To be precise: we will clarify what the test measures and how clinical research is “falsified” (sorry: designed) in order to achieve 80-100% sensitivity.
What do we measure?
Serological tests measure with great accuracy the immune response to proteins produced by recombinant technology from a given narrow, limited gene sequence. Borrelia is capable of high-level genetic modification, mainly to avoid the immune response of the human body, so the protein to be measured will not always be there. In addition, by inhibiting the entire immune response, this bacterium is able to reduce, modulate or eliminate the immune response. If these facts are true, then why are there still satisfied publications, why are these tests always included in the guidelines?
How do they influence the results of clinical research on an “industrial level”?
The author of the article analysed all publicly available Lyme diagnostic clinical research plans and, where the plan was not public, publications on research into the most common tests.
It is known that Borrelia can influence the serological response.
Nevertheless, in clinical research, the selection criterion for serological tests is the presence or absence of a serological reaction. Often, these studies only order samples from a “biobank”, where the serum is correctly documented and stored frozen. The selection criterion for the positive arm is the presence of a serological reaction, while for the negative arm, the criterion is the absence of a measurable reaction.
If I want to estimate the height of the population by requiring that they be able to walk through the door without bending down, it is easy to see that the average height will be lower because people over 2 metres tall will not fit through. But this is not a minor error; in practice, they have to come in through the door of a mud house, so even those who are 170 centimetres tall cannot get in. Is the average height of people really 150 centimetres? Impossible.
Interpretation of the example: those selected for the positive arm all show an immune response, and therefore the new “index” test will also measure this. Bravo, 99% sensitivity! And there is nothing to measure in the negative arm, hurray, 100% specificity! No, this may not be intentional; it may be that the person planning the research is not familiar with the possibilities of Lyme tests.
But there are new directions in research design, for example, one that has already been used several times in Hungary in the development of diagnostic tests: a positive case is someone who has been diagnosed by a doctor as suffering from Lyme disease. This was successfully applied at the National Institute of Public Health in the 1980s and 1990s, resulting in a breakthrough. And now the European Parliament’s Health Committee is also pushing for this.
The lesson: listen to the medical opinion based on symptoms, even if it contradicts the lab results. The serology test does not provide a diagnosis, but measures the immune response.
