Changing the Paradigm: Using an Integrative Approach to Improve Understanding of Tuberculosis Control in Michigan.

Background. In the U.S., tuberculosis (TB) continues to disproportionately affect the poor, racial/ethnic minorities, and urban dwellers, yet traditional methods of TB control focus primarily on biomedical predictors for treatment and less on social factors that could direct prevention. Although characteristics of the social and physical environment increase vulnerability to TB, declining concern over those with disease and diminished resources have stunted understanding of risk and reduced the ability to respond. Methods. Using TB case surveillance data combined with genotypic testing of samples from the Michigan Department of Health and Human Service and a novel socio-demographic survey, this dissertation takes an integrative approach to understanding the patterns of TB incidence and transmission. Research has involved: 1. Analyzing risk factors for TB incidence in Michigan; 2. Evaluating which risk factors both at the individual- and neighborhood levels were associated with pathogen genotypic and temporal clustering; and 3. Analyzing social characteristics of TB cases diagnosed in Metro Detroit to better understand how social vulnerability and behavioral contacts augment risk. Results. From 2004 through 2012, the incidence of TB throughout Michigan declined by an average of 8% per year. However, significant disparities in the average incidence rate were observed by race and nativity. Overall, 22% of the foreign-born cases of TB were estimated to be resulting from recent transmission of TB compared to 52% of the U.S.-born cases. For the U.S.-born, recent transmission was predicted more by individual-level and neighborhood-level socio-demographic factors than by clinical risk factors. Preliminary results from the socio-demographic survey suggest that while individuals with TB in Metro Detroit may be employed and have access to stable housing, they still experience significant financial strain. Conclusions: The results of this dissertation highlight some of the ways in which TB incidence is socially patterned. Interventions aimed at reducing the incidence of TB in the foreign-born population should focus on reducing reactivation of latent TB infections. However, reducing the incidence of TB among the U.S.-born will require strategies that can reduce transmission of TB among socially disadvantaged groups, both at the individual- and neighborhood-level.PhDEpidemiological ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120803/1/gnoppert_1.pd

The Modern Profile of Tuberculosis: Developing the TB Social Survey to understand contemporary social patterns in tuberculosis

Social disparities in tuberculosis have been documented for decades, yet to date there has not been a comprehensive study to examine the contemporary causes of these disparities. Local public health departments, and particularly public health nursing staff are charged with delivering directly observed therapy to individuals with tuberculosis disease. As a result of the frequency and duration of treatment, practitioners delivering therapy are often well‐acquainted with the lives and challenges of their constituents. Thus, through these practitioners there exists a deep repository of knowledge on the drivers of social disparities in tuberculosis disease. Partnering with local public health departments, we developed a survey instrument aimed at understanding the social profile of individuals with tuberculosis disease in metropolitan Detroit, Michigan. We discuss the development and implementation of the survey instrument as well as challenges in developing partnerships between academic researchers and local public health practitioners. This study can serve as a framework for both academic researchers and public health practitioners interested in addressing social disparities in infectious disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141046/1/phn12372_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141046/2/phn12372-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141046/3/phn12372.pd

Trends of sputum-smear positive tuberculosis in Zimbabwe: 2008–2011

Abstract Background Tuberculosis (TB) has remained one of the major public health problems in Zimbabwe with an estimated incidence rate of 552 per 100,000 persons in 2013. The aim of this study was to describe the trends in acid-fast bacilli (AFB) sputum-smear positive (SSP) TB overall and within subpopulations for the period during 2008–2011 in Zimbabwe. Results of this study will contribute towards the evaluation and implementation of targeted TB control interventions. Methods A cross-sectional study design was used to analyze 40, 110 SSP TB patient records routinely collected during 2008–2011. Incidence trends of SSP TB were described by province, sex, and age group. A Mantel–Haenszel Chi Statistic was calculated to compare each provincial SSP TB notification rate to the national SSP TB notification rate. Results SSP TB notification rates were higher in the two main urban provinces, the western provinces and Manicaland. The 25–44 year age group accounted for the largest proportion of notified SSP TB. However, the 55–64 year and 65+ age groups had SSP TB notification rates in 2011 higher than the 2008 value. Finally, the average SSP TB notification rate in males was 23 % higher than in females. Conclusion The findings of this study suggest that TB control has successfully decreased the notification rate of SSP TB in Zimbabwe during 2008–2011. However, the disproportionate distribution of SSP TB among different regions and subpopulations of the country highlights the need for more targeted interventions to accelerate the decline of TB in Zimbabwe.http://deepblue.lib.umich.edu/bitstream/2027.42/115461/1/13104_2015_Article_1568.pd

Race/Ethnic and Educational Disparities in the Association Between Pathogen Burden and a Laboratory-Based Cumulative Deficits Index

