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Issue 4, February 2, 2021

CDC Science Clips: Volume 13, Issue 4, February 2, 2021

This week, Science Clips is pleased to feature Community Health and Economic Prosperity: Engaging Businesses as Stewards and Stakeholders—A Report of the Surgeon General.


The health of Americans is not as good as it could be and is worse than the health of people in other wealthy nations. On average, Americans have more illness, shorter lives and pay more for healthcare. This is called the U.S. health disadvantage and it has implications for people, families, communities, businesses and the economy. The report seeks to increase awareness among businesses of the U.S. health disadvantage and to motivate businesses to engage with communities – and invest in them – to strengthen the conditions that shape the health, wealth and well-being of people. The report argues that doing so is good for business (and good for society).


Health, wealth and well-being are shaped by the vital conditions found in communities, including humane housing, meaningful work, quality education, and a thriving natural world. We all need the vital conditions in order to thrive. Some or all of the vital conditions are missing for too many Americans. This contributes to the U.S. health disadvantage and to disparities in health and economic outcomes.


The full report can be found here: https://www.hhs.gov/sites/default/files/chep-sgr-full-report.pdfpdf iconexternal icon


A concise "Business Digest" version can be found here: https://www.hhs.gov/sites/default/files/chep-sgr-business-leaders-digest.pdfpdf iconexternal icon

Additional materials, including summary documents, fact sheets and videos are available here: https://www.hhs.gov/surgeongeneral/reports-and-publications/community-health-economic-prosperity/index.htmlexternal icon

For a concise overview of the Office of the Surgeon General's Community Health and Economic Prosperity initiative, read: Community Health and Economic Prosperity: An Initiative of the Office of the Surgeon General - Ursula E. Bauer, 2019 (sagepub.com)external icon

The accompanying reading list is intended to build knowledge about business, community and health, how they influence each other and can collaborate together to improve community health and contribute to a more sustainable and equitable prosperity.

Guest Editors from Centers for Disease Control and Prevention, John Iskander and Ursula Bauer.
  1. Key Scientific Articles in Featured Topic Areas: Community Health and Economic Prosperity: Engaging Businesses as Stewards and Stakeholders-A Report of the Surgeon General
    • Community Health and Economic Prosperity: Business
      1. Stakeholders, reciprocity, and firm performanceexternal icon
        Bosse DA, Phillips R, Harrison JS.
        Strategic Management Journal. 2009 ;30(4):447-456.
        Abstract The assumption that economic actors behave in a boundedly self-interested manner promises fruitful new insights for strategic management. A growing literature spanning multiple disciplines indicates most actors' selfish utility maximizing behaviors are bounded by norms of fairness. Rather than being purely self-interested, people behave reciprocally by rewarding others whose actions they deem fair and willingly incurring costs to punish those they deem unfair. Economists show that employers who are perceived as distributionally fair by their employees generate comparatively more value due to the positively reciprocal behavior of those employees. The organizational justice literature distinguishes two additional types of fairness assessed by employees. Drawing from both these bodies of work, we employ stakeholder theory to propose how perceptions of fairness result in reciprocity (1) extending to all stakeholders of the firm and (2) affecting firm performance.


      2. The fading American dream: Trends in absolute income mobility since 1940external icon
        Chetty R, Grusky D, Hell M, Hendren N, Manduca R, Narang J.
        Science. 2017 Apr 28;356(6336):398-406.
        We estimated rates of "absolute income mobility"-the fraction of children who earn more than their parents-by combining data from U.S. Census and Current Population Survey cross sections with panel data from de-identified tax records. We found that rates of absolute mobility have fallen from approximately 90% for children born in 1940 to 50% for children born in the 1980s. Increasing Gross Domestic Product (GDP) growth rates alone cannot restore absolute mobility to the rates experienced by children born in the 1940s. However, distributing current GDP growth more equally across income groups as in the 1940 birth cohort would reverse more than 70% of the decline in mobility. These results imply that reviving the "American dream" of high rates of absolute mobility would require economic growth that is shared more broadly across the income distribution.

      3. Stakeholder relations and the persistence of corporate financial performanceexternal icon
        Choi J, Wang H.
        Strategic Management Journal. 2009 ;30(8):895-907.
        Abstract We examine the effect of a firm's relations with its nonfinancial stakeholders, including its employees, suppliers, customers, and communities, on the persistence of both superior and inferior financial performance. In particular, integrating and extending the resource-based view of the firm and stakeholder management literatures, we develop the arguments that good stakeholder relations not only enable a firm with superior financial performance to sustain its competitive advantage for a longer period of time, but more importantly, also help poorly performing firms to recover from disadvantageous positions more quickly. The arguments are supported by the analysis of a series of first-order autoregressive models. Our findings further suggest that the positive effect of good stakeholder relations on the persistence of superior performance is not as strong as that of some other firm resources, such as technological knowledge, but it is the only factor examined that promises to help a firm recover from inferior performance. Therefore, the role of positive stakeholder relations in helping poorly performing firms recover is found to be more critical than its role in helping superior firms sustain their performance advantage.

      4. Most valuable stakeholders: The impact of employee orientation on corporate financial performanceexternal icon
        de Bussy NM, Suprawan L.
        Public Relations Review. 2012 2012/06/01/;38(2):280-287.
        In sports, the most valuable player award goes to the individual or group of players who have contributed most to the success of the team. This paper presents the results of two Australian empirical studies conducted six years apart, which suggest that, in business, employees are the most valuable stakeholder group. In particular, we find evidence to support the proposition that employee orientation contributes more to corporate financial performance (CFP) than orientation towards any other individual primary stakeholder group, including customers, communities, suppliers and shareholders. These findings have practical implications for corporate level strategy and the prioritization of budgetary resources by communication managers. From a theoretical perspective, the paper contributes to the debate on the best way to conceptualize employee orientation.

      5. The impact of stakeholder orientation on innovation: Evidence from a natural experimentexternal icon
        Flammer C, Kacperczyk A.
        Management Science. 2016 ;62(7):1982-2001.
        In this study, we assess the causal impact of stakeholder orientation on innovation. To obtain exogenous variation in stakeholder orientation, we exploit the enactment of state-level constituency statutes, which allow directors to consider stakeholders’ interests when making business decisions. Using a difference-in-differences methodology, we find that the enactment of constituency statutes leads to a significant increase in the number of patents and citations per patent. We further argue and provide evidence suggesting that stakeholder orientation sparks innovation by encouraging experimentation and enhancing employees’ innovative productivity. Finally, we find that the positive effect of stakeholder orientation on innovation is larger in consumer-focused and less eco-friendly industries. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2015.2229. This paper was accepted by Lee Fleming, entrepreneurship and innovation.

      6. Institutional changes and rising wage inequality: Is there a linkage?external icon
        Fortin NM, Lemieux T.
        Journal of Economic Perspectives. 1997 ;11(2):75-96.
        In this paper, the authors analyze the role of three institutional changes--the decline in the real value of the minimum wage, deunionization, and economic deregulation--on the rise in wage inequality in the United States during the 1980s. They argue that about a third of the increase in male and female wage inequality can be traced to these institutional changes. Deunionization had a significant effect on the rise in inequality for men, while the minimum wage is what matters most for women. The authors find the direct impact of economic deregulation to be comparatively small.

      7. The corporation's social role is usually presented as a cultural phenomenon in which the corporation learns socially acceptable behaviors through voluntary social responsibility, government regulations/public policies, and/or acceptance of ethics principles. This article presents an alternative view of corporation community relations as a natural phenomenon based on complexity-chaos theory and a biological-physical conception of corporate values. Corporation and community are depicted as interacting nonlinear adaptive systems having unpredictable futures, the corporate social role is depicted as largely indeterminate, and competing values are depicted as key factors driving change in corporation community linkages. Normative duties of corporate and community leaders are described.

      8. Strategic management: A stakeholder approach
        Freeman RE.
        Cambridge, UK: Cambridge University Press. 2010.

      9. Income inequality in the United States, 1913–1998external icon
        Piketty T, Saez E.
        The Quarterly Journal of Economics. 2003 ;118(1):1-41.
        This paper presents new homogeneous series on top shares of income and wages from 1913 to 1998 in the United States using individual tax returns data. Top income and wages shares display a U-shaped pattern over the century. Our series suggest that the large shocks that capital owners experienced during the Great Depression and World War II have had a permanent effect on top capital incomes. We argue that steep progressive income and estate taxation may have prevented large fortunes from fully recovering from these shocks. Top wage shares were flat before World War II, dropped precipitously during the war, and did not start to recover before the late 1960s but are now higher than before World War II. As a result, the working rich have replaced the rentiers at the top of the income distribution.

      10. Creating shared valueexternal icon
        Porter ME, Kramer MR.
        Harvard Business Review. 2011 Jan-Feb;89:62-77.

    • Community Health and Economic Prosperity: Community
      1. The Child Opportunity Index 2.0 responds to the need for nationally comprehensive data on children’s neighborhood opportunity. The COI 2.0 is the first measure that allows us to examine and compare the neighborhood conditions that children experience today across the entire U.S. COI 2.0 data are longitudinal, which allows us to monitor how neighborhood conditions are changing over time. Additionally, we revised the indicators and methodology, making the index both more robust and more closely tied to important child outcomes. With its coverage of all neighborhoods in the U.S. and inclusion of a wide range of factors associated with child wellbeing, the COI 2.0 is the most comprehensive and detailed index of children’s neighborhood opportunity available.

      2. From funding activities to investing in results: How do we get from here to there?external icon
        Bugg-Levine A.
        In Federal Reserve Bank & San Francisco and Nonprofit Finance Fund (Eds.), What matters: Investing in results to build strong, vibrant communities (pp. 472–479). 2017 ;San Francisco, CA: Federal Reserve Bank of San Francisco and Nonprofit Finance Fund.

      3. The Opportunity Atlas: Mapping the childhood roots of social mobilityexternal icon
        Chetty R, Friedman JN, Hendren N, Jones MR, Porter SR. 2018 .
        We construct a publicly available atlas of children's outcomes in adulthood by Census tract using anonymized longitudinal data covering nearly the entire U.S. population. For each tract, we estimate children's earnings distributions, incarceration rates, and other outcomes in adulthood by parental income, race, and gender. These estimates allow us to trace the roots of outcomes such as poverty and incarceration back to the neighborhoods in which children grew up. We find that children's outcomes vary sharply across nearby tracts: for children of parents at the 25th percentile of the income distribution, the standard deviation of mean household income at age 35 is $4,200 across tracts within counties. We illustrate how these tract-level data can provide insight into how neighborhoods shape the development of human capital and support local economic policy using two applications. First, we show that the estimates permit precise targeting of policies to improve economic opportunity by uncovering specific neighborhoods where certain subgroups of children grow up to have poor outcomes. Neighborhoods matter at a very granular level: conditional on characteristics such as poverty rates in a child's own Census tract, characteristics of tracts that are one mile away have little predictive power for a child's outcomes. Our historical estimates are informative predictors of outcomes even for children growing up today because neighborhood conditions are relatively stable over time. Second, we show that the observational estimates are highly predictive of neighborhoods' causal effects, based on a comparison to data from the Moving to Opportunity experiment and a quasi-experimental research design analyzing movers' outcomes. We then identify high-opportunity neighborhoods that are affordable to low-income families, providing an input into the design of affordable housing policies. Our measures of children's long-term outcomes are only weakly correlated with traditional proxies for local economic success such as rates of job growth, showing that the conditions that create greater upward mobility are not necessarily the same as those that lead to productive labor markets.

      4. The fading American dream: Trends in absolute income mobility since 1940external icon
        Chetty R, Grusky D, Hell M, Hendren N, Manduca R, Narang J. 2016.
        We estimate rates of “absolute income mobility” – the fraction of children who earn more than their parents – by combining historical data from Census and CPS cross-sections with panel data for recent birth cohorts from de-identified tax records. Our approach overcomes the key data limitation that has hampered research on trends in intergenerational mobility: the lack of large panel datasets linking parents and children. We find that rates of absolute mobility have fallen from approximately 90%for children born in 1940 to 50% for children born in the 1980s. The result that absolute mobility has fallen sharply over the past half century is robust to the choice of price deflator, the definition of income, and accounting for taxes and transfers. In counterfactual simulations, we find that increasing GDP growth rates alone cannot restore absolute mobility to the rates experienced by children born in the 1940s. In contrast, changing the distribution of growth across income groups to the more equal distribution experienced by the 1940 birth cohort would reverse more than 70% of the decline in mobility. These results imply that reviving the “American Dream” of high rates of absolute mobility would require economic growth that is spread more broadly across the income distribution.

      5. Safe, vibrant neighborhoods are vital to health. The community development "industry"-a network of nonprofit service providers, real estate developers, financial institutions, foundations, and government-draws on public subsidies and other financing to transform impoverished neighborhoods into better-functioning communities. Although such activity positively affects the "upstream" causes of poor health, the community development industry rarely collaborates with the health sector or even considers health effects in its work. Examples of initiatives-such as the creation of affordable housing that avoids nursing home placement-suggest a strong potential for cross-sector collaborations to reduce health disparities and slow the growth of health care spending, while at the same time improving economic and social well-being in America's most disadvantaged communities. We propose a four-point plan to help ensure that these collaborations achieve positive outcomes and sustainable progress for residents and investors alike.

      6. What makes a place healthy? Neighborhood influences on racial/ethnic disparities in health over the life courseexternal icon
        Morenoff JD, Lynch JW.
        In: N. B. Anderson, R. A. Bulatao, & B. Cohen (Eds.), Critical perspectives on racial and ethnic differences in health in late life (pp. 406–449). 2004; Washington, DC: The National Academies Press.
        Our main purpose in this chapter is to suggest a conceptual framework for better understanding how characteristics of neighborhoods can affect racial/ethnic differences in health, with a special emphasis on health in aging populations. At the outset we should recognize that the specific studies in this field are sparse. However, we will try to draw from the more diverse sociological and epidemiological literature on neighborhoods and health to illustrate the potential for certain characteristics of neighborhoods to affect racial/ethnic health differences in aging.

      7. Measuring social valueexternal icon
        Mulgan G.
        Stanford Social Innovation Review. 2010 Summer.
        Funders, nonprofit executives, and policymakers are very enthusiastic about measuring social value. Alas, they cannot agree on what it is, let alone how to assess it. Their main obstacle is assuming that social value is objective, fixed, and stable. When people approach social value as subjective, malleable, and variable, they create better metrics to capture it.

      8. Measuring the impact of businesses on people’s well-being and sustainability: Taking stock of existing frameworks and initiativesexternal icon
        Shinwell M, Shamir E.
        OECD Statistics Working Papers, No. 2018/08. 2018; Paris: OECD Publishing.
        Businesses have a significant impact on people’s economic and social conditions, as well as on environmental outcomes. This paper presents an overview of the various kinds of initiatives aimed at measuring or reporting on business’ impact, or certain aspects of it. It shows that despite the proliferation of information and frameworks to measure these impacts, there is currently no common understanding and practice on how to assess the performance of businesses in different social and environmental areas. Building on the OECD’s work on measuring well-being at the national level, the paper aims at better understanding how businesses can impact people’s well-being and sustainability. It contributes to, and complements, other initiatives undertaken by the OECD on responsible business conduct and inclusive growth. This analysis is a first attempt at extending to businesses the approach used by the Organisation to assess and benchmark the well-being performance of countries and sub-national regions, in view of creating a common language and improving the quality, comparability, and coherence of information on the impact of businesses on societal progress and people’s life.

    • Community Health and Economic Prosperity: Health
      1. Variation in health outcomes: The role of spending on social services, public health, and health care, 2000-09external icon
        Bradley EH, Canavan M, Rogan E, Talbert-Slagle K, Ndumele C, Taylor L, Curry LA.
        Health Aff (Millwood). 2016 May 1;35(5):760-8.
        Although spending rates on health care and social services vary substantially across the states, little is known about the possible association between variation in state-level health outcomes and the allocation of state spending between health care and social services. To estimate that association, we used state-level repeated measures multivariable modeling for the period 2000-09, with region and time fixed effects adjusted for total spending and state demographic and economic characteristics and with one- and two-year lags. We found that states with a higher ratio of social to health spending (calculated as the sum of social service spending and public health spending divided by the sum of Medicare spending and Medicaid spending) had significantly better subsequent health outcomes for the following seven measures: adult obesity; asthma; mentally unhealthy days; days with activity limitations; and mortality rates for lung cancer, acute myocardial infarction, and type 2 diabetes. Our study suggests that broadening the debate beyond what should be spent on health care to include what should be invested in health-not only in health care but also in social services and public health-is warranted.

