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Background: Approximately 10% of the global tuberculosis (TB) burden is in children. Identification, diagnosis, and early treatment of Mycobacterium tuberculosis infection (TBI) is critical to prevent progression to TB in children. The risk of TB, including severe disease, is highest in children <5 years old. We evaluated the cascade of TBI care among child and adolescent TB contacts to identify factors associated with losses in the cascade. Methods: Close contacts ≤ 18 years old of pulmonary TB patients enrolled between 2015 and 2019 in a multi-centre Brazilian cohort were followed for up to 24 months and classified according to age groups: <5 years, 5-9 years, 10-14 years and 15-18 years. Data on clinical investigation, radiographic examination, IGRA testing at baseline and 6 months, initiation and completion of TB preventive treatment (TPT) were collected. Multivariable regression analyses identified factors associated with TBI and losses in the cascade of care in children and adolescents. Findings: Among 1795 TB contacts initially identified, 530 (29·5%) were ≤18 years old. Losses for all steps in the cascade were especially high in children <5 years old (88%) because at this age all contacts are recommended to initiate TPT. As a proportion of all children, completion of TPT was low (between 10% and 13%) in all age-groups. Furthermore, multivariable regression revealed that younger age of contacts and TB index cases who were female, had pulmonary cavities, and persistent cough were independently associated with losses in the cascade of care among persons ≤18 years old. Interpretation: Losses in the TBI cascade were the highest among children <5 years, which was the group at highest risk for TB among the four age groups. The findings highlight the need to improve screening, initiation, and completion of TPT of young children who are close contacts of people with TB in Brazil. Funding: National Institutes of Allergy and Infectious Diseases.
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BACKGROUND: There are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries. METHODS: We assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015-2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts. RESULTS: In the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7 and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users. CONCLUSION: There is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.
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BACKGROUND: A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important. METHODS: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. FINDINGS: A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. CONCLUSIONS: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases.
