Additional file 1: of Diagnostic accuracy of TB-LAMP for pulmonary tuberculosis: a systematic review and meta-analysis
Creators: name: Shete, Priya
name: Farr, Katherine
name: Strnad, Luke
name: Gray, Christen
name: Cattamanchi, Adithya
Publisher: name: figshare
Year: 2019
Subjects: subject: Medicine
subject: Molecular Biology
subject: Biotechnology
subject: Science Policy
subject: Biological Sciences not elsewhere classified
subject: Infectious Diseases
subject: FOS: Health sciences

description: Figure S1. Forrest plots of TB-LAMP diagnostic accuracy, additional reference standards. The figures show the sensitivity and specificity of TB-LAMP in individual studies in reference to all additional reference standards not judged best available for TB-LAMP as an alternative test for smear microscopy in all patients (Panel S1A and Panel S1B), TB-LAMP as an alternative test for smear microscopy in HIV-positive adults (Panel S1C), and TB-LAMP as an add-on test following smear microscopy (Panel S1D and Panel S1E). All reference standards classify patients as having TB if ≥1 positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Visual inspection of all three forest plots indicates considerable heterogeneity in sensitivity estimates but less heterogeneity in specificity estimates. Figure S2. TB-LAMP as an alternative for sputum smear microscopy: Summary Receiver Operating Characteristic (SROC) curves. The figure shows SROC curves for TB-LAMP (green line), individual study estimates (grey circle), pooled estimates (red square), and the 95% confidence region for pooled estimates (yellow dotted line) when using 3 culture-based reference standards. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Figure S3. TB-LAMP as an alternative test for smear microscopy in HIV-positives: Summary Receiver Operating Characteristic (SROC) curves. The figure shows SROC curves for TB-LAMP (green line), individual study estimates (grey circle), pooled estimates (red square), and the 95% confidence region for pooled estimates (yellow dotted line) when using 2 culture-based reference standards (no studies qualified for Standard 1). All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on the same or different sputum specimens (Standard 2); or 2) at least one negative culture (Standard 3). Figure S4. TB-LAMP as an add-on test following smear microscopy: Summary Receiver Operating Characteristic (SROC) curves. The figure shows SROC curves for TB-LAMP (green line), individual study estimates (grey circle), pooled estimates (red square), and the 95% confidence region for pooled estimates (yellow dotted line) when using 3 culture-based reference standards. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Figure S5. TB-LAMP vs. Xpert MTB/RIF: Forest plots of Xpert MTB/RIF diagnostic accuracy. The figure shows forest plots of Xpert MTB/RIF sensitivity and specificity in reference to 3 culture-based reference standards for individual studies. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Figure S6. TB-LAMP vs. Xpert MTB/RIF: Forest plots of TB-LAMP diagnostic accuracy. The figure shows forest plots of TB-LAMP sensitivity and specificity in reference to 3 culture-based reference standards for individual studies. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Figure S7. TB-LAMP vs. Xpert MTB/Rif: Forest plots of sensitivity difference. The figure shows forest plots of the sensitivity difference between TB-LAMP and Xpert MTB/Rif® for individual studies. The sensitivity of both tests was calculated in reference to 3 culture-based reference standards. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens; or 3) at least one negative culture (Standard 3). Visual inspection of forest plots and statistical testing indicate minimal heterogeneity with Standard 1 (I2 0%, p = 0.41), some heterogeneity with Standard 2 (I2 34%, p = 0.18), and significant heterogeneity with Standard 3 (I2 55%, p = 0.03). Figure S8. TB-LAMP vs. Xpert MTB/Rif®: Forest plots of specificity difference. The figure shows forest plots of the specificity difference between TB-LAMP and Xpert MTB/Rif® for individual studies. The specificity of both tests was calculated in reference to 3 culture-based reference standards. All reference standards classify patients as having TB if ≥1positive culture was confirmed as M. tuberculosis by speciation testing. To be classified as not having TB, patients were required to have no positive and at least 1) two negative cultures on two different sputum specimens (Standard 1); 2) two negative cultures on the same or different sputum specimens (Standard 2); or 3) at least one negative culture (Standard 3). Visual inspection of forest plots and statistical testing indicate minimal heterogeneity with Standard 1 (I2 28%, p = 0.25) and Standard 2 (I2 37%, p = 0.16), but significant heterogeneity with Standard 3 (I2 72%, p = 0.001). Figure S9. Proportion of indeterminate TB-LAMP results. The figure shows a forest plot of the proportion of indeterminate TB-LAMP results among all adults for individual studies. Visual inspection of forest plots and statistical testing indicate minimal heterogeneity (I2 28%, p = 0.25). Table S1. Patients included for analysis. Table S2. Signaling questions for QUADAS-2 domains. Table S3. TB-LAMP as an alternative test for smear microscopy: Exploration of heterogeneity. 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