Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context
Summary: Background: Limited access to accurate and accessible tuberculosis (TB) diagnostics remains a critical barrier to timely diagnosis and care in high burden low- and middle-income countries. Point-of-care (POC) TB Triage tests (POC-TTTs) defined as a test performed near to a patient or at th...
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537025001890 |
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| author | Kevin Komakech Derrick Semugenze Moses Joloba Frank Cobelens Willy Ssengooba |
| author_facet | Kevin Komakech Derrick Semugenze Moses Joloba Frank Cobelens Willy Ssengooba |
| author_sort | Kevin Komakech |
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| description | Summary: Background: Limited access to accurate and accessible tuberculosis (TB) diagnostics remains a critical barrier to timely diagnosis and care in high burden low- and middle-income countries. Point-of-care (POC) TB Triage tests (POC-TTTs) defined as a test performed near to a patient or at the site of patient care without need for specialized expertise or infrastructure, may bridge this gap. We systematically reviewed and meta-analyzed studies on host blood protein biomarkers for POC-TTTs including C-reactive protein (CRP), 3-gene host response (3-gene HR), monocyte-to-lymphocyte ratio (MLR), interferon-γ induced protein 10 (IP-10), hemoglobin, neutrophil-to-lymphocyte ratio (NLR), tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) for their accuracy for screening of pulmonary TB (PTB). Methods: A literature search was conducted in PubMed, EMBASE and in Web of Science from 1990 to 31st January 2025. The review included studies that used unstimulated blood of presumptive TB patients who were screened with a POC device to quantify biomarkers for PTB diagnosis. Sputum mycobacterial culture or GeneXpert MTB/Rif or Ultra were used as a reference standard. Risk of bias was assessed using QUADAS-2 tool. Random effect analysis was performed using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method to calculate summary estimates with their 95% confidence intervals (CI). Heterogeneity was tested and quantified using Cochran's Q and Higgin’s I2 test. Egger's linear regression test was used to assess small study effect. The systematic review protocol was registered in PROSPERO with an ID of CRD42023483281. Findings: We identified 282, 21, 28, 137, 132, 152, 100 and 77 studies from which 10, 6, 4, 2, 0, 0, 0 and 1 study(s) were included for CRP, 3-gene HR, MLR, hemoglobin, IP-10, TNF-a, IL-6 and NLR index tests respectively. The meta-analysis pooled sensitivity (95% CI) was 74% (58–85), 79% (59–90), 64% (15–95), 75% (18–98) and the pooled specificity was 68% (52–80), 85% (68–94), 69% (30–92) and 71% (18–100) for CRP, 3-gene HR, MLR, and hemoglobin respectively. Diagnostic odds ratios ranged from 3.70 (MLR) to 20.93 (3-gene HR) while higgin’s I2 value ranged from 87.4% (MLR) to 99.1% (hemoglobin). Meta-analysis was not performed on NLR. Interpretation: None of the POC-TTT met the WHO target product profile minimum requirements for a TB triage test of 90% sensitivity and 70% specificity when a POC device was used for screening in a typical setting studied. Further research, specifically focusing on head-to-head comparisons and combination tests are recommended. Funding: Funding was received from the Mr. Willem Bakhuys Roozeboom Foundation. Additional support was given to KK through the EDCTP grant RIA2020I-3305. |
| format | Article |
| id | doaj-art-13bdd3bca1ef491eb36ed4b2dee5fa8b |
| institution | OA Journals |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | EClinicalMedicine |
| spelling | doaj-art-13bdd3bca1ef491eb36ed4b2dee5fa8b2025-08-20T02:01:05ZengElsevierEClinicalMedicine2589-53702025-06-018410325710.1016/j.eclinm.2025.103257Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in contextKevin Komakech0Derrick Semugenze1Moses Joloba2Frank Cobelens3Willy Ssengooba4Department of Medical Microbiology, Mycobacteriology (BSL-3) Laboratory, Makerere University, Kampala, Uganda; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Medical Microbiology, Mycobacteriology (BSL-3) Laboratory, Makerere University, Kampala, Uganda; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Medical Microbiology, Makerere University College of Health Sciences, Kampala, UgandaDepartment of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, NetherlandsDepartment