Lyme disease: clarification in the grand bazaar of diagnostic tests

According to the last Weekly Epidemiological Bulletin (BEH), the review of Public Health France, the diagnosis of Lyme disease must always be carried out on a set of arguments which takes into account the clinical presentation, the context of occurrence and the laboratory examinations. A positive biological test isolated, or with a non-specific symptomatology, has no diagnostic value for BEH.

A position widely contested by certain patient associations who consider that current biological tests are not sensitive enough or that chronic pain must be treated with long-term antibiotics if a biological test is positive, whatever it is.

Laboratory examination alone does not confirm the diagnosis

A biological examination alone cannot be sufficient to make the diagnosis because 95% of people who make a serological conversion after an infectious tick bite will have no clinical signs and will not be sick. In addition, not all tick bites are infectious.

At an early stage, we must evoke this disease before the appearance of a red plaque sitting mainly on the lower limbs, from spring to autumn, in someone who has had a tick bite or who often goes to the forest. .
At a later stage, this disease should be mentioned when there are signs of damage to one or more organs (skin, joints, muscles, heart and nervous system) in professionals working in the forest, campers, hunters, golfers, fishermen, mushroom pickers, hikers …

The difficulty in diagnosing Lyme disease at this stage is that it affects many organs at the same time, and when most of the signs appear, the tick bite is usually healed and forgotten: people with the disease do not therefore not necessarily the link between the disease and a tick bite.

Validated diagnostic techniques

For the diagnosis, there are direct biological techniques (examination under a microscope, culture of the bacteria, PCR) whose objective is to demonstrate the presence of the bacteria, or its specific DNA, but these techniques are not very sensitive. and their positivity depends on the location, including for PCR.

The diagnosis is therefore most often indirect, i.e. the objective is to demonstrate the body’s response to the infection by demonstrating specific antibodies in the blood (ELISA and Western-Blot).

The gold standard for the biological diagnosis of Lyme disease is an ELISA test, so sensitive that it must then be matched with Lyme by Western-Blot (to eliminate false positives, such as those linked syphilis which is a related bacterium).

This is not a French cultural exception and all the major countries recommend this same sequence, as recent English recommendations have reminded us. Even in Germany where some doctors perform other tests, the official recommendations are the same.

The ELISA-Western-blot sequence is reliable

The minimum performances recommended by the European organizations for biological diagnosis are a specificity of 90% in ELISA and 95% for Western Blot.

Except at the stage of Chronic Erythema (beginning phase) where the ELISA is generally not yet positive (50% of cases), at the early disseminated stage where it is positive in 70 to 90% of cases and where it can be It is necessary to do it again 4 to 6 weeks later, and apart from the very rare late disseminated and seronegative forms that can be found in deeply immunocompromised people, the serological diagnosis is always positive.

A positive serology therefore does not necessarily mean that the symptoms are related to Lyme disease, but simply reflects previous contact with the bacteria without there being an evolutionary infectious process. We therefore seem far from the under-diagnosis of the disease by reference tests, alleged by some.

In addition, the “camouflaged borrelia”, which would hide from the immune system by smearing itself with tick saliva or by putting itself in a quiescent state, exist only in uncontrolled studies or under laboratory conditions incompatible with the test. life on earth according to specialists from the National Reference Center and learned societies.

Some biological techniques are not validated

The direct examination of the bacteria under a microscope in the blood, or “thick drop”, which is used for example in the diagnosis of malaria, has been advised by some in France, and especially in Germany, where laboratories of analyzes propose this technique. However, in controlled studies, this direct examination declares positive as many sick people as healthy people (many false positives).

Some countries use other tests declared to be “more sensitive” but above all more expensive and not validated, such as the “Lymphocytic Transformation Test” (or TTL). Their advantage is not always obvious since their diagnostic efficacy depends on the bacterial antigens chosen, as well as on the control population used in the validation test. Their evaluation remains poorly done with poor quality studies, too great a sensitivity and poor specificity (many false positives).

The question of PCR

An examination by “PCR” (or “Polymerase Chain Reaction”) is wrongly considered to be the reference technique. The PCR would make it possible to demonstrate the DNA (genetic heritage) of the bacteria in all the fluids and biological tissues of the body where Borellia could nestle or could have passed.

PCR is a method of “amplifying DNA”, bacterial or viral, which is used to find, for example, the AIDS virus. It is a very sensitive and very specific method (the risk of mistaking another bacterium for a Borrelia is low), provided it is used according to strict standards to avoid the risk of contamination by other genetic material.

But Borrelia only circulates in the blood transiently and does not stay there: this is why PCR cannot be considered reliable when it is used on blood samples, as is regularly the case in d ‘other European countries, such as Germany. On the other hand, it can be very interesting when an organ (skin, joint) is specifically affected by the disease, for example, in the event of an effusion of joint fluid (“arthritis”), the synovial fluid contained in the joints can be sampled. to analyze it in PCR. In the presence of neurological problems (“meningo-radiculitis” or “meningoencephalitis”), PCR in the cerebrospinal fluid (taken by lumbar puncture) is not very efficient. PCR is therefore only indicated in doubtful cases of lesion of the skin and joints, in particular patients with discrepancy between clinical and serology.

Other non-validated tests exist

The determination of the CD57 marker of NK cells has also been proposed but the evaluation files lack good quality studies to advise them and an independent study carried out by the American Institute of Health (NIH) even showed an absence of specificity.

Rapid detection (RDT) and self-diagnostic tests appear poor.

Another method called “Elispot”, which is usually used for the diagnosis of tuberculosis, is offered by some medical analysis laboratories. This test consists of identifying cells of the patient’s immune system which have been in contact with Borrelia. But it gives a very high number of false positive results, and it has never scientifically demonstrated its interest in the diagnosis of Lyme disease. The results of Elispot are therefore to be taken with suspicion, and moreover, they are expensive (around 300 euros) and it is, currently, a real business.

This BEH analysis will therefore perhaps not convince opponents of the reference diagnostic method, but it will reassure those who trust the various learned societies of infectious diseases in the United States and European countries.