Issue 37, October 12, 2021

CDC Science Clips: Volume 13, Issue 37, October 12, 2021

This week, CDC Science Clips is pleased to feature the Journal of Physical Activity & Health’s recent supplement on Progress and New Directions in Physical Activity Surveillanceexternal icon.

The supplement examines up to 20-year trends in aerobic, muscle-strengthening, and sitting behavior among adults and youth in the US.

The supplement also discusses the history of these surveillance data, and explores future directions, opportunities, and challenges for national physical activity surveillance.

Geoffrey Whitfield from CDC’s Division of Nutrition, Physical Activity, and Obesity introduces the supplement in a short video here.

For more information on CDC’s physical activity efforts, please visit Physical Activity | CDC.
  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Physical Activity
      1. Surveillance of physical activity and sedentary behavior among youth and adults in the United States: History and opportunitiesexternal icon
        Omura JD, Whitfield GP, Chen TJ, Hyde ET, Ussery EN, Watson KB, Carlson SA.
        J Phys Act Health. 2021 Aug 1;18(S1):S6-s24.
        BACKGROUND: Surveillance is a core function of public health, and approaches to national surveillance of physical activity and sedentary behavior have evolved over the past 2 decades. The purpose of this paper is to provide an overview of surveillance of physical activity and sedentary behavior in the United States over the past 2 decades, along with related challenges and emerging opportunities. METHODS: The authors reviewed key national surveillance systems for the assessment of physical activity and sedentary behavior among youth and adults in the United States between 2000 and 2019. RESULTS: Over the past 20 years, 8 surveillance systems have assessed physical activity, and 5 of those have assessed sedentary behavior. Three of the 8 originated in nonpublic health agencies. Most systems have assessed physical activity and sedentary behavior via surveys. However, survey questions varied over time within and also across systems, resulting in a wide array of available data. CONCLUSION: The evolving nature of physical activity surveillance in the United States has resulted in both broad challenges (eg, balancing content with survey space; providing data at the national, state, and local level; adapting traditional physical activity measures and survey designs; and addressing variation across surveillance systems) and related opportunities.

      2. BACKGROUND: During the past decade, guidelines for youth aerobic and muscle-strengthening physical activity remained unchanged. Active People, Healthy NationSM highlighted school and youth strategies (eg, sports and physical education [PE]) to increase physical activity. Sex, grade, and race/ethnicity disparities exist. This study examines sex-specific trends and differences by grade and race/ethnicity for the prevalence of 5 youth physical activity behaviors from 2009 to 2019. METHODS: The national Youth Risk Behavior Survey assesses adolescents (grades 9-12) meeting the aerobic, muscle-strengthening, and both guidelines (2011-2019) and sports participation and daily PE (2009-2019). Sex-stratified logistic regression assessed trends and 2009 or 2011-2019 differences by grade and racial/ethnic subgroups. RESULTS: Decreases in meeting the aerobic, muscle-strengthening, and both guidelines were observed for nearly all male subgroups by grade and race/ethnicity, whereas female subgroups exhibited declines or no change to low prevalence. Sports and PE participation remained mostly constant; select subgroups showed decreases (ie, Hispanic males [sports]; Black males and ninth-grade females [PE]). CONCLUSIONS: Past decade prevalence and patterns suggest that school-based and other strategies for all adolescents and tailored interventions for sex-specific subgroups may be needed to supplement sports and PE in promoting high school youth physical activity.

      3. A new decade of Healthy People: Considerations for comparing youth physical activity across 2 surveillance systemsexternal icon
        Chen TJ, Watson KB, Michael SL, Minnaert JJ, Fulton JE, Carlson SA.
        J Phys Act Health. 2021 Aug 1;18(S1):S94-s101.
        BACKGROUND: Healthy People 2030 includes objectives to increase meeting the aerobic physical activity guideline for ages 6-13 years (of ages 6-17 y, monitored by National Survey of Children's Health [NSCH]) and grades 9 to 12 (mostly aged 14-18+ y, monitored by Youth Risk Behavior Survey [YRBS]). This study compares methodologies, prevalence, and patterns of meeting the guideline, particularly for overlapping ages 14-17 years. METHODS: Nationally representative surveys, 2016-2017 NSCH (adult proxy report, 6-17 y) and 2015 and 2017 YRBS (self-report, grades 9-12), assess meeting the guideline of ≥60 minutes of daily moderate to vigorous physical activity. Prevalence and odds ratios were estimated by age group and demographics. RESULTS: For youth aged 14-17 years, 17.4% (95% confidence interval [CI], 16.1-18.7; NSCH) and 27.0% (95% CI, 25.6-28.5; YRBS) met the guideline. 25.9% (95% CI, 24.8-27.2) aged 6-13 years (NSCH) and 26.6% (95% CI, 25.3-28.0) in grades 9 to 12 (YRBS) met the guideline. Across surveys, fewer females (P < .001) and Asian youth (P < .001 except among NSCH 14-17 y) met the guideline. CONCLUSIONS: Neither methodology nor estimates for meeting the aerobic guideline are similar across surveys, so age continuity between juxtaposed estimates should not be assumed by magnitude nor age for separate Healthy People 2030 youth physical activity objectives.

      4. BACKGROUND: The National Health Interview Survey is unique among US federal surveillance systems with over 20 years of consistent assessment of muscle-strengthening and aerobic activity. The authors examined trends in the prevalence of US adults who met the muscle-strengthening (2 or more days per week) and the combined muscle-strengthening and aerobic physical activity (at least 150 min/wk of moderate-intensity equivalent activity) guidelines from 1998 to 2018. METHODS: The 1998-2018 National Health Interview Survey data were analyzed. Age-adjusted prevalence of meeting the muscle-strengthening and combined aerobic and muscle-strengthening guidelines by selected respondent characteristics were estimated for each year and linear and higher-order trends were assessed. RESULTS: From 1998 to 2018, prevalence of meeting the muscle-strengthening guideline increased from 17.7% to 27.6%, and meeting the combined aerobic and muscle-strengthening guidelines increased from 14.4% to 24.0%. All subgroups demonstrated significant increases in meeting both guideline measures over this period although trends varied across the 21 years; increasing trends were more commonly sustained in the second decade of monitoring. CONCLUSIONS: Although increasing trends in prevalence of meeting the muscle-strengthening and combined guidelines are encouraging, current prevalence estimates remain low. Opportunities exist for the continued promotion of muscle-strengthening activity using evidence-based approaches.

      5. Trends in meeting the aerobic physical activity guideline among adults with and without select chronic health conditions, United States, 1998-2018external icon
        Omura JD, Hyde ET, Imperatore G, Loustalot F, Murphy L, Puckett M, Watson KB, Carlson SA.
        J Phys Act Health. 2021 Aug 1;18(S1):S53-s63.
        BACKGROUND: Physical activity is central to the management and control of many chronic health conditions. The authors examined trends during the past 2 decades in the prevalence of US adults with and without select chronic health conditions who met the minimal aerobic physical activity guideline. METHODS: The 1998-2018 National Health Interview Survey data were analyzed. Prevalence of meeting the minimal aerobic physical activity guideline among adults with and without 6 chronic health conditions was estimated across 3-year intervals. Linear and higher-order trends were assessed overall and by age group. RESULTS: During the past 2 decades, prevalence of meeting the aerobic guideline increased among adults with diabetes, hypertension, coronary heart disease, stroke, cancer, and arthritis. However, the absolute increase in prevalence was lower among adults with hypertension, coronary heart disease, and arthritis compared to counterparts without each condition, respectively. Prevalence was persistently lower among those with most chronic health conditions, except cancer, and among older adults compared to their counterparts. CONCLUSIONS: Although rising trends in physical activity levels among adults with chronic health conditions are encouraging for improving chronic disease management, current prevalence remains low, particularly among older adults. Increasing physical activity should remain a priority for chronic disease management and control.

      6. Amount, type, and timing of domain-specific moderate to vigorous physical activity among US adultsexternal icon
        Saint-Maurice PF, Berrigan D, Whitfield GP, Watson KB, Patel S, Loftfield E, Sampson JN, Fulton JE, Matthews CE.
        J Phys Act Health. 2021 Aug 1;18(S1):S114-s122.
        BACKGROUND: Surveillance of domain-specific physical activity in the United States is lacking. Thus, the authors describe domain-specific moderate to vigorous physical activity (MVPA) in a nationwide sample of US adults. METHODS: Participants from the AmeriSpeak panel (n = 2649; 20-75 y; 50% female) completed the Activities Completed Over Time in 24-Hours previous-day recall. The authors estimated average MVPA duration (in hours per day) overall and in major life domains by sex, age, race/ethnicity, and education. They also described the most commonly reported MVPAs and timing of MVPA during the day. RESULTS: Across all life domains, participants reported an average of 2.5 hours per day in MVPA. Most MVPA was accumulated during work (50% of total, 1.2 h/d) and household activities (28%, 0.7 h/d) with less MVPA reported in leisure time (15%, 0.4 h/d). Time reported in MVPA varied by sex, and race/ethnicity (P < .05). Walking at work and for exercise, childcare, and walking for transportation were the most commonly reported domain-specific MVPAs. A greater proportion of MVPA took place in the morning (∼06:00 h) and evening (∼18:00 h). CONCLUSIONS: Work and household activities accounted for 78% of overall MVPA reported, while leisure-time MVPA accounted for only 15% of the total. Encouraging MVPA during leisure time and transportation remain important targets for promoting MVPA in US adults.

