Sylvia M LaCourse1,2, Patricia B Pavlinac3,2, Lisa M Cranmer4, Irene N Njuguna5,6, Cyrus Mugo7, John Gatimu7, Joshua Stern8, Judd L Walson1,3,5,9, Elizabeth Maleche-Obimbo7, Julius Oyugi10, Dalton Wamalwa7, Grace John-Stewart1,3,5,9. 1. Division of Allergy and Infectious Diseases, Department of Medicine. 2. Sylvia M. LaCourse and Patricia B. Pavlinac contributed equally to this article. 3. Department of Global Health, University of Washington, Seattle, Washington. 4. Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia. 5. Department of Epidemiology, University of Washington, Seattle, Washington, USA. 6. Kenyatta National Hospital. 7. Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya. 8. Department of Biostatistics. 9. Department of Pediatrics, University of Washington, Seattle, Washington, USA. 10. School of Medicine, University of Nairobi, Nairobi, Kenya.
Abstract
BACKGROUND: Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infected children. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed. METHODS:Hospitalized, HIV-infected children aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture. RESULTS: Among 165 HIV-infected children, median age was 24 months [interquartile range (IQR) 13-58], median CD4% was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. CONCLUSION: Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible samples.
RCT Entities:
BACKGROUND:Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infectedchildren. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed. METHODS: Hospitalized, HIV-infectedchildren aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture. RESULTS: Among 165 HIV-infectedchildren, median age was 24 months [interquartile range (IQR) 13-58], median CD4% was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. CONCLUSION: Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infectedchildren using easily accessible samples.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Azure T Makadzange; Chiratidzo E Ndhlovu; Kudakwashe Takarinda; Michael Reid; Magna Kurangwa; Philimon Gona; James G Hakim Journal: Clin Infect Dis Date: 2010-06-01 Impact factor: 9.079
Authors: Inge Kroidl; Petra Clowes; Joshua Mwakyelu; Leonard Maboko; Abubakary Kiangi; Andrea Rachow; Klaus Reither; Jutta Jung; Anthony Nsojo; Elmar Saathoff; Michael Hoelscher Journal: Scand J Infect Dis Date: 2013-11-25
Authors: Rewa K Choudhary; Kristin M Wall; Irene Njuguna; Patricia B Pavlinac; Sylvia M LaCourse; Vincent Otieno; John Gatimu; Joshua Stern; Elizabeth Maleche-Obimbo; Dalton Wamalwa; Grace John-Stewart; Lisa M Cranmer Journal: J Acquir Immune Defic Syndr Date: 2019-02-01 Impact factor: 3.731
Authors: Sylvia M LaCourse; Lisa M Cranmer; Irene N Njuguna; John Gatimu; Joshua Stern; Elizabeth Maleche-Obimbo; Judd L Walson; Dalton Wamalwa; Grace C John-Stewart; Patricia B Pavlinac Journal: Clin Infect Dis Date: 2018-05-17 Impact factor: 9.079
Authors: Stephanie Bjerrum; Ian Schiller; Nandini Dendukuri; Mikashmi Kohli; Ruvandhi R Nathavitharana; Alice A Zwerling; Claudia M Denkinger; Karen R Steingart; Maunank Shah Journal: Cochrane Database Syst Rev Date: 2019-10-21
Authors: Paul K Drain; Kristina L Bajema; David Dowdy; Keertan Dheda; Kogieleum Naidoo; Samuel G Schumacher; Shuyi Ma; Erin Meermeier; David M Lewinsohn; David R Sherman Journal: Clin Microbiol Rev Date: 2018-07-18 Impact factor: 26.132
Authors: Irene N Njuguna; Lisa M Cranmer; Anjuli D Wagner; Sylvia M LaCourse; Cyrus Mugo; Sarah Benki-Nugent; Barbra A Richardson; Joshua Stern; Elizabeth Maleche-Obimbo; Dalton C Wamalwa; Grace John-Stewart Journal: J Acquir Immune Defic Syndr Date: 2019-06-01 Impact factor: 3.731
Authors: Adrienne E Shapiro; Jennifer M Ross; Mandy Yao; Ian Schiller; Mikashmi Kohli; Nandini Dendukuri; Karen R Steingart; David J Horne Journal: Cochrane Database Syst Rev Date: 2021-03-23
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