Annelies W Mesman1, Carly Rodriguez1, Emily Ager2, Julia Coit1, Letizia Trevisi1, Molly F Franke3. 1. Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA. 2. Harvard TH Chan School of Public Health, Department of Social and Behavioral Sciences, Boston, MA, USA. 3. Harvard Medical School, Department of Global Health and Social Medicine, Boston, MA, USA. Electronic address: molly_franke@hms.harvard.edu.
Abstract
BACKGROUND: Stool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or 'in-house' molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity. METHODS: We searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children. RESULTS: We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96-99], pooled sensitivity was 57% [95%CI: 40-72] against culture and 3% [95%CI: 2-6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%). CONCLUSION: Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting.
BACKGROUND: Stool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or 'in-house' molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity. METHODS: We searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children. RESULTS: We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96-99], pooled sensitivity was 57% [95%CI: 40-72] against culture and 3% [95%CI: 2-6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%). CONCLUSION: Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting.
Authors: Elisabetta Walters; Robert Peter Gie; Anneke Catharina Hesseling; Sven Olaf Friedrich; Andreas Henri Diacon; Robert Peter Gie Journal: Pediatr Infect Dis J Date: 2012-12 Impact factor: 2.129
Authors: Aparna Mukherjee; Sarman Singh; Rakesh Lodha; Varinder Singh; A C Hesseling; Harleen M S Grewal; Sushil K Kabra Journal: Pediatr Infect Dis J Date: 2013-12 Impact factor: 2.129
Authors: Richard A Oberhelman; Giselle Soto-Castellares; Robert H Gilman; Luz Caviedes; Maria E Castillo; Lenka Kolevic; Trinidad Del Pino; Mayuko Saito; Eduardo Salazar-Lindo; Eduardo Negron; Sonia Montenegro; V Alberto Laguna-Torres; David A J Moore; Carlton A Evans Journal: Lancet Infect Dis Date: 2010-07-23 Impact factor: 25.071
Authors: Hilary Wolf; Melissa Mendez; Robert H Gilman; Patricia Sheen; Giselle Soto; Angie K Velarde; Mirko Zimic; A Roderick Escombe; Sonia Montenegro; Richard A Oberhelman; Carlton A Evans Journal: Am J Trop Med Hyg Date: 2008-12 Impact factor: 2.345
Authors: C L Jasumback; Q Dlamini; J Kahari; G Maphalala; M G Dlamini; G S Dube; A DiNardo; H L Kirchner; A Mandalakas; A W Kay Journal: Public Health Action Date: 2021-06-21
Authors: N R Pollock; A T MacIntyre; T A Blauwkamp; L Blair; C Ho; R Calderon; M F Franke Journal: Int J Tuberc Lung Dis Date: 2021-05-01 Impact factor: 2.373
Authors: Alexander W Kay; Lucia González Fernández; Yemisi Takwoingi; Michael Eisenhut; Anne K Detjen; Karen R Steingart; Anna M Mandalakas Journal: Cochrane Database Syst Rev Date: 2020-08-27
Authors: Juan A Flores; Roger Calderón; Annelies W Mesman; Martin Soto; Julia Coit; Juan Aliaga; Milagros Mendoza; Segundo R Leon; Kelika Konda; Francisco M Mestanza; Carlos J Mendoza; Leonid Lecca; Megan B Murray; Rebecca C Holmberg; Nira R Pollock; Molly F Franke Journal: Pediatr Infect Dis J Date: 2020-11 Impact factor: 3.806