      7. Trends in self-reported sitting time by physical activity levels among US adults, NHANES 2007/2008-2017/2018external icon
        Ussery EN, Whitfield GP, Fulton JE, Galuska DA, Matthews CE, Katzmarzyk PT, Carlson SA.
        J Phys Act Health. 2021 Aug 1;18(S1):S74-s83.
        BACKGROUND: High levels of sedentary behavior and physical inactivity increase the risk of premature mortality and several chronic diseases. Monitoring national trends and correlates of sedentary behavior and physical inactivity can help identify patterns of risk in the population over time. METHODS: The authors used self-reported data from the National Health and Nutrition Examination Surveys (2007/2008-2017/2018) to estimate trends in US adults' mean daily sitting time, overall, and stratified by levels of leisure-time and multidomain physical activity, and in the joint prevalence of high sitting time (>8 h/d) and physical inactivity. Trends were tested using orthogonal polynomial contrasts. RESULTS: Overall, mean daily sitting time increased by 19 minutes from 2007/2008 (332 min/d) to 2017/2018 (351 min/d) (Plinear < .05; Pquadratic < .05). The highest point estimate occurred in 2013/2014 (426 min/d), with a decreasing trend observed after this point (Plinear < .05). Similar trends were observed across physical activity levels and domains, with one exception: an overall linear increase was not observed among sufficiently active adults. The mean daily sitting time was lowest among highly active adults compared with less active adults when using the multidomain physical activity measure. CONCLUSIONS: Sitting time among adults increased over the study period but decreased in recent years.

      8. Trends in aerobic and muscle-strengthening physical activity by race/ethnicity across income levels among US adults, 1998-2018external icon
        Watson KB, Whitfield G, Chen TJ, Hyde ET, Omura JD.
        J Phys Act Health. 2021 Aug 1;18(S1):S45-s52.
        BACKGROUND: Although disparities in leisure-time physical activity (LTPA) participation by race/ethnicity and income are known, the combined association of these characteristics with LTPA participation is less understood. This study aims to describe trends and determine whether racial/ethnic differences in adult physical activity by income level have changed over the past 2 decades. METHODS: The authors estimated LTPA participation (outcomes: any aerobic activity, meeting the aerobic activity guideline, meeting the muscle-strengthening guideline, and meeting the combined aerobic and muscle-strengthening guidelines) among adults ≥18 years by race/ethnicity across income levels using 1998-2018 National Health Interview Survey data in 3-year aggregates. They also tested for trends, prevalence differences, and difference in differences using logistic regression. RESULTS: LTPA participation increased from 1998-2000 to 2016-2018 for all outcomes for non-Hispanic white, non-Hispanic black, and Hispanic adults at all income levels. Disparities narrowed for some groups but persisted between white and racial/ethnic minority groups across income levels for engaging in any aerobic activity and meeting the aerobic guideline (0.2-8.8 percentage point difference in differences). Disparities in meeting the muscle-strengthening and combined guidelines were less common. CONCLUSIONS: Opportunities exist to ensure that adults, particularly members of lower income racial/ethnic minority groups, have support to help them participate in LTPA.

      9. Purpose-based walking trips by duration, distance, and select characteristics, 2017 National Household Travel Surveyexternal icon
        Watson KB, Whitfield GP, Bricka S, Carlson SA.
        J Phys Act Health. 2021 Aug 1;18(S1):S86-s93.
        BACKGROUND: New or enhanced activity-friendly routes to everyday destinations is an evidence-based approach for increasing physical activity. Although national estimates for some infrastructure features surrounding where one lives and the types of nearby destinations are available, less is known about the places where individuals walk. METHODS: A total of 5 types of walking trips (N = 54,034) were defined by whether they began or ended at home (home based [HB]) and trip purpose (HB work, HB shopping, HB social/recreation, HB other, and not HB trip) (2017 National Household Travel Survey). Differences and trends by subgroups in the proportion of each purpose-oriented trip were tested using pairwise comparisons and polynomial contrasts. RESULTS: About 14% of U.S. adults reported ≥1 walking trip on a given day. About 64% of trips were HB trips. There were few differences in prevalence for each purpose by subgroup. For example, prevalence of trips that were not HB decreased significantly with increasing age and increased with increasing education and household income. CONCLUSIONS: Given age-related and socioeconomic differences in walking trips by purpose, planners and other professionals may want to consider trip origin and destination purposes when prioritizing investments for the creation of activity-friendly routes to everyday destinations where people live, work, and play.

      10. BACKGROUND: Adults should perform ≥150 minutes per week of moderate-intensity equivalent physical activity for substantial health benefits and >300 minutes per week for additional benefits. The authors analyzed 21 years of National Health Interview Survey data to better understand trends in aerobic physical activity participation among US adults. METHODS: The authors estimated the annual prevalence (1998-2018) of self-reported leisure-time physical inactivity, insufficient activity, meeting only the minimal aerobic guideline, and meeting the high aerobic guideline overall and by selected characteristics. Prevalence differences between 1998 and 2018 were compared across subgroups and periods of significant change were identified using JoinPoint regression. RESULTS: The prevalence of inactivity decreased from 40.5% (1998) to 25.6% (2018) while the prevalence of meeting the high aerobic guideline increased from 26.0% to 37.4%. Increases in meeting the high guideline were similar across age groups, racial/ethnic groups, levels of education, and Census regions. Increases in insufficient activity and meeting the minimal guideline were statistically significant but of relatively small magnitude. CONCLUSIONS: The prevalence of inactivity decreased and meeting the high aerobic guideline increased overall and for all subgroups from 1998 to 2018. Physical activity promotion strategies may aim to continue these trends while also narrowing persistent disparities in participation across subgroups.

  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. Health plan-based mailed fecal testing for colorectal cancer screening among dual-eligible Medicaid/Medicare enrollees: Outcomes of 2 program modelsexternal icon
        Baldwin LM, Coronado GD, West , Schwartz MR, Meenan RT, Vollmer WM, Petrik AF, Shapiro JA, Kulkarni-Sharma YR, Green BB.
        Cancer. 2021 Sep 29.
        BACKGROUND: Health insurance plans are increasingly offering mailed fecal immunochemical test (FIT) programs for colorectal cancer (CRC) screening, but few studies have compared the outcomes of different program models (eg, invitation strategies). METHODS: This study compares the outcomes of 2 health plan-based mailed FIT program models. In the first program (2016), FIT kits were mailed to all eligible enrollees; in the second program (2018), FIT kits were mailed only to enrollees who opted in after an outreach phone call. Participants in this observational study included dual-eligible Medicaid/Medicare enrollees who were aged 50 to 75 years and were due for CRC screening (1799 in 2016 and 1906 in 2018). Six-month FIT completion rates, implementation outcomes (eg, mailed FITs sent and reminders attempted), and program-related health plan costs for each program are described. RESULTS: All 1799 individuals in 2016 were sent an introductory letter and a FIT kit. In 2018, all 1906 were sent an introductory letter, and 1905 received at least 1 opt-in call attempt, with 410 (21.5%) sent a FIT. The FIT completion rate was 16.2% (292 of 1799 [95% CI, 14.5%-17.9%]) in 2016 and 14.6% (278 of 1906 [95% CI, 13.0%-16.2%]) in 2018 (P = .36). The overall implementation costs were higher in 2016 ($40,156) than 2018 ($34,899), with the cost per completed FIT slightly higher in 2016 ($138) than 2018 ($126). CONCLUSIONS: An opt-in mailed FIT program achieved FIT completion rates similar to those of a program mailing to all dual-eligible Medicaid/Medicare enrollees. LAY SUMMARY: Health insurance plans can use different program models to successfully mail fecal test kits for colorectal cancer screening to dual-eligible Medicaid/Medicare enrollees, with nearly 1 in 6 enrollees completing fecal testing.

      2. Million Hearts Cardiac Rehabilitation Think Tank: Accelerating new care modelsexternal icon
        Beatty AL, Brown TM, Corbett M, Diersing D, Keteyian SJ, Mola A, Stolp H, Wall HK, Sperling LS.
        Circ Cardiovasc Qual Outcomes. 2021 Sep 30.
        This article describes the October 2020 proceedings of the Million Hearts Cardiac Rehabilitation Think Tank: Accelerating New Care Models, convened with representatives from professional organizations, cardiac rehabilitation (CR) programs, academic institutions, federal agencies, payers, and patient representative groups. As CR delivery evolves, terminology is evolving to reflect not where activities occur (eg, center, home) but how CR is delivered: in-person synchronous, synchronous with real-time audiovisual communication (virtual), or asynchronous (remote). Patients and CR staff may interact through ≥1 delivery modes. Though new models may change how CR is delivered and who can access CR, new models should not change what is delivered-a multidisciplinary program addressing CR core components. During the coronavirus disease 2019 (COVID-19) public health emergency, Medicare issued waivers to allow virtual CR; it is unclear whether these waivers will become permanent policy post-public health emergency. Given CR underuse and disparities in delivery, new models must equitably address patient and health system contributors to disparities. Strategies for implementing new CR care models address safety, exercise prescription, monitoring, and education. The available evidence supports the efficacy and safety of new CR care models. Still, additional research should study diverse populations, impact on patient-centered outcomes, effect on long-term outcomes and health care utilization, and implementation in diverse settings. CR is evolving to include in-person synchronous, virtual, and remote modes of delivery; there is significant enthusiasm for implementing new care models and learning how new care models can broaden access to CR, improve patient outcomes, and address health inequities.

      3. Setting the stage for reimbursable pediatric healthy weight programsexternal icon
        Blanck HM, Hacker K, Petersen R.
        Child Obes. 2021 Sep;17(S1):S1-s2.

