Eleanor S Click1, Rinn Song2,3,4, Jonathan P Smith2, Walter Mchembere5,6, Mark Fajans1, Parisa Hariri2,7, Elisha Okeyo8, Kimberly D McCarthy9, Dickson Gethi8, Lazarus Odeny8, Susan Musau8, Albert Okumu8, James Orwa8, Carlos M Perez-Velez10,6, Colleen A Wright11, Mariaem Andres12, Ben J Marais13, H Simon Schaaf14, Stephen M Graham15,16, Andrea T Cruz17, Kevin P Cain9. 1. From the US Centers for Disease Control and Prevention, Atlanta, Georgia. 2. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. 3. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA. 4. Department of Pediatrics, Harvard Medical School, Boston, MA USA. 5. Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA. 6. College of Medicine, University of Arizona, Tucson, Arizona. 7. Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland. 8. Kenya Medical Research Institute - Center for Global Health Research, Kisumu, Kenya. 9. Centers for Disease Control and Prevention, Kisumu, Kenya. 10. Tuberculosis Clinic, Pima County Health Department, Tucson, Arizona. 11. Division of Anatomical Pathology, Stellenbosch University, Cape Town, South Africa. 12. Institute of Radiology, St. Luke's Medical Center, St. Luke's Medical Center, Global City, Philippines. 13. The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Australia. 14. Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa. 15. Centre for International Child Health, University of Melbourne Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia. 16. International Union Against Tuberculosis and Lung Disease (The Union), Paris, France. 17. Baylor College of Medicine, Houston, Texas USA.
Abstract
BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness.
BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness.
Authors: Stephen M Graham; Tahmeed Ahmed; Farhana Amanullah; Renee Browning; Vicky Cardenas; Martina Casenghi; Luis E Cuevas; Marianne Gale; Robert P Gie; Malgosia Grzemska; Ed Handelsman; Mark Hatherill; Anneke C Hesseling; Patrick Jean-Philippe; Beate Kampmann; Sushil Kumar Kabra; Christian Lienhardt; Jennifer Lighter-Fisher; Shabir Madhi; Mamodikoe Makhene; Ben J Marais; David F McNeeley; Heather Menzies; Charles Mitchell; Surbhi Modi; Lynne Mofenson; Philippa Musoke; Sharon Nachman; Clydette Powell; Mona Rigaud; Vanessa Rouzier; Jeffrey R Starke; Soumya Swaminathan; Claire Wingfield Journal: J Infect Dis Date: 2012-03-22 Impact factor: 5.226
Authors: Anne K Detjen; Andrew R DiNardo; Jacinta Leyden; Karen R Steingart; Dick Menzies; Ian Schiller; Nandini Dendukuri; Anna M Mandalakas Journal: Lancet Respir Med Date: 2015-03-24 Impact factor: 30.700
Authors: B J Marais; R P Gie; H S Schaaf; A C Hesseling; C C Obihara; J J Starke; D A Enarson; P R Donald; N Beyers Journal: Int J Tuberc Lung Dis Date: 2004-04 Impact factor: 2.373
Authors: Stephen M Graham; Luis E Cuevas; Patrick Jean-Philippe; Renee Browning; Martina Casenghi; Anne K Detjen; Devasena Gnanashanmugam; Anneke C Hesseling; Beate Kampmann; Anna Mandalakas; Ben J Marais; Marco Schito; Hans M L Spiegel; Jeffrey R Starke; Carol Worrell; Heather J Zar Journal: Clin Infect Dis Date: 2015-10-15 Impact factor: 9.079
Authors: Rinn Song; Eleanor S Click; Kimberly D McCarthy; Charles M Heilig; Walter Mchembere; Jonathan P Smith; Mark Fajans; Susan K Musau; Elisha Okeyo; Albert Okumu; James Orwa; Dickson Gethi; Lazarus Odeny; Scott H Lee; Carlos M Perez-Velez; Colleen A Wright; Kevin P Cain Journal: JAMA Pediatr Date: 2021-05-03 Impact factor: 16.193