      2. The dynamic relationships between economic status and health measures among working-age adults in the United Statesexternal icon
        Meraya AM, Dwibedi N, Tan X, Innes K, Mitra S, Sambamoorthi U.
        Health Econ. 2018 Aug;27(8):1160-1174.
        We examine the dynamic relationships between economic status and health measures using data from 8 waves of the Panel Study of Income Dynamics from 1999 to 2013. Health measures are self-rated health (SRH) and functional limitations; economic status measures are labor income (earnings), family income, and net wealth. We use 3 different types of models: (a) ordinary least squares regression, (b) first-difference, and (c) system-generalized method of moment (GMM). Using ordinary least squares regression and first difference models, we find that higher levels of economic status are associated with better SRH and functional status among both men and women, although declines in income and wealth are associated with a decline in health for men only. Using system-GMM estimators, we find evidence of a causal link from labor income to SRH and functional status for both genders. Among men only, system-GMM results indicate that there is a causal link from net wealth to SRH and functional status. Results overall highlight the need for integrated economic and health policies, and for policies that mitigate the potential adverse health effects of short-term changes in economic status.

      3. America's declining well-being, health, and life expectancy: Not just a white problemexternal icon
        Muennig PA, Reynolds M, Fink DS, Zafari Z, Geronimus AT.
        Am J Public Health. 2018 Dec;108(12):1626-1631.
        Although recent declines in life expectancy among non-Hispanic Whites, coined "deaths of despair," grabbed the headlines of most major media outlets, this is neither a recent problem nor is it confined to Whites. The decline in America's health has been described in the public health literature for decades and has long been hypothesized to be attributable to an array of worsening psychosocial problems that are not specific to Whites. To test some of the dominant hypotheses, we show how various measures of despair have been increasing in the United States since 1980 and how these trends relate to changes in health and longevity. We show that mortality increases among Whites caused by the opioid epidemic come on the heels of the crack and HIV syndemic among Blacks. Both occurred on top of already higher mortality rates among all Americans relative to people in other nations, and both occurred among declines in measures of well-being. We believe that the attention given to Whites is distracting researchers and policymakers from much more serious, longer-term structural problems that affect all Americans.

      4. Health care spending in the United States and other high-income countriesexternal icon
        Papanicolas I, Woskie LR, Jha AK.
        Jama. 2018 Mar 13;319(10):1024-1039.
        IMPORTANCE: Health care spending in the United States is a major concern and is higher than in other high-income countries, but there is little evidence that efforts to reform US health care delivery have had a meaningful influence on controlling health care spending and costs. OBJECTIVE: To compare potential drivers of spending, such as structural capacity and utilization, in the United States with those of 10 of the highest-income countries (United Kingdom, Canada, Germany, Australia, Japan, Sweden, France, the Netherlands, Switzerland, and Denmark) to gain insight into what the United States can learn from these nations. EVIDENCE: Analysis of data primarily from 2013-2016 from key international organizations including the Organisation for Economic Co-operation and Development (OECD), comparing underlying differences in structural features, types of health care and social spending, and performance between the United States and 10 high-income countries. When data were not available for a given country or more accurate country-level estimates were available from sources other than the OECD, country-specific data sources were used. FINDINGS: In 2016, the US spent 17.8% of its gross domestic product on health care, and spending in the other countries ranged from 9.6% (Australia) to 12.4% (Switzerland). The proportion of the population with health insurance was 90% in the US, lower than the other countries (range, 99%-100%), and the US had the highest proportion of private health insurance (55.3%). For some determinants of health such as smoking, the US ranked second lowest of the countries (11.4% of the US population ≥15 years smokes daily; mean of all 11 countries, 16.6%), but the US had the highest percentage of adults who were overweight or obese at 70.1% (range for other countries, 23.8%-63.4%; mean of all 11 countries, 55.6%). Life expectancy in the US was the lowest of the 11 countries at 78.8 years (range for other countries, 80.7-83.9 years; mean of all 11 countries, 81.7 years), and infant mortality was the highest (5.8 deaths per 1000 live births in the US; 3.6 per 1000 for all 11 countries). The US did not differ substantially from the other countries in physician workforce (2.6 physicians per 1000; 43% primary care physicians), or nursing workforce (11.1 nurses per 1000). The US had comparable numbers of hospital beds (2.8 per 1000) but higher utilization of magnetic resonance imaging (118 per 1000) and computed tomography (245 per 1000) vs other countries. The US had similar rates of utilization (US discharges per 100 000 were 192 for acute myocardial infarction, 365 for pneumonia, 230 for chronic obstructive pulmonary disease; procedures per 100 000 were 204 for hip replacement, 226 for knee replacement, and 79 for coronary artery bypass graft surgery). Administrative costs of care (activities relating to planning, regulating, and managing health systems and services) accounted for 8% in the US vs a range of 1% to 3% in the other countries. For pharmaceutical costs, spending per capita was $1443 in the US vs a range of $466 to $939 in other countries. Salaries of physicians and nurses were higher in the US; for example, generalist physicians salaries were $218 173 in the US compared with a range of $86 607 to $154 126 in the other countries. CONCLUSIONS AND RELEVANCE: The United States spent approximately twice as much as other high-income countries on medical care, yet utilization rates in the United States were largely similar to those in other nations. Prices of labor and goods, including pharmaceuticals, and administrative costs appeared to be the major drivers of the difference in overall cost between the United States and other high-income countries. As patients, physicians, policy makers, and legislators actively debate the future of the US health system, data such as these are needed to inform policy decisions.

      5. Racism as a determinant of health: A systematic review and meta-analysisexternal icon
        Paradies Y, Ben J, Denson N, Elias A, Priest N, Pieterse A, Gupta A, Kelaher M, Gee G.
        PLoS One. 2015 ;10(9):e0138511.
        Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants. Protocol PROSPERO registration number: CRD42013005464.

      6. A century of change: the U.S. labor force, 1950–2050external icon
        Toossi M.
        Monthly Labor Review. 2002 May:15–28.
        This article profiles and projects U.S. labor force trends for a period of 100 years, from 1950 to 2050, on a decennial basis. Changes in both growth rates of the population and labor force participation rates have created a steadily growing labor force that, compared with 1950, is today older, more diversified, and increasingly made up of women. The same forces that have influenced the size and composition of the U.S. labor force over the past 50 years are expected to shape the future of the workforce as well.

      7. Racism and health: Evidence and needed researchexternal icon
        Williams DR, Lawrence JA, Davis BA.
        Annu Rev Public Health. 2019 Apr 1;40:105-125.
        In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and the empirical evidence that indicates that socioeconomic factors alone do not account for racial/ethnic inequities in health. Racism is considered a fundamental cause of adverse health outcomes for racial/ethnic minorities and racial/ethnic inequities in health. This article provides an overview of the evidence linking the primary domains of racism-structural racism, cultural racism, and individual-level discrimination-to mental and physical health outcomes. For each mechanism, we describe key findings and identify priorities for future research. We also discuss evidence for interventions to reduce racism and describe research needed to advance knowledge in this area.

      8. Health disparities by racial or ethnic group or by income or education are only partly explained by disparities in medical care. Inadequate education and living conditions-ranging from low income to the unhealthy characteristics of neighborhoods and communities-can harm health through complex pathways. Meaningful progress in narrowing health disparities is unlikely without addressing these root causes. Policies on education, child care, jobs, community and economic revitalization, housing, transportation, and land use bear on these root causes and have implications for health and medical spending. A shortsighted political focus on reducing spending in these areas could actually increase medical costs by magnifying disease burden and widening health disparities.

      9. Life expectancy and mortality rates in the United States, 1959-2017external icon
        Woolf SH, Schoomaker H.
        Jama. 2019 Nov 26;322(20):1996-2016.
        IMPORTANCE: US life expectancy has not kept pace with that of other wealthy countries and is now decreasing. OBJECTIVE: To examine vital statistics and review the history of changes in US life expectancy and increasing mortality rates; and to identify potential contributing factors, drawing insights from current literature and an analysis of state-level trends. EVIDENCE: Life expectancy data for 1959-2016 and cause-specific mortality rates for 1999-2017 were obtained from the US Mortality Database and CDC WONDER, respectively. The analysis focused on midlife deaths (ages 25-64 years), stratified by sex, race/ethnicity, socioeconomic status, and geography (including the 50 states). Published research from January 1990 through August 2019 that examined relevant mortality trends and potential contributory factors was examined. FINDINGS: Between 1959 and 2016, US life expectancy increased from 69.9 years to 78.9 years but declined for 3 consecutive years after 2014. The recent decrease in US life expectancy culminated a period of increasing cause-specific mortality among adults aged 25 to 64 years that began in the 1990s, ultimately producing an increase in all-cause mortality that began in 2010. During 2010-2017, midlife all-cause mortality rates increased from 328.5 deaths/100 000 to 348.2 deaths/100 000. By 2014, midlife mortality was increasing across all racial groups, caused by drug overdoses, alcohol abuse, suicides, and a diverse list of organ system diseases. The largest relative increases in midlife mortality rates occurred in New England (New Hampshire, 23.3%; Maine, 20.7%; Vermont, 19.9%) and the Ohio Valley (West Virginia, 23.0%; Ohio, 21.6%; Indiana, 14.8%; Kentucky, 14.7%). The increase in midlife mortality during 2010-2017 was associated with an estimated 33 307 excess US deaths, 32.8% of which occurred in 4 Ohio Valley states. CONCLUSIONS AND RELEVANCE: US life expectancy increased for most of the past 60 years, but the rate of increase slowed over time and life expectancy decreased after 2014. A major contributor has been an increase in mortality from specific causes (eg, drug overdoses, suicides, organ system diseases) among young and middle-aged adults of all racial groups, with an onset as early as the 1990s and with the largest relative increases occurring in the Ohio Valley and New England. The implications for public health and the economy are substantial, making it vital to understand the underlying causes.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Manhattan Vision Screening and Follow-up Study in Vulnerable Populations (NYC-SIGHT): Design and methodologyexternal icon
        Hark LA, Kresch YS, De Moraes CG, Horowitz JD, Park L, Auran JD, Gorroochurn P, Stempel S, Maruri SC, Stidham EM, Banks AZ, Saaddine JB, Lambert BC, Pizzi LT, Sapru S, Price S, Williams OA, Cioffi GA, Liebmann JM.
        J Glaucoma. 2021 Jan 22.
        PRCIS: The Manhattan Vision Screening and Follow-up Study in Vulnerable Populations is a 5-year prospective, cluster-randomized study to improve detection and management of glaucoma and other eye diseases in vulnerable populations living in affordable housing developments. PURPOSE: To describe the study design and methodology of the Manhattan Vision Screening and Follow-up Study in Vulnerable Populations, which aims to investigate whether community-based vision screenings can improve detection and management of glaucoma, vision impairment, cataract, and other eye diseases among vulnerable populations living in affordable housing developments in upper Manhattan. METHODS: This 5-year prospective, cluster-randomized, controlled trial consists of vision screening and referral for follow-up eye care among eligible residents aged 40 and older. Visual acuity, intraocular pressure (IOP), and fundus photography are measured. Participants with visual worse than 20/40, or IOP 23-29 mmHg, or unreadable fundus images fail the screening and are scheduled with the on-site optometrist. If IOP is ≥30 mmHg, participants are assigned as "fast-track" and referred to ophthalmology. Participants living in seven developments randomized to the Enhanced Intervention Group who fail the screening and need vision correction receive complimentary eyeglasses. Those referred to ophthalmology receive enhanced support with patient navigators to assist with follow-up eye care. Participants living in three developments randomized to the Usual Care Group who fail the screening and need vision correction are given an eyeglasses prescription only and a list of optical shops. No enhanced support is given to the Usual Care Group. All participants referred to ophthalmology are assisted in making their initial eye exam appointment. CONCLUSION: This study targets vulnerable populations where they live to ensure improved access to and utilization of eye-care services in those who are least likely to seek eye care.

      2. Epidemiological studies of low-dose ionizing radiation and cancer: Summary bias assessment and meta-analysisexternal icon
        Hauptmann M, Daniels RD, Cardis E, Cullings HM, Kendall G, Laurier D, Linet MS, Little MP, Lubin JH, Preston DL, Richardson DB, Stram DO, Thierry-Chef I, Schubauer-Berigan MK, Gilbert ES, Berrington de Gonzalez A.
        J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):188-200.
        BACKGROUND: Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. METHODS: Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. RESULTS: Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P  = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P  = .001), also after exclusion of 5 positive studies with potential positive bias (P  = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. CONCLUSIONS: Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

      3. Impact of COVID-19 on cervical cancer screening rates among women aged 21-65 years in a large integrated health care system - southern California, January 1-September 30, 2019, and January 1-September 30, 2020external icon
        Miller MJ, Xu L, Qin J, Hahn EE, Ngo-Metzger Q, Mittman B, Tewari D, Hodeib M, Wride P, Saraiya M, Chao CR.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):109-113.
        On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,(†) including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.(§) Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.(¶) Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.

      4. Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implicationsexternal icon
        Piani F, Melena I, Tommerdahl KL, Nokoff N, Nelson RG, Pavkov ME, van Raalte DH, Cherney DZ, Johnson RJ, Nadeau KJ, Bjornstad P.
        J Diabetes Complications. 2020 Dec 31:107841.
        Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.

      5. Alabama Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (AL-SIGHT): Study design and methodologyexternal icon
        Rhodes LA, Register S, Asif I, McGwin G, Saaddine J, Nghiem VT, Owsley C, Girkin CA.
        J Glaucoma. 2021 Jan 22.
        PRCIS: This paper presents the methods and protocol of a community-based telemedicine program to identify glaucoma and other eye diseases. PURPOSE: To describe the study rationale and design of the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine (AL-SIGHT) project. METHODS: The study will implement and evaluate a telemedicine-based detection strategy for glaucoma, diabetic retinopathy, and other eye diseases in at-risk patients seen at federally qualified health centers located in rural Alabama. The study will compare the effectiveness of the remote use of structural and functional ocular imaging devices to an in-person exam. Study participants will receive a remote ocular assessment consisting of visual acuity, intraocular pressure, visual field testing, and imaging of the retina and optic nerve with spectral domain optical coherence tomography, and the data will be reviewed by an ophthalmologist and optometrist. It will also compare the effectiveness of financial incentives along with a validated patient education program versus a validated patient education program alone in improving follow-up adherence. Finally, cost and cost-effectiveness analyses will be performed on the telemedicine program compared to standard in-person care using effectiveness measured in numbers of detected eye disease cases. CONCLUSIONS: The study aims to develop a model eye health system using telemedicine to prevent vision loss and address eye health among underserved and at-risk populations.

      6. The first genome-wide association study for type 2 diabetes in youth: The Progress in Diabetes Genetics in Youth (ProDiGY) Consortiumexternal icon
        Srinivasan S, Chen L, Todd J, Divers J, Gidding S, Chernausek S, Gubitosi-Klug RA, Kelsey MM, Shah R, Black MH, Wagenknecht LE, Manning A, Flannick J, Imperatore G, Mercader JM, Dabelea D, Florez JC.
        Diabetes. 2021 Jan 21.
        The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multi-ethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth type 2 diabetes cases (mean age 15.1±2.9 y) and 6,061 diabetes-free adult controls (mean age 54.2±12.4 y). After stratifying by principal component-clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified 7 genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P=3.2×10(-8), odds ratio [OR]=1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P=8.0×10(-20), OR 1.58), rs72982988 near MC4R (P=4.4×10(-14), OR=1.53), rs200893788 in CDC123 (P=1.1×10(-12), OR= 1.32), rs2237892 in KCNQ1 (P=4.8×10(-11), OR=1.59), rs937589119 in IGF2BP2 (P=3.1×10(-9), OR=1.34) and rs113748381 in SLC16A11 (P=4.1×10(-8), OR=1.04). Secondary analysis with 856 diabetes-free youth controls uncovered an additional locus in CPEB2 (P=3.2×10(-8), OR=2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome wide association study (GWAS) of youth-onset type 2 diabetes.

