Nutritional intervention and novel diagnostics to improve community-based control of tuberculosis

Tuberculosis (TB) is a major public health problem in developing countries as well as in the Republic of South Africa (RSA). Despite significant strides in case detection and treatment, the prevalence of TB continues to rise at an alarming, also in the RS A. 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 positive predictive v alue (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 (M.tb), the causative agent of TB. New blood-based in vitro IFN-gamma release assays (IGRA s), based on ESAT-6 antigens, are more specific than the Mantoux skin test and have shown to have enhanced sensitivity in diagnosing active TB disease in HIV-infected and malnourished HIV-infected children. We hereby propose to evaluate the diagnostic val ue and utility of the new ESAT-6-based IGRAs to detect M.tb infection and predict TB disease in HIV-infected and uninfected South African 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 randomised controlled trial will assess the effect of adjunctive micronutrient supplementation, administered as part of the established Directly Obser ved Treatment Short-course (DOTS), on treatment outcome among pulmonary TB patients. Depending on the magnitude and range of effects, the data from this trial could lead to national and international policy recommendations to include micronutrient supplem entation as an adjunct to standard anti-TB treatment.