the resulting information never used. Before you have labs drawn, ask yourself and your doctor: “Will the information from this lab — or any other diagnostic test — influence my approach to getting well?” If the answer is no, then you may want to reconsider having that particular test performed.

For chronic illnesses like chronic Lyme disease, fibromyalgia, and chronic fatigue syndrome, general lab evaluations are usually unremarkable. In these cases, the greatest value of labs is ruling out the possibility of a more threatening condition. Mildly abnormal labs generally return to normal as your health improves.

The following is a guide to the labs that I’ve found to be most valuable in evaluating chronic illnesses like chronic Lyme and fibromyalgia. It is, by no means, an absolute or exclusive list.

Basic Lab Tests Everyone Needs

There are certain basic tests and a few specialized ones that have great value. These are the tests that everyone who suspects they have Lyme should consider getting. In addition to taking a detailed medical history, the following list of labs can be ordered by any healthcare provider. Typically, these tests are covered by health insurance.

Complete Blood Count (CBC with Differential)

This test measures cellular components of blood:

• White Blood Cell count (WBC): Low WBC (< 4,000) can indicate chronic infection with a virus or low-virulence bacteria such as mycoplasma, but it can also occur in healthy people. Elevated WBC (>11,500) can indicate an active infection.
• Differential (diff): This measures different types and ratios of white blood cells present. Sometimes, it can be helpful for defining a particular type of infection (bacteria vs. viral vs. parasite), but it is not always absolute.
• Hemoglobin (Hb): Anemia is indicated by Hb < 12.0. Anemia can be caused by blood loss due to factors like heavy periods, inadequate production of red blood cells (RBCs), and increased destruction of RBCs from malaria, babesia, bartonella, or other infections. Hb levels > 16.0 can be associated with smoking, living at altitude, and excessive iron stores in the body (hemochromatosis).

Blood Chemistries

These are a measure of common chemical components of the body, including:

• Electrolytes: Sodium, potassium, chloride, CO2; these are generally normal, unless you are really sick.
• Liver function: Abnormal values suggest an elevated rate of liver compromise, possibly from toxins or viruses such as hepatitis. Elevated bilirubin suggests increased breakdown and turnover of red blood cells (babesia, bartonella). Certain low-virulence microbes (bartonella) destroy red blood cells.
• Kidney function: BUN (blood urea nitrogen) and creatinine screen for kidney disease.

Glucose Metabolism

Excessive carbohydrate consumption is a major system disrupter that must be controlled before recovery is possible. Three primary tests — fasting blood glucose, hemoglobin A1c, and fasting insulin — define insulin resistance and abnormal glucose metabolism:

• Fasting blood glucose: Levels >100 mg/dl suggest pre-diabetes. Levels >126 mg/dl suggest overt diabetes.
• Fasting insulin: Levels defined as elevated suggest insulin resistance (normal range varies depending on the lab). Insulin resistance is a factor contributing to immune dysfunction and hormone imbalances.
• Hemoglobin A1c (HbA1c): HbA1c measures the cumulative damage done by excessive carbohydrate consumption. Ideal is 4.8-5.2%. Levels > 5.6% indicate pre-diabetes. Levels > 6.4% indicate overt diabetes.

Minerals

Magnesium and calcium are the primary minerals measured:

• Magnesium: Magnesium levels are often low during chronic illness. Aggressive magnesium supplements, however, can often worsen Lyme symptoms. Generally, magnesium levels will return to normal as health improves.
• Calcium: Persistently elevated calcium levels can indicate the presence of a small benign tumor producing excessive parathyroid hormone (PTH). Symptoms can mimic fibromyalgia and chronic Lyme. Follow-up testing should include PTH levels.

Thyroid Function

Complete thyroid function should include thyroid stimulating hormone (TSH), free T₄, free T₃, and thyroid antibodies. Illnesses associated with chronic immune dysfunction are commonly associated with abnormal thyroid function. Correcting abnormal thyroid function can accelerate recovery. Testing for thyroid antibodies (TPO and thyroglobulin) is important to identify Hashimoto’s disease, a form of autoimmune thyroid dysfunction.

Lipid Panel

This is a basic evaluation for cardiovascular risk. Cholesterol commonly increases with age and/or a decline in liver function. Cholesterol can be lowered by following specific nutritional guidelines. Significantly elevated cholesterol, however, should be addressed by your healthcare provider and may require medication.

Autoimmune Testing

Chronic immune dysfunction and stealth microbes like borrelia play a major role in autoimmunity. The type of autoimmune illness that occurs is related to the factors that disrupt immune function, the person’s genetics, and the spectrum of stealth microbes.

Though diagnosis of specific autoimmune illnesses is complex and requires extensive testing, basic screening for autoimmunity can be done with two tests:

• Rheumatoid factor: A standard test, it reveals if severe arthritis is present
• ANA titer: Positive in many types of autoimmune disease

C-Reactive Protein (CRP)

CRP is a measure of inflammation. It is probably more valuable for monitoring health habits than anything else. High levels (>10) correlate with poor health habits and increased risk of disease.

Normal CRP levels, however, are often present in individuals who follow good dietary habits and yet still suffer from a chronic illness.

Vitamin D

Vitamin D is not only important for healthy bones, but also very important for normal immune function. There are several forms of vitamin D; calcidiol (25 OH vitamin D) is the most commonly measured form in blood tests.

Both normal ranges for blood levels of vitamin D and indications for supplementation are controversial, and various medical organizations and nonprofit groups don’t seem close to reaching a consensus just yet. For example, the Institute of Medicine (IOM) considers up to 4,000 IU of vitamin D3 a safe dosage for most adults. But the Endocrine Society suggests a safe dose for most adults can go all the way up to 10,000 IU.

With the differing viewpoints, how do you know what to do? For starters, know that levels of >40 ng/ml have been associated with reduced risk for many cancers and for chronic disease in general. And achieving consistent vitamin D levels of >40 ng/ml is also important for Lyme disease, chronic fatigue syndrome, and fibromyalgia recovery.

Ultimately, the best way to stay on top of your vitamin D levels is to work with your healthcare provider to determine which dose is right for you. Ideally, have your levels checked every six months.

Vitamin B12

Low B12 levels (normal ranges vary between labs) can be a sign of low intake (sometimes seen in vegetarians), but more commonly it’s a sign of inadequate absorption and gastric dysfunction. Vitamin B12 generally increases spontaneously with improved health habits, but in the short term, B12 injections or sublingual (under the tongue) supplements can improve energy levels. Activated forms like methylcobalamin or hydroxocobalamin of B12 are better absorbed orally than the more common inactive form, cyanocobalamin, used in most multivitamin products.

Ferritin

Ferritin measures iron stores. Low ferritin levels can indicate low stores of iron in the body, which can be associated with fatigue. High ferritin levels indicate abnormal retention of iron in the body (called hemochromatosis), which can be associated with liver damage and nonspecific symptoms. High levels can also be associated with autoimmunity and chronic infection.

Urinalysis

Test strips for urine testing can be obtained online without a prescription. Here’s what they measure for:

• pH: Urine pH should be consistently alkaline, reflecting high consumption of vegetables and fruit. A normal range is 4.5 to 7.8.
• WBCs, nitrites: These tests show evidence of a urinary tract infection.
• Protein: Elevated levels can indicate kidney disease.
• Bilirubin: Elevated levels show increased turnover or destruction of red blood cells.

Mold and Mycotoxins

Evaluation for mold is indicated anytime there is any suspicion of mold. It is possibly the most important evaluation you can do. Mycotoxins (mold toxins) are potent immune disruptors and cause a wide spectrum of nonspecific symptoms, including a chronic inflammatory response, neurological symptoms, and persistent insomnia. If mold sensitivity is an issue, the only option for complete relief is eradicating mold from your environment.

