Constructed numerical example.

<p>Assumed sensitivity and specificity of the three tests: index test, 80% and 90%; test A, 50% and 100%; test B, 85% and 85%. Comparing the index test to a CRS = (fever) AND ((test A positive) OR (test B positive)). Fever, test A, and test B are independent conditional on disease status. Index test is independent of fever conditional on disease status.</p><p>Constructed numerical example.</p

PRISMA flowchart.

<p>Study flow depicting search strategy, inclusion/exclusion criteria, and summary of systematic review.</p

Meta-analysis results.

<p>Graphical illustration of sensitivities (y-axis) and specificities (x-axis) corresponding to comparisons included in the meta-analysis: PCR-based assays (A), anti-LPS assays (B), TUBEX^® assays (C), anti-<i>S</i>. <i>typhi</i> assays (D), Typhidot assays (E), Widal assays (F). Meta-analysis was performed using bivariate random effects binomial regression (STATA command: <i>metandi</i>). Sizes of individual study estimates (grey circle) represent sample size. Summary point (red square), hierarchical summary receiver operating characteristic curves (green line), 95% confidence regions (yellow dashed line), and 95% prediction regions (grey dashed line) are depicted.</p

Comparisons by reference test.

<p>Summary of the 139 papers by reference test, including 413 index/reference comparisons. Of the culture reference tests, 80% were blood culture, making up 57% of all reference tests.</p

Quality assessment of diagnostic accuracy studies.

<p>Summary of variables included in the QUADAS-2 tool assessing the quality of diagnostic accuracy studies. The criteria determined a study’s risk of bias or concern of applicability. When the domain-specific criteria were not met, the study had a high risk of bias or concern of applicability with respect to that domain. When the domain-specific criteria were all unclear, the risk of bias or concern of applicability was unclear.</p><p>¹ The currently available tests to detect typhoid fever are not sufficiently accurate; therefore, this question was problematic.</p><p>² “Unclear” = missing.</p><p>Quality assessment of diagnostic accuracy studies.</p

Meta-analysis results by study quality.

<p>Summary diagnostic accuracies of index tests with five or more comparisons and blood culture as the reference test. Meta-analysis performed using bivariate random effects binomial regression.</p><p>¹ Could not be determined.</p><p>Meta-analysis results by study quality.</p

STARD (STAndards for the Reporting of Diagnostic accuracy) flow diagram for MODS Kit for TB detection.

<p>Kappa value 0.94, agreement 97.4%. +ve = TB culture positive, -ve = TB culture negative. Contaminated & indeterminate results are culture outcomes following reprocessing if necessary according to protocol.</p

Proportion of samples positive by each culture method.

<p>Total samples: N = 2446, culture positive by any method: n = 778 (31.8%), culture negative by all methods: n = 1603 (65.5%), contaminated samples without a positive parallel culture: n = 65 (2.7%).</p

Direct DST result by MODS Kit compared with indirect DST result by proportions method (with discrepant analysis by Genotype MTB-DR plus).

<p>Data in table indicate consolidated reference indirect test result after discrepant analysis employing Genotype MTB-DR plus line probe assay as arbiter test (Genotype MTB-DR plus determined final true result in those samples for which MODS Kit and proportions method were discordant).</p><p>concordant DST, n = 687 (shaded grey).</p><p>discordant DST, n = 15 (no shading).</p><p>Direct DST result by MODS Kit compared with indirect DST result by proportions method (with discrepant analysis by Genotype MTB-DR plus).</p