Unconventional diagnostic tests for Lyme borreliosis: a systematic review.
Level 1 - systematic review of randomized trials
Systematic review of diagnostic accuracy and observational studies
PubMed 31306793 · doi:10.1016/j.cmi.2019.06.033
What was done
Authors conducted a systematic review following PRISMA-DTA and Cochrane guidelines (searching PubMed and Cochrane Library from 1983 to 2018) to evaluate unconventional biological diagnostic tests for Lyme borreliosis (LB) in adults meeting ESG-LB or IDSA definitions, or with strongly suspected LB. Study quality was appraised using the QUADAS-2 tool by independent reviewers.
What was found
Forty studies were included (2 meta-analyses, 25 prospective controlled, 5 prospective uncontrolled, 6 retrospective controlled, and 2 case reports). Biological assays fell into five categories: - Proven diagnostic efficacy: CXCL-13 (for neuroborreliosis), though not yet standardized. - Requiring further clinical evaluation: CCL-19, OspA, and interferon-alpha. - Uncertain diagnostic efficacy due to controversial findings or poor methodology: lymphocyte transformation test, interferon-gamma, and ELISPOT. - Unacceptably low sensitivity and/or specificity: CD57+ natural killer cells and rapid diagnostic tests. - Restricted to research settings: microscopy and xenodiagnoses. QUADAS-2 assessment demonstrated a high risk of bias in 25/40 studies and applicability concerns in 32/40 studies.
Why it matters
This review critically evaluates alternative Lyme disease tests, showing that commonly marketed assays (such as LTT, ELISPOT, and CD57 counts) lack reliable diagnostic accuracy, whereas CXCL-13 is supported for neuroborreliosis diagnosis.
Limits
The primary literature is heavily limited by methodological flaws: 62.5% of included studies had a high risk of bias, and 80% had applicability concerns. Sensitivity and specificity values were frequently under-evaluated, heterogeneous, or unassessed across studies. The review was limited to adults and literature indexed through 2018.
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