The complexity of the adherence‐response relationship in tuberculosis treatment: why are we still in the dark and how can we get out?

Non-adherence to tuberculosis (TB) treatment is a major challenge to global TB control because it increases the risk of treatment failure, relapse and the emergence of drug-resistant TB. Although the problem is widely acknowledged, there is still no clarity about the exact impact of different levels and patterns of non-adherence on treatment outcome. This hampers the provision of adequate advice to patients and clinicians, and it challenges the development and evaluation of adherence-promoting interventions. In this article, we explain why we are still in the dark with respect to predicting how different types of non-adherence to TB treatment affect treatment outcome. We show that we lack uniformity in how we define and measure non-adherence, that we have no easily accessible treatment success indicators, and that the relationship between treatment adherence and outcome is influenced by a number of pathogenic, immunological and pharmacological factors that are only partly understood. We conclude that an integral 'bench and bedside approach' that incorporates experimental studies with in vitro models and animals, as well as observational studies in patients with TB, is needed to help us get out of the dark regarding the adherence-response relationship in TB treatment.     

Defining the research agenda to reduce the joint burden of disease from Diabetes mellitus and Tuberculosis

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low‐income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus–TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non‐diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis ‘DOTS’ model for diabetes mellitus management; and (iv) the development and evaluation of better point‐of‐care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A_1c (HbA_1c) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.