      4. Trends in chronic kidney disease care in the US by race and ethnicity, 2012-2019external icon
        Chu CD, Powe NR, McCulloch CE, Crews DC, Han Y, Bragg-Gresham JL, Saran R, Koyama A, Burrows NR, Tuot DS.
        JAMA Netw Open. 2021 Sep 1;4(9):e2127014.
        IMPORTANCE: Significant racial and ethnic disparities in chronic kidney disease (CKD) progression and outcomes are well documented, as is low use of guideline-recommended CKD care. OBJECTIVE: To examine guideline-recommended CKD care delivery by race and ethnicity in a large, diverse population. DESIGN, SETTING, AND PARTICIPANTS: In this serial cross-sectional study, adult patients with CKD that did not require dialysis, defined as a persistent estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or a urine albumin-creatinine ratio of 30 mg/g or higher for at least 90 days, were identified in 2-year cross-sections from January 1, 2012, to December 31, 2019. Data from the OptumLabs Data Warehouse, a national data set of administrative and electronic health record data for commercially insured and Medicare Advantage patients, were used. EXPOSURES: The independent variables were race and ethnicity, as reported in linked electronic health records. MAIN OUTCOMES AND MEASURES: On the basis of guideline-recommended CKD care, the study examined care delivery process measures (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker prescription for albuminuria, statin prescription, albuminuria testing, nephrology care for CKD stage 4 or higher, and avoidance of chronic nonsteroidal anti-inflammatory drug prescription) and care delivery outcome measures (blood pressure and diabetes control). RESULTS: A total of 452 238 patients met the inclusion criteria (mean [SD] age, 74.0 [10.2] years; 262 089 [58.0%] female; a total of 7573 [1.7%] Asian, 49 970 [11.0%] Black, 15 540 [3.4%] Hispanic, and 379 155 [83.8%] White). Performance on process measures was higher among Asian, Black, and Hispanic patients compared with White patients for angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use (79.8% for Asian patients, 76.7% for Black patients, and 79.9% for Hispanic patients compared with 72.3% for White patients in 2018-2019), statin use (72.6% for Asian patients, 69.1% for Black patients, and 74.1% for Hispanic patients compared with 61.5% for White patients), nephrology care (64.8% for Asian patients, 72.9% for Black patients, and 69.4% for Hispanic patients compared with 58.3% for White patients), and albuminuria testing (53.9% for Asian patients, 41.0% for Black patients, and 52.6% for Hispanic patients compared with 30.7% for White patients). Achievement of blood pressure control to less than 140/90 mm Hg was similar or lower among Asian (71.8%), Black (63.3%), and Hispanic (69.8%) patients compared with White patients (72.9%). Achievement of diabetes control with hemoglobin A1c less than 7.0% was 50.1% in Asian patients, 49.3% in Black patients, and 46.0% in Hispanic patients compared with 50.3% for White patients. CONCLUSIONS AND RELEVANCE: Higher performance on CKD care process measures among Asian, Black, and Hispanic patients suggests that differences in medication prescription and diagnostic testing are unlikely to fully explain known disparities in CKD progression and kidney failure. Improving care delivery processes alone may be inadequate for reducing these disparities.

      5. Evaluation of a pharmacists' patient care process approach for hypertensionexternal icon
        Rivera MD, Johnson M, Choe HM, Durthaler JM, Elmi JR, Fulmer EB, Hawkins NA, Jordan JK, MacLeod KE, Ortiz AM, Shantharam SS, Yarnoff BO, Soloe CS.
        Am J Prev Med. 2021 Sep 20.
        INTRODUCTION: An estimated 116 million American adults (47.3%) have hypertension. Most adults with hypertension do not have it controlled-3 in 4 (92.1 million) U.S. adults with hypertension have a blood pressure ≥130/80 mmHg. The Pharmacists' Patient Care Process is a standardized patient-centered approach to the provision of pharmacist care that is done in collaboration with other healthcare providers. Through the Michigan Medicine Hypertension Pharmacists' Program, pharmacists use the Pharmacists' Patient Care Process to provide hypertension management services in collaboration with physicians in primary care and community pharmacy settings. In 2019, the impact of Michigan Medicine Hypertension Pharmacists' Program patient participation on blood pressure control was evaluated. METHODS: Propensity scoring was used to match patients in the intervention group with patients in the comparison group and regression analyses were then conducted to compare the 2 groups on key patient outcomes. Negative binomial regression was used to examine the number of days with blood pressure under control. The findings presented in this brief are part of a larger multimethod evaluation. RESULTS: More patients in the intervention group than in the comparison group achieved blood pressure control at 3 months (66.3% vs 42.4%) and 6 months (69.1% vs 56.5%). The intervention group experienced more days with blood pressure under control within a 3-month (18.6 vs 9.5 days) and 6-month period (57.0 vs 37.4 days) than the comparison group did. CONCLUSIONS: Findings support the effectiveness of the Michigan Medicine Hypertension Pharmacists' Program approach to implementing the Pharmacists' Patient Care Process to improve blood pressure control.

    • Communicable Diseases
      1. Challenges in LTBI care in the United States identified using a nationwide TB medical consultation databaseexternal icon
        Agathis NT, Bhavaraju R, Shah V, Chen L, Haley CA, Goswami ND, Patrawalla A.
        Public Health Action. 2021 Sep 21;11(3):162-166.
        BACKGROUND: Identifying and treating individuals with latent TB infection (LTBI) represents a critical and challenging component of national TB elimination. Medical consultations by the Centers for Disease Control and Prevention (CDC) funded TB Centers of Excellence (COEs) are an important resource for healthcare professionals (HCPs) caring for individuals with LTBI. This study aimed to identify the most common clinical concerns regarding LTBI care and to describe epidemiologic and clinical features of patients discussed in these consultations. METHODS: This mixed-methods study randomly sampled 125 consultation inquiries related to LTBI from the COEs' medical consultation database in 2018. Text from consultation records were reviewed and coded to identify reasons for the inquiries and common epidemiologic and clinical patient characteristics. RESULTS: The most common topics of inquiry for consultation included accurate LTBI diagnosis (36%), management of LTBI treatment-related issues (22%), and choice of appropriate LTBI treatment regimen (17%). Patients for whom consultations were requested commonly had another medical condition (34%), were non-U.S. born (31%), were children (25%), and had a history of travel to TB-endemic areas (18%). CONCLUSION: Our findings emphasize the challenge of managing patients with either suspected or confirmed LTBI, highlighting the need for ongoing medical consultation support for nuanced clinical and epidemiologic scenarios.

      2. Multiple transmission chains within COVID-19 cluster, Connecticut, USA, 2020(1)external icon
        Bart SM, Flaherty E, Alpert T, Carlson S, Fasulo L, Earnest R, White EB, Dickens N, Brito AF, Grubaugh ND, Hadler JL, Sosa LE.
        Emerg Infect Dis. 2021 ;27(10):2669-2672.
        In fall 2020, a coronavirus disease cluster comprising 16 cases occurred in Connecticut, USA. Epidemiologic and genomic evidence supported transmission among persons at a school and fitness center but not a workplace. The multiple transmission chains identified within this cluster highlight the necessity of a combined investigatory approach.

      3. Pediatric COVID-19 cases in counties with and without school mask requirements - United States, July 1-September 4, 2021external icon
        Budzyn SE, Panaggio MJ, Parks SE, Papazian M, Magid J, Eng M, Barrios LC.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1377-1378.
        Consistent and correct mask use is a critical strategy for preventing the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). CDC recommends that schools require universal indoor mask use for students, staff members, and others in kindergarten through grade 12 (K-12) school settings (2). As U.S. schools opened for the 2021-22 school year in the midst of increasing community spread of COVID-19, some states, counties, and school districts implemented mask requirements in schools. To assess the impact of masking in schools on COVID-19 incidence among K-12 students across the United States, CDC assessed differences between county-level pediatric COVID-19 case rates in schools with and without school mask requirements.

      4. Identification of United States counties at elevated risk for congenital syphilis using predictive modeling and a risk scoring system, 2018external icon
        Cuffe KM, Torrone E, Hong J, Leichliter JS, Gift TL, Thorpe PG, Bernstein KT.
        Sex Transm Dis. 2021 Sep 22.
        BACKGROUND: The persistence of congenital syphilis (CS) remains an important concern in the United States. We use 2018 data to refine a previous predictive model that identifies US counties at elevated risk for CS in 2018. METHODS: Using county-level socioeconomic and health related data from various sources, we developed a logistic regression predictive model to identify county-level factors associated with a county having had ≥1 CS case reported to the National Notifiable Diseases Surveillance System in 2018. We developed a risk scoring algorithm, identified the optimal risk-score cut-point to identify counties at elevated risk, and calculated the live birth to CS case-ratio for counties by predicted risk level to compare counties at elevated risk with counties not at elevated risk. RESULTS: We identified several county-level factors associated with a county having ≥1 CS case in 2018 (area under the curve: 88.6%; Bayesian information criterion: 1551.1). Using a risk score cut-off of ≥8 (sensitivity: 83.2%, specificity: 79.4%), this model captured 94.7% (N = 1,253) of CS cases born in 2018 and identified 850 (27%) counties as being at elevated risk for CS. The live birth to CS case-ratio was lower in counties identified as at elevated risk (2,482) compared to counties categorized as not at elevated risk (10,621). CONCLUSIONS: Identifying which counties are at highest risk for CS can help target prevention efforts and interventions. The relatively low live birth to CS case-ratio in elevated risk counties suggests that implementing routine 28-week screening among pregnant women in these counties may be an efficient way to target CS prevention efforts.

