Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates

Abstract

Background Multidrug-resistant tuberculosis (MDR-TB) threatens to reverse recent reductions in global tuberculosis (TB) incidence. Although children under 15 years of age constitute >25% of the worldwide population, the global incidence of MDR-TB disease in children has never been quantified. Methods Our approach for estimating regional and global annual incidence of MDR-TB in children required development of two models: one to estimate the setting-specific risk of MDR-TB among child TB cases, and a second to estimate the setting-specific incidence of TB disease in children. The model for MDR-TB risk among children with TB required a systematic literature review. We multiplied the setting-specific estimates of MDR-TB risk and TB incidence to estimate regional and global incidence of MDR-TB disease in children in 2010. Findings We identified 3,403 papers, of which 97 studies met inclusion criteria for the systematic review of MDR-TB risk. Thirty-one studies reported the risk of MDR-TB among both children and treatment-naïve adults with TB and were used for evaluating the linear association between MDR-TB risk in these two patient groups. We found that the setting-specific risk of MDR-TB was nearly identical in children and treatment-naïve adults with TB, consistent with the assertion that MDR-TB in both groups reflects the local risk of transmitted MDR-TB. Applying these calculated risks, we estimated that around 1,000,000 (95% Confidence Interval: 938,000 – 1,055,000) children developed TB disease in 2010, among whom 32,000 (95% Confidence Interval: 26,000 – 39,000) had MDR-TB. Interpretation Our estimates highlight a massive detection gap for children with TB and MDR-TB disease. Future estimates can be refined as more and better TB data and new diagnostic tools become available.