Testing may be difficult when the standard diagnostic test fails. The gold standard, the identification of the organism by DNA or culture is frequently not feasible or available. Several antibody tests have been developed which may be helpful, but these tests have a low sensitivity, missing many cases. As an adjunct, a newer technology involves lymphocyte stimulation. When cells (T lymphocytes) are exposed to proteins derived from the pathogen, cell mediated responses such as the release of gamma interferon can be measured indicating prior exposure to the pathogen. This test may have limitations and likely should only be used adjunctively.
Of course, we are talking about diagnostic procedures for Mycobacterium (tuberculosis).
Let’s talk about Lyme.
Testing for Lyme remains problematic. Tests have been inaccurate, unreliable and at times prohibitively expensive.
We depend on clinical diagnosis. But sometimes we are not sure.
All currently available tests have pros and cons.
A lot of labs are suddenly getting into the Lyme testing business. Many tests are in development.
The Western Blot remains the first line test. It is important that a Western Blot be ordered, not just an ELISA with reflex to Western Blot. The ELISA is not dependable. An alternative ELISA, the C6 peptide may be ordered, occasionally it is positive and is highly specific. A C6 from LabCorp/Quest is not adequate, a numerical value, available from various reference laboratories is needed. (MDL, IgeneX, many others)
PCR (polymerase chain reaction) is a test which measures the presence of specific DNA. Most consider this the gold standard. Unfortunately, when it comes to Lyme it doesn’t work as well as it does on all the crime - detective TV shows. Blood tests have a low yield because Lyme is a tissue pathogen and may be present in the blood in very small numbers. Many labs are working on ways to improve the sensitivity of the test. If Lyme DNA is detected, the organism is there (dead or alive). An alternative is offered by several labs (including Quest). Urine is tested rather than blood. Lyme lives in the bladder and is shed in urine. There is a much greater chance of finding Lyme DNA.
This is not to be confused with the antigen capture test or the nanotechnology test, both of which also test urine samples.
Let’s then address the Nanotrap test, the new kid on the block. I haven’t liked the test – but that is about to change. This is a urine test which captures tiny amounts of proteins found on the surface of the Lyme bacteria. The test has been using only one protein: outer surface protein A, or OspA. This protein corresponds with the 31 band of the Western Blot. Remember, Lyme is a clever “shape shifter.” This protein is expressed when the spirochete is attached to the gut of the tick. After infection, this protein disappears (downregulated) and Osp C (upregulated) takes its place. So, the current test is really only helpful for acute Lyme and -- maybe late-stage Lyme. After many months of infection, this protein (OspA) may reappear.
Now I know more. When scientists (Center for Applied Proteonomics and Molecular Medicine, George Mason University) started working on the test they were incredulous (blown away) that the so-called experts in the field insisted that chronic Lyme is not real. To prove the concept of the test, and to get the blessing of the IDSA, ILADS and the CDC, the new test was designed to detect acute Lyme. The CDC admits that current testing (two tier test) for acute Lyme is flawed, and THERE IS AN X-PRIZE) award for the first lab to develop an accurate acute Lyme test! Usually acute Lyme is easy to diagnose, but the test as it stands, may be useful for poorly informed doctors on the frontline.
Now there is general proof of concept. An improved test which includes many proteins, including OspC is promised within 2-3 months. Now this something to be excited about. The only major drawback I see is cost. About $400.00. A Lyme Western Blot from MDL, with images, is about $80.00 and insurance will likely pick up the tab.
A culture test from ASL is available. After being slammed by the CDC, the lab is actively engaged in studies to achieve FDA clearance. The blood culture test has two drawbacks: cost and the patient must be off antibiotics for 2 months before the test is performed. Otherwise, it may be a very good test.
Another test, Lymphocyte transformation test, is available from Pharmasan and a lab in Germany, Arminlabs. This test is based on a completely different concept and technology, based on the same, FDA approved technology, used for TB testing. The test does not look for direct evidence of infection, as do all the other tests. The tests measures responses of memory T cells. T cell lymphocytes are the first line of defense. Killer T cells attack offending antigen (Lyme), as an innate immune response, long before antibodies are made with the acquired immune response. Here is the concept: T memory cells exposed to Lyme antigens react (by releasing gamma interferon, a potent cytokine). This reaction is measured, qualitatively and quantitively. This test may be considered a complement to Western Blot testing. The drawback again, is cost, about $350.00.
From a cost perspective, it is best to start with a Western Blot (MDL) and maybe add a urine DNA test (if covered by insurance). More advanced testing can be ordered as desired.
A fair question might be: since the Western Blot only shows exposure to Lyme, not the presence of infection, shouldn’t a test that directly measures Lyme infection be done, to prove it’s there?
Here is my answer: If Lyme persists in mice, dogs and monkeys and test tubes and the patient is sick, I assume the patient is infected with Lyme spirochetes (Borrelia species). Further testing is not needed. Additional tests may have false negative results only adding a layer of unneeded confusion. The goal of therapy is remission of symptoms, not eradication of organisms.
Bottom line: There are lots of tests out there. You can likely find the diagnosis without spending a fortune.