Determinants of Losses in the Tuberculosis Infection Cascade of Care Among Children and Adolescent Contacts of Pulmonary Tuberculosis Cases in Brazil

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-center 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 in the cascade were especially high in children <5 years old (88%); children 10-14 years old had the lowest percentage (9.8%) of compliance with recommended TPT. 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 highest among children < 5 years old—the group at highest risk of TB. These observations highlight the need to improve screening and TPT initiation of young children who are close contacts of persons with TB in Brazil.Funding: The study was supported by the Intramural Research Program of the Fundação Oswaldo Cruz (B.B.A.), Intramural Research Program of the Fundação José Silveira (B.B.A., M.S.R.), Departamento de Ciência e Tecnologia (DECIT) - Secretaria de Ciência e Tecnologia (SCTIE) – Ministério da Saúde (MS), Brazil [25029.000507/2013-07 to V.C.R.], Fogarty International Center and National Institute of Child Health & Human Development of the National Institutes of Health under [Award Number D43 TW009763 through a research scholarship awarded to M.B.A.], and the National Institutes of Allergy and Infectious Diseases [U01- AI069923 to T.R.S, ABS, MBA, BMFN, MSR, AB, ASRM, JGO, VCR, BD, JRLS, ALK, SC, TRS, BBA, and MCS and U01-AI115940 to B.B.A.]. M.B.A. received a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB). MAP and B.B.D received a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance code: 001). B.B.A, J.R.L.S and A.K. are senior investigators whereas A.B.S. is a PhD fellow from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. J.R.L.S. and A.K are recipients of the Scientist of our State fellowship from Rio de Janeiro Research Council/FAPERJ.Declaration of Interest: None to declare. Ethical Approval: All regulatory documents were approved by the Research Ethics Committee of all participating sites. (CAAE: 25102414.3.2009.5543). Written informed consent was obtained from each participant or their legally responsible guardians, at the time of study enrollment.