Background Rapid on-site diagnosis facilitates tuberculosis control. Performing Xpert MTB/RIF (Xpert) at point of care is feasible, even when performed by minimally trained health-care workers, and when compared with point-of-care smear microscopy, reduces time to diagnosis and pretreatment loss to follow-up. However, whether Xpert is cost-effective at point of care remains unclear. Methods We empirically collected cost (US$, 2014) and clinical outcome data from participants presenting to primary health-care facilities in four African countries (South Africa, Zambia, Zimbabwe, and Tanzania) during the TB-NEAT trial. Costs were determined using an bottom-up ingredients approach. Effectiveness measures from the trial included number of cases diagnosed, initiated on treatment, and completing treatment. The primary outcome was the incremental cost-effectiveness of point-of-care Xpert relative to smear microscopy. The study was performed from the perspective of the health-care provider. Findings Using data from 1502 patients, we calculated that the mean Xpert unit cost was lower when performed at a centralised laboratory (Lab Xpert) rather than at point of care ($23•00 [95% CI 22•12-23•88] vs $28•03 [26•19-29•87]). Per 1000 patients screened, and relative to smear microscopy, point-of-care Xpert cost an additional $35 529 (27 054-40 025) and was associated with an additional 24•3 treatment initiations ([-20•0 to 68•5]; $1464 per treatment), 63•4 same-day treatment initiations ([27•3-99•4]; $511 per same-day treatment), and 29•4 treatment completions ([-6•9 to 65•6]; $1211 per completion). Xpert costs were most sensitive to test volume, whereas incremental outcomes were most sensitive to the number of patients initiating and completing treatment. The probability of point-of-care Xpert being cost-effective was 90% at a willingness to pay of $3820 per treatment completion. Interpretation In southern Africa, although point-of-care Xpert unit cost is higher than Lab Xpert, it is likely to offer good value for money relative to smear microscopy. With the current availability of point-of-care nucleic acid amplification platforms (eg, Xpert Edge), these data inform much needed investment and resource allocation strategies in tuberculosis endemic settings. Funding European Union European and Developing Countries Clinical Trials Partnership and the South African Medical Research Council.

We found that assessment of HRQoL of participants in TB-HIV treatment using the FAHI instrument was useful in evaluating treatment responses. It showed improvement consistent with decrease in adverse events and signs and symptoms of TB. Number and type of AEs was related to lower HRQoL in spite of TB cure.

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Phenotypic TB drug resistance, also known as drug tolerance, has been previously attributed to slowed bacterial growth in vivo. The increased activity and expression of efflux systems can lower the intracellular concentration of many antibiotics thus reducing their efficacy. We hypothesized that efflux pump activation and expression could be a risk factor for TB drug tolerance in patients initiated on treatment. Analyses of gene expression levels of six select efflux pumps associated with drug tolerance in Mycobacterium tuberculosis and its correlation with the cell’s ability to efflux ethidium bromide (a common efflux substrate) were assayed. Efflux pump gene expression differed significantly between the strains from treatment failures and treatment successes. Efflux of ethidium bromide by M. tuberculosis isolates revealed that isolates from treatment failures rapidly efflux ethidium bromide more than isolates from treatment successes or the H37Rv control strains. The efflux pumps efpA, jefA (Rv2459c), Rv1258c, p55 and mmpL7 may have a role in TB drug tolerance. Quantifying the expression levels of M. tuberculosis efflux pump genes may be a new method to diagnose clinically persistent tuberculosis. High efflux pump activity and expression at baseline can be associated with tuberculosis treatment failure even when the Mycobacterium tuberculosis does not have established resistance mutations.Journal of Medical and Biomedical Sciences (2017) 6(1), 8-17Keywords: drug resistance, Efflux, Mycobacterium tuberculosis, expression, treatment outcome