Background The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. Methods We tested the single-nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as induration ≥5 mm after a negative TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models. Results Among the 526 contacts, 60 had TST conversion and 44 developed active TB during follow-up. Multivariable regression analysis demonstrated that male sex (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.1–4.6), as well as SNPs in TLR4 genes (OR: 62.8, 95% CI: 7.5–525.3) and TNFA (OR: 4.2, 95% CI: 1.9–9.5) were independently associated with TST conversion. Moreover, a positive TST at baseline (OR: 4.7, 95% CI: 2.3–9.7) and SNPs in TLR4 (OR: 6.5, 95% CI: 1.1–36.7) and TNFA (OR: 12.4, 95% CI:5.1–30.1) were independently associated with incident TB. Conclusions SNPs in TLR4 and TNFA predicted both TST conversion and active TB among contacts of TB cases in Brazil.

Background It is unclear whether diabetes or prediabetes affect unfavorable treatment outcomes and death in people with tuberculosis (PWTB). Methods Culture-confirmed drug-susceptible PWTB, enrolled in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil between 2015-2019 (n=643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable TB outcome was defined as treatment failure or modification, recurrence or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (n=20,989). Logistic regression models evaluated associations between glycemic status and outcomes. Results In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use and HIV infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted Relative Risk [aRR]: 2.45, p<0.001) and SINAN (aRR: 1.76, p<0.001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR:2.16, p=0.040) and SINAN (aRR:1.93, p= 0.001). Conclusion Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve tuberculosis treatment outcomes in persons with diabetes are needed.

Background It is unknown whether dysglycemia is associated with M. tuberculosis transmission. Methods We assessed epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB and their close contacts, enrolled in a multicenter prospective cohort in Brazil. Contacts were investigated at baseline and 6 months after enrollment. QuantiFERON positivity at baseline and conversion (from negative to positive at month 6) were compared between subgroups of contacts according to glycemic status of persons with tuberculosis (PWTB) as diabetes mellitus (DM) or prediabetes. Multivariable mixed-effects logistic regression models were performed to test independent associations with baseline QuantiFERON-positive and QuantiFERON-conversion. Results There were 592 PWTB (153 DM, 141 prediabetes, 211 normoglycemic) and 1784 contacts, of whom 658 were QuantiFERON-positive at baseline and 106 converters. Multivariable analyses demonstrated that TB-prediabetes cases, acid-fast bacilli-positive, pulmonary cavities, and living with someone who smoked, were independently associated with QuantiFERON-positive in contacts at baseline. DM, persistent cough, AFB-positive and pulmonary cavities in TB source cases were associated with QuantiFERON-conversion. Conclusion Contacts of persons with pulmonary TB and dysglycemia were at increased risk of being QuantiFERON-positive at baseline or month 6. Increased focus on such close contacts could improve TB control.