    • Communicable Diseases
      1. SARS-CoV-2 transmission associated with high school wrestling tournaments - Florida, December 2020-January 2021external icon
        Atherstone C, Siegel M, Schmitt-Matzen E, Sjoblom S, Jackson J, Blackmore C, Neatherlin J.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):141-143.
        On December 7, 2020, local public health officials in Florida county A were notified of a person with an antigen-positive SARS-CoV-2 test* result who had attended two high school wrestling tournaments held in the county on December 4 and 5. The tournaments included 10 participating high schools from three counties. The host school (school A in county A) participated in the tournaments on both days; five high school teams from two counties participated the first day only; four additional high school teams from the three counties participated the second day. A total of 130 wrestlers, coaches, and referees attended the tournaments (Table). During December 8-9, 13 wrestlers from school A received positive SARS-CoV-2 test results (Figure), including nine who were symptomatic, two who were asymptomatic, and two for whom symptom status at time of specimen collection was unknown. Local public health officials in the three counties initiated an investigation(†) and tested specimens from an additional 40 attendees from nine of the 10 participating schools. A total of 54 (41.5%) of the 130 tournament attendees received testing, and 38 cases of SARS-CoV-2 infection were identified; the minimum attack rate was 30.2% (38 of 126(§)), and 70.4% (38 of 54) of tests had a positive result. Among contacts of the 38 COVID-19 patients, 446 were determined by investigators to meet the CDC definition of a close contact,(¶) including 62 who were household contacts and 384 who were in-school contacts (classmates, teachers, noncompeting wrestling team members, and other school athletic team members). Among these 446 contacts, five had received a diagnosis of COVID-19 during June-November and were excluded from attack rate calculations. Among 95 (21.3%) contacts who received SARS-CoV-2 testing, 41 (43.2%) received a positive test result (minimum attack rate = 9.3% [41 of 441]); 21 (51.2%) persons with positive test results were symptomatic, eight (19.5%) were asymptomatic, and symptom status for 12 (29.3%) was unknown at the time of specimen collection. Among contacts, attack rates were highest among household members (30.0%) and wrestling team members who did not attend the tournament (20.3%), as were the percentages of positive test results (60.0% among household members and 54.2% among team members). Among all contacts, the odds of receiving a positive test result were highest among household contacts (odds ratio = 2.7; 95% confidence interval = 1.2-6.0). Local health authorities reported the death of one adult contact aged >50 years.

      2. Evidence of SARS-CoV-2 replication and tropism in the lungs, airways and vascular endothelium of patients with fatal COVID-19: An autopsy case-seriesexternal icon
        Bhatnagar J, Gary J, Reagan-Steiner S, Estetter LB, Tong S, Tao Y, Denison AM, Lee E, DeLeon-Carnes M, Li Y, Uehara A, Paden CR, Leitgeb B, Uyeki TM, Martines RB, Ritter JM, Paddock CD, Shieh WJ, Zaki SR.
        J Infect Dis. 2021 Jan 27.
        BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.

      3. Implementation of tuberculosis preventive treatment among people living with HIV, south Sudanexternal icon
        Boyd AT, Lodiongo DK, Benson JM, Aragaw S, Pasquale MS, Ayalneh H, Olemukan R, Avaku I, Baabe N, Achut V, Chun H, Bunga S.
        Bull World Health Org. 2021 ;99(1):34-40.
        Objective: To describe an intervention to scale up tuberculosis preventive treatment for people living with human immunodeficiency virus (HIV) in South Sudan, 2017-2020.

      4. COVID-19-related hospitalization rates and severe outcomes among veterans from 5 Veterans Affairs Medical Centers: Hospital-based surveillance studyexternal icon
        Cardemil CV, Dahl R, Prill MM, Cates J, Brown S, Perea A, Marconi V, Bell L, Rodriguez-Barradas MC, Rivera-Dominguez G, Beenhouwer D, Poteshkina A, Holodniy M, Lucero-Obusan C, Balachandran N, Hall AJ, Kim L, Langley G.
        JMIR Public Health Surveill. 2021 Jan 22;7(1):e24502.
        BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the United States. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, are needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among US veterans by using a multisite surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers located in Atlanta, Bronx, Houston, Palo Alto, and Los Angeles, collectively serving more than 396,000 patients annually. From February 27 to July 17, 2020, we actively identified inpatient cases with COVID-19 by screening admitted patients and reviewing their laboratory test results. We then manually abstracted the patients' medical charts for demographics, underlying medical conditions, and clinical outcomes. Furthermore, we calculated hospitalization incidence and incidence rate ratios, as well as relative risk for invasive mechanical ventilation, intensive care unit admission, and case fatality rate after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed, hospitalized COVID-19 cases. The median age of the patients was 70 years, with 65.7% (408/621) aged ≥65 years and 94% (584/621) male. Most COVID-19 diagnoses were among non-Hispanic Black (325/621, 52.3%) veterans, followed by non-Hispanic White (153/621, 24.6%) and Hispanic or Latino (112/621, 18%) veterans. Hospitalization rates were the highest among veterans who were ≥85 years old, Hispanic or Latino, and non-Hispanic Black (430, 317, and 298 per 100,000, respectively). Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with those aged 18-29 years (95% CI: 5.7-34.6), whereas Hispanic or Latino and Black veterans had a 4.6- and 4.2-fold increased rate of hospitalization, respectively, compared with non-Hispanic White veterans (95% CI: 3.6-5.9). Overall, 11.6% (72/621) of the patients required invasive mechanical ventilation, 26.6% (165/621) were admitted to the intensive care unit, and 16.9% (105/621) died in the hospital. The adjusted relative risk for invasive mechanical ventilation and admission to the intensive care unit did not differ by age group or race and ethnicity, but veterans aged ≥65 years had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged <65 years (95% CI: 2.4-8.6). CONCLUSIONS: COVID-19 surveillance at the 5 Veterans Affairs Medical Centers across the United States demonstrated higher hospitalization rates and severe outcomes among older veterans, as well as higher hospitalization rates among Hispanic or Latino and non-Hispanic Black veterans than among non-Hispanic White veterans. These findings highlight the need for targeted prevention and timely treatment for veterans, with special attention to older aged, Hispanic or Latino, and non-Hispanic Black veterans.

      5. Homotypic and heterotypic protection and risk of reinfection following natural norovirus infection in a highly endemic settingexternal icon
        Chhabra P, Rouhani S, Browne H, Peñataro Yori P, Siguas Salas M, Paredes Olortegui M, Moulton LH, Kosek MN, Vinjé J.
        Clin Infect Dis. 2021 Jan 27;72(2):222-229.
        BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide, yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time reverse-transcription polymerase chain reaction followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HRs) of infection among children with vs without prior exposure. RESULTS: Norovirus was detected in 1288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR, 0.35; P = .015), GI.7 (HR, 0.19; P = .022), GII.4 (HR, 0.39; P < .001), and GII.6 (HR, 0.52; P = .006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR, 0.52; P = .005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to reinfection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.

      6. Secular trends in breast cancer risk among women with HIV initiating aRT in North Americaexternal icon
        Coburn SB, Shiels M, Silverberg M, Horberg M, Gill MJ, Brown TT, Visvanathan K, Connor AE, Napravnik S, Marcus J, Moore RD, Mathews WC, Mayor AM, Sterling T, Li J, Rabkin C, D'Souza G, Lau B, Althoff KN.
        J Acquir Immune Defic Syndr. 2021 Jan 20.
        BACKGROUND: Studies suggest lower risk of breast cancer in women with versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating ART. We hypothesized breast cancer risk would increase over time as mortality decreased. SETTING: Women with HIV prescribed ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997-2016. METHODS: We estimated breast cancer hazard (cause-specific hazard ratios [csHR]) and cumulative incidence accounting for competing risks (subdistribution hazard ratios [sdHR]) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. RESULTS: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths (73,445 person-years [median follow-up=4.5 years]). Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (csHR and sdHR: 0.89, 95% CI 0.87, 0.91) which remained within and across calendar periods. CONCLUSION: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV.

      7. Development, assessment and outcomes of a community-based model of anti-retroviral care in western Kenya through a cluster-randomized control trialexternal icon
        Goodrich S, Siika A, Mwangi A, Nyambura M, Naanyu V, Yiannoutsos C, Spira T, Bateganya M, Toroitich-Ruto C, Otieno-Nyunya B, Wools-Kaloustian K.
        J Acquir Immune Defic Syndr. 2021 Jan 21.
        OBJECTIVE: To develop and assess an alternative care model using community-based care groups for PLHIV and facilitated by trained lay personnel. METHODS: Geographic locations in the Academic Model Providing Access to Healthcare Kitale clinic catchment were randomized to standard of care versus a community-based care group (ART Co-op). Adults stable on ART and virally suppressed were eligible. Research Assistant led ART Co-ops met in the community every three months. Participants were seen in the HIV clinic only if referred by study staff or by self-referral. CD4 count and viral load were measured in clinic at enrollment and after 12 months. . Retention, viral suppression, and clinic utilization were compared between groups using Chi square, Fishers exact and Wilcoxon rank sum test. RESULTS: At 12 months there were no significant differences in mean CD4 count or viral load suppression. There was a significant difference in patient retention in assigned study group between the intervention and control group (81.6% versus 98.6%; p<0.001), with a number of intervention patients withdrawing due to stigma, relocation, pregnancy, and work conflicts. All study participants, however, were retained in a HIV care program for the study duration. The median number of clinic visits was lower for the intervention group than the control group (0 vs 3; p<0.001). CONCLUSION: Individuals retained in a community-based HIV care model had clinical outcomes equivalent to those receiving clinic-based care. This innovative model of HIV care addresses the problems of insufficient healthcare personnel and patient retention barriers including time, distance, and cost to attend clinic, and has the potential for wider implementation.

      8. Age-specific social mixing of school-aged children in a US setting using proximity detecting sensors and contact surveysexternal icon
        Grantz KH, Cummings DA, Zimmer S, Vukotich C, Galloway D, Schweizer ML, Guclu H, Cousins J, Lingle C, Yearwood GM, Li K, Calderone P, Noble E, Gao H, Rainey J, Uzicanin A, Read JM.
        Sci Rep. 2021 Jan 27;11(1):2319.
        Comparisons of the utility and accuracy of methods for measuring social interactions relevant to disease transmission are rare. To increase the evidence base supporting specific methods to measure social interaction, we compared data from self-reported contact surveys and wearable proximity sensors from a cohort of schoolchildren in the Pittsburgh metropolitan area. Although the number and type of contacts recorded by each participant differed between the two methods, we found good correspondence between the two methods in aggregate measures of age-specific interactions. Fewer, but longer, contacts were reported in surveys, relative to the generally short proximal interactions captured by wearable sensors. When adjusted for expectations of proportionate mixing, though, the two methods produced highly similar, assortative age-mixing matrices. These aggregate mixing matrices, when used in simulation, resulted in similar estimates of risk of infection by age. While proximity sensors and survey methods may not be interchangeable for capturing individual contacts, they can generate highly correlated data on age-specific mixing patterns relevant to the dynamics of respiratory virus transmission.

      9. In household-based surveys that include rapid HIV testing services (HTS), passive referral systems that give HIV-positive participants information about how and where to access ART but minimal follow-up support from survey staff may result in suboptimal linkage. In the 2017 Namibia Population-based HIV Impact Assessment (NAMPHIA), we piloted a system of active linkage to care and ART (ALCART) that utilized the infrastructure of existing community-based partner organizations (CBPOs). All HIV-positive participants age 15-64 years not on ART were given standard passive referrals to ART plus the option to participate in ALCART. Cases were assigned to CBPOs in participants' localities. Healthcare workers from the CBPO's contacted cases and facilitated their linkage to facility-based ART. A total of 510 participants were eligible and consented to ALCART. The majority were new diagnoses (80.8%), while the remainder were previously diagnosed but not on ART (19.2%). Of the 510, 473 (92.7%) were successfully linked into care. Of these, all but one initiated ART. Our ALCART system used existing CBPOs and contributed to >90% linkage-to-care and >99% ART-initiation among linked participants in a large, nationally-representative survey. This approach can be used to improve the potential benefits of HTS in other large population-based surveys.


      10. Sensitivity of the BinaxNOW COVID-19 Ag Card test (BinaxNOW) was 51.6% among asymptomatic healthcare employees relative to rRT-PCR. Odds of a positive BinaxNOW test decreased as cycle threshold value increased. BinaxNOW could facilitate rapid detection and isolation of asymptomatically infected persons in some settings while rRT-PCR results are pending.

      11. BACKGROUND: The Ending the HIV Epidemic: A Plan for America initiative aims to reduce new infections by 2030. Routine assessment of incident and prevalent HIV by transmission risk is essential for monitoring the impact of national, state, and local efforts to end the HIV epidemic. METHODS: Data reported to the National HIV Surveillance System were used to estimate numbers of incident and prevalent HIV infection attributed to sexual transmission in the United States in 2018. The first CD4 result after diagnosis and a CD4 depletion model were used to generate estimates by transmission category, sex at birth, age group, and race/ethnicity. RESULTS: In 2018, there were an estimated 32,600 (50% CI: 31,800, 33,400) incident and 984,000 (50% CI: 977,000, 990,900) prevalent HIV infections attributed to sexual transmission in the United States. Male-to-male sexual contact comprised 74.8% and 69.1% of incident and prevalent HIV infections, respectively. Persons aged 25-34 years comprised 39.6% (12,900; 50% CI: 12,400, 13,400) of incident infections; however, the number of prevalent infections was highest among persons 55 years and older [29.3%; 288,300 (50% CI: 285,600, 291,000)]. There were racial/ethnic differences in numbers of incident and prevalent infections among both men who have sex with men (MSM) and persons with HIV attributable to heterosexual contact. CONCLUSIONS: In 2018, most incident sexually transmitted HIV infections occurred in MSM and the burden was disproportionate for persons aged 24-35 years, and Black/African American and Hispanic/Latino adults and adolescents. Efforts to increase use of effective biomedical and behavioral prevention methods must be intensified to reach the goal to end the HIV epidemic in the United States.

      12. Characteristics of Salmonella recovered from stools of children enrolled in the Global Enteric Multicenter Studyexternal icon
        Kasumba IN, Pulford CV, Perez-Sepulveda BM, Sen S, Sayed N, Permala-Booth J, Livio S, Heavens D, Low R, Hall N, Roose A, Powell H, Farag T, Panchalingham S, Berkeley L, Nasrin D, Blackwelder WC, Wu Y, Tamboura B, Sanogo D, Onwuchekwa U, Sow SO, Ochieng JB, Omore R, Oundo JO, Breiman RF, Mintz ED, O'Reilly CE, Antonio M, Saha D, Hossain MJ, Mandomando I, Bassat Q, Alonso PL, Ramamurthy T, Sur D, Qureshi S, Zaidi AK, Hossain A, Faruque AS, Nataro JP, Kotloff KL, Levine MM, Hinton JC, Tennant SM.
        Clin Infect Dis. 2021 Jan 25.
        BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics. CONCLUSION: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.

      13. Intrapartum antibiotic exposure and body mass index in childrenexternal icon
        Koebnick C, Sidell MA, Getahun D, Tartof SY, Rozema E, Taylor B, Xiang AH, Spiller MW, Sharma AJ, Mukhopadhyay S, Puopolo KM, Schrag SJ.
        Clin Infect Dis. 2021 Jan 25.
        BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) reduce a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). METHODS: Retrospective cohort study of infants (n=223,431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For Cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using non-linear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding and childhood antibiotic exposure. RESULTS: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P<0.0001 for all time points, Δ BMI at age 5 years 0.12 kg/m 2, 95% CI 0.07 to 0.16 kg/m 2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In Cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P<0.05 for 0.7-0.8 years, P<0.0001 for all other time points) compared to other antibiotics (Δ BMI at age 5 years 0.24 kg/m 2, 95% CI 0.14 to 0.34 kg/m 2). Breastfeeding did not modify these associations. CONCLUSION: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

      14. Sexually transmitted infections among US women and men: Prevalence and incidence estimates, 2018external icon
        Kreisel KM, Spicknall IH, Gargano JW, Lewis FM, Lewis RM, Markowitz LE, Roberts H, Satcher Johnson A, Song R, St Cyr SB, Weston EJ, Torrone EA, Weinstock HS.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States (US) were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the US for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by gender and age group. Primary estimates are represented by medians and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1=66.6, Q3=68.7) million prevalent and 26.2 (Q1=24.0, Q3=28.7) million incident STIs in the US. Chlamydia, trichomoniasis, genital herpes, and HPV comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15-24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the US is high. Almost half of incident STIs occurred in persons aged 15-24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

      15. Estimates of the prevalence and incidence of chlamydia and gonorrhea among US men and women, 2018external icon
        Kreisel KM, Weston EJ, St Cyr SB, Spicknall IH.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: The most recent prevalence and incidence estimates for chlamydia and gonorrhea, the two most reported nationally notifiable conditions in the United States (US), were for 2008. We present updated estimates for the number of prevalent and incident chlamydial and gonococcal infections for 2018. METHODS: We estimated chlamydial prevalence directly from the 2015-2018 cycles of the National Health and Nutrition Examination Survey (NHANES) and chlamydial incidence using a mathematical model primarily informed by NHANES and case report data. Total and antimicrobial resistant (AMR) gonococcal prevalence and incidence were estimated using mathematical models primarily informed by case report and Gonococcal Isolate Surveillance Program data. Estimates were calculated for the total population, all women, and all men aged 15-39 years, stratified by age group. Primary estimates represent medians and uncertainty intervals represent the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each infection. RESULTS: Among persons aged 15-39 years in the US in 2018, we estimate 2.35 (Q1=2.20, Q3=2.51) million prevalent and 3.98 (Q1=3.77, Q3=4.22) million incident chlamydial infections, and an estimated 209,000 (Q1=183,000, Q3=241,000) prevalent and 1.57 (Q1=1.44, Q3=1.72) million incident gonococcal infections. Of all gonococcal infections, there were 107,000 (Q1=94,000, Q3=124,000) prevalent and 804,000 (Q1=738,000, Q3=883,000) incident infections demonstrating AMR or elevated minimum inhibitory concentrations (MICs) to selected antibiotics. CONCLUSIONS: Chlamydia and gonorrhea were very common in the US in 2018. Estimates show that more than 800,000 newly acquired gonococcal infections in 2018 demonstrated resistance or elevated MICs to currently or previously recommended antibiotics.

