IMPROVING DIAGNOSIS, TREATMENT AND CONTROL OF CHILDHOOD TUBERCULOSIS

Tuberculosis (TB) is a major public health problem. Despite strides in case detection and treatment, the prevalence of TB continues to rise at an alarming rate. Globally, childhood TB contributes to 15% of the total TB disease caseload, predominantly in d eveloping countries. More effective diagnostic methods are required as early diagnosis is the cornerstone of effective TB control. The inexpensive standard Mantoux skin test which is currently used to identify TB suffers from poor specificity and poor pos itive predictive value (PPV) because the antigens are present in environmental bacteria as well as in the BCG vaccine. The ESAT-6 antigens are specific for Mycobacterium tuberculosis (Mtb), the causative agent of TB. We hereby propose to measure the diagn ostic value and utility of novel ESAT-6-based TB tests, which we anticipate will identify TB with a specificity and PPV that are substantially higher than that of the Mantoux test, without compromising sensitivity. The diagnosis of TB is a particular chal lenge in children and even more so in those with HIV infection. We will in a prospective, community-based longitudinal study evaluate the performance of these tests in detecting Mtb infection and active disease in HIV-infected as well as in HIV-uninfected children. TB drugs are often administered to malnourished individuals, despite the fact that specific micronutrient deficiencies may negatively affect drug kinetics, decrease their efficacy and increase their toxicity. A randomized controlled trial (us ing a 2 x 2 factorial design) will assess the effect of adjunctive micronutrient supplementation administered as part of the established Directly Observed Treatment Short-course, on treatment outcome among paediatric pulmonary TB patients. Depending on th e magnitude and range of effects, the data from this trial could lead to national and international policy recommendations to include micronutrient supplementation as an adjunct to standard anti-TB treatment.