Table 1.
Inclusion and exclusion criteria
| Patients with confirmed Lyme borreliosis | |
| Inclusion criteria: | |
| Patient ≥18 years with confirmed proven or probable, early localized or disseminated Lyme borreliosis manifestation.a | |
| In case of an EM reported at www.tekenradar.nl, the EM has been present < 3 months and the clinical diagnosis has been confirmed by the general practitioner. | |
| Subjects live or stay on the mainland of the Netherlands. | |
| Exclusion criteria: | |
| Subjects unable to provide informed consent or do not have sufficient proficiency in the Dutch language. | |
| Subjects having started antibiotic treatment > 4 days before inclusion (for subjects included online) or > 7 days before inclusion (for subjects included through the clinical expert centers). | |
| Subjects having ongoing signs or symptoms attributed to a previous episode of Lyme borreliosis. | |
| Healthy controls | |
| Inclusion criterium: | |
| Participant ≥18 years old. | |
| Exclusion criteria: | |
| Uncontrolled HIV-infection, if known. This is defined as an HIV-1 viral load > 40 copies/ml and/or CD4+ count < 500 × 106 cells/liter in the past 12 months. | |
| Active syphilis or leptospirosis, an active infection with EBV/CMV, or an auto-immune disease, if known. | |
| Current LB with typical symptoms. A past episode or Borrelia seropositivity is not an exclusion criterium. | |
| Immunomodulating medication including > 7.5 mg prednisone daily, methotrexate, biologicals. Medication such as hydroxychloroquine, sulfazalazine or NSAIDs are accepted. | |
| Known immunodeficiency, hematologic malignancies in the medical history or chemotherapy during the past year. | |
| Subjects unable to provide informed consent or do not have sufficient proficiency in the Dutch language. | |
| Potentially cross-reactive controls | |
| Inclusion criteria: | |
| Participant ≥18 years old. | |
| AND | |
| 1. Patients with syphilis: | |
| EITHER clinical symptoms suspected of secondary syphilis, in combination with a positive RPR card POCT result. | |
| OR early latent syphilis infection with VDRL/RPR ≥ 1:32. | |
| 2. Patients with Epstein Barr-virus or cytomegalovirus: | |
| Compatible signs and symptoms. | |
| Positive IgM or Paul-Bunnell of EBV/CMV on plasma. | |
| 3. Patients with leptospirosis: | |
| Compatible signs and symptoms. | |
| Positive serology (MAT), preferably confirmed by culture or PCR. | |
| 4. Patients with autoimmune diseases: | |
| EITHER confirmed rheumatoid arthritis. | |
| OR other autoimmune disorders diagnosed according to the leading guidelines. | |
| Exclusion criteria: | |
| Uncontrolled HIV-infection, if known. This is defined as an HIV-1 viral load > 40 copies/ml and/or CD4+ count < 500 × 106 cells/liter in the past 12 months. | |
| More than one of the listed potentially cross-reactive conditions, if known. | |
| Ever an episode of LB, ever treated for LB or a known tick bite in the past 6 months. | |
| Immunomodulating medication including > 7.5 mg prednisone daily, methotrexate, biologicals. Medication such as hydroxychloroquine, sulfazalazine or NSAIDs are accepted. | |
| Known immunodeficiency, hematologic malignancies in the medical history or chemotherapy during the past year. | |
| Subjects unable to provide informed consent or do not have sufficient proficiency in the Dutch language. | |
| Observational cohort | |
| Inclusion criteria: | |
| Participants ≥18 years old. | |
| Presenting at the specialized Lyme centers of the Amsterdam UMC or Radboudumc. | |
| Exclusion criterium: | |
| Subjects unable to give informed consent or do not have sufficient proficiency in the Dutch language. |
a Specific criteria for each manifestation of confirmed Lyme borreliosis are identical to the criteria listed in the LymeProspect study protocol [34].