Impact of Point-of-Care Xpert MTB/RIF on Tuberculosis Treatment Initiation. A Cluster-randomized Trial

Abstract

Scientific Knowledge on the SubjectCentralised laboratory-based diagnostic systems for tuberculosis are associated with substantial loss to follow-up and delays prior to treatment. Whether decentralised, point-of-care diagnostic systems can reduce loss to follow-up and treatment delay has not been adequately investigated. What This Study Adds to the FieldThis is the first randomised trial to make a direct comparison between point-of-care and laboratory use of a molecular TB diagnostic. The point-of-care strategy shortened the time to appropriate treatment for people with rifampicin-susceptible TB; three-quarters of Xpert-positive/rifampicinsusceptible cases received same-day diagnosis and treatment. Under both strategies, there were delays for people with drug-resistant TB and people with Xpert-negative/culture-positive TB, highlighting the need for more sensitive rapid diagnostics and further strengthening of health and laboratory systems.This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org Objective: To evaluate the effect of a POC diagnostic strategy on initiation of appropriate TB treatment. Methods:A cluster randomised trial of adults with cough who were HIV positive and/or at high risk of drug-resistant TB. Two-week time blocks were randomised to two strategies (i) Xpert performed at district hospital laboratory (ii) POC Xpert performed at primary health care clinic.All participants provided two sputum specimens: one for Xpert and the other for culture as reference standard. The primary outcome was the proportion of culture-positive pulmonary TB (PTB) cases initiated on appropriate TB treatment within 30 days. Measurements and Main IntroductionTuberculosis (TB) remains one of the most important causes of global mortality, causing around 5000 deaths every day (1). In sub-Saharan Africa, the human immunodeficiency virus (HIV) epidemic and the spread of drug-resistant TB (DR-TB) contributed to a failure to achieve targets for reduction in TB prevalence and mortality in the United Nations Millennium Development Goals (MDG) (2). Timely detection and treatment of adult pulmonary TB cases is important, not only to limit individual morbidity and mortality but also to interrupt transmission. Centralised laboratory-based TB diagnostic systems are associated with substantial loss to follow-up and delays prior to treatment (3, 4). While diagnostics with improved sensitivity for detecting TB disease could have substantial clinical and public health impact, additional benefit might be achieved by positioning diagnostics at more peripheral levels of the health system (5, 6), however, there is little high quality evidence as to whether implementation of diagnostics at the point of care (POC) improves patient-relevant outcomes.This evidence is important to inform the scale-up of existing technologies and to guide the development of new diagnostics (7, 8). The aim of this trial was to determine whether a diagnostic strategy involving a rapid mol...

Time to treatment for rifampicin-resistant tuberculosis: systematic review and meta-analysis

“…Molecular testing methods result in more rapid laboratory turnaround times, 12 , 68–70 and are therefore likely to reduce time to treatment. This was confirmed in our analysis, with genotypic testing resulting in significantly shorter time to treatment than phenotypic methods; our findings are consistent with the results of a randomized trial 71 and a retrospective cohort study published after our search was concluded. 72 Xpert is of particular interest due to the feasibility of testing in peripheral laboratories, 73 , 74 potentially reducing reliance on transport and resulting in more rapid communication of results.…”

Dynamics of within-hostMycobacterium tuberculosisdiversity and heteroresistance during treatment

“…This may be because time to treatment initiation has decreased with health systems changes, including introduction of the Xpert MTB/RIF rapid diagnostic (53,54). We did not identify any factors associated with risk of mixed infection and contrary to previous studies did not detect worse outcomes in patients with mixed infection, although we compared sixmonth rather than end of treatment outcome and our studies were heavily weighted for patients with DR-TB.…”

Update in Tuberculosis and Nontuberculous Mycobacteria 2017

“…In the Journal, Lessells et al reported the results of a cluster randomised-controlled trial examining the impact of point-of-care compared to hospital laboratory implementation of Xpert MTB/RIF, a molecular test for TB and rifampicin resistance(10), on TB treatment initiation among individuals who were either HIV positive (92.5%), and/or had risk-factors for MDR-TB (45%) (11). There was no difference between the point-of-care and laboratory arms in the primary outcome of the proportion of The WHO has recently endorsed the new Xpert Ultra assay as an alternative to Xpert MTB/RIF (12).…”