The first step in evaluating for mold is using your nose and eyes to search for it. Moisture is necessary for mold to grow. Mold, however, can be hidden in walls, crawl spaces, attics, and more. It is possible to test for mold with simple kits that can be ordered online. It is also possible to test for mycotoxins in urine or the potential for mold exposure through blood tests. Ones that could potentially be useful include:

• HLA-DR: This genetic blood test determines whether a person has the genes that trigger the immune system to properly recognize and excrete mycotoxins from the body.
• C4a: C4a is a complement protein known as an anaphylatoxin, a substance that creates a response similar to an allergic reaction. It also executes tasks related to the immune system and inflammation. An elevated C4a may be present in individuals who have been exposed to mycotoxins. Note that C4a levels may also be elevated in patients with Lyme disease and lupus.
• MSH (Melanocyte-Stimulating Hormone): The hormone MSH is produced in the hypothalamus and the pituitary gland. It regulates neuroimmune pathways, including melatonin, cortisol, cytokines, sex hormones, and the integrity of mucous membranes. Among mold patients who developed Chronic Inflammatory Response Syndrome (CIRS), 95% have decreased MSH functioning.
• VCS (Visual Contrast Sensitivity): A VCS test measures your ability to detect changes in visual contrast, a function that may be impaired in individuals who have been exposed to biotoxins. The test is available online or can be completed in a doctor’s office.

However, with or without testing, the solution to a mold problem is completely avoiding mold. Testing may only be needed if you’re not getting better within weeks or months after complete elimination of the mold problem.

Advanced Laboratory Testing

The following tests are discussed because they are often recommended, but they seldom influence the status of recovery. These tests should be reserved for special circumstances or when recovery is not progressing, but not performed routinely.

Omega-3/Omega-6 Ratio

The ratio of omega-3 fatty acids to omega-6 fatty acids is a marker for balance of inflammatory factors in the body. Proper diet and supplementation generally result in satisfactory omega fatty acid ratios.

Cytokine Testing (Th1/Th2)

Cytokines are the messengers of the immune system. Cells of the immune system use cytokines to signal to each other and pass directions. Stealth microbes manipulate cytokines to generate inflammation and redirect immune functions in favor of the microbe.

Though the immune system and its interactions with different microbes is extremely complex (still beyond our complete understanding), effort has been made to simplify immune functions into two pathways important for chronic illnesses associated with stealth microbes. Below, “Th” stands for T helper cells:

• Th1 pathway: Associated with cell-mediated immunity and intracellular pathogens. When the Th1 pathway is overactive, it’s associated with inflammation and autoimmunity.
• Th2 pathway: Associated with antibody-mediated immunity and extracellular parasites. When overactive, the Th2 pathway is associated with asthma and allergies.

This is, of course, an oversimplification of a very complex process. In general, chronic Lyme and other illnesses associated with chronic immune dysfunction and stealth microbes are Th1 dominant.

Many herbs help balance this dysfunction by reducing overactive cytokines associated with inflammation and enhancing antibody and functional cell mediated immunity. A few herbs that stimulate Th1 functions (astragalus, echinacea) should be avoided during the early stages of recovery. Generally, measuring cytokines is unnecessary for recovery.

Adrenal Hormone Testing

Adrenal dysfunction or adrenal fatigue is a given in any chronic illness. Elevated cortisol levels, associated with increased physical and emotional stress, contribute to sleeplessness, stress intolerance, agitation, and anxiety. Prolonged adrenal stress can deplete cortisol, with resulting symptoms of extreme fatigue, total stress intolerance, and excessive sleeping (but sleep is dysfunctional and not restful).

Because adrenal dysfunction is always present in chronic illness and generally normalizes with proper therapy, measurement of adrenal hormone levels is generally not necessary. On rare occasions when a patient is not improving, measurement of cortisol can be beneficial.