      5. Household transmission of influenza A and B within a prospective cohort during the 2013-2014 and 2014-2015 seasonsexternal icon
        Dahlgren FS, Foppa IM, Stockwell MS, Vargas CY, LaRussa P, Reed C.
        Stat Med. 2021 Sep 27.
        People living within the same household as someone ill with influenza are at increased risk of infection. Here, we use Markov chain Monte Carlo methods to partition the hazard of influenza illness within a cohort into the hazard from the community and the hazard from the household. During the 2013-2014 influenza season, 49 (4.7%) of the 1044 people enrolled in a community surveillance cohort had an acute respiratory illness (ARI) attributable to influenza. During the 2014-2015 influenza season, 50 (4.7%) of the 1063 people in the cohort had an ARI attributable to influenza. The secondary attack rate from a household member was 2.3% for influenza A (H1) during 2013-2014, 5.3% for influenza B during 2013-2014, and 7.6% for influenza A (H3) during 2014-2015. Living in a household with a person ill with influenza increased the risk of an ARI attributable to influenza up to 350%, depending on the season and the influenza virus circulating within the household.

      6. Measles in the 21st century: Progress toward achieving and sustaining eliminationexternal icon
        Gastañaduy PA, Goodson JL, Panagiotakopoulos L, Rota PA, Orenstein WA, Patel M.
        J Infect Dis. 2021 Sep 30;224(Supplement_4):S420-s428.
        The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles.

      7. Viral etiology of acute gastroenteritis among forcibly displaced Myanmar nationals and adjacent host population in Bangladeshexternal icon
        Hossian ME, Islam MM, Miah M, Haque W, Vinjé J, Rahman MZ, Faruque AS, Khan AI, Ahmed T, Rahman M.
        J Infect Dis. 2021 Sep 29.
        BACKGROUND: Since August 2017 Myanmar nationals from Rakhine state have crossed the border into Bangladesh and settled in Cox's Bazar, the World's largest refugee camp. Due to overcrowding, poor sanitation, and hygienic practices they have been under significant health risks including diarrheal diseases. OBJECTIVE: To determine the viral etiology of acute gastroenteritis (AGE) among forcibly displaced Myanmar nationals (FDMN) and adjacent Bangladeshi local host population (AHP). METHODS: From April 2018 to April 2019, we collected stool specimens from 764 FDMN and 1159 AHP of all ages. We tested 100 randomly selected specimens from each group for the most common acute gastroenteritis viruses. RESULTS: Among 200 diarrhea patients, 55% and 64% of FDMN and AHP patients respectively had viral infections; the most common viruses were rotavirus (29% vs 44%), adenovirus (24% vs 31%) and norovirus (14% vs 10%). In both populations, viral infections were significantly higher in children less than five years; compared to bacterial infections which were higher in patients older than five years of age (p=<0.05). CONCLUSION: Disparities in viral and bacterial prevalence among various age groups warrant careful antibiotic usage, especially in children less than five years.

      8. Association between K-12 school mask policies and school-associated COVID-19 outbreaks - Maricopa and Pima Counties, Arizona, July-August 2021external icon
        Jehn M, McCullough JM, Dale AP, Gue M, Eller B, Cullen T, Scott SE.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1372-1373.
        CDC recommends universal indoor masking by students, staff members, faculty, and visitors in kindergarten through grade 12 (K-12) schools, regardless of vaccination status, to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Schools in Maricopa and Pima Counties, which account for >75% of Arizona's population (2), resumed in-person learning for the 2021-22 academic year during late July through early August 2021. In mid-July, county-wide 7-day case rates were 161 and 105 per 100,000 persons in Maricopa and Pima Counties, respectively, and 47.6% of Maricopa County residents and 59.2% of Pima County residents had received at least 1 dose of a COVID-19 vaccine. School districts in both counties implemented variable mask policies at the start of the 2021-22 academic year (Table). The association between school mask policies and school-associated COVID-19 outbreaks in K-12 public noncharter schools open for in-person learning in Maricopa and Pima Counties during July 15-August 31, 2021, was evaluated.

      9. The first epidemiological and virological influenza surveillance in the Republic of Guinea revealed the predominance of influenza A/H3N2 and B Victoria virusesexternal icon
        Keita MB, Pierre F, Ndjomou J, Traoré B, Tohonamou P, Soumaré M, Mamadi S, Keita MA, Ebi Bile C, Pallawo RB, Rajatonirina SC, Barry A, Koivogui L, Camara R, Touré A.
        Epidemiol Infect. 2021 Sep 28:1-20.

      10. Burden of influenza-associated respiratory hospitalizations, Vietnam, 2014-2016external icon
        Khanh NC, Fowlkes AL, Nghia ND, Duong TN, Tu NH, Tu TA, McFarland JW, Nguyen TT, Ha NT, Gould PL, Thanh PN, Trang NT, Mai VQ, Thi PN, Otsu S, Azziz-Baumgartner E, Anh DD, Iuliano AD.
        Emerg Infect Dis. 2021 Oct;27(10):2648-2657.
        Influenza burden estimates are essential to informing prevention and control policies. To complement recent influenza vaccine production capacity in Vietnam, we used acute respiratory infection (ARI) hospitalization data, severe acute respiratory infection (SARI) surveillance data, and provincial population data from 4 provinces representing Vietnam's major regions during 2014-2016 to calculate provincial and national influenza-associated ARI and SARI hospitalization rates. We determined the proportion of ARI admissions meeting the World Health Organization SARI case definition through medical record review. The mean influenza-associated hospitalization rates per 100,000 population were 218 (95% uncertainty interval [UI] 197-238) for ARI and 134 (95% UI 119-149) for SARI. Influenza-associated SARI hospitalization rates per 100,000 population were highest among children <5 years of age (1,123; 95% UI 946-1,301) and adults >65 years of age (207; 95% UI 186-227), underscoring the need for prevention and control measures, such as vaccination, in these at-risk populations.

      11. Progress toward poliomyelitis eradication - Pakistan, January 2020-July 2021external icon
        Mbaeyi C, Baig S, Khan Z, Young H, Kader M, Jorba J, Safdar MR, Jafari H, Franka R.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1359-1364.
        When the Global Polio Eradication Initiative began in 1988, wild poliovirus (WPV) transmission was occurring in 125 countries; currently, only WPV type 1 (WPV1) transmission continues, and as of August 2021, WPV1 transmission persists in only two countries (1,2). This report describes Pakistan's progress toward polio eradication during January 2020-July 2021 and updates previous reports (3,4). In 2020, Pakistan reported 84 WPV1 cases, a 43% reduction from 2019; as of August 25, 2021, Pakistan has reported one WPV1 case in 2021. Circulating vaccine-derived poliovirus (cVDPV) emerges as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations and can lead to paralysis. In 2019, 22 cases of cVDPV type 2 (cVDPV2) were reported in Pakistan, 135 cases were reported in 2020, and eight cases have been reported as of August 25, 2021. Because of the COVID-19 pandemic, planned supplementary immunization activities (SIAs)* were suspended during mid-March-June 2020 (3,5). Seven SIAs were implemented during July 2020-July 2021 without substantial decreases in SIA quality. Improving the quality of polio SIAs, vaccinating immigrants from Afghanistan, and implementing changes to enhance program accountability and performance would help the Pakistan polio program achieve its goal of interrupting WPV1 transmission by the end of 2022.

      12. BACKGROUND AND AIMS: Information is limited regarding HBV genotype and the outcome of chronic HBV (CHB) infection. We examined the effect of HBV genotype on HCC occurrence in Alaska Native (AN) persons with CHB, where five HBV genotypes are found: A2, B6, C2, D, and F1. APPROACH AND RESULTS: We calculated HCC incidence per 1,000 person-years of follow-up to determine which groups by age, sex, and genotype met current American Association for the Study of Liver Diseases (AASLD) HCC surveillance criteria. We used Poisson regression to compare HCC risk by genotype, age, sex, and Alaska region. Incidence of HCC was calculated using the sex-specific AASLD cutoff recommended for the Asian population of 50 years for women and 40 years for men. HCC screening was conducted semiannually using alpha-fetoprotein levels and abdominal ultrasound. Among 1,185 AN persons, median follow-up was 35.1 years; 667 (63%) were male. The HBV genotype distribution was 49% D, 18% F, 13% A, 6% C, 3% B, 0.1% H, and 12% undetermined. Sixty-three cases of HCC occurred. HCC incidence for genotype F was 5.73 per 1,000 person-years of follow-up, followed by 4.77 for C, 1.28 for A, 0.47 for D, and 0.00 for B. The HCC risk was higher for genotypes F (relative rate [RR], 12.7; 95% CI, 6.1-26.4), C (RR, 10.6; 95% CI, 4.3-26.0), and A (RR, 2.9; 95% CI, 1.0-8.0) compared to genotypes B and D. Among men < 40 years of age and women < 50 years of age, genotype F had the highest incidence (4.79/1,000 person-years). CONCLUSIONS: HBV genotype was strongly associated with HCC. HBV genotype should be considered in risk factor stratification.

      13. Causes of death in HIV-infected and HIV-uninfected children in the child health and mortality prevention surveillance study-Kenyaexternal icon
        Onyango DO, Akelo V, van der Sande MA, Ridzon R, Were JA, Agaya JA, Oele EA, Wandiga S, Igunza AK, Young PW, Blau DM, Joseph RH, Yuen CM, Zielinski-Gutierrez E, Tippet-Barr BA.
        Aids. 2021 Sep 29.
        OBJECTIVES: Describe the causes of death among infants and children <5 years stratified by HIV status. DESIGN: Cross-sectional analysis of causes of death ascertained through minimally invasive tissue sampling (MITS) in the Kenya Child Health and Mortality Prevention Surveillance site. METHODS: We included decedents aged 28 days to <5 years, whose death was reported within 36 hours, underwent MITS, and had HIV test results and causes of death determined. MITS specimens were tested using Taqman Array Cards, culture, cytology, histopathology and immunohistochemistry and HIV polymerase chain reaction. A panel evaluated epidemiologic, clinical, verbal autopsy and laboratory data to assign causes of death using ICD10 guidelines. Causes of death and etiological agents were stratified by HIV status. RESULTS: Of 176 included decedents, 14% (n = 25) were HIV-infected, median viral load was 112,205 copies per milliliter (interquartile range [IQR] = 9,349-2,670,143). HIV-disease (96%; n = 24) and malnutrition (23%; n = 34) were the leading underlying causes of death in HIV-infected and HIV-uninfected decedents, respectively. Malnutrition was more frequent in the causal chain of HIV-infected (56%; n = 14) than HIV-uninfected decedents (31%; n = 49) (p-value = 0.03). Viral pneumonia was twice as common in HIV-infected (50%; n = 9) than HIV-uninfected decedents (22%; n = 7) (p-value = 0.04). CONCLUSION: Nearly all HIV-infected decedents' underlying cause of death was HIV disease which was associated with malnutrition. Our findings underscore the need for strengthening early identification and management of HIV-infected children. Prevention, early diagnosis and treatment of malnutrition could be instrumental in improving the survival of HIV-infected and HIV-uninfected children.

