Introduction

These are a set of prospective studies aimed at determining the diagnostic value of novel tests for detecting TB in children with suspected pulmonary or extrapulmonary TB presenting. The studies are currently set at two sites,  with both high TB and HIV prevalence. The core study site being Red Cross War Memorial Children’s Hospital (a paediatric hospital in Cape Town, South Africa) and a satellite study site at Dora Nginza Hospital in Port Elizabeth (Eastern Cape).

Children (both HIV-infected and HIV non-infected up to the age of 15 years are enrolled and are followed up to 6 months post-TB treatment or 12 months. Participants undergo a clinical examination and a number of investigations are performed which include the collection of biological specimens (blood, urine, sputum, and tongue swabs), lung function testing, breath tests, and chest x-rays among others. 

The study has two main aims:

  1. To improve the rapid diagnosis (within 1 day) of TB disease in HIV-infected children by investigating the sensitivity and specificity of the following diagnostic techniques (using culture-proven TB as the gold-standard).
  2. Discover, test, and validate tests for triage and screening of symptomatic, clinical, and asymptomatic, subclinical TB disease.

Several important sub-studies are associated with study which a focus on computer-assisted interpretation of chest x-rays, molecular testing, biomarkers, MRIs, testing of volatile compounds on expelled breath from children with suspected TB, lung and cough sounds, and tongue swabs.
 
The study has supported several post-doctoral studies over the years including a number of MMeds, Masters Students, and PhD Students.

Selected list of Papers and publications for this study:

  1. Bobak CA, Kang L, Workman L, Bateman L, Khan MS, Prins M, May L, Franchina FA, Baard C, Nicol MP, Zar HJ, Hill JE. Breath can discriminate tuberculosis from other lower respiratory illness in children. Sci Rep. 2021 Feb 1;11(1):2704. doi: 10.1038/s41598-021-80970-w. PMID: 33526828; PMCID: PMC7851130.
  2. Cox H, Workman L, Bateman L, Franckling-Smith Z, Prins M, Luiz J, Van Heerden J, Edries LAT, Africa S, Allen V, Baard C, Zemanay W, Nicol MP, Zar HJ. Oral Swab Specimens Tested With Xpert MTB/RIF Ultra Assay for Diagnosis of Pulmonary Tuberculosis in Children: A Diagnostic Accuracy Study. Clin Infect Dis. 2022 May 17. http://dx.doi.org/10.1093/cid/ciac332. PMID: 35579497. 
  3. Jaganath D, Nabeta P, Nicol MP, Castro R, Wambi P, Zar HJ, Workman L, Lodha R, Singh UB, Bavdekar A, Sanghavi S, Trollip A, Mace A, Bonnet M, Lounnas M, de Haas P, Tiemersma E, Alland D, Banada P, Cattamanchi A, Ruhwald M, Wobudeya E, Denkinger CM; Stool H2H Study Team. Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study. medRxiv [Preprint]. 2024 Dec 18:2024.12.17.24317956. doi: 10.1101/2024.12.17.24317956. PMID: 39763536; PMCID: PMC11702738.
  4. Nicol MP, Workman L, Prins M, Bateman L, Ghebrekristos Y, Mbhele S, Denkinger C, Zar H. Accuracy of Xpert MTB/RIF Ultra for the Diagnosis of Pulmonary Tuberculosis in Children. PIDJ. 2018 Oct;37(10):e261-e263.doi:10.1097/INF0000000000001960. E-pub 22 Feb 2018.
  5. Nicol MP, Schumacher SG, Workman L, Broger T, Baard C, Prins M, Bateman L, du Toit E, van Heerden J, Szekely R, Zar HJ, Denkinger CM. Accuracy of a novel urine test, Fujifilm SILVAMP TB LAM, for the diagnosis of pulmonary tuberculosis in children. Clin Infect Dis. 2020 Aug 6:ciaa1052. doi: 10.1093/cid/ciaa1052. PMID: 32761178.
  6. Zar HJ, Workman LJ, Prins M, Bateman LJ, Mbhele SP, Whitman CB, Denkinger CM, Nicol MP. Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens. AM Journal of Resp and Crit Care Med. 2019 Dec 15;200(12):1531-1538. doi: 10.1164/rccm.201904-0772OC. PMID: 31381861 PMCID: PMC6909828.

Project Manager:
Cynthia Baard
Tel: 021-658-5518
Email: cynthia.baard@uct.ac.za