• Salivary cortisol: Measured four times over 24 hours, it’s the best measure of adrenal function, but symptoms are often a better guide.
• Dehydroepiandrosterone sulphate (DHEAS): DHEAS measures adrenal function; high levels indicate excessive function, and low levels indicate inadequate function. This test is often performed, but it is not as reliable as cortisol measurement (which is also usually unnecessary, as symptoms are generally adequate to evaluate adrenal function). It is useful in only select circumstances.

Reproductive Hormones

Menopause can exacerbate the symptoms of any chronic illness. Though usually obvious (with the absence of periods), menopause can be confirmed by an elevated pituitary hormone called FSH: levels >25 indicate menopause. Other hormone levels, including estrogen and progesterone, are generally not necessary to measure, but may be recommended by your healthcare provider. In men with fatigue, total and free testosterone are sometimes indicated.

• Female: Salivary or blood E1, E2, E3, free testosterone, progesterone, FSH (screening FSH, Estradiol levels)
• Male: Free testosterone, total testosterone

Testing for Toxins

Build-up of heavy metals and other toxins can be a hidden factor in chronic illness. However, every person living on the planet today is carrying some heavy metals, and no one really knows how much is enough to cause disease. The biggest source of concern is amalgam dental fillings (though recent opinions are suggesting that amalgam fillings do not shed as much mercury as once thought).

A healthful diet and lifestyle along with key supplements will generally reduce heavy metals in the body. Save heavy metal testing for last on the list; if you are still not getting better, ask your doctor about testing.

• Hair samples: This is the least reliable method of testing for heavy metals.
• Blood test: It’s valuable only for testing acute exposure.
• 24-hour urine after DMSA: This is the most accurate assessment. Urine is collected for 24 hours after use of 100 mg of DMSA (Dimercaptosuccinic acid, a chelation medication) to pull heavy metals out of tissues.

The presence of organic toxins (pesticides, plastic residues) is almost a given and can be addressed with dietary and lifestyle modifications. Chlorella is excellent for pulling organic toxins out of the body.

Food Sensitivities

Chronic gastrointestinal dysfunction is often associated with sensitivities to commonly consumed foods (which is not the same as food allergies, like a peanut allergy). Symptoms associated with food sensitivities are commonly delayed for 1-2 days after the food is consumed. Typical symptoms include fatigue, joint pain, muscle pain, and general achiness — in fact, food sensitivities alone can be the root of many symptoms.

• Food sensitivities are best determined by an elimination diet — a diet designed to selectively eliminate and identify problem foods.
• Problem foods can also be delineated with specific IgG and IgA testing. Currently, there are several food sensitivity tests on the market, and many of them can be customized to test a range of foods, preservatives, medications, and more, and some can be delivered to your home. Depending on the company used and number of items tested, prices vary from just under $200 to several hundreds of dollars.

Comprehensive Stool Analysis

Stool analysis is valuable for defining gastrointestinal dysfunction and diagnosing parasites and yeast overgrowth. This expensive test is generally reserved for extreme cases when dietary modifications and supplements are not enough to overcome gastrointestinal problems. It is rarely necessary.

Folate and Methylation

There are about 40 different genetic mutations that can affect MTHFR, a gene that plays an important role in the body’s ability to use folate or folic acid. About 40% of the population has one abnormal gene and are moderately affected. About 12% of the population has two abnormal genes and is more significantly affected.

Problems associated with MTHFR mutations include elevated risk of stroke and heart attack, increased cancer risk, defects in embryo development (spinal tube defects), and neurological symptoms including insomnia, irritability, depression, brain fog, neuropathy (burning tingling feet and hands), and restless legs syndrome. It also can be a factor in recovery from fibromyalgia and Lyme disease.

For folks who want the technical details:

MTHFR is a gene that codes for an enzyme called methylenetetrahydrofolate reductase. This enzyme is vital for creating 5-methyltetrahydrofolate, an essential substance for converting the amino acid homocysteine into the amino acid methionine.

