Based on the references to the medical literature, outlined on this website, it can be stated that the pathogenesis of Lyme borreliosis is strongly influenced by the host’s immune response. There is a fluctuation of the IgM and IgG antibody levels and a delay in or a complete lack of long-term immune response. Therefore, the host immune response cannot always form a basis for the laboratory diagnosis.
In view of this, additional immunological methods are being investigated. They are partly based on further improvement of the traditional serological methods (fine tuning of cut-off levels, identification of further antigens, etc.) and partly on the use of new phenomena for diagnostic purposes (e.g. Lymphocyte Transformation Test, LTT). These methods are inherently dependent on the duration of the development of the host immune response, so, above all, diagnosis in the early stage and the control of the efficacy of treatment are not expected to be addressed by serology.
That is why the development of direct methods for diagnostic purposes should not be discontinued.
Various modern PCR methods, aimed at testing DNA which is present in a small amount or RNA which is present in a larger amount but is less stable, strive to avoid false positive results while also trying to increase sensitivity. Diagnosis is made more difficult by the genetic variability of Borrelia, the small number of pathogenic bacteria in the samples and the rapid deterioration of the sample.
We are aware of the development of laboratory culture methods which are in the experimental stage. But in these, in addition to the low cell count, the slow reproduction of Borrelia, its extreme sensitivity to the medium and the environment, also pose problems.
We also know of several microscopic methods that are based on the testing of native blood and use a dark-field, or perhaps phase-contrast or so-called “grey-field” microscopy. The problems discussed previously also apply to these methods, including the issue of the small number of pathogenic bacteria, artefacts and sample stability, Also, the demands on a qualified investigator are higher as each test may take 30 to 40 minutes.
The Resolution of the European Parliament of 15 November 2018 on Lyme disease (Borreliosis) (2018/2774 RSP) confirms that the diagnosis of Lyme borreliosis is far from being resolved, and the resolution proposes the establishing of the diagnosis based on clinical symptoms as well as calling for more research effort into further methods. This resolution also mentions the DualDur method as a good example.