Project Details

Optimizing diagnostic algorithms for prompt detection of childhood tuberculosis

Meredith Brooks, PhD, MPH

Summary

BACKGROUND: One million children fall sick with tuberculosis (TB) each year. Children are a uniquely vulnerable and under-diagnosed population because of difficulty obtaining bacteriological confirmation of TB, high risk of infection due to prolonged and intense exposure by a co-habiting adult with infectious TB, and rapid progression to disease once infected. METHODS: Between 2009 and 2012 in Lima, Peru, we conducted a prospective cohort study of children and adults who were living with adults diagnosed with pulmonary TB. We used classification and regression tree analysis to examine potential predictors of incident tuberculosis disease in three age groups of children (0-4, 5-9, 10-14 years old). We calculated the relative risks for each of the top predictors. Through prospective screening of children in Lima, Peru, from 2019-2020, we assessed the predictive utility of the important predictors for TB disease that were identified in the decision trees. RESULTS: Among 4,545 children 0-14 years old, 156 (3.4%) were diagnosed with TB disease within a year of follow-up (3.4%, 2.3%, and 4.7% in children 0-4, 5-9, and 10-14 years old, respectively). The most important predictor of TB disease for all age groups was having a positive TST result, with relative risks of 6.6 (95% CI: 4.0-10.7; p-value <0.01), 6.6 (95% CI: 3.2-13.6; p-value <0.01), and 5.2 (95% CI: 3.0-9.0; p-value <0.01) in the 0-4, 5-9, and 10-14 year age groups, respectively. In children 0-4 with a positive TST result, those who did not receive isoniazid preventive therapy had a further increased risk of TB disease (RR: 12.2; 95% CI: 3.8-39.1; p-value <0.01). We prospectively screened 294 children 0-14 years old for TB infection and disease (81 [27.6%] 0-4, 105 [35.7%] 5-9, and 108 [36.7%] 10-14). In total, 8 (2.7%) children were diagnosed with TB disease (0%, 3.6%, and 0.9% in the respective age groups). The negative predictive values of a TB infection test for predicting TB disease were 96.4% (95% CI: 91.9-98.4) in the 5-9 year group and 86.1% (95% CI: 78.1-92.0) in the 10-14 year group. IMPACT: We present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up. These diagnostic algorithms can serve as an integrative decision support system to enable front-line providers to target specific tools for use in children at highest risk and increase efficiency in resource utilization. Further validation and impact analysis should be conducted prior to implementation of these tools in a clinical setting.

Publications:

Brooks MB, Lecca L, Contreras C, Calderon R, Yataco R, Galea J, Huang CC, Murray MB, Becerra MC. Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home. Open Forum Infect Dis. 2021 Nov 16;8(11):ofab487. doi: 10.1093/ofid/ofab487. PMID: 34805431; PMCID: PMC8599776.