      14. COVID-19-related school closures and learning modality changes - United States, August 1-September 17, 2021external icon
        Parks SE, Zviedrite N, Budzyn SE, Panaggio MJ, Raible E, Papazian M, Magid J, Ahmed F, Uzicanin A, Barrios LC.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1374-1376.
        Beginning in January 2021, the U.S. government prioritized ensuring continuity of learning for all students during the COVID-19 pandemic (1). To estimate the extent of COVID-19-associated school disruptions, CDC and the Johns Hopkins University Applied Physics Laboratory used a Hidden Markov Model (HMM) (2) statistical approach to estimate the most likely actual learning modality based on patterns observed in past data, accounting for conflicting or missing information and systematic Internet searches (3) for COVID-19-related school closures. This information was used to assess how many U.S. schools were open, and in which learning modalities, during August 1-September 17, 2021. Learning modalities included 1) full in-person learning, 2) a hybrid of in-person and remote learning, and 3) full remote learning.

      15. Performance of existing and novel surveillance case definitions for COVID-19 in household contacts of PCR-confirmed COVID-19external icon
        Reses HE, Fajans M, Lee SH, Heilig CM, Chu VT, Thornburg NJ, Christensen K, Bhattacharyya S, Fry A, Hall AJ, Tate JE, Kirking HL, Nabity SA.
        BMC Public Health. 2021 Sep 25;21(1):1747.
        BACKGROUND: Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control. METHODS: We assessed diagnostic performance of existing cases definitions (e.g. influenza-like illness, COVID-like illness) using symptoms reported from 185 household contacts to a PCR-confirmed case of COVID-19 in Wisconsin and Utah, United States. We stratified analyses between adults and children. We also constructed novel case definitions for comparison. RESULTS: Existing COVID-19 case definitions generally showed high sensitivity (86-96%) but low positive predictive value (PPV) (36-49%; F-1 score 52-63) in this community cohort. Top performing novel symptom combinations included taste or smell dysfunction and improved the balance of sensitivity and PPV (F-1 score 78-80). Performance indicators were generally lower for children (< 18 years of age). CONCLUSIONS: Existing COVID-19 case definitions appropriately screened in household contacts with COVID-19. Novel symptom combinations incorporating taste or smell dysfunction as a primary component improved accuracy. Case definitions tailored for children versus adults should be further explored.

      16. Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an increased risk of viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, which can be either placentally mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1% to 3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. The National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in situ hybridization with antisense probe (detects replication) or a sense probe (detects viral messenger RNA) or immunohistochemistry to detect viral nucleocapsid or spike proteins. If the abovementioned methods are not possible, reverse transcription polymerase chain reaction detection or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling and the use of validated reagents and sample protocols (included as appendices).

      17. Genotyping indicates marked heterogeneity of tuberculosis transmission in the United States, 2009-2018external icon
        Rodriguez CA, Li T, Self JL, Jenkins HE, Horsburgh CR, White LF.
        Epidemiol Infect. 2021 .
        Heterogeneity in the number of secondary tuberculosis (TB) cases per source case, the effective reproductive number, R, is important in modelling prevention strategies' impact on incidence. We estimated mean R (Rm) and calculate the dispersion parameter of this distribution, k, using surveillance and genotyping data for U.S. cases during 2009-2018. We modeled transmission assuming cases in a cluster have matching genotypes and share characteristics related to geography, temporal proximity (i.e. serial interval), and time since U.S. arrival among non-U.S.-born persons. Complete data were available for 55,330/85,958 cases. Varying the serial interval and geographic proximity used to derive clusters, we consistently estimated Rm1.0 and k0.08; the low value of k indicates a small number of source cases produce a disproportionate number of secondary cases. U.S. TB reproductive number has a highly skewed distribution, indicating a minority of source cases disproportionately contribute to transmission. © 2021 Cambridge University Press. All rights reserved.

      18. Severe acute respiratory syndrome coronavirus 2 transmission in Georgia, USA, February 1-July 13, 2020external icon
        Wang Y, Siesel C, Chen Y, Lopman B, Edison L, Thomas M, Adams C, Lau M, Teunis PF.
        Emerg Infect Dis. 2021 Oct;27(10):2578-2587.
        The serial interval and effective reproduction number for coronavirus disease (COVID-19) are heterogenous, varying by demographic characteristics, region, and period. During February 1-July 13, 2020, we identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. We examined how various transmission characteristics were affected by symptoms, demographics, and period (during shelter-in-place and after subsequent reopening) and estimated the time course of reproduction numbers for all 159 Georgia counties. Transmission varied by time and place but also by persons' sex and race. The mean serial interval decreased from 5.97 days in February-April to 4.40 days in June-July. Younger adults (20-50 years of age) were involved in most transmission events occurring during or after reopening. The shelter-in-place period was not long enough to prevent sustained virus transmission in densely populated urban areas connected by major transportation links.

      19. Temporal trends in pre-ART patient characteristics and outcomes before the test and treat era in Central Kenyaexternal icon
        Wekesa P, McLigeyo A, Owuor K, Mwangi J, Isavwa L, Katana A.
        BMC Infect Dis. 2021 Sep 26;21(1):1007.
        BACKGROUND: Retention of patients who did not initiate antiretroviral therapy (ART) has been persistently low compared to those who initiated ART. Understanding the temporal trends in clinical outcomes prior to ART initiation may inform interventions targeting patients who do not initiate ART immediately after diagnosis. METHODS: A retrospective cohort analysis of known HIV-infected patients who did not initiate ART from healthcare facilities in Central Kenya was done to investigate temporal trends in characteristics, retention, and mortality outcomes. The data were sourced from the Comprehensive Care Clinic Patient Application Database (CPAD) and IQ care electronic patient-level databases for those enrolled between 2004 and 2014. RESULTS: A total of 13,779 HIV-infected patients were assessed, of whom 30.7% were men.There were statisitically significant differences in temporal trends relating to marital status, WHO clinical stage, and tuberculosis (TB) status from 2004 to 2014. The proportion of widowed patients decreased from 9.1 to 6.0%. By WHO clinical stage at enrollment in program, those in WHO stage I increased over time from 8.7 to 43.1%, while those in WHO stage III and IV reduced from 28.5 to 10.8% and 4.0 to 1.1% respectively. Those on TB treatment during their last known visit reduced from 8.3 to 3.9% while those with no TB signs increased from 58.5 to 86.8%. Trends in 6 and 12 month retention in the program, loss to follow-up (LTFU) and mortality were statistically significant. At 6 months, program retention ranged between 36.0% in 2004 to a high of 54.1% in 2013. LTFU at 6 months remained around 50.0% for most of the cohorts, while mortality at 6 months was 7.5% in 2004 but reduced to 3.8% in 2014. At 12 months, LTFU was above 50.0% across all the cohorts while mortality rate reached 3.9% in 2014. CONCLUSION: Trends in pre ART enrollment suggested higher enrollment among patients who were women and at earlier WHO clinical stages. Retention and mortality outcomes at 6 and 12 months generally improved over the 11 year follow-up period, though dipped as enrollment in asymptomatic disease stage increased.

    • Disaster Control and Emergency Services
      1. The World Trade Center Health Program: Twenty years of health effects researchexternal icon
        Daniels RD, Kubale TL, Reissman DB, Howard J.
        Am J Ind Med. 2021 Oct;64(10):797-802.
        It has been 20 years since the devastating terrorist attacks on September 11, 2001. Thousands were injured or killed during the attacks and many more are at risk of adverse health stemming from physical, psychological, and emotional stressors born out of the attacks. Private, federal, state, and local resources were gathered soon after the attacks to address impacts to the community, including the health and well-being of both responders and survivors. Many of these efforts are now largely consolidated under the federally mandated World Trade Center (WTC) Health Program. This program provides medical monitoring and treatment of qualifying conditions among the 9/11-exposed population and supports related physical and mental health research. In this commentary, we describe the WTC Health Program, with emphasis on the health-effects research it has funded since inception in 2011. We describe sentinel research publications, and how science has impacted the program. We provide examples relating studies in this special issue to important roles in the WTC Health Program research agenda. Finally, we provide a perspective on future research needs.

      2. Notes from the Field: Deaths related to Hurricane Ida reported by media - nine states, August 29-September 9, 2021external icon
        Hanchey A, Schnall A, Bayleyegn T, Jiva S, Khan A, Siegel V, Funk R, Svendsen E.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1385-1386.

