Decline in Calmette-Guérin Bacillus Vaccination Coverage and Change in the Spatiotemporal Pattern of Extrapulmonary Tuberculosis in Children and Adolescents in Brazil: An Ecological Study, 2004-2023.

Abstract

Objective: To investigate the association between municipal BCG vaccination coverage and extrapulmonary tuberculosis (EPTB) notification rates among children and adolescents in Brazil and to describe their temporal, spatial, and spatiotemporal patterns from 2004 to 2023.

Methods: We conducted an ecological study using national Brazilian administrative databases. Temporal trends in EPTB notification rates were assessed using Joinpoint regression and spatiotemporal clusters using retrospective space-time scan statistics. The association between municipal BCG coverage and EPTB notification rates was examined using municipality-year negative binomial models with an offset for the population aged 0-19 years. The main model adjusted for calendar year, primary health care team density, and municipal Human Development Index, with sensitivity analyses incorporating urbanicity, HIV case mix, and a CNES-based proxy of registered diagnostic infrastructure. Factors associated with extrapulmonary versus pulmonary presentation were evaluated using multivariable logistic regression.

Results: EPTB notification rates declined overall but increased among children aged 0-4 years. Mortality showed a U-shaped temporal pattern, with a nadir around 2013. Local spatial autocorrelation identified high-high clusters concentrated mainly in the Southeast, Northeast, and North. Space-time scan analyses identified recurrent high-risk clusters, including a large early cluster in 2004-2007, a localized cluster in 2015-2016, and a recent cluster in 2019-2023. Higher municipal BCG coverage was associated with lower EPTB notification rates after adjustment (IRR per 10-percentage-point increase, 0.9755; 95% CI, 0.9646-0.9864). Urbanicity had minimal impact, whereas inclusion of registered diagnostic infrastructure shifted estimates toward the null. At the individual level, extrapulmonary presentation was associated with ages 5-9 and 10-14 years, male sex, and HIV positivity.

Conclusions: Lower municipal BCG coverage was associated with higher EPTB notification rates among children and adolescents in Brazil. The association was modest and sensitive to contextual adjustment, particularly to indicators of diagnostic and service infrastructure.