of Medical Microbiology, Mycobacteriology (BSL-3) Laboratory, Makerere University, Kampala, Uganda; Makerere University, Lung Institute (MLI), Makerere University College of Health Sciences, Kampala, Uganda; Corresponding author. Mycobacteriology (BSL-3) Laboratory, Department of Medical Microbiology, Makerere University, Kampala, Uganda.Summary: Background: Limited access to accurate and accessible tuberculosis (TB) diagnostics remains a critical barrier to timely diagnosis and care in high burden low- and middle-income countries. Point-of-care (POC) TB Triage tests (POC-TTTs) defined as a test performed near to a patient or at the site of patient care without need for specialized expertise or infrastructure, may bridge this gap. We systematically reviewed and meta-analyzed studies on host blood protein biomarkers for POC-TTTs including C-reactive protein (CRP), 3-gene host response (3-gene HR), monocyte-to-lymphocyte ratio (MLR), interferon-γ induced protein 10 (IP-10), hemoglobin, neutrophil-to-lymphocyte ratio (NLR), tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) for their accuracy for screening of pulmonary TB (PTB). Methods: A literature search was conducted in PubMed, EMBASE and in Web of Science from 1990 to 31st January 2025. The review included studies that used unstimulated blood of presumptive TB patients who were screened with a POC device to quantify biomarkers for PTB diagnosis. Sputum mycobacterial culture or GeneXpert MTB/Rif or Ultra were used as a reference standard. Risk of bias was assessed using QUADAS-2 tool. Random effect analysis was performed using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method to calculate summary estimates with their 95% confidence intervals (CI). Heterogeneity was tested and quantified using Cochran's Q and Higgin’s I2 test. Egger's linear regression test was used to assess small study effect. The systematic review protocol was registered in PROSPERO with an ID of CRD42023483281. Findings: We identified 282, 21, 28, 137, 132, 152, 100 and 77 studies from which 10, 6, 4, 2, 0, 0, 0 and 1 study(s) were included for CRP, 3-gene HR, MLR, hemoglobin, IP-10, TNF-a, IL-6 and NLR index tests respectively. The meta-analysis pooled sensitivity (95% CI) was 74% (58–85), 79% (59–90), 64% (15–95), 75% (18–98) and the pooled specificity was 68% (52–80), 85% (68–94), 69% (30–92) and 71% (18–100) for CRP, 3-gene HR, MLR, and hemoglobin respectively. Diagnostic odds ratios ranged from 3.70 (MLR) to 20.93 (3-gene HR) while higgin’s I2 value ranged from 87.4% (MLR) to 99.1% (hemoglobin). Meta-analysis was not performed on NLR. Interpretation: None of the POC-TTT met the WHO target product profile minimum requirements for a TB triage test of 90% sensitivity and 70% specificity when a POC device was used for screening in a typical setting studied. Further research, specifically focusing on head-to-head comparisons and combination tests are recommended. Funding: Funding was received from the Mr. Willem Bakhuys Roozeboom Foundation. Additional support was given to KK through the EDCTP grant RIA2020I-3305.http://www.sciencedirect.com/science/article/pii/S2589537025001890Diagnostic accuracyPoint-of-care TB triage testsBacteriologically confirmed pulmonary tuberculosis |
| spellingShingle | Kevin Komakech Derrick Semugenze Moses Joloba Frank Cobelens Willy Ssengooba Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context EClinicalMedicine Diagnostic accuracy Point-of-care TB triage tests Bacteriologically confirmed pulmonary tuberculosis |
| title | Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context |
| title_full | Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context |
| title_fullStr | Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context |
| title_full_unstemmed | Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context |
| title_short | Diagnostic accuracy of point-of-care triage tests for pulmonary tuberculosis using host blood protein biomarkers: a systematic review and meta-analysisResearch in context |
| title_sort | diagnostic accuracy of point of care triage tests for pulmonary tuberculosis using host blood protein biomarkers a systematic review and meta analysisresearch in context |
| topic | Diagnostic accuracy Point-of-care TB triage tests Bacteriologically confirmed pulmonary tuberculosis |
| url | http://www.sciencedirect.com/science/article/pii/S2589537025001890 |
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