@sarah darwins , I hope you don't mind if I take a stab at the question you posed to paolo since I have a little experience with diagnostics.
You understand the distinction between sensitivity and specificity. Sensitivity refers back to the true positive rate, or the portion of actual positives that is picked up. Specificity refers to the true negative rate. The statistics get pretty rough, fast, at least they do for me. But suffice it to say in an ideal world, a perfect test would boast 100% sensitivity and 100% specificity. I actually ignore the stats and just embrace specificity to mean it's SPECIFIC to a given pathogen, and sensitivity to the test's ability to sweep like sonar and determine if an antibody is present. I'm sure there are immunologists cringing out there...
The gold standard in infectious testing is the culture test, where you are able to actually identify the pathogen directly, through serum or CSF fluid or blood. This is ideal
There are some diseases where capturing the pathogen directly has proven very difficult, if not impossible. A famous example is Syphilis.
In such cases, frequently, the tests revert to a hunt for antibodies. This is where sensitivity/specificity come into play. The ability of a test to register high values determines its usefulness.
Ok, how is this relevant to Lyme? Although it
is possible to isolate the Borrelia Burgdorferi spirochete - the agent of Lyme - and culture it, that is a very difficult and expensive thing to do, except when biopsing the bull's eye rash, i.e., Eythema Migrans. It
can be done outside of the rash, but it is very rare, and for all intents and purposes, it isn't done. Why? The Bb spirochetes don't care much for blood (ironic since their carriers, ticks, feast on blood). Upon entering a human, they flee the blood for safer harbors like organs and joints and tissues.
Because of this, once the bull's eye rash has faded - or the ACA in Europe, which typically occurs later in the disease - testing for Lyme becomes a hunt for signs, principally signs for antibodies.
The controversy centers around a dispute about the
accuracy of antibody testing. The IDSA says tests like the ELISA and Western Blot are highly effective for testing for Lyme, and when used in tandem (the CDC's Two-Tier Testing), those two tests are really very very good relative to both sensitivity and specificity.
Many doctors and researchers and patients disagree. They can and do point to stats which suggest a more dismal performance. Worse, they suggest the 2T test actually presents artificial barriers to finding patients and getting them diagnosed and, accordingly, treated. Somewhat oddly, this is very important in Lyme, this ability to get a diagnosis, because there are rules strangely specific to Lyme that direct doctors away from treatment without a positive test in hand.
The first part of the 2T is the ELISA, and groups who oppose it say its efficacy is only slightly better than 50 to 60% - around the same as a flip of a coin. So in theory, about half of the patients tested have results which may be wrong. This problem is compounded by the fact that the Western Blot, which is better than the ELISA, but still is limited, literally cannot be used on a patient in many States in the US if that patient tested negative on the ELISA.
There are even more rules, many rooted in general biological immune principals that some claim do not apply to Lyme. For instance - and Dr. Edwards can correct me if I err here - a body's first line of immune defenses is its IgM's. These are what can be responsible for generating fevers, etc. They typically only hang around for a few weeks, when they are relieved by IgG's. IgG's do mop up duty, but IgG's can stay around for long, almost indefinite periods - even for the rest of the body's life.
So, one of the rules in Lymeland is that if a patient tests IgM positive say within 60 days of an EM, then that patient can be said to have tested positive for exposure to Lyme. But if that patient should test IgM positive
after 60 days, and not IgG positive, according to mainstream Lyme diagnostic protocol, that's a false reading. That's a false positive. And, for most other diseases, this distinction may hold true. But for Lyme, it may not. The reason is the outer surface of the Lyme spirochete has proteins and antigens. It is these that our antibodies react to. But with Lyme, the outer surface proteins are constantly shifting. In effect, when Lyme first introduces itself to the body, it wears a certain face, and all the body's IgM's attack that face. And as that is happening, many spirochetes are changing their appearance, presenting with new outer surface proteins. The body thinks it's a different infection because it doesn't recognize the face, so it sends in a new wave of antibodies. This process of constantly generating an IgM response can be repeated over and over and over again. It is because of this process - which the IDSA argues doesn't happen in Lyme -that some Lyme patients only present with positive IgM's.
Wow. I've written a lot but barely scratched the surface. Perhaps links are the better way to go.
Ok, I will try to wrap up. This is only the tip of the iceberg. See, there are like 35 Lyme Species worldwide, and within each Species are many strains. Could be well over a hundred strains out there. Now, some of those Species don't seem to cause illness in humans. Enough do however, and this generates some problems because tests for one Species may not be able to pick up another Species. Same holds true even down to strains. So entire arsenals of test may be useless if they are being used against the wrong Species/strain.
This dilemma is a worrisome one throughout Lymeland.
Ok, other tests like PCR and, Antibody Index in CSF exams, are very specific, but not very sensitive. The tradeoff with tests like these is that if you test positive, Great!, you have more proof for your argument you have Lyme (you will need it). But if you test
negative, well, that value doesn't necessarily mean you don't have Lyme. It may just mean that the test wasn't sensitive enough to find the antibody at the time it was administered.
So, to wrap up, many believe most Lyme tests suck, and according to those individuals it's hard to get good treatment, fast or long enough, due in large measure to those testing inadequacies.
I am going to stop here because I've squandered my word allocation for the morning.