      3. Disaster preparedness among women with a recent live birth in Hawaii - results from the Pregnancy Risk Assessment Monitoring System (PRAMS), 2016external icon
        Strid P, Fok CC, Zotti M, Shulman HB, Awakuni J, House LD, Morrow B, Kern J, Shim M, Ellington SR.
        Disaster Med Public Health Prep. 2021 Sep 27:1-10.
        OBJECTIVE: The aim of this study was to examine emergency preparedness behaviors among women with a recent live birth in Hawaii. METHODS: Using the 2016 Hawaii Pregnancy Risk Assessment Monitoring System, we estimated weighted prevalence of 8 preparedness behaviors. RESULTS: Among 1010 respondents (weighted response rate, 56.3%), 79.3% reported at least 1 preparedness behavior, and 11.2% performed all 8 behaviors. The prevalence of women with a recent live birth in Hawaii reporting preparedness behaviors includes: 63.0% (95% CI: 58.7-67.1%) having enough supplies at home for at least 7 days, 41.3% (95% CI: 37.1-45.6%) having an evacuation plan for their child(ren), 38.7% (95% CI: 34.5-43.0%) having methods to keep in touch, 37.8% (95% CI: 33.7-42.1%) having an emergency meeting place, 36.6% (95% CI: 32.6-40.9%) having an evacuation plan to leave home, 34.9% (95% CI: 30.9-39.2%) having emergency supplies to take with them if they have to leave quickly, 31.8% (95% CI: 27.9-36.0%) having copies of important documents, and 31.6% (95% CI: 27.7-35.8%) having practiced what to do during a disaster. CONCLUSIONS: One in 10 women practiced all 8 behaviors, indicating more awareness efforts are needed among this population in Hawaii. The impact of preparedness interventions implemented in Hawaii can be tracked with this question over time.

    • Disease Reservoirs and Vectors
      1. Preliminary report of the insecticide susceptibility status of Aedes albopictus in Bangladeshexternal icon
        Al-Amin HM, Irish S, Lenhart A, Alam MS.
        Am J Trop Med Hyg. 2021 Sep 27.
        Aedes albopictus is a highly invasive mosquito species and a vector of human arboviral diseases including dengue, chikungunya, and Zika. There are no effective drugs or vaccines for the treatment or prevention of most of these diseases, so the primary option for disease prevention and control is to target mosquitoes, often using insecticides. Despite vector control efforts, cases of arboviral diseases are increasing in Bangladesh and it is important to understand if this escalation is associated with the presence of insecticide resistance in Aedes populations, including Ae. albopictus. The CDC bottle bioassays performed on Ae. albopictus from two districts in Bangladesh detected resistance to permethrin but susceptibility to deltamethrin, malathion, and bendiocarb. The detection of permethrin resistance is worrisome, since arbovirus vector control strategies in Bangladesh currently include the use of permethrin. Routine monitoring of the susceptibility status of key vector populations in Bangladesh will allow a better understanding of resistance trends, enabling the strengthening of control strategies.

      2. Use of mosquitoes to indirectly assess West Nile virus activity among colonial waterbirdsexternal icon
        Felix TA, Young G, Panella NA, Burkhalter KL, Komar N.
        Waterbirds. 2021 ;43(3-4):314-320.
        West Nile virus activity was evaluated within an island waterbird nesting colony with > 1,250 birds at Riverside Reservoir, Weld County, Colorado, USA. To avoid disturbance of nesting birds, blood-engorged mosquitoes (Culex tarsalis) were used to sample blood indirectly from birds rather than capturing, sampling, and releasing live birds. Local virus activity was confirmed by West Nile virus-positive feather samples from 26% of 46 carcasses collected during monthly visits to the colony from June to September 2009, including American White Pelican (Pelecanus erythrorhynchos; n = 7), California Gull (Larus californicus; n = 1), Snowy Egret (Egretta thula; n = 2), and Cattle Egret (Bubulcus ibis; n = 2). Of 22 blood-engorged mosquitoes collected and the blood meal host identified to species, one West Nile virus infection was detected (putatively from a Snowy Egret), and West Nile virus-specific antibodies were detected in eight samples: Snowy Egret (n = 5), Great Blue Heron (Ardea herodias; n = 2), and American White Pelican (n = 1). The engorgement rate of female Culex tarsalis at the nesting colony was 34%, sixfold higher than that at a nearby mainland site of 5.3%. The utilization of mosquitoes for sampling blood from wild animals may have broader application, and potentially reduce human disturbance of sensitive nesting bird species. © 2021 The Waterbird Society. All rights reserved.

    • Environmental Health
      1. The article focuses on the Environmental Health and Land Reuse (EHLR) Certificate Program, an initiative that aims to increase knowledge about the danger of brownfield sites. Topics include the partnership of Agency for Toxic Substances and Disease Registry (ATSDR) with stakeholders throughout the Navajo Nation, the environmental health and land reuse training under the Summer Internship Program (SIP), and the challenges brought by COVID-19 pandemic in implementing the virtual SIP.

      2. Associations of maternal serum perfluoroalkyl substances concentrations with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) Studyexternal icon
        Buckley JP, Kuiper JR, Lanphear BP, Calafat AM, Cecil KM, Chen A, Xu Y, Yolton K, Kalkwarf HJ, Braun JM.
        Environ Health Perspect. 2021 Sep;129(9):97011.
        BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional. OBJECTIVES: We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y. METHODS: Among 206 mother-child pairs enrolled in a prospective cohort (2003-2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) z-scores for six skeletal sites. We estimated covariate-adjusted z-score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child's sex or mediated by whole-body lean mass. RESULTS: In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC z-scores in children. Differences in forearm BMC z-scores were - 0.17 [95% confidence interval (CI): - 0.35, 0.01] and - 0.24 (95% CI: - 0.44, - 0.05) per doubling of PFOA and PFNA, respectively, and - 0.18 (95% CI: - 0.34, - 0.02) per quartile increase in the PFAS mixture. Child's sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD z-score per doubling were - 0.31 (95% CI: - 0.58, - 0.03) among males and 0.07 (95% CI: - 0.16, 0.30) among females (modification p = 0.04). Except for PFNA among females, these associations were not mediated by whole-body lean mass. DISCUSSION: Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence.

      3. Objective: The current population-based study examines the association between county-level ambient air pollution and childhood asthma.Methods: Data from the nationally representative 2010-2015 National Health Interview Survey were linked to nationwide fine particulate matter (PM(2.5)) air pollution data at the county-level from the National Environmental Public Health Tracking Network which utilizes air quality monitoring stations and modeled PM(2.5) measurements (Downscaler model data) and adjusted by county-level socioeconomic characteristics data from the 2010-2015 American Community Survey. Multilevel modeling techniques were used to assess the association between PM(2.5) annual concentrations (quartiles <8.11, 8.11-9.50, 9.51-10.59, ≥ 10.60 µg/m(3)) and current childhood asthma along with two asthma outcomes (episode in the past year, emergency room (ER) visit due to asthma).Results: From 2010-2015, there were significant declines in PM(2.5) concentrations and asthma outcomes. In unadjusted models, children living in areas with higher PM(2.5) concentrations were more likely to have current asthma, ≥1 asthma episode in the past year, and ≥1 ER visit due to asthma compared with children living in areas with the lowest quartile (< 8.11 µg/m(3)). After adjusting for characteristics at the county, geographic, and child and family-level, significant associations remained for asthma episode, and ER visit among children living in areas with PM(2.5) annual concentrations between 9.51-10.59 µg/m(3) (3rd quartile) compared with children living in areas with the lowest quartile.Conclusions: This study adds to the limited literature by incorporating nationally representative county-, child-, and family-level data to provide a multi-level analysis of the associations between air pollution and childhood asthma in the U.S.

      4. Prenatal maternal phthalate exposures and trajectories of childhood adiposity from four to twelve yearsexternal icon
        Kupsco A, Wu H, Calafat AM, Kioumourtzoglou MA, Cantoral A, Tamayo-Ortiz M, Pantic I, Pizano-Zárate ML, Oken E, Braun JM, Deierlein AL, Wright RO, Téllez-Rojo MM, Baccarelli AA, Just AC.
        Environ Res. 2021 Sep 23;204(Pt B):112111.
        BACKGROUND/AIM: Adiposity trajectories reflect dynamic process of growth and may predict later life health better than individual measures. Prenatal phthalate exposures may program later childhood adiposity, but findings from studies examining these associations are conflicting. We investigated associations between phthalate biomarker concentrations during pregnancy with child adiposity trajectories. METHODS: We followed 514 mother-child pairs from the Mexico City PROGRESS cohort from pregnancy through twelve years. We measured concentrations of nine phthalate biomarkers in 2nd and 3rd trimester maternal urine samples to create a pregnancy average using the geometric mean. We measured child BMI z-score, fat mass index (FMI), and waist-to-height ratio (WHtR) at three study visits between four and 12 years of age. We identified adiposity trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We estimated associations of phthalates biomarkers with class membership using multinomial logistic regression. We used quantile g-computation to estimate the potential effect of the total phthalate mixture and assessed effect modification by sex. RESULTS: We identified three trajectories of child adiposity, a "low-stable", a "low-high", and a "high-high" group. A doubling of the sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHP), was associated with 1.53 (1.08, 2.19) greater odds of being in the "high-high" trajectory in comparison to the "low-stable" group, whereas a doubling in di-isononyl phthalate metabolites (ΣDiNP) was associated with 1.43 (1.02, 2.02) greater odds of being in the "low-high" trajectory and mono (carboxy-isononyl) phthalate (MCNP) was associated with 0.66 (0.45, 97) lower odds of being in the "low-high" trajectory. No sex-specific associations or mixture associations were observed. CONCLUSIONS: Prenatal concentrations of urinary DEHP metabolites, DiNP metabolites, and MCNP, a di-isodecyl phthalate metabolite, were associated with trajectories of child adiposity. The total phthalate mixture was not associated with early life child adiposity.

