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Diagnosis of Tuberculosis in HIV-infected children-development of microbiological and immunological strategies.

Introduction
This is a prospective study of the diagnostic value of novel tests for TB children with suspected pulmonary or extrapulmonary TB presenting. The study is currently set at two sites,  both a high HIV and high TB prevalence area. 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 15years are enrolled and are followed up to 12months. Participants undergo a clinical examination and a number of investigations are performed which include the collection of biological specimens (blood, urine, sputum, nasal swabs and stool), lung function testing, ultrasound 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).
    1.1   A novel fully automated real-time PCR-based test (Xpert™ MTB, Cepheid/FIND) for the detection of MTB DNA and associated rifampicin resistance 
  2. To improve the yield and speed of microscopy and culture-based diagnosis of TB disease in HIV-infected children:    2.1  To determine the optimum specimen collection protocol by comparing the yield from repeated induced sputum and nasopharyngeal aspirates (NPA)

Several important sub-studies are associated with study which a focus on chest x-rays, GeneXpert ULTRA testing, MRIs, testing of volatile compounds on expelled breath from children with suspected TB.
 
The study has supported several post-doctoral studies over the years and currently supports four MMEDS and four PhDs.

Selected list of Papers and publications for this study:

  1. Zar HJ, Workman L, Isaacs W, Munro J, Black F, Eley B, Allen V, Boehme CC, Zemanay W, Nicol MP. Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens. Clin Infect Dis 2012, 55(8):1088-95
  2. Zar HJ, Workman L, Isaacs W, Dheda K, Zemanay W, Nicol MP. Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting using Xpert MTB/RIF on respiratory specimens: a prospective study. Lancet Glob Health 2013, 1(2): 97-104.
  3. Bélard S, Isaacs W, Black F, Bateman L, Madolo L, Munro J, Workman L, Grobusch MP, Zar HJ. Treatment of childhood tuberculosis. Paediatr Int Child Health 2014, 0 (0): 1-5
  4. Nicol MP, Workman L, Isaacs W,  Munro J, Black F, Eley B, Boehme CC, Zemanay W,  Zar HJ. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in hospitalized children in a high HIV-prevalence area. Lancet Infect Dis 2011,11(11):819-24
  5. Nicol MP, Zar HJ. New specimens and laboratory diagnostics for childhood pulmonary TB: progress and prospects. Paediatr Respir Rev 2011, 12(1):16-21

Project Manager:
Natasha Abraham
Tel: 021-658-5522 or 021-686-3163
Email:Natasha.Abraham@uct.ac.za