Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease. Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up. Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up. Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration.

Background: Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors. Methods: Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015–2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome. Results: Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0–9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7–4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1–3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2–6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1–4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4–19.7), diabetes (aOR = 3.1; 95% CI, 1.4–6.7), and PWH (aOR = 3.9; 95% CI, 1.3–11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3–.9) and death (aOR = 0.5; 95% CI, .2–1.0). Conclusions: The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes.

Laryngeal tuberculosis (LTB) is the most frequent granulomatous disease of the larynx and represents less than 2% of extrapulmonary TB cases. There are no pathognomonic clinical and endoscopic features of this disease and studies on LTB that can assist in its diagnostic characterization are lacking. To identify factors associated with clinical and topographical features of LTB. a retrospective cross-sectional study was conducted from the medical records of 36 patients with confirmed LTB diagnosis. Dysphonia and cough were the main symptoms presented by patients and the true vocal folds the most frequently affected site. The average of the duration of the disease evolution was significantly higher in patients with dysphonia than in patients without this symptom. We observed association between dysphonia and true vocal fold lesions and between odynophagia and lesions in the epiglottis, arytenoids and aryepiglottic folds. Odynophagia was more frequent in individuals with lesions in four or more laryngeal sites. Weight loss equal or above 10% of the body weight was more frequent in patients with odynophagia as first symptom and in patients with ulcerated lesion. Dyspnea on exertion was more frequent in individuals with more extensive laryngeal lesions. The percentage of smokers with lesions in four or more laryngeal sites was greater than that found in non-smokers. Laryngeal tissue fragment bacilloscopy and culture examinations were less positive than sputum ones. Smoking appears to be associated with the development of more extensive LTB lesions, and LTB with dyspnea on exertion and odynophagia with consequent impairment of nutritional status. We emphasize the need for histopathologic confirmation, once positive sputum bacteriological examinations seem not to necessarily reflect laryngeal involvement.

Introduction: Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil.Methods: Close contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6–24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Multivariable regressions were used to identify determinants of losses in the LTBI cascade.Results: Among 4145 TB contacts initially identified, 1901 were examined (54% loss). Among those examined, 933 were people living with HIV, ≤5 years old and/or had positive IGRA results, and therefore had a recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (54% of those initiating; 26% of those in whom treatment was recommended) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy and black/pardo(brown) race were independently associated with losses in the cascade.Conclusion: There were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts of low socioeconomic status and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil.

Background: Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes. Methods: A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information: race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes. Results: 550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR: 2.32; 95% CI:1.34–3.99) and illicit-drug use (OR:2.02; 95% CI:1.15–3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 3/4-ADR (18.36%), especially “liver and biliary system disorders”. Lower CD4 counts (<100 cells/uL) were associated with hepatotoxicity (p = 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients. Conclusion: Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression.