Reply to Lacout et al., “Value of Patient Population Selection and Lyme Borreliosis Tests”

REPLY

We recently compared diagnostic parameters of different commercial serological kits based on three different antigen types and correlated test results with the status of the patient’s Borrelia infection (1). We thank Lacout et al. for comments on our article expressed in their comment letter (2).

Their objections mostly concern controversial issues, such as persistent polymorphic symptomatology after tick-bite (PPSTB), posttreatment Lyme disease syndrome (PTLDS), persistent or chronic Borrelia disease, etc., discussed in laboratory and clinical diagnostics of Lyme borreliosis for more than 30 years. These are extensive issues, which, in our opinion, are outside the scope of the original communication, so in a brief comment, there is no space for a qualified discussion on this controversial topic.

The selection of patients and their inclusion in clinical groups were performed in accordance with the national (3) and European (4, 5) standards and case definitions. Only patients with a typical, well-defined disease were included in the study.

Thus, the serological test results are compared between different clinical forms of the disease.

The statement of Lacout et al. that “the ‘sick patients’ sample does not appear to be reliable in this article because this might exclude a too-large population of patients” is irrelevant.

The purpose of the study was not to capture all patients with different forms of Lyme borreliosis but to compare the diagnostic parameters between the laboratory tests.

The negative-control group selection was also performed in accordance with the standard laboratory and clinical practice. The serum used was taken from blood donors who did not report recent clinical signs of the disease, and this approach is completely acceptable for a general comparison between serological tests. Therefore, in view of the stated aims of the study, the claims that “the selection of the control population ... is therefore debatable” and that the resulting sensitivity and specificity of the tests were not valid have to be rejected.

However, Lacout et al. are correct that it is impossible to calculate the absolute sensitivity and specificity of any serological test. As we have shown in our article, these values are always related to the nature of all “positive” and “control” samples in the respective panel. It cannot be ruled out that some of the blood donors were not actually negative and may have experienced asymptomatic borreliosis (we do not call them carriers since they do not pass borreliosis to another person) or even may not have admitted that they had clinical signs.

By comparing the diagnostic parameters obtained by different methods on the same panel, we yield relative results; we find out which of the methods has a higher or lower sensitivity/specificity than the other, with no absolute values.

However, the inclusion of unclearly defined clinical units of Lyme borreliosis, especially when “current serology cannot be used as a diagnostic marker of PTLDS” (6), as indirectly suggested by Lacout et al., not only would not improve the sensitivity and specificity of serological tests but would even have the opposite effect.