Methionine is essential for amino acid synthesis, formation of glutathione (an important intracellular antioxidant), formation of DNA, and detoxification. Methionine is also important for formation of SAMe, which plays a key role in metabolism of dopamine, serotonin, and melatonin. Without this important enzyme, all these pathways are blocked.

Testing for MTHFR mutations involves a simple blood test or DNA cheek swab that costs about $100 to $200; the blood test may be covered by insurance. Checking for elevations of homocysteine and RBC folate in the blood is an indirect way to check for the problem.

The best solution for elevated levels is getting plenty of natural 5-methyltetrahydrofolate (methylfolate for short). Leafy greens are a great source, but if you have a mutation, supplementing is a good idea. Folic acid, found in most multivitamin products, will not work because it must be converted by the deficient enzyme.

You must supplement with 5-methyltetrahydrofolate; 400-800 micrograms daily is generally adequate for anyone with a single mutation (especially if you eat plenty of leafy greens). If you have a double mutation, it is a good idea to take an extra 400-800 micrograms. For additional benefit, you can add 400-800 mg of SAMe daily, in the evening. SAMe supports detoxification and can improve sleep.

Chemical components called “methyl groups” that are essential for proper detoxification can also be supplied by vitamins B6 and B12. It is, however, important to get the activated forms of these important vitamins. The activated form of vitamin B6 is pyridoxal 5-phosphate, and the active form of vitamin B12 is methylcobalamin.

Healthful diet and adequate supplementation of methyl donors is generally adequate for recovery. MTHFR testing is only necessary if recovery is not progressing.

In my medical practice, I had the fortune of working with a lab that measured MTHFR for no charge. For the five years it was available, I tested all my patients. Surprisingly, I found it played a more minor role in recovery than I expected. I had chronic Lyme sufferers who were severely symptomatic who had no mutations, and perfectly healthy people who had double mutations.

Testing Beyond the Lab

Certain types of symptoms require evaluation by diagnostic procedures conducted by specialists in their respective fields. These symptoms include:

• Neurological symptoms: Severe neurological symptoms are evaluated with a nerve conduction test and MRI of the brain to assess the nervous system. The purpose is ruling out multiple sclerosis.
• Cardiac symptoms: Heart symptoms like chest pain and irregular heartbeat are evaluated by EKG and Holter monitor (a wearable device for tracking your heart rhythm). Findings may lead to cardiac catheterization.
• GI symptoms: Stomach pain and symptoms are often evaluated by an upper endoscopy. Lower intestinal and colon symptoms are evaluated by colonoscopy. Routine colon cancer screening with colonoscopy is recommended every 10 years for everyone over 50.

Testing for Microbes

Testing for microbes in chronic illness is often like opening up a can of worms. Detection of a microbe in the body is only as good as the technology, and right now, the technology for diagnosing borrelia and other low-virulence stealth microbes is fair at best (they’re called “stealth” microbes for a reason).

And that’s for the species of microbes we know about. Research continues to press on in the search for stealth microbes that play a role in Lyme disease, including new forms of borrelia.

The long and the short of it is, all ticks carry potentially pathogenic microbes. If you have ever been bitten by a tick, you have been exposed to microbes, and you likely harbor one or more stealth microbes in your body. If you have all the signs and symptoms of chronic Lyme disease, then the chances that you are carrying some species of borrelia is high — no matter what the testing shows.

When you consider that borrelia has been prevalent in ticks worldwide for thousands of years, and that asymptomatic carriers are extremely common, borrelia is probably much more prevalent than is widely accepted.

The other side of the story is that as testing gets better and better, it will likely reveal that many healthy people have borrelia, and that everyone harbors some stealth microbes — Lyme coinfections like mycoplasma, bartonella, chlamydia, and many others are remarkably common.

The key to being healthy is robust immune function.

When you start seeing chronic Lyme disease for what it is — chronic immune dysfunction, with a pot of stealth microbes boiling over — the compulsion to test for specific microbes becomes less relevant. There are always possibilities that can’t be accounted for.

