Impact of vaccines on diagnosis and outcomes of infectious diseases: all-cause pneumonia in PCV13-era, impact of BCG vaccination on tuberculin skin test, and cost effectiveness of screening for latent tuberculosis infection
MetadataShow full item record
Vaccination is one of the most successful public health interventions in history, and is estimated to save lives of 3 million children globally each year. Ongoing surveillance is warranted to identify further evolution of the epidemiology of vaccine preventable diseases, and to evaluate the effects of vaccines provided. This dissertation aims to explore the impact of vaccines on disease burden, and effectiveness of diagnostic tools for two important infectious diseases; pneumonia and tuberculosis (TB). The first study employed a large electronic health record data, Massachusetts Health Disparities Repository (MHDR), to evaluate impact of 13-valent conjugated pneumococcal vaccine (PCV13) on all-cause pneumonia among children who receive primary care at Boston Medical Center (BMC). We extracted all-cause pneumonia cases diagnosed at both inpatient and outpatient settings among children younger than 8 years of age. Using interrupted time-series regression analysis monthly rates estimated for years after (2011–2013) implementation of PCV13 were compared to expected rates calculated from pre-PCV13 era (2007–2009). The year of PCV13 introduction (2010) was excluded. We also extracted cases of urinary tract infection and evaluated as control outcome. At the end of 2013 compared to prePCV13 era, among children younger than 2 years of age there was a 35.3% (95% CI 5.4–65.3) reduction in all-cause pneumonia cases. In children with comorbidity, pneumonia declined by 38.8% (95% CI 11.1 to 65.4) in those younger than 2 years of age, and 28.7% (95% CI 2.9 to 54.5) in those 2 to 8 years of age. The results of this study contribute to the growing body of evidence supporting the benefit of indirect protection with conjugated vaccines, and emphasize the importance of high sustainable vaccine coverage rates. The second and the third studies used data from the Tuberculosis Epidemiologic Studies Consortium (TBESC) Study-1, a 10-site collaboration of academic institutions and state and local TB control programs that is funded and administered by the Division of Tuberculosis Elimination at the Centers for Disease Control and Prevention (CDC). The second study evaluated the impact of Bacille Calmette Guérin (BCG) vaccination, which continues to be the only vaccine available for prevention of TB, on tuberculin skin testing (TST) results. Using the data collected TBESC Study-1 between September 2012 and September 2014, we examined the association between BCG vaccination and TST positivity. Logistic regression models were used to calculate adjusted prevalence ratios (PR) and 95% confidence intervals (CI). Prior BCG vaccination had no impact on the TST results once adjusted for history of household contacts (adjusted PR 1.0, 95% CI 0.4–1.5). The results of this study add further evidence that BCG vaccination has little impact on TST results in children, particularly in older age groups. The third study examined the cost-effectiveness of three different screening strategies compared to no screening for latent tuberculosis infection (LTBI) in a population with high proportion of foreign-born individuals who have different risk levels for developing TB. In this study, everyone was tested with using all available tools for LTBI: TST, and interferon-gamma release assays (IGRAs) during their enrollment visit. We used decision tree analysis and Markov models to compare TST only, IGRA only, TST followed by IGRA among those who were TST positive, and no screening strategies. Regardless of the assumptions and tests used, screening provided better health outcomes such as less TB cases and less TB related mortality compared to no screening. The incremental cost-effectiveness ratio (ICER) of TST followed by IGRA compared to no screening was $75,094 per QALY gained. The results of this study suggest that prioritizing certain groups for targeted LTBI screening such as foreign-born individuals, and using TST followed by IGRA can maximize the impact of public health resources allocated to eradicate TB in the U.S. The findings from these studies will contribute to the further understanding of the impact of the vaccines and the changing epidemiology of vaccine-preventable diseases providing more insight to formulate new strategies to improve overall health of children.