Background: Disparities in adult morbidity and mortality may be rooted in patterns of biological dysfunction in early life. We sought to examine the association between pathogen burden and a cumulative deficits index (CDI), conceptualized as a pre-clinical marker of an unhealthy biomarker profile, specifically focusing on patterns across levels of social disadvantage. Methods: Using the data from the National Health and Nutrition Examination Survey 2003–2004 wave (aged 20–49 years), we examined the association of pathogen burden, composed of seven pathogens, with the CDI. The CDI comprised 28 biomarkers corresponding to available clinical laboratory measures. Models were stratified by race/ethnicity and education level. Results: The CDI ranged from 0.04 to 0.78. Nearly half of Blacks were classified in the high burden pathogen class compared with 8% of Whites. Among both Mexican Americans and other Hispanic groups, the largest proportion of individuals were classified in the common pathogens class. Among educational classes, 19% of those with less than a high school education were classified in the high burden class compared with 7% of those with at least a college education. Blacks in the high burden pathogen class had a CDI 0.05 greater than those in the low burden class (P < 0.05). Whites in the high burden class had a CDI only 0.03 greater than those in the low burden class (P < 0.01). Discussion: Our findings suggest there are significant social disparities in the distribution of pathogen burden across race/ethnic groups, and the effects of pathogen burden may be more significant for socially disadvantaged individuals. © 2019, W. Montague Cobb-NMA Health Institute

Investigating pathogen burden in relation to a cumulative deficits index in a representative sample of US adults

Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes. © 2018 Cambridge University Press

Persistent socioeconomic and racial and ethnic disparities in pathogen burden in the United States, 1999-2014

The disproportionate burden of prevalent, persistent pathogens among disadvantaged groups may contribute to socioeconomic and racial/ethnic disparities in long-term health. We assessed if the social patterning of pathogen burden changed over 16 years in a U.S.-representative sample. Data came from 17 660 National Health and Nutrition Examination Survey participants. Pathogen burden was quantified by summing the number of positive serologies for cytomegalovirus, herpes simplex virus-1, HSV-2, human papillomavirus and Toxoplasma gondii and dividing by the number of pathogens tested, giving a percent-seropositive for each participant. We examined sex- and age-adjusted mean pathogen burdens from 1999-2014, stratified by race/ethnicity and SES (poverty-to-income ratio (PIR); educational attainment). Those with a PIR 3.5, with no change over time. Educational disparities were even greater and showed some evidence of increasing over time, with the mean pathogen burden among those with less than a high school education approximately twice that of those who completed more than high school. Non-Hispanic Black, Mexican American and other Hispanic participants had a mean pathogen burden 1.3-1.9 times non-Hispanic Whites. We demonstrate that socioeconomic and racial/ethnic disparities in pathogen burden have persisted across 16 years, with little evidence that the gap is closing

Biological expressions of early life trauma in the immune system of older adults

Background Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Methods Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Findings Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Interpretation Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course

A Geography of Risk: Structural Racism and Coronavirus Disease 2019 Mortality in the United States

Coronavirus disease 2019 (COVID-19) is disproportionately burdening racial and ethnic minority groups in the United States. Higher risks of infection and mortality among racialized minorities are a consequence of structural racism, reflected in specific policies that date back centuries and persist today. Yet our surveillance activities do not reflect what we know about how racism structures risk. When measuring racial and ethnic disparities in deaths due to COVID-19, the Centers for Disease Control and Prevention statistically accounts for the geographic distribution of deaths throughout the United States to reflect the fact that deaths are concentrated in areas with different racial and ethnic distributions from those of the larger United States. In this commentary, we argue that such an approach misses an important driver of disparities in COVID-19 mortality, namely the historical forces that determine where individuals live, work, and play, and that consequently determine their risk of dying from COVID-19. We explain why controlling for geography downplays the disproportionate burden of COVID-19 on racialized minority groups in the United States. Finally, we offer recommendations for the analysis of surveillance data to estimate racial disparities, including shifting from distribution-based to risk-based measures, to help inform a more effective and equitable public health response to the pandemic

Biological expressions of early life trauma in the immune system of older adults

Background Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Methods Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Findings Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Interpretation Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course

Immune function, cortisol, and cognitive decline & dementia in an aging latino population

Background: The etiology of dementias and cognitive decline remain largely unknown. It is widely accepted that inflammation in the central nervous system plays a critical role in the pathogenesis of dementia. However, less is known about the role of the peripheral immune system and interactions with cortisol, though evidence suggests that these, too, may play a role. Methods: Using data from 1337 participants aged 60+ years from the Sacramento Area Latino Study of Aging (observational cohort) we investigated variation in trajectories of cognitive decline by pathogen IgG and cytokine levels. Linear mixed effects models were used to examine the association between baseline Interleukin (IL)−6, C-reactive protein, tumor necrosis factor (TNF)-α, and five persistent pathogens’ IgG response and trajectories of cognition over 10 years, and to examine interactions between immune biomarkers and cortisol. Stratified cumulative incidence functions were used to assess the relation between biomarkers and incident dementia. Inverse probability weights accounted for loss-to-follow-up and confounding. Results: IL-6, TNF-α, and CMV IgG were statistically significantly associated with a higher log of Modified Mini-Mental State Examination errors (IL-6, β = 0.0935 (95%CI: 0.055, 0.13), TNF-alpha β = 0.0944 (95%CI: 0.032, 0.157), and CMV, β = 0.0409 (95%CI: 0.013, 0.069)). Furthermore, cortisol interacted with HSV-1 and IL-6, and CRP for both cross-sectional cognitive function and rate of decline. No statistically significant relationship was detected between biomarkers and incidence of dementia. Conclusions: These findings support the theory that the peripheral immune system may play a role in cognitive decline but not incident dementia. Furthermore, they identify specific markers amenable for intervention for slowing decline