The global burden of drug-resistant tuberculosis in children: a mathematical model

Abstract

Background: Following infection with M. tuberculosis, children are at increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications, and suggest there is much more isoniazid-resistant and multidrug-resistant (MDR) disease than is identified. No work has yet quantified the burden of drug-resistant infection, considered other types of drug-resistance, or accounted for sampling uncertainty. Methods: We combined a mathematical model of tuberculosis in children with an analysis of drug-resistance patterns to produce country-level, regional, and global estimates of drug-resistant infection and disease. We estimated the proportions of tuberculosis cases at a country-level with: isoniazid-monoresistance (HMR), rifampicin mono-resistance, MDR, fluoroquinolone-resistant MDR, second-line injectable resistant MDR, and MDR with resistance to both a fluoroquinolone and a second-line injectable (XDR). Findings: We estimate 850,000 children developed tuberculosis in 2014; 58,000 with HMR-tuberculosis, 25,000 with MDR-tuberculosis, and 1,200 with XDR-tuberculosis. We estimate 67 million children are infected with M. tuberculosis; 5 million with HMR, 2 million with MDR, and 100,000 with XDR. Africa and South-East Asia have the highest numbers of tuberculosis in children, but WHO EMR, EUR and WPR regions also contribute substantially to the burden of drug-resistant tuberculosis due to their much higher proportions of resistance. Interpretation: Far more drug-resistant tuberculosis occurs in children than is diagnosed, and there is a large pool of drug-resistant infection. This has implications for approaches to empiric treatment and preventive therapy in some regions.