Does directly observed therapy improve tuberculosis treatment? More evidence is needed to guide tuberculosis policy

Abstract

BackgroundTuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only “supportive treatment supervision by treatment partners”, many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure.DiscussionDOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma.To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide.SummaryRigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.

Both Pharmacokinetic Variability and Granuloma Heterogeneity Impact the Ability of the First-Line Antibiotics to Sterilize Tuberculosis Granulomas

“…Each of these antibiotics has side effects associated with their use that, together with the lengthy treatment duration, make it difficult for patients to properly adhere to the regimen (Yee et al, 2003;Munro et al, 2007). Efforts such as directly observed therapy (DOT) attempt to increase patient adherence but are not tractable on a global scale (Steffen et al, 2010;McLaren et al, 2016). Emergence of multidrug-resistant (defined as resistant to INH and RIF) and extensively drugresistant TB (resistant to INH, RIF, and a second-line injectable) further complicates treatment (Global tuberculosis report, 2018).…”

Cattle‐associated risk factors for human tuberculosis in rural livestock‐keeping communities, Uganda

“…Tuberculosis (TB), caused by infection with members of the Mycobacterium tuberculosis (MTB) complex, is a leading infectious cause of death worldwide, with an estimated annual cost of over US$12 billion (McLaren, Milliken, Meyer, & Sharp, ). While the majority of human TB cases are non‐zoonotic, most members of this complex are zoonotic pathogens, and the WHO estimates that between 0.4% and 10% of TB cases in Africa are zoonotic (Firdessa et al, ; Michel, Müller, & van Helden, ).…”

Applying Optimization Algorithms to Tuberculosis Antibiotic Treatment Regimens

“…5,39 Programs such as DOT (directly observed treatment) have been put into place to track drug compliance, but this is costly and untenable for many TB patients worldwide. 36,50 Additional antibiotics are currently being developed or repurposed to treat TB. 55,56 Comparing treatments can involve large meta-analysis studies, and head-to-head comparisons of alternative protocols are often lacking.…”