When I evaluate a person with possible chronic Lyme disease, it’s easier to just assume that borrelia and other stealth microbes are present. This allows me to have less reliance on unreliable lab results.

To Test or Not To Test

Our ability to test for microbes species is limited to a small piece of a much larger pie of unknowns. The total microbiome of the body consists of many thousands of microbe species; who knows how many of them are stealth microbes or opportunistic pathogens. A comprehensive herbal protocol covers for most possibilities, both known and unknown.

Which brings up the question: “Why test at all?”

Frankly, the most pressing reason to test is academic — that “need to know” quality that we all share as humans.

If you choose a conventional route of therapy, however, testing will likely be necessary. In fact, many doctors will not consider writing a prescription until testing is done and results are available. Considering the extreme limitations of the present state of testing for stealth microbes, it is one of the major drawbacks to pursuing a conventional route of therapy.

If you choose a natural route of therapy, testing is much less necessary. A comprehensive herbal protocol covers for borrelia and most other possibilities (without the toxicity associated with drugs and synthetic antibiotics). Many people have gotten well without doing any testing at all.

The biggest reason to test is if you are not improving. Sometimes testing can uncover the presence of other vector-borne diseases (babesia, ehrlichia, rickettsia, anaplasma), or viral reactivation of a herpes-type virus for which a prescription antimicrobial may provide benefit.

That nagging need to know, however, is a fundamental characteristic of human nature. “Could there be something present that could be easily treated?” is a question that often lingers in the back of everyone’s mind. Before proceeding any further, however, know that testing for microbes can unnecessarily complicate your recovery.

There are no absolutes when it comes to stealth microbes. A negative test does not rule out the possibility of a certain microbe being present or the possibility of other microbes being present. Diagnosis should not rely on labs alone. It’s a matter of adding up all the clues, including the symptom profile, prevalence of possible microbes in the geographic area, and any other factors that may be helpful in making the diagnosis.

If you decide to do lab testing, the place to start is with labs covered by your medical insurance. Insurance policies are highly variable, however, and it is up to you (not your doctor) to find out what is and isn’t covered.

Most healthcare insurance policies will cover testing for borrelia and possible coinfections with in-network labs. Most in-network labs, however, only do basic-level testing, which often carries a low probability of actually diagnosing an offending microbe.

Specialty labs do more advanced and sophisticated lab testing, but are generally not covered by insurance, and they can be pricey. Expense is the primary reason these tests are not covered by insurance. Testing for borrelia alone is not sufficient; if you are going to do testing, you really need to test for all the known possibilities. This can run $1,000 or substantially more.

Because of demand, there is a proliferation of specialty labs doing testing. The oldest and possibly best-known is IGeneX, but there are many new and innovative testing labs coming on the scene. Blood can be drawn at the doctor’s office and sent to a specialty lab, but you will probably be responsible for the bill.

Reasons to Test

Here are some of the more compelling arguments in favor of testing:

• Needing to know
• Some stealth microbes are more virulent than others and respond better to antibiotic therapy; a positive test can help direct therapy.
• Obtaining lab tests for microbes supports research and increases the knowledge base of stealth microbes.
• Financial support for labs and institutions doing testing.
• Testing for a specific microbe is primarily valuable for acute symptoms after a tick bite.
• Testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and other herpes-type viruses (there are eight that commonly infect humans) can be valuable because high titers associated with reactivation of these viruses may respond to antiviral therapy.

