Performing TB Research in Children – Issues to Consider

Tuberculosis (TB) control programs place an almost exclusive emphasis on adults with sputum smear-positive disease, as they represent the most infectious cases that sustain the TB epidemic. However, although pre-adolescent children contribute little to TB transmission, they contribute significantly to the global TB caseload and experience considerable TB-related morbidity and mortality, especially in high burden settings(1-4). Despite TB being an easily treatable disease few children in these settings have access to TB treatment, as evidenced by the absence of child friendly drug formulations in many high burden countries. Luckily this is changing and there is increased awareness and commitment at an international level to reduce the TB disease burden in children. The World Health Organization (WHO) recently published guidelines for national TB programs on the management of TB in children(5), and for the first time the Global Drug Facility (GDF) has made child friendly drug formulations available to poor countries. These positive developments focus the attention on the tenacious problem of establishing an accurate TB diagnosis in children, particularly in TB-endemic settings with limited resources that carry the brunt of the disease burden. The diagnosis of TB in children is complicated by the absence of a practical “gold standard ” test, as sputum smears, the “gold standard ” used in adults, are positive in less than 10-15 % of children diagnosed with TB(6). For research purposes accurate case definition is essential and revolves mainly around the ability to differentiate primary infection from active disease. Primary infection occurs when a previously uninfected child inhale