Evidence map›Paper›PMID 27013465›Full record

SynthesisBMC infectious diseases2016

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

M M G Leeflang, C W Ang, J Berkhout, H A Bijlmer, W Van Bortel, A H Brandenburg, N D Van Burgel, A P Van Dam, R B Dessau, V Fingerle and 11 more

Open access · goldAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in BMC infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 7 pooled it
25.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 7 syntheses or guidelines pooled it, 224 citations in OpenAlex.

  1. Pooled it
  2. Incidence of Lyme Borreliosis in Europe: A Systematic Review (2005-2020).Vector borne and zoonotic diseases (Larchmont, N.Y.) · 2023
    Pooled it
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  8. Serum Borrelia IgG as a rule-out test in suspected lyme neuroborreliosis: a large retrospective cohort study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Lyme borreliosis.Nature reviews. Disease primers · 2026
    Review
  13. Silent Spread ofHealthcare (Basel, Switzerland) · 2025
    Article
  14. Article
  15. Health science reports · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Evaluation of different standard and modified two-tier testing strategies for the laboratory diagnosis of lyme borreliosis in a European setting.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024
    Article
  20. Article

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 13 institutions in 5 countries.

M M G LeeflangDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands. m.m.leeflang@amc.uva.nl.
C W AngVU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
J BerkhoutCanisius-Wilhelmina Hospital, PO Box 9015, 6500 GS, Nijmegen, The Netherlands.
H A BijlmerNational Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands.
W Van BortelEuropean Centre for Disease Prevention and Control (ECDC), 171 83, Stockholm, Sweden.
A H BrandenburgIzore Centre for Infectious Diseases Friesland, PO Box 21020, 8900 JA, Leeuwarden, The Netherlands.
N D Van BurgelHagaZiekenhuis, Leyweg 275, 2545 CH, The Hague, Netherlands.
A P Van DamDepartment of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, P.O. Box 95500, 1090 HM, Amsterdam, The Netherlands.
R B DessauSlagelse Hospital, Fælledvej 1, 4200, Slagelse, Region Zealand, Denmark.
V FingerleGerman National Reference Centre for Borrelia, Bavarian Health and Food Safety Authority, Veterinärstraße 2, 85764, Oberschleißheim, Germany.
J W R HoviusCentre for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
B JaulhacNational Reference Centre for Borrelia, Department Laboratory of Bacteriology, Strasbourg University Hospital, 1 Place de l'Hôpital, Strasbourg, France.
B MeijerLaboratory for Infectious Diseases, PO Box 30039, 9700 RM, Groningen, The Netherlands.
W Van PeltNational Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands.
J F P SchellekensLaboratory for Infectious Diseases, PO Box 30039, 9700 RM, Groningen, The Netherlands.
R SpijkerDutch Cochrane Centre, Julius Center for Health Sciences and Primary Care/University Medical Center, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
F F StelmaRadboud University Nijmegen Medical Centre, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.
G StanekInstitute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, Austria.
F Verduyn-LunelDepartment of Medical Microbiology University Medical Center Utrecht (UMC), P.O. Box 85500, 3508GA, Utrecht, The Netherlands.
H ZellerEuropean Centre for Disease Prevention and Control (ECDC), 171 83, Stockholm, Sweden.
H SprongNational Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, The Netherlands.
National Institute for Public Health and the Environment · NLAcademic Medical Center · NLEuropean Centre for Disease Prevention and Control · SEUniversity Medical Center Utrecht · NLUniversity of Groningen · NLAmsterdam UMC Location VUmc · NLCanisius-Wilhelmina Ziekenhuis · NLHaga Hospital · NLMedical University of Vienna · ATOLVG · NLRadboud University Nijmegen · NLSlagelse Hospital · DKUniversité de Strasbourg · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInterpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe.

methodsWe searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy.

resultsSeventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches.

conclusionsThe observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

Indexed as

Area Under CurveDatabases, FactualEnzyme-Linked Immunosorbent AssayEuropeHumansLyme DiseaseROC CurveSensitivity and SpecificitySerologic TestsLyme borreliosismeta-analysissensitivity and specificityserology

Identifiers

PMID27013465
PMCPMC4807538
OpenAlexW2309534723

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.