Determinants of losses in the tuberculosis infection cascade of care among children and adolescent contacts of pulmonary tuberculosis cases: A Brazilian multi-centre longitudinal study

Abstract

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.

Keywords: Children; Contact; Latent tuberculosis; Pediatric; TBI cascade.

Figure 1

Cascade in TBI care in contacts of TB cases and factors associated to losses in the TBI cascade in contacts ≤18 years old. (A) Losses and drop-outs at each stage of the TBI cascade of care in ≤18 years old, percentages were calculated among the number of contacts initially identified. Percentages were calculated among the number of contacts initially identified. (B) Sankey diagram display the number of contacts who initiated treatment and those who completed treatment according to the category of TPT recommendation. (C) Generalized estimating equations analysis to evaluate association between epidemiological and clinical characteristics and losses in the TBI cascade of care in ≤18 years old. The study population was stratified according to complete TPT in the TBI cascade (variables included in the adjusted model: age (years), sex (female), cavities on chest X-ray exhibited univariate p-values≤0.2 (See Table 1 for details). Significant p-values are shown in bold-type font. * This group also includes 8 contacts in the group ≤18 years old who initiated TPT without recommendation of the RePORT-Brazil medical staff. **This group includes the 2 contacts (≤18 years) who initiated TPT without the recommendation of the RePORT-Brazil medical staff. Abbreviations: TB: tuberculosis, TPT: Tuberculosis preventive treatment.

Figure 2

Cascade in TBI care in contacts of TB cases according to the age group. Losses and drop-outs at each stage of the TBI cascade of care in ≤18 years old, percentages were calculated among the number of contacts initially identified in (A) <5 years old (B) 5–9 years old (C) 10–14 years old and (D) 15–18 years old. Age categories: based on the previous study. Percentages were calculated among the number of contacts initially identified. Abbreviations: TB: tuberculosis, TPT: Tuberculosis preventive treatment.

Figure 3

Cascade in TBI care in contacts of TB cases according to TPT recommendation and type of losses in the TBI cascade of care according to the age group. Sankey diagrams display the number of contacts who initiated treatment and those who completed treatment according to the category of TPT recommendation in (A) <5 years old (B) 5–9 years old (C) 10–14 years old and (D) 15–18 years old. Age categories: based on the previous study. Percentages were calculated among the number of contacts initially identified. (E) Distribution of type of losses in the TBI cascade of care (%) by age groups. The comparisons of IGRA results frequencies (%) between the types of losses were made with the chi-square test (χ²). * This group also includes 2 contacts who initiated TPT without recommendation of the RePORT-Brazil medical staff. **This group includes the 6 contacts who initiated TPT without the recommendation of the RePORT-Brazil medical staff. *** This group also includes 2 contacts who initiated TPT without recommendation of the RePORT-Brazil medical staff. Abbreviations: TB: tuberculosis, TPT: Tuberculosis preventive treatment, IGRA: Interferon-Gamma Release Assays.