Background
The diagnosis of childhood tuberculosis remains a major challenge of TB control, especially in developing countries. Causes of misdiagnosis include non-specific clinical signs or symptoms and low sensitivities of e.g. AFB microscopy, especially in HIV co-infected children.
This pilot study started in May 2008 with the objective to provide an improved approach to TB diagnosis in HIV infected and uninfected children through evaluation of emerging innovative diagnostic methods. Furthermore, in an extension to the original study, a closer look is taken at the clinical and immunological treatment outcome of TB infected children and at the diagnosis and prevalence of immune reconstitution inflammatory syndromes (IRIS) in HIV co-infected children.
Date of first enrolment was the 29th May 2008. Eligible participants are all children between the age of 6 weeks and 14 years of age with clinical suspicion of having either intra- or extra-pulmonary TB.
Objectives
The overall objective of this study is to provide an improved approach to TB diagnosis in HIV infected and uninfected children through evaluation of emerging innovative diagnostic methods.
Methods
A prospective clinical study, enrolling suspected TB-infected Children of more than 6 weeks and less than 14 years of age. Children with clinically suspected TB are screened using standard microscopy and culture (MGIT, LJ, HAIN Assay) for Mycobacterium tuberculosis from induced sputum, other body fluid or histology samples. Results are related to clinical/radiological signs and symptoms. New diagnostic approaches (e.g. INF-gamma release assays (IGRA), mycobacterial lipoarabinomannan (LAM) detection from urine and PCR-based MTBDR-plus assay from Hain Company are compared to the standard microbiology tests and clinical findings at baseline and evaluated during a 12 months follow-up period. Follow-up visits are scheduled to monitor the treatment outcome (after 3, 6, 12 months). HIV testing is performed and TB treatment and/or ART initiated when indicated, according to the Tanzanian National guidelines.
Preliminary findings
The amended number of participants aimed for was 175 Tb suspects. This target was achieved by the 1st November 2010. Of the 175 TB suspects, 37 had confirmed TB; in 25 cases the results were still outstanding. In 48 cases TB could be ruled out as an alternative diagnosis was established or the children recovered on treatment other than TB treatment.
Progress
Recruitment has been rather slow but picked up in the third quarter of this year again. Collaboration with the hospital and other referring facilities is good and well established. The initial aim of enrolling 250 participants was changed to 175 as less new diagnostic tools were evaluated as initially planned.
Future plans
The study is still ongoing although new recruitments have been completed recently. However, all participants will have at least one year of follow up visits which will bring the end of the study to November 2011. Data evaluation has started and first conclusions are being drawn, but final recommendations will have to wait until the end of the study.
Study Coordinator
Dr Petra Clowes
Sponsors
The TB Diagnosis in children study is part of the ADAT (Active Detection of Active Tuberculosis) project, which is funded by the European Union as part of EuropAid, contract number SANTE/2006/129-931.