      16. Bioaerosol sampling for SARS-CoV-2 in a referral center with critically ill COVID-19 patients March-May 2020external icon
        Lane MA, Brownsword EA, Babiker A, Ingersoll JM, Waggoner J, Ayers M, Klopman M, Uyeki TM, Lindsley WG, Kraft CS.
        Clin Infect Dis. 2021 Jan 28.
        BACKGROUND: Previous research has shown that rooms of patients with COVID-19 present the potential for healthcare-associated transmission through aerosols containing SARS-CoV-2. However, data on the presence of these aerosols outside of patient rooms are limited. We investigated whether virus-containing aerosols were present in nursing stations and patient room hallways in a referral center with critically ill COVID-19 patients. METHODS: Eight National Institute for Occupational Safety and Health BC 251 two-stage cyclone samplers were set up throughout six units, including nursing stations and visitor corridors in intensive care units and general medical units, for six hours each sampling period. Samplers were placed on tripods which held two samplers positioned 102 cm and 152 cm above the floor. Units were sampled for three days. Extracted samples underwent reverse transcription polymerase chain reaction for selected gene regions of the SARS-CoV-2 virus nucleocapsid and the housekeeping gene human RNase P as an internal control. RESULTS: The units sampled varied in the number of laboratory-confirmed COVID-19 patients present on the days of sampling. Some of the units included patient rooms under negative pressure, while most were maintained at a neutral pressure. Of 528 aerosol samples collected, none were positive for SARS-CoV-2 RNA by the estimated limit of detection of 8 viral copies/m 3 of air. CONCLUSION: Aerosolized SARS-CoV-2 outside of patient rooms was undetectable. While healthcare personnel should avoid unmasked close contact with each other, these findings may provide reassurance for the use of alternatives to tight-fitting respirators in areas outside of patient rooms during the current pandemic.

      17. Incidence and prevalence of Trichomonas vaginalis infection among persons aged 15-59: United States, 2018external icon
        Lewis FM, Spicknall IH, Flagg EW, Papp JR, Kreisel KM.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: Trichomonas vaginalis (TV) is a sexually transmitted parasite associated with multiple adverse outcomes in women. Estimating TV incidence is challenging due to its largely asymptomatic presentation. METHODS: Per capita prevalence was estimated using the National Health and Nutrition Examination Survey, 2013-2018. Incidence was estimated using ordinary differential equations assuming static incidence at steady state and fit using Bayesian techniques. Model inputs included estimates of: proportion of asymptomatic cases, natural clearance, and time to symptomatic treatment seeking. Posterior distributions were drawn, and uncertainty reported, from 25th (Q1) to 75th (Q3) percentiles. Aggregated measures were estimated by combining component distributions. RESULTS: Among 15-59 year-olds in 2018, the number of prevalent TV infections was 2.5 (Q1=2.4, Q3=2.7) million overall, 435,000 (Q1=382,000, Q3=492,000) among men, and 2.1 (Q1=2.0, Q3=2.2) million among women; the number of incident infections was 7.4 (Q1=6.6, Q3=8.3) million, 4.1 (Q1=3.5, Q3=4.9) million, and 3.2 (Q1=2.7, Q3=3.7) million among all persons, men, and women, respectively. Persons aged 15-24 years comprised 15.7% and 17.6% of all prevalent and incident infections, respectively; prevalence and incidence in both sexes increased with age. Incidence in both sexes were highly dependent upon estimates of natural clearance, which were based on little data. CONCLUSIONS: Prevalence and incidence of TV are substantial in the United States, particularly among those aged ≥25 years. Though estimated prevalence is higher in women, estimated incidence is higher in men. Data on key parameters of TV infection are limited; future research should focus on clarifying the natural history of TV.

      18. Estimated prevalence and incidence of disease-associated HPV types among 15-59-year-olds in the United Statesexternal icon
        Lewis RM, Laprise JF, Gargano JW, Unger ER, Querec TD, Chesson H, Brisson M, Markowitz LE.
        Sex Transm Dis. 2021 Jan 23.
        INTRODUCTION: Human papillomavirus (HPV) can cause anogenital warts and several types of cancer, including cervical cancers and precancers. We estimated the prevalence, incidence, and number of persons with prevalent and incident HPV infections in the United States in 2018. METHODS: Prevalence and incidence were estimated for infections with any HPV (any of 37 types detected using Linear Array) and disease-associated HPV, two types that cause anogenital warts plus 14 types detected by tests used for cervical cancer screening (HPV 6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68). We used the 2013-2016 National Health and Nutrition Examination Survey to estimate prevalence among 15-59-year-olds, overall and by sex. Incidences in 2018 were estimated per 10,000 persons using an individual-based transmission-dynamic type-specific model calibrated to US data. We estimated number of infected persons by applying prevalences and incidences to 2018 US population estimates. RESULTS: Prevalence of infection with any HPV was 40.0% overall, 41.8% in males and 38.4% in females; prevalence of infection with disease-associated HPV was 24.2% in males and 19.9% in females. An estimated 23.4 and 19.2 million males and females had a disease-associated HPV type infection in 2018. Incidences of any and disease-associated HPV infection were 1222 and 672 per 10,000 persons; incidence of disease-associated HPV infection was 708 per 10,000 males and 636 per 10,000 females. An estimated 6.9 and 6.1 million males and females had an incident infection with a disease-associated HPV type in 2018. CONCLUSIONS: We document a high HPV burden of infection in the United States in 2018, with 42 million persons infected with disease-associated HPV and 13 million persons acquiring a new infection. While most infections clear, some disease-associated HPV type infections progress to disease. The HPV burden highlights the need for continued monitoring of HPV-associated cancers, cervical cancer screening, and HPV vaccination to track and prevent disease.

      19. Preference for using a variety of future HIV pre-exposure prophylaxis products among men who have sex with men in three US citiesexternal icon
        Mansergh G, Kota KK, Stephenson R, Hirshfield S, Sullivan P.
        J Int AIDS Soc. 2021 Jan;24(1):e25664.
        BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) is available and recommended for men who have sex with men (MSM) at risk for HIV infection. Other HIV prevention products are being developed, including long-acting injectable (LAI) and event-based oral and topical formulations. Understanding preferences for potential products by MSM can help direct further development of prevention messaging. METHODS: We present baseline data from HIV-negative participants enrolled in the US Mobile Messaging for Men (M-cubed) Study. Participants were asked their likelihood of and rank order preference for using daily oral PrEP and various potential prevention products (one- to -three-month injections, 2-1-1 sexual event oral dosing, anal or penile gel, or anal suppository), and their sociodemographic characteristics. Bivariate and multivariable logistics regression assessed demographic associations with likelihood of use and rank order preference. RESULTS: Overall, most MSM reported a likelihood of using LAI (74%), sexual event-based pills (67%) and penile gel (64%). Men who reported recent unprotected (condomless and PrEPless) anal sex most preferred a penile gel formulation (74%), followed closely by LAI and event-based pills (73% each). Current PrEP users (vs. non-users) had greater odds of reporting likelihood to use LAI (AOR = 3.29, 95% CI = 2.12 to 5.11), whereas men reporting recent unprotected anal sex had a greater odds of likelihood to use a penile gel (AOR = 1.79, 95% CI = 1.27 to 2.52) and an anal suppository (AOR = 1.48, 95% CI = 1.08 to 2.02). Hispanic/Latino (vs. White) MSM (AOR = 2.29, 95% CI = 1.40 to 3.73) and, marginally, Black MSM (AOR = 1.54, 95% CI = 1.00 to 2.38) had greater odds of reporting likelihood to use penile gel. Similar patterns were found for rank ordering preference of products, including condoms. CONCLUSIONS: Most MSM were interested in using various potential future HIV prevention products, especially LAI. However, two typologies of potential users emerged: men who prefer sexual event-based methods (condoms, event-based pill, sexual gels and suppositories) and men who prefer non-sexual event-based methods (daily pill, LAI). Men who reported recent unprotected anal sex preferred a penile gel product most, followed closely by sexual event-based pills and LAI. Racial/ethnic differences were noted as well. These findings on product preferences can help in formulation development and messaging.

      20. Trends in outbreak-associated cases of COVID-19 - Wisconsin, March-November 2020external icon
        Pray IW, Kocharian A, Mason J, Westergaard R, Meiman J.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):114-117.
        During September 3-November 16, 2020, daily confirmed cases of coronavirus disease 2019 (COVID-19) reported to the Wisconsin Department of Health Services (WDHS) increased at a rate of 24% per week, from a 7-day average of 674 (August 28-September 3) to 6,426 (November 10-16) (1). The growth rate during this interval was the highest to date in Wisconsin and among the highest in the United States during that time (1). To characterize potential sources of this increase, the investigation examined reported outbreaks in Wisconsin that occurred during March 4-November 16, 2020, with respect to their setting and number of associated COVID-19 cases.

      21. Incidence and prevalence of sexually transmitted hepatitis B, United States, 2013 - 2018external icon
        Roberts H, Jiles R, Harris AM, Gupta N, Teshale E.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: Sexual transmission of hepatitis B virus (HBV) is common in the United States. In 2008, an estimated 50% of HBV infections were attributed to sexual transmission. Among 21,600 acute infections that occurred in 2018, the proportion attributable to sexual transmissions is unknown. METHODS: Objectives of this study were to estimate incidence and prevalence of hepatitis B attributable to sexual transmission among the US population aged 15 years and older for 2013-2018. Incidence estimates were calculated for confirmed cases submitted to CDC from 14 states. A hierarchical algorithm defining sexually transmitted acute HBV infections as the absence of injection drug use among persons reporting sexual risk factors, was applied to determine proportion of hepatitis B infections attributable to sexual transmission nationally. NHANES public use data files were analyzed to calculate prevalence estimates of hepatitis B among US households and proportion attributed to sexual transmission was conservatively determined for HBV infected non-US born Americans who migrated from HBV endemic countries. RESULTS: During 2013-2018, an estimated 47,000 [95% CI (27,000, 116,000)] or 38.2% of acute HBV infections in the United States were attributable to sexual transmission. During 2013-2018, among the US non-institutionalized population, an estimated 817,000 [95% CI (613,000, 1,100,000)] persons aged 15 years and older were living with hepatitis B, with an estimated 103,000 [95% CI (89,000, 118,000)] infections or 12.6% attributable to sexual transmission. CONCLUSION: These findings provide evidence sexually transmitted HBV infections remain a public health problem and underscore the importance of interventions to improve vaccination among at-risk populations.

      22. Estimates of the prevalence and incidence of genital herpes, United States, 2018external icon
        Spicknall IH, Flagg EW, Torrone EA.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: Although there are more recent estimate of genital herpes prevalence, incidence estimates in the United States (US) have not been updated since 2008. METHODS: We estimated genital herpes prevalence and incidence for 2018 among adults aged 18-49 years. We estimated prevalence using 2015-2018 NHANES herpes simplex virus (HSV) type 2 (HSV-2) seroprevalence data among the non-institutionalized civilian population and extrapolated this prevalence to the full US population using 2018 American Community Survey data. We estimated incidence using 2011-2018 NHANES HSV-2 data as inputs to a simple mathematical model. We used Monte Carlo simulation to generate 10,000 input parameter sets for age and sex subpopulations and summarized our estimates by their median; uncertainty intervals for these estimates are characterized by their first (Q1) and third (Q3) quartiles. We conducted sensitivity analyses investigating the impact of HSV type 1 (HSV-1) infection on estimates of genital herpes burden. RESULTS: In 2018, there were an estimated 18.6 (Q1=18.1, Q3=19.0) million prevalent and 572,000 (Q1=479,000, Q3=673,000) incident genital herpes infections among 18-49-year-olds. Women accounted for two-thirds of prevalent infections with an estimated 12.1 (Q1=11.9, Q3=12.5) million infections. Incidence was highest among 18-24-year-olds with an estimated 242,000 (Q1=210,000, Q3= 274,000) infections. Sensitivity analyses indicated that HSV-1 could be responsible for millions more prevalent genital herpes infections, and tens of thousands of additional incident genital herpes infections, depending on the percentage of HSV-1 infections that are genital. DISCUSSION: Genital herpes is a common sexually transmitted disease in the United States. Future research to understand the burden of genital infections attributable to HSV-1 would refine estimates of genital herpes burden.

      23. Estimates of the prevalence and incidence of syphilis in the United States, 2018external icon
        Spicknall IH, Kreisel KM, Weinstock H.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: Syphilis is a genital ulcerative disease caused by the bacterium Treponema pallidum that is associated with significant complications if left untreated and can facilitate the transmission and acquisition of HIV infection. The last prevalence and incidence estimates of the burden of syphilis in the United States were for 2008. METHODS: We generate syphilis prevalence and incidence estimates for 2018 among adults aged 14-49 years. We fit a simple mathematical model to 2018 case report data to generate 10,000 sets of estimates for age and sex subpopulations and summarize our estimates by their median (50th percentile); uncertainty intervals are characterized by their 25th (Q1) and 75th (Q3) percentiles. We also used our methodology to re-estimate 2008 prevalence and incidence estimates. RESULTS: In 2018, there were an estimated 156,000 (Q1=132,000, Q3=184,000) prevalent and 146,000 (Q1=126,000, Q3=170,000) incident syphilitic infections in people aged 14-49 years. Men accounted for roughly 70% of prevalent infections and more than 80% of incident infections. In both sexes, there were more prevalent and incident infections in 25-49-year-olds than 14-24-year-olds. Using these methods to re-analyze 2008 data, syphilis prevalence and incidence estimates have increased 164% and 175%, respectively, between 2008 and 2018. DISCUSSION: Although not as common as other sexually transmitted infections, syphilis should be monitored due to its devastating sequelae. As it continues to increase in frequency, it will be important for future work to continue to track its trajectory and burden.

      24. SARS-CoV-2 transmission dynamics in a sleep-away campexternal icon
        Szablewski CM, Chang KT, McDaniel CJ, Chu VT, Yousaf AR, Schwartz NG, Brown M, Winglee K, Paul P, Cui Z, Slayton RB, Tong S, Li Y, Uehara A, Zhang J, Sharkey SM, Kirking HL, Tate JE, Dirlikov E, Fry AM, Hall AJ, Rose DA, Villanueva J, Drenzek C, Stewart RJ, Lanzieri TM.
        Pediatrics. 2021 Jan 27.

      25. Genital mycoplasma, shigellosis, Zika, pubic lice, and other sexually transmitted infections: Neither gone nor forgottenexternal icon
        Torrone E, Lewis F, Kirkcaldy RD, Bernstein K, Ryerson AB, de Voux A, Oliver S, Quilter L, Weinstock H.
        Sex Transm Dis. 2021 Jan 23.
        Most estimates of the combined burden and cost of sexually transmitted infections (STIs) in the United States have focused on eight common STIs with established national surveillance strategies (chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus, and sexually transmitted HIV and hepatitis B). However, over 30 STIs are primarily sexually transmitted or sexually transmissible. In this manuscript, we review what is known about the burden of "other STIs" in the United States, including those where sexual transmission is not the primary transmission route of infection. Although the combined burden of these other STIs may be substantial, accurately estimating their burden due to sexual transmission is difficult due to diagnostic and surveillance challenges. Developing better estimates will require innovative strategies, such as leveraging existing surveillance systems, partnering with public health and academic researchers outside of the STI field, and developing methodology to estimate the frequency of sexual transmission, particularly for new and emerging STIs.Monitoring the burden of sexually transmitted infections (STIs) in the United States is critical to inform and evaluate interventions and guide public health action. Most estimates of the combined burden of STIs in the United States have focused on eight common STIs with established national surveillance strategies (chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus [HPV], and sexually-transmitted HIV and hepatitis B); (1-5) however, there are over 30 pathogens that are sexually transmitted or transmissible (6-8) and these combined estimates underestimate the total burden and economic impact of STIs. "Other STIs" include infections that are primarily sexually transmitted in adults, but their public health significance has not been well established or there are no specific prevention or control programs for them (e.g., pubic lice, Mycoplasma genitalium) and infections where sexual transmission is not the primary transmission route (e.g., shigella, Zika). In this manuscript, we describe what is known about the burden (e.g., prevalence or incidence) of "other STIs" in the US based on a review of published manuscripts and surveillance reports and identify strategies that could be used to better estimate their burden.

