A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference

PLoS One. 2015 Nov 13;10(11):e0142364. doi: 10.1371/journal.pone.0142364. eCollection 2015.

Abstract

Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS) can improve estimation of diagnostic accuracy. Numerous studies have used a CRS to evaluate new typhoid diagnostics; however, there is no consensus on an appropriate CRS. In order to evaluate existing tests for use as a reference test or inclusion in a CRS, we performed a systematic review of the typhoid literature to include all index/reference test combinations observed. We described the landscape of comparisons performed, showed results of a meta-analysis on the accuracy of the more common combinations, and evaluated sources of variability based on study quality. This wide-ranging meta-analysis suggests that no single test has sufficiently good performance but some existing diagnostics may be useful as part of a CRS. Additionally, based on findings from the meta-analysis and a constructed numerical example demonstrating the use of CRS, we proposed necessary criteria and potential components of a typhoid CRS to guide future recommendations. Agreement and adoption by all investigators of a standardized CRS is requisite, and would improve comparison of new diagnostics across independent studies, leading to the identification of a better reference test and improved confidence in prevalence estimates.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Diagnostic Tests, Routine / methods
  • Diagnostic Tests, Routine / standards
  • Humans
  • Reference Standards
  • Salmonella typhi / isolation & purification*
  • Typhoid Fever / blood
  • Typhoid Fever / diagnosis*

Grants and funding

This research was made possible by a grant from the Bill and Melinda Gates Foundation (grant #OPP1063918, www.gatesfoundation.org). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.