Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis.

We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9-12 months (the "shorter regimen") and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences.

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014-2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

Risk factors associated with loss to follow-up from tuberculosis treatment in Tajikistan: a case-control study.

BACKGROUND: There are very few studies on reasons for loss to follow-up from TB treatment in Central Asia. This study assessed risk factors for LTFU and compared their occurrence with successfully treated (ST) patients in Tajikistan. METHODS: This study took place in all TB facilities in the 19 districts with at least 5 TB patients registered as loss to follow-up (LTFU) from treatment. With a matched case control design we included all LTFU patients registered in the selected districts in 2011 and 2012 as cases, with ST patients from the same districts being controls. Data were copied from patient records and registers. Conditional logistic regressions were run to analyse associations between collected variables and LTFU as dependent variable. RESULTS: Three hundred cases were compared to 592 controls. Half of the cases had migrated or moved. In multivariate analysis, risk factors associated with increased LTFU were migration to another country (OR 10.6, 95% CI 6.12-18.4), moving within country (OR 11.0, 95% CI 3.50-34.9), having side effects of treatment (OR 3.67, 95% CI 1.68-8.00) and being previously treated for TB (OR 2.03, 95% CI 1.05-3.93). Medical staff also mentioned patient refusal, stigma and family problems as risk factors. CONCLUSIONS: LTFU of TB patients in Tajikistan is largely a result of migration, and to a lesser extent associated with side-effects and previous treatment. There is a need to strengthen referral between health facilities within Tajikistan and with neighbouring countries and support patients with side effects and/or previous TB to prevent loss to follow-up from treatment.

TB case detection in Tajikistan - analysis of existing obstacles.

BACKGROUND: Tajikistan National TB Control Program. OBJECTIVE: (1) To identify the main obstacles to increasing TB Detection in Tajikistan. (2) To identify interventions that improve TB detection. METHODS: Review of the available original research data, health normative base, health systems performance and national economic data, following WHO framework for detection of TB cases, which is based on three scenarios of why incident cases of TB may not be notified. RESULTS: Data analysis revealed that some aspects of TB case detection are more problematic than others and that there are gaps in the knowledge of specific obstacles to TB case detection. The phenomenon of "initial default" in Tajikistan has been documented; however, it needs to be studied further. The laboratory services detect infectious TB cases effectively; however, referrals of appropriate suspects for TB diagnosis may lag behind. The knowledge about TB in the general population has improved. Yet, the problem of TB related stigma persists, thus being an obstacle for effective TB detection. High economic cost of health services driven by under-the-table payments was identified as another barrier for access to health services. CONCLUSION: Health system strengthening should become a primary intervention to improve case detection in Tajikistan. More research on reasons contributing to the failure to register TB cases, as well as factors underlying stigma is needed.