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3-13] patients completing initial assessment per 100 starting). Several other interventions reduced losses at specific cascade steps, but evidence for these interventions came from single studies and could not be pooled.CONCLUSIONS Although there is limited evidence that any single intervention significantly improves the LTBI cascade, many studies provide information about effective ways to strengthen it.OBJECTIVE To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection.SETTING and DESIGN We used 2011-2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB.RESULTS A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6-72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1-8.3) among those who had had previous TB disease.CONCLUSION The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.SETTING Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient’s time was spent under the care of primary healthcare facilities this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. HPPE mw Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.Alcohol use is associated with increased risk of developing tuberculosis (TB) disease, yet the impact of alcohol use on TB treatment outcomes has not been summarized. We aimed to quantitatively review evidence of the relationship between alcohol use and poor TB treatment outcomes. We conducted a systematic review of PubMed, EMBASE, and Web of Science (January 1980-May 2018). We categorized studies as having a high- or low-quality alcohol use definition and examined poor treatment outcomes individually and as two aggregated definitions (i.e., including or excluding loss to follow-up [LTFU]). We analyzed drug-susceptible (DS-) and multidrug-resistant (MDR-) TB studies separately. Our systematic review yielded 111 studies reporting alcohol use as a predictor of DS- and MDR-TB treatment outcomes. Alcohol use was associated with increased odds of poor treatment outcomes (i.e., death, treatment failure, and LTFU) in DS (OR 1.99, 95% CI 1.57-2.51) and MDR-TB studies (OR 2.00, 95% CI 1.73-2.32). This association persisted for aggregated poor treatment outcomes excluding LTFU, each individual poor outcome, and across sub-group and sensitivity analyses. Only 19% of studies used high-quality alcohol definitions. Alcohol use significantly increased the risk of poor treatment outcomes in both DS- and MDR-TB patients. This study highlights the need for improved assessment of alcohol use in TB outcomes research and potentially modified treatment guidelines for TB patients who consume alcohol.SETTING The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group ( less then 75 mg/kg/week, 95%CI 1.09-1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01-1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29-2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01-1.33) were also associated with an increased risk of hearing loss.CONCLUSION MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, n = 2727; RR 1.