Incidence and risk factors of tuberculosis among 420 854 household contacts of patients with tuberculosis in the 100 Million Brazilian Cohort (2004-18): a cohort study

Abstract

Background: Although household contacts of patients with tuberculosis are known to be particularly vulnerable to tuberculosis, the published evidence focused on this group at high risk within the low-income and middle-income country context remains sparse. Using nationwide data from Brazil, we aimed to estimate the incidence and investigate the socioeconomic and clinical determinants of tuberculosis in a cohort of contacts of tuberculosis patients.

Methods: In this cohort study, we linked individual socioeconomic and demographic data from the 100 Million Brazilian Cohort to mortality data and tuberculosis registries, identified contacts of tuberculosis index patients diagnosed from Jan 1, 2004 to Dec 31, 2018, and followed up the contacts until the contact's subsequent tuberculosis diagnosis, the contact's death, or Dec 31, 2018. We investigated factors associated with active tuberculosis using multilevel Poisson regressions, allowing for municipality-level and household-level random effects.

Findings: We studied 420 854 household contacts of 137 131 tuberculosis index patients. During the 15 years of follow-up (median 4·4 years [IQR 1·9-7·6]), we detected 8953 contacts with tuberculosis. The tuberculosis incidence among contacts was 427·8 per 100 000 person-years at risk (95% CI 419·1-436·8), 16-times higher than the incidence in the general population (26·2 [26·1-26·3]) and the risk was prolonged. Tuberculosis incidence was associated with the index patient being preschool aged (<5 years; adjusted risk ratio 4·15 [95% CI 3·26-5·28]) or having pulmonary tuberculosis (2·84 [2·55-3·17]).

Interpretation: The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination.

Funding: Wellcome Trust and Brazilian Ministry of Health.

Figure 1

Hierarchical conceptual framework for adjusted multilevel Poisson regression model CadÚnico=Brazil National Registry for Social Programmes (Cadastro Único). SINAN-TB=Sistema de Informação de Agravos de Notificação for tuberculosis database. *Information from CadÚnico. †Information from the database of a previous study. ‡Information from SINAN-TB.

Figure 2

Selection of study population CadÚnico=Brazil National Registry for Social Programmes (Cadastro Único). SINAN-TB=Sistema de Informação de Agravos de Notificação for tuberculosis database. *Population used as a proxy of non-exposed to calculate the percent attributable risk of being a household contact. †Population used to calculate tuberculosis incidence among contacts and its associated factors.

Figure 3

Tuberculosis cumulative hazard among household contacts overall (A), and by index patient clinical classification (B), age of the contact (C), and performance of tuberculosis indicators in the municipality (D) Follow-up time limited to 12 years to facilitate visualisation. 95% CIs for age-specific risks for the final years of follow-up in the older age category were too large and therefore not computed as they would compromise the graph visualisation. Group A represents municipalities with the highest quality performance for tuberculosis indicators; Group B represents municipalities with medium quality performance for tuberculosis indicators; Group C represents municipalities with the lowest quality performance for tuberculosis indicators.