ABSTRACT
BACKGROUND: Understanding the geographic distribution and factors associated with delayed TB diagnosis may help target interventions to reduce delays and improve patient outcomes. METHODS: We conducted a secondary analysis of adults undergoing TB evaluation within a public health demonstration project in Uganda. Using Global Moran's I (GMI) and Getis-Ord GI* statistics, we evaluated for residential clustering and hotspots associated with patient-related and health system-related delays. We performed multivariate logistic regression to identify individual predictors of both types of delays. RESULTS: Of 996 adults undergoing TB evaluation (median age: 37 years, IQR 28-49), 333 (33%) experienced patient delays, and 568 (57%) experienced health system delays. Participants were clustered (GMI 0.47-0.64, P ⩽ 0.001) at the sub-county level, but there were no statistically significant hotspots for patient or health system delays. Married individuals were less likely to experience patient delays (OR 0.6, 95% CI 0.48-0.75; P < 0.001). Those aged 38-57 years (OR 1.2, 95% CI 1.07-1.38; P = 0.002) were more likely than those aged ⩾58 years to experience patient delays. Knowledge about TB (OR 0.8, 95% CI 0.63-0.98; P = 0.03) protected against health system delays. CONCLUSIONS: We did not identify geographic hotspots for TB diagnostic delays. Instead, delays were associated with individual factors such as age, marital status and TB knowledge.
CONTEXTE: Comprendre la distribution géographique et les facteurs associés aux retards de diagnostic de la TB peut aider à cibler les interventions visant à réduire les retards et à améliorer les résultats pour les patients. MÉTHODES: Nous avons effectué une analyse secondaire des adultes soumis à une évaluation de la TB dans le cadre d'un projet de démonstration de santé publique en Ouganda. À l'aide des statistiques Global Moran's I (GMI) et Getis-Ord GI*, nous avons évalué les regroupements résidentiels et les points critiques associés aux retards liés aux patients et au système de santé. Nous avons effectué une régression logistique multivariée pour identifier les prédicteurs individuels des deux types de retards. RÉSULTATS: Sur les 996 adultes soumis à une évaluation de la TB (âge médian : 37 ans, IQR 2849), 333 (33%) ont subi des retards liés aux patients et 568 (57%) ont subi des retards liés au système de santé. Les participants étaient regroupés (GMI 0,470,64 ; P ⩽ 0,001) au niveau du sous-comté, mais il n'y avait pas de points critiques statistiquement significatifs pour les retards des patients ou du système de santé. Les personnes mariées étaient moins susceptibles de subir des retards de la part des patients (OR 0,6 ; 95% CI 0,480,75 ; P < 0,001). Les personnes âgées de 38 à 57 ans (OR 1,2 ; 95% CI 1,071,38 ; P = 0,002) étaient plus susceptibles que celles âgées de ⩾58 ans de subir des retards. Les connaissances sur la TB (OR 0,8 ; 95% CI 0,630,98 ; P = 0,03) protégeaient contre les retards du système de santé. CONCLUSIONS: Nous n'avons pas identifié de points critiques géographiques pour les retards de diagnostic de la TB. Les retards étaient plutôt associés à des facteurs individuels tels que l'âge, la situation matrimoniale et les connaissances sur la TB.
ABSTRACT
SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To quantify Mycobacterium tuberculosis in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment.DESIGN: We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines. We collected overnight sputum samples before treatment and weekly. Sputum samples were cultured on Middlebrook 7H11S agar to measure colony-forming units per mL (cfu/mL) and in MGIT™ 960™ media to measure time to detection (TTD). Linear mixed-effects regression was used to estimate the relational change in log10 cfu/mL and TTD.RESULTS: Twelve adults (median age: 27 years) were enrolled. Half were women, and two-thirds were HIV-positive. At baseline, median log10 cfu/mL was 5.1, decreasing by 0.29 log10 cfu/mL/week. The median TTD was 116.5 h, increasing in TTD by 36.97 h/week. The weekly change was greater in the first 2 weeks (-1.04 log10 cfu/mL/week and 120.02 h/week) than in the remaining 6 weeks (-0.17 log10 cfu/mL/week and 26.11 h/week).CONCLUSION: Serial quantitative culture measures indicate a slow, uneven rate of decline in sputum M. tuberculosis over 8 weeks of standardized pulmonary MDR-TB treatment.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Adult , Female , Humans , Male , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Agar/pharmacology , Uganda , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiologySubject(s)
Antibiotics, Antitubercular , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antibiotics, Antitubercular/pharmacology , Antibiotics, Antitubercular/therapeutic use , Drug Resistance, Bacterial , Humans , Rifampin/pharmacology , Sensitivity and Specificity , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapyABSTRACT
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is considered to be less transmissible due to the fitness cost associated with drug resistance-conferring mutations in essential genes. OBJECTIVE: To test the hypothesis that TB drug resistance-conferring mutations with fitness cost are more frequent among human immunodeficiency virus (HIV) positive than among HIV-negative patients. DESIGN: We analysed all strains from the two TB drug resistance surveys conducted in Uganda between 2008 and 2011. Strains phenotypically susceptible to rifampicin and/or isoniazid were assumed to be wild-type; in all other cases, we performed whole-genome sequencing. Mutations at the rpoB531 and katG315 codons were considered without fitness loss, whereas other rpoB codons and non-katG were considered with fitness loss. RESULTS: Of the 897 TB patients, 286 (32.1%) were HIV-positive. Mutations with fitness loss in HIV-positive and HIV-negative patients were respectively as follows: non-531 rpoB: 1.03% (n = 3), 0.71% (n = 4) (OR 1.46, 95%CI 0.58-3.68); non-katG: 0.40% (n = 1), 1.0% (n = 6) (OR 0.40, 95%CI 0.07-2.20); rpoB531: 1.49% (n = 4), 0.69% (n = 4) (OR 2.29, 95%CI 0.83-5.77); katG315: 3.86% (n = 11), 2.55% (n = 15) (OR 1.54, 95%CI 0.81-2.90). The odds of mutations with and without fitness cost were higher for patients with a history of previous anti-tuberculosis treatment. CONCLUSIONS: Our data do not support the hypothesis that resistance-conferring mutations with fitness cost are likely to be often present in HIV-positive individuals.