Limitations of Testing

Current testing options are indeed limited, and results often don’t contribute to faster or more successful recovery. Here’s a summary of testing limitations:

• Multiple microbes are always present; a positive test for one does not rule out the presence of others.
• During chronic infection, stealth microbes occur in very low concentrations in isolated areas of the body, making diagnosis by any means very challenging.
• Stealth microbes commonly live inside cells, and some can exist in cyst forms (especially when they are under pressure). Both are factors that make diagnosis a real challenge.
• Stealth microbes readily manipulate the immune system — detection depends on antibody production.
• Cross-reactivity with other bacteria is common, including normal flora.
• Most testing is species specific; many species of each type (genera) of microbe are possible, for which there is no available testing.
• Symptoms of chronic Lyme can occur without the presence of borrelia and can be caused by other stealth microbes (though borrelia may be present with a false negative test).
• Everyone harbors stealth microbes; the microbiome is extremely complex.
• The concept of testing for chronic infections with stealth microbes is relatively new; most testing is focused on acute illness.
• False negative rates are high for all forms of testing; false positives are also possible.
• Testing for the many possibilities can run several thousands of dollars, often not covered by insurance.
• A positive test for a specific microbe can provide false peace of mind.
• A negative test does not exclude the presence of a microbe (especially during chronic illness).

Common Types of Testing for Microbes

Testing is getting better, and there are a variety of different ways to test, but none of them are anywhere near 100% accurate. Testing is mostly useful for diagnosing acute illness. This is especially true when symptoms of illness suggest infection with a higher virulence microbe that might respond to acute treatment with antibiotics. New innovations may gradually improve testing for chronic illness associated with stealth microbes.

Direct Testing

Direct testing includes visualizing the microbe directly in tissue or blood samples, or growing the microbe out of tissue or blood samples in a media that is specific for that microbe. Direct testing is not species specific, so any species of the microbe can be diagnosed. Polymerase chain reaction (PCR) tests look directly for the microbe’s DNA and are species specific (uncommon species may be present but will not be diagnosed).

These forms of testing are most useful for diagnosing acute infections. Direct methods are not reliable for chronic infections because stealth microbes occur in such low concentrations in the body during chronic infection, are not present in the blood in high numbers, can occur in dormant or cyst forms, live inside cells, and gravitate toward isolated recesses of the body.

Examples of direct testing:

• Tissue/Blood: Direct visualization
• Tissue/Blood Culture: Uses culture media specific for the microbe to grow the microbe in culture
• Polymerase Chain Reaction (PCR): Direct detection of microbe DNA in tissues, blood, and urine

Indirect Testing (Serology)

Indirect testing relies on antibody production to the microbe (serology). Evidence of acute infection is best evaluated with IgM antibodies and late acute or chronic infection with IgG antibodies. Some testing regimens require serial titers (testing at different time intervals) to distinguish between acute and chronic infections.

Different types of serology are available for different microbes. Accuracy for testing chronic illness associated with stealth microbes is greatly limited by low concentrations of the microbe in the body with reduced or inadequate antibody response for testing.

Examples of indirect testing include:

• Enzyme-Linked Immunoassay (ELISA test, EIA): It measures antibodies in the patient’s serum that are specific to microbial antigens (part of the microbe) by using labeled enzymes to bind the antibodies for measurement.
• Immunofluorescence Assay (IFA): This test utilizes fluorescent dyes to identify the presence of microbe-specific antibodies in the patient’s serum.
• Western Blot: Detects antibodies to multiple different microbial antigens by measuring different protein bands. Collectively, the presence of multiple bands allows diagnosis of infection with a specific microbe. A Western Blot is more sensitive than ELISA for borrelia.

Diagnosing Borrelia

The stealth nature of Borrelia burgdorferi makes it very difficult to diagnose. Developing tests to detect it is a real challenge because it:

• Stays deep in tissues
• Has the ability to live inside cells (intracellular)
• Has elaborate ways of tricking the immune system
• Changes its genetic signature readily
• Doesn’t require high concentrations of microbes to cause illness

In the United States, mainstream Lyme testing is specific for Borrelia burgdorferi, but there are presently 21 other species of Borrelia that can cause Lyme disease. In Europe, two other species of borrelia — Borrelia afzelii and Borrelia garinii — are more common than Borrelia burgdorferi as a cause of Lyme disease.

Because of the mobility of people, different borrelia species are circulating around the world. This contributes to another layer of difficulty in diagnosis. It is becoming evidence that other species are much more common than once thought.