      26. The management of multidrug-resistant tuberculosis (MDR TB) is notably complex among patients with human immunodeficiency virus (HIV). TB treatment recommendations typically include very little information specific to HIV and MDR TB, which often is derived from clinical trials conducted in low-resource settings. Mortality rates among patients with HIV and MDR TB remain high. We reviewed the published literature and recommendations to synthesize possible patient management approaches demonstrated to improve treatment outcomes in high-resourced countries for patients with MDR TB and HIV. Approaches to diagnostic testing, impact and timing of antiretroviral therapy on mortality, anti-MDR TB and antiretroviral drug interactions, and the potential role for short-course MDR TB therapy are examined. The combination of antiretroviral therapy with expanded TB drug therapy, along with the management of immune reconstitution inflammatory syndrome, other potential HIV-associated opportunistic diseases, and drug toxicities, necessitate an integrated multidisciplinary patient care approach using public health case management and provider expertise in drug-resistant TB and HIV management.

    • Disaster Control and Emergency Services
      1. Delivering health interventions to women, children, and adolescents in conflict settings: what have we learned from ten country case studies?external icon
        Singh NS, Ataullahjan A, Ndiaye K, Das JK, Wise PH, Altare C, Ahmed Z, Sami S, Akik C, Tappis H, Mirzazada S, Garcés-Palacio IC, Ghattas H, Langer A, Waldman RJ, Spiegel P, Bhutta ZA, Blanchet K.
        Lancet. 2021 Jan 22.
        Armed conflict disproportionately affects the morbidity, mortality, and wellbeing of women, newborns, children, and adolescents. Our study presents insights from a collection of ten country case studies aiming to assess the provision of sexual, reproductive, maternal, newborn, child, and adolescent health and nutrition interventions in ten conflict-affected settings in Afghanistan, Colombia, Democratic Republic of the Congo, Mali, Nigeria, Pakistan, Somalia, South Sudan, Syria, and Yemen. We found that despite large variations in contexts and decision making processes, antenatal care, basic emergency obstetric and newborn care, comprehensive emergency obstetric and newborn care, immunisation, treatment of common childhood illnesses, infant and young child feeding, and malnutrition treatment and screening were prioritised in these ten conflict settings. Many lifesaving women's and children's health (WCH) services, including the majority of reproductive, newborn, and adolescent health services, are not reported as being delivered in the ten conflict settings, and interventions to address stillbirths are absent. International donors remain the primary drivers of influencing the what, where, and how of implementing WCH interventions. Interpretation of WCH outcomes in conflict settings are particularly context-dependent given the myriad of complex factors that constitute conflict and their interactions. Moreover, the comprehensiveness and quality of data remain limited in conflict settings. The dynamic nature of modern conflict and the expanding role of non-state armed groups in large geographic areas pose new challenges to delivering WCH services. However, the humanitarian system is creative and pluralistic and has developed some novel solutions to bring lifesaving WCH services closer to populations using new modes of delivery. These solutions, when rigorously evaluated, can represent concrete response to current implementation challenges to modern armed conflicts.

    • Environmental Health
      1. Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trialexternal icon
        Lin PD, Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Calafat AM, Webster TF, Horton ES, Oken E.
        Environ Int. 2021 Jan 19;148:106375.
        Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m(2)) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m(2) lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

    • Epidemiology and Surveillance
      1. Lessons from the Field: Integrated survey methodologies for neglected tropical diseasesexternal icon
        Harding-Esch EM, Brady MA, Angeles CA, Fleming FM, Martin DL, McPherson S, Hurtado HM, Nesemann JM, Nwobi BC, Scholte RG, Taleo F, Talero SL, Solomon AW, Saboyá-Díaz MI.
        Trans R Soc Trop Med Hyg. 2021 Jan 28;115(2):124-126.
        The 2021-2030 Neglected Tropical Diseases road map calls for intensified cross-cutting approaches. By moving away from vertical programming, the integration of platforms and intervention delivery aims to improve efficiency, cost-effectiveness and programme coverage. Drawing on the direct experiences of the authors, this article outlines key elements for successful integrated surveys, the challenges encountered, as well as future opportunities and threats to such surveys. There are multiple advantages. Careful planning should ensure that integration does not result in a process that is less efficient, more expensive or that generates data driving less reliable decisions than conducting multiple disease-specific surveys.

    • Food Safety
      1. Observed potential cross-contamination in retail delicatessensexternal icon
        Holst M, Brown LG, Viveiros B, Faw B, Hedeen N, McKelvey W, Nicholas D, Ripley D, Hammons S.
        J Food Prot. 2021 Jan 28.
        Listeria monocytogenes (L. monocytogenes) is a persistent public health concern in the United States and is the third leading cause of death from foodborne illness. Cross-contamination of L. monocytogenes is common in delis (between contaminated and uncontaminated equipment, food and hands) and likely plays a role in the associated with retail deli meats. In 2012, EHS-Net conducted a study to describe deli characteristics related to cross-contamination with L. monocytogenes. The study included 298 retail delis in six state and local health departments' jurisdictions and assessed how well deli practices complied with the Food and Drug Administration (FDA) Food Code provisions. Among delis observed using wet wiping cloths for cleaning, 23.6% did not store the cloths in a sanitizing solution between uses. Observed potential cross-contamination of raw meats and ready-to-eat foods during preparation (e.g., same knife used on raw meats and ready-to-eat foods, without cleaning in between) was present in 9.4% of delis. In 24.6% of delis with a cold storage unit, raw meats were not stored separately from ready-to-eat products in containers, bins, or trays. A proper food safety management plan can reduce gaps in cross-contamination and include the adoption of procedures to minimize food safety risks, training with instructions and in-person demonstrations and certifying staff on those procedures, and monitoring to ensure procedures are followed.

    • Health Disparities
      1. An innovative United States-Mexico community outreach initiative for Hispanic and Latino people in the United States: A collaborative public health networkexternal icon
        Flynn MA, Rodriguez Lainz A, Lara J, Rosales C, Feldstein F, Dominguez K, Wolkin A, Sierra Medal IR, Tonda J, Romero-Steiner S, Dicent-Taillepierre J, Rangel Gómez MG.
        Public Health Rep. 2021 Jan 21.
        Collaborative partnerships are a useful approach to improve health conditions of disadvantaged populations. The Ventanillas de Salud (VDS) ("Health Windows") and Mobile Health Units (MHUs) are a collaborative initiative of the Mexican government and US public health organizations that use mechanisms such as health fairs and mobile clinics to provide health information, screenings, preventive measures (eg, vaccines), and health services to Mexican people, other Hispanic people, and underserved populations (eg, American Indian/Alaska Native people, geographically isolated people, uninsured people) across the United States. From 2013 through 2019, the VDS served 10.5 million people (an average of 1.5 million people per year) at Mexican consulates in the United States, and MHUs served 115 461 people from 2016 through 2019. We describe 3 community outreach projects and their impact on improving the health of Hispanic people in the United States. The first project is an ongoing collaboration between VDS and the Centers for Disease Control and Prevention (CDC) to address occupational health inequities among Hispanic people. The second project was a collaboration between VDS and CDC to provide Hispanic people with information about Zika virus infection and health education. The third project is a collaboration between MHUs and the University of Arizona to provide basic health services to Hispanic communities in Pima and Maricopa counties, Arizona. The VDS/MHU model uses a collaborative approach that should be further assessed to better understand its impact on both the US-born and non-US-born Hispanic population and the public at large in locations where it is implemented.

    • Health Economics
      1. Estimated lifetime HIV-related medical costs in the United Statesexternal icon
        Bingham A, Shrestha RK, Khurana N, Jacobson E, Farnham PG.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: Lifetime cost estimates are a useful tool in measuring the economic burden of HIV in the United States. Previous estimation methods need to be updated, given improving antiretroviral therapy regimens and updated costs. METHODS: We used an updated version of the agent-based model Progression and Transmission of HIV (PATH) 3.0 to reflect current regimens and costs. We simulated a cohort of those infected in 2015 until the last person had died to track the lifetime costs for treatment of HIV, including HIV health care utilization costs (inpatient, outpatient, opportunistic infection (OI) prophylaxis, non-HIV medication, and emergency department), OI treatment costs, and testing costs. We assumed a median per-person diagnosis delay of 3 years and a 3% base monthly probability of dropout from care for a base-case scenario. Additionally, we modeled a most-favorable scenario (median diagnosis delay of 1 year and 1% base dropout rate) and a least-favorable scenario (median diagnosis delay of 5 years and 5% base dropout rate). RESULTS: We estimated an average lifetime HIV-related medical cost for a person with HIV of $420,285 (2019 US$) discounted (3%) and $1,079,999 undiscounted for a median 3-year diagnosis delay and 3% base dropout rate. Our discounted cost estimate was $490,045 in our most-favorable scenario and $326,411 in our least-favorable scenario. CONCLUSIONS: Lifetime per-person HIV-related medical costs depend on the time from infection to diagnosis and the likelihood of dropping out of care. Our results, which are similar to previous studies, reflect updated ART regimens and costs for HIV treatment.

      2. BACKGROUND: The purpose of this study was to estimate the number and lifetime medical cost of HIV infections attributable to incident sexually transmitted infections (STIs) in the United States in 2018. METHODS: We combined data from published models regarding the number or percentage of HIV infections attributable to STIs with updated estimates of the lifetime medical cost per HIV infection. We used two distinct calculation methods. Our first calculation used recent estimates of the percentage of HIV infections in men who have sex with men (MSM) attributable to gonorrhea and chlamydia. Our second calculation, based on older studies, used estimates of the expected number of STI-attributable HIV infections per new STI infection, for gonorrhea, chlamydia, syphilis, and trichomoniasis. RESULTS: Our first calculation method suggested that 2,489 (25th-75th percentile: 1,895-3,000) HIV infections in 2018 among MSM could be attributed to gonorrhea and chlamydia, at an estimated lifetime medical cost of $1.05 billion (25th-75th percentile: $0.79-1.26 billion). Our second calculation method suggested that 2,349 (25th-75th percentile: 1,948-2,744) HIV infections in the general population (including MSM) could be attributed to chlamydia, gonorrhea, syphilis, and trichomoniasis acquired in 2018, at an estimated lifetime medical cost of $0.99 billion (25th-75th percentile: $0.80-1.16 billion). CONCLUSIONS: Despite ambiguity regarding the degree to which STIs affect HIV transmission, our combination of data from published STI/HIV transmission models and an HIV lifetime medical cost model can help to quantify the estimated burden of STI-attributable HIV infections in the United States.

      3. The estimated lifetime medical cost of diseases attributable to human papillomavirus infections acquired in 2018external icon
        Chesson HW, Laprise JF, Brisson M, Martin D, Ekwueme DU, Markowitz LE.
        Sex Transm Dis. 2021 Jan 23.
        INTRODUCTION: We estimated the lifetime medical costs of diagnosed cases of diseases attributable to human papillomavirus (HPV) infections acquired in 2018. METHODS: We adapted an existing mathematical model of HPV transmission and associated diseases to estimate the lifetime number of diagnosed cases of disease (genital warts; cervical intraepithelial neoplasia; and cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers) attributable to HPV infections that were acquired in 2018. For each of these outcomes, we multiplied the estimated number of cases by the estimated lifetime medical cost per case obtained from previous studies. We estimated the costs of recurrent respiratory papillomatosis in a separate calculation. Future costs were discounted at 3% annually. RESULTS: The estimated discounted lifetime medical cost of diseases attributable to HPV infections acquired in 2018 among people aged 15-59 years was $774 million (in 2019 U.S. dollars), of which about half was accounted for by infections in those aged 15-24 years. HPV infections in women accounted for about 90% of the lifetime number of diagnosed cases of disease and 70% of the lifetime cost attributable to HPV infections acquired in 2018 among ages 15-59 years. CONCLUSIONS: We estimated the lifetime medical costs of diseases attributable to HPV infections acquired in 2018 to be $774 million. This estimate is lower than previous estimates and likely represents the impact of HPV vaccination. The lifetime cost of disease attributable to incident HPV infections is expected to decrease further over time as HPV vaccination coverage increases.

      4. BACKGROUND: The purpose of this study was to estimate the cost of syphilis in the United States, in terms of the average lifetime direct medical cost per infection. METHODS: We used a decision tree model of the natural history of syphilis. The model allowed for numerous possible outcomes of infection, including treatment for syphilis at various stages, inadvertent treatment, and late syphilis outcomes in those who are alive and still infected 30 years after acquisition. Future costs were discounted at 3% annually. Model inputs such as the cost and probability of each outcome were based on published sources. The probabilities we applied yielded outcomes consistent with reported cases of syphilis by stage from national surveillance data and number of deaths due to late syphilis from national mortality data. RESULTS: The estimated, discounted lifetime cost per infection was $1,190 under base case assumptions (2019 dollars). Treatment costs associated with late syphilis outcomes such as cardiovascular syphilis accounted for only $26 of the average lifetime cost per infection. Results were most sensitive to assumptions regarding the treatment cost per case of unknown duration or late syphilis. In the probabilistic sensitivity analyses, the 2.5th and 97.5th percentiles of the 10,000 simulations of the lifetime cost per infection were $729 and $1,884, respectively. CONCLUSIONS: Our estimate of the lifetime cost per infection is about 50% higher than in a previous study, a difference due in large part to our higher cost assumptions for benzathine penicillin G.s.

      5. The estimated direct lifetime medical costs of sexually transmitted infections acquired in the United States in 2018external icon
        Chesson HW, Spicknall IH, Bingham A, Brisson M, Eppink ST, Farnham PG, Kreisel KM, Kumar S, Laprise JF, Peterman TA, Roberts H, Gift TL.
        Sex Transm Dis. 2021 Jan 23.
        BACKGROUND: We estimated the lifetime medical costs attributable to STIs acquired in 2018, including sexually acquired HIV. METHODS: We estimated the lifetime medical costs of infections acquired in 2018 in the United States for eight STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs such as STI prevention. For each STI except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually. RESULTS: Incident STIs in 2018 imposed an estimated $15.9 billion (25th-75th percentile: $14.9-16.9 billion) in discounted, lifetime direct medical costs (2019 U.S. dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one-fourth of the cost of incident STIs when including HIV, but about three-fourths when excluding HIV. STIs among 15-24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs. CONCLUSIONS: Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.

      6. BACKGROUND: The purpose of this study was to estimate the lifetime direct medical costs per incident case of genital herpes in the United States. METHODS: We used medical claims data to construct a cohort of people continuously enrolled in insurance for at least 48 consecutive months between 2010 and 2018. From this cohort, we identified initial genital herpes diagnoses as well as the cost of related clinical visits and medication during the 36 months following an initial diagnosis. Lifetime costs beyond 36 months were estimated based on treatment use patterns observed in the 36 months of follow-up. RESULTS: The present value of lifetime direct medical costs of genital herpes was estimated to be $972 per treated case or $165 per infection (2019 dollars), not including costs associated with prevention or treatment of neonatal herpes. The clinical visit at which genital herpes was first diagnosed accounted for 27% of lifetime costs. Subsequent clinical visits and medications related to genital herpes accounted for an additional 13% and 60% of lifetime costs, respectively. CONCLUSIONS: The results from this study can inform cost-effectiveness analysis of GH control interventions as well as help quantify the cost burden of sexually transmitted infections in the United States.

      7. Costs implications of pneumococcal vaccination of adults aged 30-60 with a recent diagnosis of diabetesexternal icon
        Hutton DW, McCullough JS, Prosser L, Ye W, Herman WH, Zhang P, Pilishvili T, Pike J.
        Vaccine. 2021 Jan 22.
        OBJECTIVE: The 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease. RESEARCH DESIGN AND METHODS: We used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005 to 2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes. RESULTS: Overall rates of pneumococcal polysaccharide vaccination among adults 30-60 years old were <1%/year. Rates of pneumococcal polysaccharide vaccination were higher for adults with diabetes. Pneumococcal polysaccharide vaccination rates more than doubled from 2.9% per year in 2005 to 6.0% per year in 2014 for adults vaccinated during the same year as their diabetes diagnosis. Using a two-part differences-in-differences model on a propensity-score matched dataset, pneumococcal polysaccharide vaccination may reduce average annual per-person pneumococcal disease costs by $90.54 [95% CI: $183.59, -$2.49, (p = 0.056)] in persons with diabetes from two years before to two years after vaccination. CONCLUSIONS: Non-elderly adults with diabetes have low but rising rates of pneumococcal polysaccharide vaccination. Pneumococcal polysaccharide vaccination has a modest impact reducing overall costs of pneumococcal disease in this population.

