Implementation of new diagnostics for tuberculosis: Bridging the gap between global policy and local practice

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide with an estimated 9.0 million people who developed TB in 2013, of whom around one-third remained undiagnosed. The release of global guidance on new TB diagnostics has accelerated since 2007, but there remains a gap in local implementation. This thesis investigated the extent of this gap and generated evidence to support implementation of the most recently recommended test for TB and drug-resistant TB, the Xpert MTB/RIF assay.
This thesis showed that by 2009 only half of high-burden TB and multidrug-resistant TB countries had started introduction of new TB diagnostic methods and were aware of recent global guidelines. Also, there was substantial lack of published scientific evidence to support the translation of global TB diagnostic policies into local practice. More operational research was needed to provide evidence on scale-up of new TB diagnostics for both local and global policy-makers.
Field studies presented in this thesis found that the introduction of the Xpert MTB/RIF assay was feasible and effective in Indonesia and Kazakhstan, as well as cost-effective in India, South Africa and Uganda. Xpert MTB/RIF helped to start more drug-resistant TB patients on appropriate treatment and initiate treatment earlier than conventional methods. However, under- and over-treatment after diagnosis can undermine the impact of any new test on patient-important outcomes. Future studies should take into account operational aspects that reflect the mismatch between diagnosis and treatment, including patient drop-out rates, diagnostic delays, clinical decision-making processes and rates of empirical treatment.