Diagnostic accuracy of commercially available serological tests for the detection of measles and rubella viruses: a systematic review and meta-analysis

ABSTRACT Measles and rubella serological diagnoses are done by IgM detection. The World Health Organization Global Measles and Rubella Laboratory Network previously endorsed Siemens Enzygnost enzyme-linked immunosorbant assay kits, which have been discontinued. A recommended replacement has not been determined. We aimed to search for suitable replacements by conducting a systematic review and meta-analysis of IgM detection methods that are currently available for measles and rubella. A systematic literature search was performed in Medline, Embase, Global Health, Cochrane Central, and Scopus on March 22 and on 27 September 2023. Studies reporting measles and/or rubella IgM detection with terms around diagnostic accuracy were included. Risk of bias was assessed using QUADAS tools. Meta-DiSc and R were used for statistical analysis. Clinical samples totalling 5,579 from 28 index tests were included in the measles meta-analysis. Sensitivity and specificity of the individual measles studies ranged from 0.50 to 1.00 and 0.53 to 1.00, respectively. Pooled sensitivity and specificity of all measles IgM detection methods were 0.94 (CI: 0.90–0.97) and 0.94 (CI: 0.91–0.97), respectively. Clinical samples totalling 4,983 from 15 index tests were included in the rubella meta-analysis. Sensitivity and specificity of the individual rubella studies ranged from 0.78 to 1.00 and 0.52 to 1.00, respectively. Pooled sensitivity and specificity of all rubella IgM detection methods were 0.97 (CI: 0.93–0.98) and 0.96 (CI: 0.93–0.98), respectively. Although more studies would be ideal, our results may provide valuable information when selecting IgM detection methods for measles and/or rubella.


Section/topic # PRISMA-DTA Checklist Item Reported in section
Meta-analysis D2 Report the statistical methods used for meta-analyses, if performed.

Data analysis methods
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre- specified.

RESULTS
Study selection 17 Provide numbers of studies screened, assessed for eligibility, included in the review (and included in meta-analysis, if applicable) with reasons for exclusions at each stage, ideally with a flow diagram.
Literature search results

Study characteristics 18
For each included study provide citations and present key characteristics including: a) participant characteristics (presentation, prior Risk of bias and applicability 19 Present evaluation of risk of bias and concerns regarding applicability for each study.

Results of individual studies
20 For each analysis in each study (e.g.unique combination of index test, reference standard, and positivity threshold) report 2x2 data (TP, FP, FN, TN) with estimates of diagnostic accuracy and confidence intervals, ideally with a forest or receiver operator characteristic (ROC) plot.
Figures 2, 3, 4 and 5 Synthesis of results 21 Describe test accuracy, including variability; if meta-analysis was done, include results and confidence intervals.Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression; analysis of index test: failure rates, proportion of inconclusive results, adverse events).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence.

Discussion
Limitations 25 Discuss limitations from included studies (e.g.risk of bias and concerns regarding applicability) and from the review process (e.g.incomplete retrieval of identified research).

Discussion
Conclusions 26 Provide a general interpretation of the results in the context of other evidence.Discuss implications for future research and clinical practice (e.g. the intended use and clinical role of the index test).

FUNDING
Funding 27 For the systematic review, describe the sources of funding and other support and the role of the funders.
testing), b) clinical setting, c) study design, d) target condition definition, e) index test, f) reference standard, g) sample size, h) funding sources Characteristics of studies included & Tables 1 & 2

Figure S1 .Figure S2 .Figure S3 .Figure S4 .
Figure S1.SROC curves for mealses IgM (right) and rubella IgM (left) of studies included in the meta-analysis.Squares indicate capture ELISA tests, circle indicate CLIA tests and triangles indicate indirect ELISAs