      8. In June 2019, the Advisory Committee on Immunization Practices (ACIP) changed the recommendation for routine 13-valent pneumococcal conjugate vaccine (PCV13) use in immunocompetent adults aged ≥65 years, including those with select chronic medical conditions (CMC). ACIP now recommends PCV13 for this group of adults based on shared clinical decision-making. Because adults with CMC continue to be at increased risk for pneumococcal disease, we assessed the cost-effectiveness of administering PCV13 in series with the recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥19 years with CMC. We used a probabilistic model following a cohort of 19-year-old adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$], societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. We used PCV13 efficacy and post-licensure vaccine effectiveness (VE) data to estimate VE against PCV13 type disease (separately for disease by serotype 3 [ST3], the most common PCV13 type, and all other PCV13 serotypes). We considered a range of estimates for sensitivity analyses. Analyses were performed in 2019. In the base case, assuming no PCV13 effectiveness against ST3 disease, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY gained. This declined to $79,416 per QALY if VE against ST3 was estimated to be equivalent to other PCV13-types. Administering PCV13 in series with the recommended PPSV23 for adults with CMC was not cost saving. Results were sensitive to estimated PCV13 VE against ST3 disease.

      9. Limited existing evidence suggests that adults with intellectual and developmental disabilities (IDD) experience substantial disparities in numerous areas of health care, including quality ambulatory care. A multistate cohort of adults with IDD was analyzed for patterns of inpatient admissions and emergency department utilization. Utilization was higher (inpatient [RR = 3.2], emergency department visits [RR = 2.6]) for adults with IDD, particularly for ambulatory care-sensitive conditions (eg, urinary tract [RR = 6.6] and respiratory infections [RRs = 5.5-24.7]), and psychiatric conditions (RRs = 5.8-15). Findings underscore the importance of access to ambulatory care skilled in IDD-related needs to recognize and treat ambulatory care-sensitive conditions and to manage chronic medical and mental health conditions.

      10. Economic burden of influenza illness among children under 5 years in Suzhou, China: Report from the cost surveys during 2011/12 to 2016/17 influenza seasonsexternal icon
        Wang Y, Chen L, Cheng F, Biggerstaff M, Situ S, Zhou S, Gao J, Liu C, Zhang J, Millman AJ, Zhang T, Tian J, Zhao G.
        Vaccine. 2021 Jan 22.
        BACKGROUND: Data are limited on the economic burden of seasonal influenza in China. We estimated the cost due to influenza illness among children < 5-year-old in Suzhou, China. METHODS: This study adopted a societal perspective to estimate direct medical cost, direct non-medical cost, and indirect cost related to lost productivity. Data to calculate costs and rates of three influenza illness outcomes (non-medically attended, outpatient and hospitalization) were collected from prospective community-based cohort studies and hospital-based enhanced laboratory-confirmed influenza surveillance in Suzhou during the 2011/12 to 2016/17 influenza seasons. We used mean cost-per-episode, annual incidence rates of episodes of each outcome, and annual population size to estimate the total annual economic burden of influenza illnesses among children < 5-year-old for Suzhou. All costs were reported in 2017 U.S. dollars. RESULTS: The mean cost-per-episode (standard deviation) was $9.92 (13.26) for non-medically attended influenza, $161.05 (176.98) for influenza outpatient illnesses, and $1425.95 (603.59) for influenza hospitalizations. By applying the annual incidence rates to the population size, we estimated an annual total of 4,919 episodes of non-medically attended influenza, 21,994 influenza outpatient, and 2,633 influenza hospitalization. Total annual economic burden of influenza to society among children < 5-year-old in Suzhou was $7.37 (95% confidence interval, 6.9-7.8) million, with estimated costs for non-medically attended influenza of $49,000 (46,000-52,000), influenza outpatients $3.5 (3.3-3.8) million, and influenza hospitalizations $3.8 (3.6-3.9) million. Among outpatients, the indirect cost was 36.3% ($1.3 million) of total economic burden, accounting for 21,994 days of lost productivity annually. Among inpatients, the indirect cost was 22.1% ($829,000), accounting for 18,431 days of lost productivity annually. CONCLUSIONS: Our findings show that influenza in children < 5-year-oldcauses substantial societal economic burden in Suzhou, China. Assessing the potential economic benefit of increasing influenza vaccination coverage in this population is warranted.

    • Healthcare Associated Infections
      1. New HIV infections from blood transfusions averted in 28 countries supported by PEPFAR blood safety programs, 2004-2015external icon
        Mili FD, Teng Y, Shiraishi RW, Yu J, Bock N, Drammeh B, Watts DH, Benech I.
        Transfusion. 2021 Jan 28.
        BACKGROUND: To quantify the impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the risk of HIV transmission through infected blood donations in countries supported by PEPFAR blood safety programs. METHODS: Data reported to the World Health Organization Global Database on Blood Safety were analyzed from 28 countries in sub-Saharan Africa (SSA), Asia, and the Caribbean during 2004-2015. We used the Goals model of Spectrum Spectrum System Software, version 5.53, to perform the modeling, assuming laboratory quality for HIV testing had 91.9% sensitivity and 97.7% specificity irrespective of testing method based on results of two external quality assurance and proficiency testing studies of transfusion screening for HIV in SSA blood centers. We calculated the number of new HIV infections from the number of transfusions and the prevalence of HIV infection acquired from blood transfusions with infected blood donations. We determined the impact of laboratory testing programs by estimating the number of new HIV infections averted since PEPFAR implementation. RESULTS: Assuming that HIV testing would not be performed in any of these countries without PEPFAR funding, the number of new HIV infections acquired from blood transfusions averted by laboratory testing increased over time in all 28 countries. The total number of HIV infections averted was estimated at 229 278 out of 20 428 373 blood transfusions during 2004-2015. CONCLUSION: Our mathematical modeling suggests a positive impact achieved over 12 years of PEPFAR support for blood safety. Standardized HIV testing of donated blood has reduced the risk of HIV transmission through blood transfusions in SSA, Asia, and the Caribbean.

      2. Carriage of antimicrobial-resistant bacteria in a high-density informal settlement in Kenya is associated with environmental risk-factorsexternal icon
        Omulo S, Lofgren ET, Lockwood S, Thumbi SM, Bigogo G, Ouma A, Verani JR, Juma B, Njenga MK, Kariuki S, McElwain TF, Palmer GH, Call DR.
        Antimicrob Resist Infect Control. 2021 Jan 22;10(1):18.
        BACKGROUND: The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi-Kenya, characterized by high population density, high burden of respiratory disease and diarrhea. METHODS: Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥ 18 years) and one child (≤ 5 years) participated per household. Biweekly interviews (n = 1516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2341 stool, 2843 hand swabs and 1490 drinking water samples collected. Presumptive E. coli (n = 34,042) were isolated and tested for susceptibility to nine antibiotics. RESULTS: Eighty percent of presumptive E. coli were resistant to ≥ 3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27-0·80 log(10) and 0·22-0·51 log(10) respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log(10) depending on the antibiotic tested). CONCLUSIONS: Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.

      3. BACKGROUND: Catheter associated urinary tract infections (CAUTI) and central line-associated bloodstream infections (CLABSI) represent a substantial portion of healthcare-associated infections (HAIs) reported in the United States. The Targeted Assessment for Prevention (TAP) Strategy is a quality improvement framework to reduce HAIs. Data from the TAP Facility Assessments were used to determine common infection prevention gaps for CAUTI and CLABSI. METHODS: Data from 2,044 CAUTI and 1,680 CLABSI Assessments were included in the analysis. Items were defined as potential gaps if ≥33% respondents answered Unknown, ≥33% No, or ≥50% No or Unknown or Never, Rarely, Sometimes, or Unknown to questions pertaining to those areas. Review of response frequencies and stratification by respondent role were performed to highlight opportunities for improvement. RESULTS: Across CAUTI and CLABSI Assessments, lack of physician champions (<35% Yes) and nurse champions (<55% Yes), along with lack of awareness of competency assessments, audits, and feedback were reported. Lack of practices to facilitate timely removal of urinary catheters were identified for CAUTI and issues with select device insertion practices, such as maintaining aseptic technique, were perceived as areas for improvement for CLABSI. CONCLUSIONS: These data suggest common gaps in critical components of infection prevention and control programs. The identification of these gaps has the potential to inform targeted CAUTI and CLABSI prevention efforts.

      4. Leveraging vaccines to reduce antibiotic use and prevent antimicrobial resistance: a WHO Action Frameworkexternal icon
        Vekemans J, Hasso-Agopsowicz M, Kang G, Hausdorff WP, Fiore A, Tayler E, Klemm EJ, Laxminarayan R, Srikantiah P, Friede M, Lipsitch M.
        Clin Infect Dis. 2021 Jan 25.
        The growing burden of antimicrobial-resistant (AMR) microbes constitutes a significant global threat. Vaccines are effective tools to prevent infections could help to control and prevent AMR. In this Viewpoint we present an Action Framework for vaccines to contribute fully, sustainably and equitably to the prevention and control of AMR by preventing infections and reducing antimicrobial use. The document identifies a series of priority actions in three areas: expanding the use of licensed vaccines to maximize impact on AMR, developing new vaccines that contribute to the prevention and control of AMR, and expanding and sharing knowledge about the impact of vaccines on AMR. The objective of this document is to support an alignment of activities among international vaccine and AMR partners, and structure and articulate key priority actions.

      5. Genomic drivers of multidrug-resistant Shigella affecting vulnerable patient populations in the United States and abroadexternal icon
        Worley JN, Javkar K, Hoffmann M, Hysell K, Garcia-Williams A, Tagg K, Kanjilal S, Strain E, Pop M, Allard M, Francois Watkins L, Bry L.
        mBio. 2021 Jan 26;12(1).
        Multidrug-resistant (MDR) Shigella infections have been identified globally among men who have sex with men (MSM). The highly drug-resistant phenotype often confounds initial antimicrobial therapy, placing patients at risk for adverse outcomes, the development of more drug-resistant strains, and additional treatment failures. New macrolide-resistant Shigella strains complicate treatment further as azithromycin is a next-in-line antibiotic for MDR strains, and an antibiotic-strain combination confounded by gaps in validated clinical breakpoints for clinical laboratories to interpret macrolide resistance in Shigella We present the first high-resolution genomic analyses of 2,097 U.S. Shigella isolates, including those from MDR outbreaks. A sentinel shigellosis case in an MSM patient revealed a strain carrying 12 plasmids, of which two carried known resistance genes, the pKSR100-related plasmid pMHMC-004 and spA-related plasmid pMHMC-012. Genomic-epidemiologic analyses of isolates revealed high carriage rates of pMHMC-004 predominantly in U.S. isolates from men and not in other demographic groups. Isolates genetically related to the sentinel case further harbored elevated numbers of unique replicons, showing the receptivity of this Shigella lineage to plasmid acquisition. Findings from integrated genomic-epidemiologic analyses were leveraged to direct targeted clinical actions to improve rapid diagnosis and patient care and for public health efforts to further reduce spread.IMPORTANCE Multidrug-resistant Shigella isolates with resistance to macrolides are an emerging public health threat. We define a plasmid/pathogen complex behind infections seen in the United States and globally in vulnerable patient populations and identify multiple outbreaks in the United States and evidence of intercontinental transmission. Using new tools and sequence information, we experimentally identify the drivers of antibiotic resistance that complicate patient treatment to facilitate improvements to clinical microbiologic testing for their detection. We illustrate the use of these methods to support multiagency efforts to combat multidrug-resistant Shigella using publicly available tools, existing genomic data, and resources in clinical microbiology and public health laboratories to inform credible actions to reduce spread.

    • Immunity and Immunization
      1. What do pregnant women think about influenza disease and vaccination practices in selected countriesexternal icon
        Arriola CS, Suntarattiwong P, Dawood FS, Soto G, Das P, Hunt DR, Sinthuwattanawibool C, Kurhe K, Thompson MG, Wesley MG, Saha S, Hombroek D, Brummer T, Kittikraisak W, Kaoiean S, Neyra J, Romero C, Patel A, Bhargav S, Khedikar V, Garg S, Mott JA, Gonzales O, Cabrera S, Florian R, Parvekar S, Tomyabatra K, Prakash A, Tinoco YO.
        Hum Vaccin Immunother. 2021 Jan 26:1-9.
        Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries. Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression. Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value<0.01). Despite significant differences in sociodemographic characteristics in the three populations, most participants across sites who were aware of influenza prior to study enrollment believe they and their infants are at risk of influenza and related complications and believe influenza vaccination is safe and effective. Half of women in Lima had verified receipt of influenza vaccine compared to <5% in Bangkok and Nagpur (p < .05). For further analysis conducted among women in Lima only, household income above the poverty line (aOR: 1.38; 95%CI: 1.01, 1.88), having 8+ antenatal visits, compared to 0-4 (aOR: 2.41; 95%CI: 1.39, 2.87, respectively), having 0 children, compared to 2+ (aOR: 1.96; 95%CIs: 1.23, 3.12), and vaccination recommended by a health-care provider (aOR: 8.25; 95%CI: 6.11, 11.14) were strongly associated with receipt of influenza vaccine during pregnancy. Conclusions: Our findings identify opportunities for targeted interventions to improve influenza vaccine uptake among pregnant women in these settings.

      2. Effect of vaccination on preventing influenza-associated hospitalizations among children during a severe season associated with B/Victoria viruses, 2019-2020external icon
        Campbell AP, Ogokeh C, Weinberg GA, Boom JA, Englund JA, Williams JV, Halasa NB, Selvarangan R, Staat MA, Klein EJ, McNeal M, Michaels MG, Sahni LC, Stewart LS, Szilagyi PG, Harrison CJ, Lively JY, Rha B, Patel M.
        Clin Infect Dis. 2021 Jan 27.
        BACKGROUND: The 2019-2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among U.S. children. METHODS: We assessed VE among children 6 months-17 years with acute respiratory illness and ≥10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined mid-turbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive versus negative for influenza. RESULTS: Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone.VE was 62% (95% confidence interval [CI], 52%-71%) for influenza-related hospitalization, 54% (95% CI, 33%-69%) for B/Victoria viruses and 64% (95% CI, 49%-75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%-65%) for an influenza-related ED visit, 55% (95% CI, 40%-66%) for B/Victoria viruses and 53% (95% CI, 37%-65%) for A(H1N1)pdm09. CONCLUSIONS: Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.

      3. Use of high-dose influenza and live attenuated influenza vaccines by US primary care physiciansexternal icon
        Cataldi JR, Hurley LP, Lindley MC, O'Leary ST, Gorman C, Brtnikova M, Beaty BL, Crane LA, Shay DK, Kempe A.
        J Gen Intern Med. 2021 Jan 22.
        BACKGROUND: Several different types of influenza vaccine are licensed for use in adults in the USA including high-dose inactivated influenza vaccine (HD-IIV) and live attenuated influenza vaccine (LAIV). HD-IIV is licensed for use in adults ≥ 65 years, and recommendations for use of LAIV have changed several times in recent years. OBJECTIVE: We sought to examine family physicians' (FPs) and general internal medicine physicians' (GIMs) perceptions, knowledge, and practices for use of HD-IIV and LAIV during the 2016-2017 and 2018-2019 influenza seasons. DESIGN: E-mail and mail surveys conducted February-March 2017, January-February 2019. PARTICIPANTS: Nationally representative samples of FPs and GIMs. MAIN MEASURES: Surveys assessed HD-IIV practices (2017), knowledge and perceptions (2019), and LAIV knowledge and practices (2017, 2019). KEY RESULTS: Response rates were 67% (620/930) in 2017 and 69% (642/926) in 2019. Many physicians believed HD-IIV is more effective than standard dose IIV in patients ≥ 65 years (76%) and reported their patients ≥ 65 years believe they need HD-IIV (67%). Most respondents incorrectly thought ACIP preferentially recommends HD-IIV for adults ≥ 65 years (88%); 65% "almost always/always" recommended HD-IIV for adults ≥ 65 years. Some physicians incorrectly thought ACIP preferentially recommends HD-IIV for adults < 65 years with cardiopulmonary disease (38%) or immunosuppression (48%); some respondents recommended HD-IIV for these groups (25% and 28% respectively). In 2017, 88% of respondents knew that ACIP recommended against using LAIV during the 2016-2017 influenza season, and 4% recommended LAIV to patients. In 2019, 63% knew that ACIP recommended that LAIV could be used during the 2018-2019 influenza season, and 8% recommended LAIV. CONCLUSIONS: Many physicians incorrectly thought ACIP had preferential recommendations for HD-IIV. Physicians should be encouraged to use any available age-appropriate influenza vaccine to optimize influenza vaccination particularly among older adults and patients with chronic conditions who are more vulnerable to severe influenza disease.