      5. Prenatal exposure to a mixture of organophosphate esters and intelligence among 8-year-old children of the HOME Studyexternal icon
        Percy Z, Vuong AM, Xu Y, Xie C, Ospina M, Calafat AM, Lanphear BP, Braun JM, Cecil KM, Dietrich KN, Chen A, Yolton K.
        Neurotoxicology. 2021 Sep 25;87:149-155.
        Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children's cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior.

      6. Making data-driven decisions for safe waterpdf iconexternal icon
        Sabogal R.
        J Environ Health. 2021 ;84(3):38-40.
        The article focuses on the environmental health programs for the reduction of harmful exposures from wells and private water systems. Topics include the funding opportunities by the Centers for Disease Control and Prevention (CDC) that focus on identifying and accessing private well data sources, the action of Safe Water for Community Health (Safe WATCH) partners in monitoring the quality of well water, and the importance of high-quality in making important public health decisions.

      7. Correlates of persistent endocrine-disrupting chemical mixtures among reproductive-aged Black womenexternal icon
        Schildroth S, Wise LA, Wesselink AK, De La Cruz P, Bethea TN, Weuve J, Fruh V, Botelho JC, Sjodin A, Calafat AM, Baird DD, Claus Henn B.
        Environ Sci Technol. 2021 Sep 30.
        Black women are exposed to multiple endocrine-disrupting chemicals (EDCs), but few studies have examined their profiles of exposure to EDC mixtures. We identified biomarker profiles and correlates of exposure to EDC mixtures in a cross-sectional analysis of data from a prospective cohort study of 749 Black women aged 23-35 years. We quantified plasma concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS) in nonfasting samples collected at baseline. Demographic, behavioral, dietary, and reproductive covariates were also collected at baseline. We used k-means clustering and principal component analysis (PCA) to describe concentration profiles of EDC mixtures (17 PCBs, 6 PBDEs, 4 OCPs, 6 PFAS), followed by multinomial logistic and multivariable linear regression to estimate mean differences in PCA scores (β) and odds ratios (ORs) of cluster membership with their respective 95% confidence intervals (CIs). Older age (per 1 year increase: β = 0.47, CI = 0.39, 0.54; OR = 1.27, CI = 1.20, 1.35), lower body mass index (per 1 kg/m(2) increase: β = -0.14, CI = -0.17, -0.12; OR = 0.91, CI = 0.89, 0.94), and current smoking (≥10 cigarettes/day vs never smokers: β = 1.37, CI = 0.20, 2.55; OR = 2.63, CI = 1.07, 6.50) were associated with profiles characterized by higher concentrations of all EDCs. Other behaviors and traits, including dietary factors and years since last birth, were also associated with EDC mixtures.

      8. 'Pollen potency': the relationship between atmospheric pollen counts and allergen exposureexternal icon
        Tegart LJ, Johnston FH, Borchers Arriagada N, Workman A, Dickinson JL, Green BJ, Jones PJ.
        Aerobiologia. 2021 .
        Pollen allergies are responsible for a considerable global public health burden, and understanding exposure is critical to addressing the health impacts. Atmospheric pollen counts are routinely used as a predictor of risk; however, immune responses are triggered by specific proteins known as allergens, which occur both within and on the surface of the pollen grain. The ratio between atmospheric pollen counts and allergen concentrations (‘pollen potency’) has been shown to be inconsistent, with potentially important implications for pollen monitoring practice. Despite this, there has been no previous synthesis of the literature and our understanding of the factors that influence pollen potency remains poor. We conducted a scoping review with the aim of deriving a current understanding of: (a) the factors that influence pollen potency; (b) its variation through time, between taxa and by location; and (c) the implications for pollen monitoring practice. Our synthesis found that pollen potency is highly variable within and between seasons, and between locations; however, much of this variability remains unexplained and has not been deeply investigated. We found no predictable pollen potency patterns relating to taxon, geography or time, and inconclusive evidence regarding possible driving factors. With respect to human health, the studies in our synthesis generally reported larger associations between atmospheric allergen loads and allergy symptoms than whole pollen counts. This suggests that pollen potency influences public health risk; however, the evidence base remains limited. Further research is needed to better understand both pollen potency variability and its implications for health. © 2021, The Author(s).

      9. Per- and Polyfluoroalkyl Substances Multi-Site Studypdf iconexternal icon
        Uzochukwu C, Weems M, Pavuk M, Bove F, Reh C, Breysse P.
        J Environ Health. 2021 ;84(3):34-37.
        The article provides information on the health effects of drinking water exposed to per- and polyfluoroalkyl substances (PFAS). Topics include the Multi-Site Study (MSS) of the Health Implications of Exposure to PFAS-Contaminated Drinking Water, the establishment of pharmacokinetic modeling and historical reconstruction work groups, and the community engagement efforts to provide answers regarding the potential effects of elevated PFAS level on public health.

    • Food Safety
      1. Novel outbreak-associated food vehicles, United Statesexternal icon
        Whitham HK, Sundararaman P, Dewey-Mattia D, Manikonda K, Marshall KE, Griffin PM, Gleason BL, Subramhanya S, Crowe SJ.
        Emerg Infect Dis. 2021 Oct;27(10):2554-2559.
        Novel outbreak-associated food vehicles (i.e., foods not implicated in past outbreaks) can emerge as a result of evolving pathogens and changing consumption trends. To identify these foods, we examined data from the Centers for Disease Control and Prevention Foodborne Disease Outbreak Surveillance System and found 14,216 reported outbreaks with information on implicated foods. We compared foods implicated in outbreaks during 2007-2016 with those implicated in outbreaks during 1973-2006. We identified 28 novel food vehicles, of which the most common types were fish, nuts, fruits, and vegetables; one third were imported. Compared with other outbreaks, those associated with novel food vehicles were more likely to involve illnesses in multiple states and food recalls and were larger in terms of cases, hospitalizations, and deaths. Two thirds of novel foods did not require cooking after purchase. Prevention efforts targeting novel foods cannot rely solely on consumer education but require industry preventive measures.

    • Health Disparities
      1. Inequalities in glycemic control in youth with type 1 diabetes over time: Intersectionality between socioeconomic position and race and ethnicityexternal icon
        Liese AD, Reboussin BA, Kahkoska AR, Frongillo EA, Malik FS, Imperatore G, Saydah S, Bellatorre A, Lawrence JM, Dabelea D, Mendoza JA.
        Ann Behav Med. 2021 Sep 27.
        BACKGROUND: Racial/ethnic health inequities have been well-documented among youth and young adults with type 1 diabetes (T1D), yet little is known about how socioeconomic position (SEP) intersects with the risk marker of race/ethnicity to predict inequities in longitudinal glycemic control. PURPOSE: To identify patterns of SEP, race/ethnicity, and clinical characteristics that differentiate hemoglobin A1c (HbA1c) trajectories among youth and young adults after T1D diagnosis. METHODS: The SEARCH for Diabetes in Youth cohort includes youth with diabetes diagnosed from 2002 to 2006 and 2008 who were followed through 2015. We analyzed data from 1,313 youth and young adults with T1D with ≥3 HbA1c measures. Classification tree analysis identified patterns of baseline demographic, SEP, and clinical characteristic that best predicted HbA1c trajectories over an average of 8.3 years using group-based trajectory modeling. RESULTS: Two HbA1c trajectories were identified: Trajectory 1 (77%) with lower baseline HbA1c and mild increases (from mean 7.4% to 8.4%) and Trajectory 2 (23%) with higher baseline HbA1c and major increases (from 8.5% to 11.2%). Race/ethnicity intersected with different SEP characteristics among non-Hispanic white (NHW) than in non-whites. Public health insurance predicted high-risk Trajectory 2 membership in non-whites, whereas parental education, household structure, diagnosis age and glucose checking frequency predicted membership for NHW youth and young adults. Two characteristics, race/ethnicity and parental education alone identified 80% of the Trajectory 2 members. CONCLUSIONS: Race/ethnicity intersects with multiple SEP and clinical characteristics among youth and young adults with T1D, which is associated with particularly high risk of poor long-term glycemic control.

      2. Disparities in COVID-19 vaccination status, intent, and perceived access for noninstitutionalized adults, by disability status - National Immunization Survey Adult COVID Module, United States, May 30-June 26, 2021external icon
        Ryerson AB, Rice CE, Hung MC, Patel SA, Weeks JD, Kriss JL, Peacock G, Lu PJ, Asif AF, Jackson HL, Singleton JA.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1365-1371.
        Estimates from the 2019 American Community Survey (ACS) indicated that 15.2% of adults aged ≥18 years had at least one reported functional disability (1). Persons with disabilities are more likely than are those without disabilities to have chronic health conditions (2) and also face barriers to accessing health care (3). These and other health and social inequities have placed persons with disabilities at increased risk for COVID-19-related illness and death, yet they face unique barriers to receipt of vaccination (4,5). Although CDC encourages that considerations be made when expanding vaccine access to persons with disabilities,* few public health surveillance systems measure disability status. To describe COVID-19 vaccination status and intent, as well as perceived vaccine access among adults by disability status, data from the National Immunization Survey Adult COVID Module (NIS-ACM) were analyzed. Adults with a disability were less likely than were those without a disability to report having received ≥1 dose of COVID-19 vaccine (age-adjusted prevalence ratio [aPR] = 0.88; 95% confidence interval [CI] = 0.84-0.93) but more likely to report they would definitely get vaccinated (aPR = 1.86; 95% CI = 1.43-2.42). Among unvaccinated adults, those with a disability were more likely to report higher endorsement of vaccine as protection (aPR = 1.29; 95% CI = 1.16-1.44), yet more likely to report it would be or was difficult to get vaccinated than did adults without a disability (aPR = 2.69; 95% CI = 2.16-3.34). Reducing barriers to vaccine scheduling and making vaccination sites more accessible might improve vaccination rates among persons with disabilities.