      4. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine - United States, December 21, 2020-January 10, 2021external icon
        CDC COVID-19 Response Team , Food and Drug Administration .
        MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):125-129.
        As of January 20, 2021, a total of 24,135,690 cases of coronavirus disease 2019 (COVID-19) and 400,306 associated deaths had been reported in the United States (https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days). On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Moderna COVID-19 vaccine administered as 2 doses, 1 month apart to prevent COVID-19. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of Moderna COVID-19 vaccine (1). As of January 10, 2021, a reported 4,041,396 first doses of Moderna COVID-19 vaccine had been administered in the United States, and reports of 1,266 (0.03%) adverse events after receipt of Moderna COVID-19 vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS). Among these, 108 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis. Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours (2). Among these case reports, 10 cases were determined to be anaphylaxis (a rate of 2.5 anaphylaxis cases per million Moderna COVID-19 vaccine doses administered), including nine in persons with a documented history of allergies or allergic reactions, five of whom had a previous history of anaphylaxis. The median interval from vaccine receipt to symptom onset was 7.5 minutes (range = 1-45 minutes). Among eight persons with follow-up information available, all had recovered or been discharged home. Among the remaining case reports that were determined not to be anaphylaxis, 47 were assessed to be nonanaphylaxis allergic reactions, and 47 were considered nonallergic adverse events. For four case reports, investigators have been unable to obtain sufficient information to assess the likelihood of anaphylaxis. This report summarizes the clinical and epidemiologic characteristics of case reports of allergic reactions, including anaphylaxis and nonanaphylaxis allergic reactions, after receipt of the first dose of Moderna COVID-19 vaccine during December 21, 2020-January 10, 2021, in the United States. CDC has issued updated interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States (3) and interim considerations for preparing for the potential management of anaphylaxis (4).

      5. Effectiveness of the seven- and thirteen valent pneumococcal conjugate vaccines against vaccine-serotype otitis mediaexternal icon
        Dagan R, van der Beek BA, Ben-Shimol S, Pilishvili T, Givon-Lavi N.
        Clin Infect Dis. 2021 Jan 28.
        BACKGROUND: Despite the demonstrated impact of pneumococcal vaccine (PCV) implementation on otitis media (OM), demonstration of real-life serotype-specific effectiveness of the 7- and 13-valent PCVs (PCV7 and PCV13) is lacking due to the paucity of culture-positive cases. . Furthermore, pre-licensure PCV13 efficacy against OM was not studied. METHODS: The study was conducted from October 2009 to July 2013. Cases were children aged 5-35 months-old with OM (mostly complex OM [recurrent/non-responsive, spontaneously draining, chronic with effusion) from whom middle-ear fluid (MEF) culture was obtained; controls were contemporary children with rotavirus-negative gastroenteritis in a prospective population-based rotavirus surveillance, from the same age group with similar ethnic distribution and geographic location. Vaccine effectiveness (VE, 95% CI) was estimated as one minus odds ratio using unconditional logistic regression, adjusting for time since PCV implementation, age and ethnicity. RESULTS: 223 cases and 1,370 controls were studied. Serotypes 19F and 19A together caused 56.1% of all vaccine-serotype OM. VE of ≥2 PCV doses in children 5-35m was demonstrated as follows: PCV7 against OM due to PCV7 serotypes (VT7-OM), 57.2% (6.0-80.5); PCV13 against VT13-OM, 77.4% (53.3-92.1), PCV13 against OM due to the 6 additional non-VT7 serotypes 67.4%, (17.6-87.1), PCV13 against 19F-OM, 91.3% (1.4-99.2); and PCV13 against serotype 3-OM, 85.2% (23.9-98.4%). PCV7 and PCV13 VE against serotype 19A-OM in children 12-35m was 72.4 (6.2-91.9) and 94.6% (33.9-99.6), respectively. CONCLUSIONS: PCV7 and PCV13 were effective against complex OM caused by the targeted serotypes.

      6. Evaluation of vaccine safety after the first public sector introduction of typhoid conjugate vaccine - Navi Mumbai, India, 2018external icon
        Longley AT, Date K, Luby SP, Bhatnagar P, Bentsi-Enchill AD, Goyal V, Shimpi R, Katkar A, Yewale V, Jayaprasad N, Horng L, Kunwar A, Harvey P, Haldar P, Dutta S, Gidudu J.
        Clin Infect Dis. 2021 Jan 27.
        BACKGROUND: In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV) (Typbar-TCV). While no safety concerns were identified in pre- and post-licensure studies, WHO's Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July-August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world's first public sector TCV introduction. Per administrative reports, 113,420 children 9 months-14 years old received TCV. METHODS: We evaluated adverse events following immunization (AEFI) using passive and active surveillance via 1) reports from the passive NMMC AEFI surveillance system, 2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days post-vaccination, and 3) chart abstraction for adverse events of special interest (AESI) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. RESULTS: We identified 222/113,420 (0.2%) AEFI through the NMMC AEFI surveillance system: 211 (0.19%) minor, 2 (0.002%) severe, and 9 (0.008%) serious. At 48 hours post-vaccination, 1,852/5,605 (33%) caregivers reported one or more AEFI, including injection site pain (n=1,452, 26%), swelling (n=419, 7.5%), and fever (n=416, 7.4%). Of the 4,728 interviews completed at 7 days post-vaccination, the most reported AEFI included fever (n=200, 4%), pain (n=52, 1%), and headache (n=42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESI were causally associated with TCV. CONCLUSIONS: No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months-14 years old.

    • Laboratory Sciences
      1. This guidance provides clear, concise strategies for identifying coronaviruses by transmission electron microscopy of ultrathin sections of tissues or infected tissue cultures. These include a description of virus morphology as well as cell organelles that can resemble viruses. Biochemical testing and caveats are discussed. Numerous references provide information for documentation and further study.

      2. Physiological responses to cryoprotectant treatment in an early larval stage of the malaria mosquito, Anopheles gambiaeexternal icon
        Campbell JB, Dosch A, Hunt CM, Dotson EM, Benedict MQ, Rajamohan A, Rinehart JP.
        Cryobiology. 2020 Dec 3.
        The development of cryopreservation protocols for Anopheles gambiae could significantly improve research and control efforts. Cryopreservation of any An. gambiae life stage has yet to be successful. The unique properties of embryos have proven to be resistant to any practical cryoprotectant loading. Therefore, we have chosen to investigate early non-feeding first instar larvae as a potential life stage for cryopreservation. In order to determine an appropriate cryoprotective compound, larvae were treated with progressively better glass-forming cryoprotective mixtures. Toxicity evaluation in combination with calorimetry-based water content and supercooling point depression assessments were used to determine the cryoprotectants that could be used for cryostorage of viable larvae. Approximately 35-75% of the larvae were viable after reasonably high osmotic and biochemical challenge. This study provides ample evidence for an active osmoregulatory response in the Anopheles larvae to counter the permeation of cryoprotectants from the surrounding medium. The data show a strong correlation between the larval mortality and water content, indicating an osmoregulatory crisis in the larva due to certain cryoprotectants such as the higher concentrations of ethane diol (ED). The observations also indicate that the ability of the larvae to regulate permeation and water balance ceases at or within 20 min of cryoprotectant exposure, but this is strongly influenced by the treatment temperature. Among the compound cryoprotectants tested, 25% ED + 10% dimethyl sulfoxide (DMSO) and 40% ED + 0.5 M trehalose seem to present a compromise between viability, larval water content, supercooling point depression, and glass forming abilities.

      3. Carriage dynamics of pneumococcal serotypes in naturally colonized infants in a rural African setting during the first year of lifeexternal icon
        Chaguza C, Senghore M, Bojang E, Lo SW, Ebruke C, Gladstone RA, Tientcheu PE, Bancroft RE, Worwui A, Foster-Nyarko E, Ceesay F, Okoi C, McGee L, Klugman KP, Breiman RF, Barer MR, Adegbola RA, Antonio M, Bentley SD, Kwambana-Adams BA.
        Front Pediatr. 2020 ;8:587730.
        Streptococcus pneumoniae (the pneumococcus) carriage precedes invasive disease and influences population-wide strain dynamics, but limited data exist on temporal carriage patterns of serotypes due to the prohibitive costs of longitudinal studies. Here, we report carriage prevalence, clearance and acquisition rates of pneumococcal serotypes sampled from newborn infants bi-weekly from weeks 1 to 27, and then bi-monthly from weeks 35 to 52 in the Gambia. We used sweep latex agglutination and whole genome sequencing to serotype the isolates. We show rapid pneumococcal acquisition with nearly 31% of the infants colonized by the end of first week after birth and quickly exceeding 95% after 2 months. Co-colonization with multiple serotypes was consistently observed in over 40% of the infants at each sampling point during the first year of life. Overall, the mean acquisition time and carriage duration regardless of serotype was 38 and 24 days, respectively, but varied considerably between serotypes comparable to observations from other regions. Our data will inform disease prevention and control measures including providing baseline data for parameterising infectious disease mathematical models including those assessing the impact of clinical interventions such as pneumococcal conjugate vaccines.

      4. Cross-protection by inactivated H5 prepandemic vaccine seed strains against diverse Goose/Guangdong lineage H5N1 highly pathogenic avian influenza virusesexternal icon
        Criado MF, Sá E. Silva M, Lee DH, Salge CA, Spackman E, Donis R, Wan XF, Swayne DE.
        J Virol. 2020 Nov 23;94(24).
        The highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world and has caused sporadic lethal infections in humans. Vaccines are important in HPAIV control both for poultry and in prepandemic preparedness for humans. This study assessed inactivated prepandemic vaccine strains in a One Health framework across human and agricultural and wildlife animal health, focusing on the genetic and antigenic diversity of field H5N1 Gs/GD viruses from the agricultural sector and assessing cross-protection in a chicken challenge model. Nearly half (47.92%) of the 48 combinations of vaccine and challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death times (MDT), and the virus-shedding titers were significantly lower than those of the sham-vaccinated group (P ≤ 0.05). The antibody titers in the prechallenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination-inhibiting (HI) antibodies against the homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters and homologous or closely related vaccine and challenge viruses gave the best prediction of protection. Through additional analysis, we identified a pattern of epitope substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV in the agricultural sector and for human prepandemic preparedness. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.IMPORTANCE The sustained circulation of highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 (Gs/GD) lineage in the agricultural sector and some wild birds has led to the evolution and selection of distinct viral lineages involved in escape from vaccine protection. Our results using inactivated vaccine candidates from the human pandemic preparedness program in a chicken challenge model identified critical antigenic conformational epitopes on H5 hemagglutinin (HA) from different clades that were associated with antibody recognition and escape. Even though other investigators have reported epitope mapping in the H5 HA, much of this information pertains to epitopes reactive to mouse antibodies. Our findings validate changes in antigenic epitopes of HA associated with virus escape from antibody neutralization in chickens, which has direct relevance to field protection and virus evolution. Therefore, knowledge of these immunodominant regions is essential to proactively develop diagnostic tests, improve surveillance platforms to monitor AIV outbreaks, and design more efficient and broad-spectrum agricultural and human prepandemic vaccines.

      5. Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of R. rickettsii have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using in vivo and in vitro methods, we identified multiple phenotypic differences among six geographically distinct isolates of R. rickettsii, representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (Cavia porcellus), allowed separation of these isolates into three categories: non-virulent (Iowa); mildly virulent (Sawtooth and Gila), and highly virulent (Sheila Smith(T), Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between a mildly and a highly virulent isolate. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provide insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts.

      6. Quantitative differences between intra-host HCV populations from persons with recently established and persistent infectionsexternal icon
        Icer Baykal PB, Lara J, Khudyakov Y, Zelikovsky A, Skums P.
        Virus Evol. 2021 Jan;7(1):veaa103.
        Detection of incident hepatitis C virus (HCV) infections is crucial for identification of outbreaks and development of public health interventions. However, there is no single diagnostic assay for distinguishing recent and persistent HCV infections. HCV exists in each infected host as a heterogeneous population of genomic variants, whose evolutionary dynamics remain incompletely understood. Genetic analysis of such viral populations can be applied to the detection of incident HCV infections and used to understand intra-host viral evolution. We studied intra-host HCV populations sampled using next-generation sequencing from 98 recently and 256 persistently infected individuals. Genetic structure of the populations was evaluated using 245,878 viral sequences from these individuals and a set of selected features measuring their diversity, topological structure, complexity, strength of selection, epistasis, evolutionary dynamics, and physico-chemical properties. Distributions of the viral population features differ significantly between recent and persistent infections. A general increase in viral genetic diversity from recent to persistent infections is frequently accompanied by decline in genomic complexity and increase in structuredness of the HCV population, likely reflecting a high level of intra-host adaptation at later stages of infection. Using these findings, we developed a machine learning classifier for the infection staging, which yielded a detection accuracy of 95.22 per cent, thus providing a higher accuracy than other genomic-based models. The detection of a strong association between several HCV genetic factors and stages of infection suggests that intra-host HCV population develops in a complex but regular and predictable manner in the course of infection. The proposed models may serve as a foundation of cyber-molecular assays for staging infection, which could potentially complement and/or substitute standard laboratory assays.

      7. Rumor surveillance in support of minimally invasive tissue sampling for diagnosing the cause of child death in low-income countries: A qualitative studyexternal icon
        Islam MS, Al-Masud A, Maixenchs M, Cossa S, Guilaze R, Diarra K, Fofana I, Hussain F, Blevins J, Kone A, Arifeen SE, Mandomando I, Bassat Q, Sage EO, Gurley ES, Munguambe K.
        PLoS One. 2021 ;16(1):e0244552.
        In low-and middle-income countries, determining the cause of death of any given individual is impaired by poor access to healthcare systems, resource-poor diagnostic facilities, and limited acceptance of complete diagnostic autopsies. Minimally invasive tissue sampling (MITS), an innovative post-mortem procedure based on obtaining tissue specimens using fine needle biopsies suitable for laboratory analysis, is an acceptable proxy of the complete diagnostic autopsy, and thus could reduce the uncertainty of cause of death. This study describes rumor surveillance activities developed and implemented in Bangladesh, Mali, and Mozambique to identify, track and understand rumors about the MITS procedure. Our surveillance activities included observations and interviews with stakeholders to understand how rumors are developed and spread and to anticipate rumors in the program areas. We also engaged young volunteers, local stakeholders, community leaders, and study staff to report rumors being spread in the community after MITS launch. Through community meetings, we also managed and responded to rumors. When a rumor was reported, the field team purposively conducted interviews and group discussions to track, verify and understand the rumor. From July 2016 through April 2018, the surveillance identified several rumors including suspicions of organs being harvested or transplanted; MITS having been performed on a living child, and concerns related to disrespecting the body and mistrust related to the study purpose. These rumors, concerns, and cues of mistrust were passed by word of mouth. We managed the rumors by modifying the consent protocol and giving additional information and support to the bereaved family and to the community members. Rumor surveillance was critical for anticipating and readily identifying rumors and managing them. Setting up rumor surveillance by engaging community residents, stakeholders, and volunteers could be an essential part of any public health program where there is a need to identify and react in real-time to public concern.

      8. A new genetic approach to distinguish strains of Anaplasma phagocytophilum that appear not to cause human diseaseexternal icon
        Liveris D, Aguero-Rosenfeld ME, Daniels TJ, Karpathy S, Paddock C, Adish S, Keesing F, Ostfeld RS, Wormser GP, Schwartz I.
        Ticks Tick Borne Dis. 2021 Jan 19;12(3):101659.
        Genetic diversity of Anaplasma phagocytophilum was assessed in specimens from 16 infected patients and 16 infected Ixodes scapularis ticks. A region immediately downstream of the 16S rRNA gene, which included the gene encoding SdhC, was sequenced. For the A. phagocytophilum strains from patients no sequence differences were detected in this region. In contrast, significantly fewer ticks had a sequence encoding SdhC that was identical to that of the human strains (11/16 vs. 16/16, p = 0.04). This variation is consistent with the premise that not all A. phagocytophilum strains present in nature are able to cause clinical illness in humans. A strain referred to as A. phagocytophilumVariant-1 that is regarded as non-pathogenic for humans was previously described using a different typing method. Data from the current study suggest that both typing methods are identifying the same non-pathogenic strains.

      9. Isolation of Borrelia miyamotoi and other Borreliae using a modified BSK mediumexternal icon
        Replogle AJ, Sexton C, Young J, Kingry LC, Schriefer ME, Dolan M, Johnson TL, Connally NP, Padgett KA, Petersen JM.
        Sci Rep. 2021 Jan 21;11(1):1926.
        Borrelia spirochetes are the causative agents of Lyme borreliosis (LB) and relapsing fever (RF). Despite the steady rise in infections and the identification of new species causing human illness over the last decade, isolation of borreliae in culture has become increasingly rare. A modified Barbour-Stoenner-Kelly (BSK) media formulation, BSK-R, was developed for isolation of the emerging RF pathogen, Borrelia miyamotoi. BSK-R is a diluted BSK-II derivative supplemented with Lebovitz's L-15, mouse and fetal calf serum. Decreasing the concentration of CMRL 1066 and other components was essential for growth of North American B. miyamotoi. Sixteen B. miyamotoi isolates, originating from Ixodes scapularis ticks, rodent and human blood collected in the eastern and upper midwestern United States, were isolated and propagated to densities > 10(8) spirochetes/mL. Growth of five other RF and ten different LB borreliae readily occurred in BSK-R. Additionally, primary culture recovery of 20 isolates of Borrelia hermsii, Borrelia turicatae, Borrelia burgdorferi and Borrelia mayonii was achieved in BSK-R using whole blood from infected patients. These data indicate this broadly encompassing borreliae media can aid in in vitro culture recovery of RF and LB spirochetes, including the direct isolation of new and emerging human pathogens.

      10. Proteus mirabilis targets atherosclerosis plaques in human coronary arteries via DC-SIGN (CD209)external icon
        Xue Y, Li Q, Park CG, Klena JD, Anisimov AP, Sun Z, Wei X, Chen T.
        Front Immunol. 2020 ;11:579010.
        Bacterial DNAs are constantly detected in atherosclerotic plaques (APs), suggesting that a combination of chronic infection and inflammation may have roles in AP formation. A series of studies suggested that certain Gram-negative bacteria were able to interact with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN; cluster of differentiation (CD) 209] or langerin (CD207), thereby resulting in deposition of CD209s at infection sites. We wondered if Proteus mirabilis (a member of Proteobacteria family) could interact with APs through CD209/CD207. In this study, we first demonstrated that CD209/CD207 were also receptors for P. mirabilis that mediated adherence and phagocytosis by macrophages. P. mirabilis interacted with fresh and CD209s/CD207-expressing APs cut from human coronary arteries, rather than in healthy and smooth arteries. These interactions were inhibited by addition of a ligand-mimic oligosaccharide and the coverage of the ligand, as well as by anti-CD209 antibody. Finally, the hearts from an atherosclerotic mouse model contained higher numbers of P. mirabilis than that of control mice during infection-challenging. We therefore concluded that the P. mirabilis interacts with APs in human coronary arteries via CD209s/CD207. It may be possible to slow down the progress of atherosclerosis by blocking the interactions between CD209s/CD207 and certain atherosclerosis-involved bacteria with ligand-mimic oligosaccharides.

    • Maternal and Child Health
      1. Many young children with autism who use psychotropic medication do not receive behavior therapy: A multisite case-control studyexternal icon
        Wiggins LD, Nadler C, Rosenberg S, Moody E, Reyes N, Reynolds A, Alexander A, Daniels J, Thomas K, Giarelli E, Levy SE.
        J Pediatr. 2021 Jan 22.
        OBJECTIVES: to explore how many pre-school aged children with autism spectrum disorder (ASD) used psychotropic medication, (child and geographic factors associated with psychotropic medication use, and how many children who used psychotropic medication did or did not ever receive behavior therapy. STUDY DESIGN: Children 2-5 years of age were enrolled from 2012-2016 in a multisite case-control study designed to investigate the development and risk factors of ASD. Children with a positive ASD screen or ASD diagnosis upon enrollment were asked to complete a comprehensive evaluation to determine ASD status and developmental level. Caregivers completed a services and treatments questionnaire (STQ) and multiple self-administered questionnaires to determine child use of psychotropic medication, ever receipt of behavior therapy, and presence of co-occurring symptoms. RESULTS: 763 children were classified as ASD and had data collected on the STQ. Of those, 62 (8.1%) used psychotropic medication to treat behavioral symptoms and 28 (3.7%) were three years of age or younger when medication was first started. Attention problems (aOR=7.65; 95% CI=3.41,16.1; P<.001) and study site (aOR=2.62; 95% CI=1.04, 6.56; P = .04) were significantly associated with psychotropic medication use after controlling for maternal race/ethnicity. More than half (59.7%) of those who used psychotropic medication did not ever receive behavior therapy. CONCLUSIONS: Many preschool-aged children with ASD who use psychotropic medication do not receive behavior therapy. Pediatricians are an important resource for children and families and can help facilitate behavioral treatment for children with ASD and other disorders.

    • Mining
      1. Large-scale explosion propagation testing of treated and non-treated rock dust when overlain by a thin layer of coal dustexternal icon
        Perera IE, Harris ML, Sapko MJ, Dyduch Z, Cybulski K, Hildebrandt R, Goodman GV.
        Min Metall Explor. 2021 .
        To prevent coal dust explosion propagations, rock dust needs to be lifted and suspended in the air with the coal dust during an explosion. The addition of anti-caking agents prevents caking of rock dust in the presence of water. Mining and rock dusting processes can frequently create alternating layers of rock dust and float coal dust on mine surfaces. For this test series, a thin layer of coal dust was distributed on top of a layer of either treated or non-treated rock dust in the Experimental Mine Barbara, Poland. The experimental results compare the effectiveness of treated and non-treated rock dusts to attenuate a propagating coal dust explosion initiated with either strong or weak methane explosions. Experimental results indicate that the treated rock dust performs better than non-treated rock dust in arresting a propagating explosion, especially in the presence of moisture.

    • Occupational Safety and Health
      1. Coccidioidomycosis outbreak among inmate wildland firefighters: California, 2017external icon
        Laws RL, Jain S, Cooksey GS, Mohle-Boetani J, McNary J, Wilken J, Harrison R, Leistikow B, Vugia DJ, Windham GC, Materna BL.
        Am J Ind Med. 2021 Jan 23.
        BACKGROUND: In California, state prison inmates are employed to fight wildfires, which involves performing soil-disrupting work. Wildfires have become more common, including areas where Coccidioides, the soil-dwelling fungus that causes coccidioidomycosis, proliferates. However, work practices that place wildland firefighters at risk for coccidioidomycosis have not been investigated. METHODS: On August 17, 2017, the California Department of Public Health was notified of a cluster of coccidioidomycosis cases among Wildfire A inmate wildland firefighters. We collected data through medical record abstraction from suspected case-patients and mailed a survey assessing potential job task risk factors to Wildfire A inmate firefighters. We described respondent characteristics and conducted a retrospective case-control investigation to assess coccidioidomycosis risk factors. RESULTS: Among 198 inmate firefighters who worked on Wildfire A, 112 (57%) completed the survey. Of 10 case-patients (four clinical and six laboratory-confirmed), two were hospitalized. In the case-control analysis of 71 inmate firefighters, frequently cutting fire lines with a McLeod tool (odds ratio [OR]: 5.5; 95% confidence interval [CI]: 1.1-37.2) and being in a dust cloud or storm (OR: 4.3; 95% CI: 1.1-17.4) were associated with illness. Two of 112 inmate firefighters reported receiving coccidioidomycosis training; none reported wearing respiratory protection on this wildfire. CONCLUSIONS: Wildland firefighters who use hand tools and work in dusty conditions where Coccidioides proliferates are at risk for coccidioidomycosis. Agencies that employ them should provide training about coccidioidomycosis and risk reduction, limit dust exposure, and implement respiratory protection programs that specify where respirator use is feasible and appropriate.

      2. Occupational health research in the commercial fishing industryexternal icon
        Lincoln JM, Carruth A, Cherry D, Kincl L, Syron LN.
        J Agromedicine. 2021 Jan 25.

      3. Young workers in many industrialized countries experience a higher rate of largely preventable occupation-related injuries compared with adults. Safety education and training are considered critical to the prevention of these incidents. This can be promoted by the dissemination and scale-out of an evidence-based, safety training programs in vocational education. The aim of this study was to identify the intervention core components that comprise the "active ingredients" of a safety training intervention for young workers and assess the impact on student outcomes of interest. Fidelity of implementation was operationalized using measures of adherence and quality of intervention delivery. For this study, data were collected through a school-based, cluster randomized trial conducted in 2015 in eight Finnish upper secondary-level vocational schools (n = 229 students in 22 groups, each with one teacher). Results indicate that the intervention core components (safety skills training, safety inoculation training, a positive atmosphere for safety learning, and active learning techniques) had differing associations with student outcomes. Adherence related to the acquisition of safety skills training was the strongest active ingredient in terms of positive effects. Furthermore, quality of delivery in terms of fostering positive learning atmosphere and utilizing active learning methods was associated especially with motivational outcomes. These findings indicate that different active ingredients complemented each other. Contrary to expectations, we found no statistically significant relationship between any of the core components and risk-taking attitudes. The current study advances prevention science by identifying the active ingredients of an evidence-based intervention, implemented in Finnish vocational school settings, that helps protect young workers from work-related morbidity and mortality.

      4. Standing up against workplace bullying behavior: recommendations from newly licensed nursesexternal icon
        Smith CR, Palazzo SJ, Grubb PL, Gillespie GL.
        J Nurs Educ Pract. 2020 Jul;10(7):35-45.
        Objective: Workplace bullying exists in today's healthcare system and often targets newly licensed nurses. Experiences of workplace bullying behavior may negatively affect the nurses' physical and psychological health and impact job satisfaction and staff turnover rates at an organizational level. The purpose of this study was to explore strategies suggested by newly licensed nurses to prevent and intervene during incidents of workplace bullying behavior. Methods: An exploratory qualitative design guided this study. Three open-ended questions asked included: What do you think could be done to prevent a future, similar incident of workplace bullying? If you or someone else attempted to the stop the bullying incident, please describe the actions taken. If you or someone else did not attempt to stop the bullying incident, please state what would need to happen for you to intervene on behalf of yourself or someone else. Surveys were distributed electronically to newly licensed nurses from three baccalaureate nursing programs who had participated in a workplace bullying education intervention study as students. A total of 79 responses were received. Responses to three open-ended questions about recent incidents of workplace bullying behavior were coded and analyzed. Then the Social-Ecological Model was used to organize results into individual, relationship, and organizational level strategies. Results: Most respondents reported experiencing workplace bullying behaviors in the previous six months. Three domains of strategies were identified: Preventing Future Bullying Behavior, Stopping Incidents of Bullying Behavior, and Promoting Others to Act. Conclusions: Results indicated newly licensed nurses desire to be supported by their peers and organization as well as strategies to intervene when bullying behaviors occur. Implications for clinical practice and education are presented.

    • Occupational Safety and Health - Mining
      1. Longwall mining, shale gas production, and underground miner safety and healthexternal icon
        Su DW, Zhang P, Dougherty H, Van Dyke M, Kimutis R.
        Int J Min Sci Technol. 2021 .
        This paper presents the results of a unique study conducted by the National Institute for Occupational Safety and Health (NIOSH) from 2016 to 2019 to evaluate the effects of longwall-induced subsurface deformations on shale gas well casing integrity and underground miner safety and health. At both deep-cover and shallow-cover instrumentation sites, surface subsidence measurements, subsurface in-place inclinometer measurements, and underground pillar pressure measurements were conducted as longwall panels were mined. Comparisons of the deep-cover and shallow-cover test site results with those from a similar study under medium cover reveal an interesting longwall-induced response scenario. Under shallow and medium covers, measured horizontal displacements within the abutment pillar are one order of magnitude higher than those measured under deep cover. On the other hand, measured vertical compressions under deep cover are one order of magnitude higher than those under shallow and medium covers. However, FLAC3D simulations of the casings indicate that, in all three cases, the P-110 production casings remain intact under longwall-induced deformations and compressions, which has serious implications for future mine design in areas where shale gas wells have been drilled ahead of mining.

    • Parasitic Diseases
      1. Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trialexternal icon
        Wagman JM, Varela K, Zulliger R, Saifodine A, Muthoni R, Magesa S, Chaccour C, Gogue C, Tynuv K, Seyoum A, Dengela D, Saúte F, Richardson JH, Fornadel C, Linton YM, Slutsker L, Candrinho B, Robertson M.
        Malar J. 2021 Jan 21;20(1):54.
        BACKGROUND: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. METHODS: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. RESULTS: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI(95) 33-59%; p < 0.001) in indoor light traps and by 74% (CI(95) 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI(95) 1.00-1.21) in no-IRS villages and 0.88 (CI(95) 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI(95) 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI(95) 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI(95) 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. CONCLUSION: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

    • Reproductive Health
      1. Reliability of maternal recall of delivery and immediate newborn care indicators in Sarlahi, Nepalexternal icon
        Carter ED, Chang KT, Mullany LC, Khatry SK, LeClerq SC, Munos MK, Katz J.
        BMC Pregnancy Childbirth. 2021 Jan 25;21(1):82.
        BACKGROUND: The intrapartum period is a time of high mortality risk for newborns and mothers. Numerous interventions exist to minimize risk during this period. Data on intervention coverage are needed for health system improvement. Maternal report of intrapartum interventions through surveys is the primary source of coverage data, but they may be invalid or unreliable. METHODS: We assessed the reliability of maternal report of delivery and immediate newborn care for a sample of home and health facility births in Sarlahi, Nepal. Mothers were visited as soon as possible following delivery (< 72 h) and asked to report circumstances of labor and delivery. A subset was revisited 1-24 months after delivery and asked to recall interventions received using standard household survey questions. We assessed the reliability of each indicator by comparing what mothers reported immediately after delivery against what they reported at the follow-up survey. We assessed potential variation in reliability of maternal report by characteristics of the mother, birth event, or intervention prevalence. RESULTS: One thousand five hundred two mother/child pairs were included in the reliability study, with approximately half of births occurring at home. A higher proportion of women who delivered in facilities reported "don't know" when asked to recall specific interventions both initially and at follow-up. Most indicators had high observed percent agreement, but kappa values were below 0.4, indicating agreement was primarily due to chance. Only "received any injection during delivery" demonstrated high reliability among all births (kappa: 0.737). The reliability of maternal report was typically lower among women who delivered at a facility. There was no difference in reliability based on time since birth of the follow-up interview. We observed over-reporting of interventions at follow-up that were more common in the population and under-reporting of less common interventions. CONCLUSIONS: This study reinforces previous findings that mothers are unable to report reliably on many interventions within the peripartum period. Household surveys which rely on maternal report, therefore, may not be an appropriate method for collecting data on coverage of many interventions during the peripartum period. This is particularly true among facility births, where many interventions may occur without the mother's full knowledge.

    • Statistics as Topic
      1. Developing excellence in biostatistics leadership, training and science in Africa: How the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB) training unites expertise to deliver excellenceexternal icon
        Chirwa TF, Matsena Zingoni Z, Munyewende P, Manda SO, Mwambi H, Kandala NB, Kinyanjui S, Young T, Musenge E, Simbeye J, Musonda P, Mahande MJ, Weke P, Onyango NO, Kazembe L, Tumwesigye NM, Zuma K, Yende-Zuma N, Omanyondo Ohambe MC, Kweku EN, Maposa I, Ayele B, Achia T, Machekano R, Thabane L, Levin J, Eijkemans MJ, Carpenter J, Chasela C, Klipstein-Grobusch K, Todd J.
        AAS Open Res. 2020 ;3:51.
        The increase in health research in sub-Saharan Africa (SSA) has led to a high demand for biostatisticians to develop study designs, contribute and apply statistical methods in data analyses. Initiatives exist to address the dearth in statistical capacity and lack of local biostatisticians in SSA health projects. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) led by African institutions was initiated to improve biostatistical capacity according to the needs identified by African institutions, through collaborative masters and doctoral training in biostatistics. SACCAB has created a critical mass of biostatisticians and a network of institutions over the last five years and has strengthened biostatistics resources and capacity for health research studies in SSA.  SSACAB comprises 11 universities and four research institutions which are supported by four European universities.  In 2015, only four universities had established Masters programmes in biostatistics and SSACAB supported the remaining seven to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics Masters programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of whom 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling of limited biostatistics resources in SSA combined with co-funding from external partners has shown to be an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates.

    • Zoonotic and Vectorborne Diseases
      1. Human T-cell lymphotropic virus type 1 transmission dynamics in rural villages in the Democratic Republic of the Congo with high nonhuman primate exposureexternal icon
        Halbrook M, Gadoth A, Shankar A, Zheng H, Campbell EM, Hoff NA, Muyembe JJ, Wemakoy EO, Rimoin AW, Switzer WM.
        PLoS Negl Trop Dis. 2021 Jan 28;15(1):e0008923.
        The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to simian retroviruses yet little is known about the extent of zoonotic simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic viruses (HTLV), a retrovirus group of simian origin, in a large population of persons with frequent NHP exposures and a history of simian foamy virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen's swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with simian foamy virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity.

      2. Notes from the field: An outbreak of West Nile virus - Arizona, 2019external icon
        Ruberto I, Kretschmer M, Zabel K, Sunenshine R, Smith K, Townsend J, Richard D, Erhart LM, Staab N, Komatsu K, Venkat H.
        MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):123-124.


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