      3. Census tract socioeconomic indicators and COVID-19-associated hospitalization rates-COVID-NET surveillance areas in 14 states, March 1-April 30, 2020external icon
        Wortham JM, Meador SA, Hadler JL, Yousey-Hindes K, See I, Whitaker M, O'Halloran A, Milucky J, Chai SJ, Reingold A, Alden NB, Kawasaki B, Anderson EJ, Openo KP, Weigel A, Monroe ML, Ryan PA, Kim S, Reeg L, Lynfield R, McMahon M, Sosin DM, Eisenberg N, Rowe A, Barney G, Bennett NM, Bushey S, Billing LM, Shiltz J, Sutton M, West N, Talbot HK, Schaffner W, McCaffrey K, Spencer M, Kambhampati AK, Anglin O, Piasecki AM, Holstein R, Hall AJ, Fry AM, Garg S, Kim L.
        PLoS One. 2021 ;16(9):e0257622.
        OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

    • Health Economics
      1. Heterogeneity in autism spectrum disorder case-finding algorithms in United States Health Administrative Database analysesexternal icon
        Grosse SD, Nichols P, Nyarko K, Maenner M, Danielson ML, Shea L.
        J Autism Dev Disord. 2021 Sep 28.
        Strengthening systems of care to meet the needs of individuals with autism spectrum disorder (ASD) is of growing importance. Administrative data provide advantages for research and planning purposes, including large sample sizes and the ability to identify enrollment in insurance coverage and service utilization of individuals with ASD. Researchers have employed varying strategies to identify individuals with ASD in administrative data. Differences in these strategies can limit the comparability of results across studies. This review describes implications of the varying strategies that have been employed to identify individuals with ASD in US claims databases, with consideration of the strengths and limitations of each approach.

      2. Public health impacts of underemployment and unemployment in the United States: Exploring perceptions, gaps and opportunitiesexternal icon
        Pratap P, Dickson A, Love M, Zanoni J, Donato C, Flynn MA, Schulte PA.
        Int J Environ Res Public Health. 2021 ;18(19).
        Background: Unemployment, underemployment, and the quality of work are national occupational health risk factors that drive critical national problems; however, to date, there have been no systematic efforts to document the public health impact of this situation. Methods: An environmental scan was conducted to explore the root causes and health impacts of underemployment and unemployment and highlight multilevel perspectives and factors in the landscape of underemploy-ment and unemployment. Methods: included a review of gray literature and research literature, followed by key informant interviews with nine organizational representatives in employment research and policy, workforce development, and industry to assess perceived needs and gaps in practice. Results: Evidence highlights the complex nature of underemployment and unemployment, with multiple macro-level underlying drivers, including the changing nature of work, a dynamic labor market, inadequate enforcement of labor protection standards, declining unions, wage de-pression, and weak political will interacting with multiple social determinants of health. Empirical literature on unemployment and physical, mental, and psychological well-being, substance abuse, depression in young adults, and suicides is quite extensive; however, there are limited data on the impacts of underemployment on worker health and well-being. Additionally, organizations do not routinely consider health outcomes as they relate to their work in workforce or policy development. Discussion and Conclusions: Several gaps in data and research will need to be addressed in order to assess the full magnitude of the public health burden of underemployment and unemployment. Public health needs to champion a research and practice agenda in partnership with multisector stakeholders to illuminate the role of employment quality and status in closing the gap on health inequities, and to integrate workforce health and well-being into labor and economic development agendas across government agencies and industry. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

      3. A Veterans' Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysisexternal icon
        Yoo M, Madaras-Kelly K, Nevers M, Fleming-Dutra KE, Hersh AL, Ying J, Haaland B, Samore M, Nelson RE.
        Infect Control Hosp Epidemiol. 2021 Sep 29:1-7.
        OBJECTIVES: The Core Elements of Outpatient Antibiotic Stewardship provides a framework to improve antibiotic use, but cost-effectiveness data on implementation of outpatient antibiotic stewardship interventions are limited. We evaluated the cost-effectiveness of Core Element implementation in the outpatient setting. METHODS: An economic simulation model from the health-system perspective was developed for patients presenting to outpatient settings with uncomplicated acute respiratory tract infections (ARI). Effectiveness was measured as quality-adjusted life years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug events (ADEs), and healthcare utilization were obtained from the literature. Probabilities for antibiotic treatment and appropriateness, ADEs, hospitalization, and return ARI visits were estimated from 16,712 and 51,275 patient visits in intervention and control sites during the pre- and post-implementation periods, respectively. Data for materials and labor to perform the stewardship activities were used to estimate intervention cost. We performed a one-way and probabilistic sensitivity analysis (PSA) using 1,000,000 second-order Monte Carlo simulations on input parameters. RESULTS: The proportion of ARI patient-visits with antibiotics prescribed in intervention sites was lower (62% vs 74%) and appropriate treatment higher (51% vs 41%) after implementation, compared to control sites. The estimated intervention cost over a 2-year period was $133,604 (2018 US dollars). The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared to usual care. In the PSA, the intervention was dominant in 63% of iterations. CONCLUSIONS: Implementation of the CDC Core Elements in the outpatient setting was a cost-effective strategy.

    • Healthcare Associated Infections
      1. Antimicrobial susceptibility of western hemisphere isolates of Burkholderia pseudomallei: Phenotypic and genomic analysesexternal icon
        Bugrysheva JV, Lascols C, McLaughlin HP, Gee JE, Elrod MG, Sue D.
        Microb Drug Resist. 2021 Sep;27(9):1176-1185.
        Current antimicrobial treatment recommendations for melioidosis, the disease caused by Burkholderia pseudomallei, are largely based on studies of strains isolated from the Eastern Hemisphere (EH), where most human cases are identified and reported. In this study, we evaluated the antimicrobial susceptibility of 26 strains in the CDC (Centers for Diseases Control and Prevention) collection from the Western Hemisphere (WH) isolated from 1960 to 2015. Minimal inhibitory concentration (MIC) values were measured by standard broth microdilution for 16 antimicrobials following Clinical and Laboratory Standards Institute (CLSI) guidelines. Twenty-four of the 26 WH strains were susceptible to the six antimicrobials with CLSI-defined MIC susceptibility interpretive criteria for B. pseudomallei: amoxicillin/clavulanate, ceftazidime, imipenem, doxycycline, tetracycline, and trimethoprim/sulfamethoxazole. One WH strain demonstrated intermediate amoxicillin/clavulanate resistance and another strain had intermediate resistance to tetracycline. For all antimicrobials tested, the susceptibility profiles of WH isolates were comparable with previously reported MIC results of EH strains. The overall similarities suggest that the same antimicrobials are useful for melioidosis treatment in both the WH and EH. Using in silico analyses of WH genomes, we identified a novel amino acid substitution P258S in the beta-lactamase PenA, which may contribute to decreased susceptibility to amoxicillin/clavulanate in B. pseudomallei.

      2. Population genetic structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in children in Argentinaexternal icon
        Gagetti P, Lo SW, Hawkins PA, Gladstone RA, Regueira M, Faccone D, Sireva-Argentina G, Klugman KP, Breiman RF, McGee L, Bentley SD, Corso A.
        Microb Genom. 2021 Sep;7(9).
        Invasive disease caused by Streptococcus pneumoniae (IPD) is one of the leading causes of morbidity and mortality in young children worldwide. In Argentina, PCV13 was introduced into the childhood immunization programme nationwide in 2012 and PCV7 was available from 2000, but only in the private market. Since 1993 the National IPD Surveillance Programme, consisting of 150 hospitals, has conducted nationwide pneumococcal surveillance in Argentina in children under 6 years of age, as part of the SIREVA II-OPS network. A total of 1713 pneumococcal isolates characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, belonging to three study periods: pre-PCV7 era 1998-1999 (pre-PCV), before the introduction of PCV13 2010-2011 (PCV7) and after the introduction of PCV13 2012-2013 (PCV13), were available for inclusion. Fifty-four serotypes were identified in the entire collection and serotypes 14, 5 and 1 represented 50 % of the isolates. Resistance to penicillin was 34.9 %, cefotaxime 10.6 %, meropenem 4.9 %, cotrimoxazole 45 %, erythromycin 21.5 %, tetracycline 15.4 % and chloramphenicol 0.4 %. All the isolates were susceptible to levofloxacin, rifampin and vancomycin. Of 1713 isolates, 1061 (61.9 %) were non-susceptible to at least one antibiotic and 235(13.7 %) were multidrug resistant. A subset of 413 isolates was randomly selected and whole-genome sequenced as part of Global Pneumococcal Sequencing Project (GPS). The genome data was used to investigate the population structure of S. pneumoniae defining pneumococcal lineages using Global Pneumococcal Sequence Clusters (GPSCs), sequence types (STs) and clonal complexes (CCs), prevalent serotypes and their associated pneumococcal lineages and genomic inference of antimicrobial resistance. The collection showed a great diversity of strains. Among the 413 isolates, 73 known and 36 new STs were identified belonging to 38 CCs and 25 singletons, grouped into 52 GPSCs. Important changes were observed among vaccine types when pre-PCV and PCV13 periods were compared; a significant decrease in serotypes 14, 6B and 19F and a significant increase in 7F and 3. Among non-PCV13 types, serogroup 24 increased from 0 % in pre-PCV to 3.2 % in the PCV13 period. Our analysis showed that 66.1 % (273/413) of the isolates were predicted to be non-susceptible to at least one antibiotic and 11.9 % (49/413) were multidrug resistant. We found an agreement of 100 % when comparing the serotype determined by Quellung and WGS-based serotyping and 98.4 % of agreement in antimicrobial resistance. Continued surveillance of the pneumococcal population is needed to reveal the dynamics of pneumococcal isolates in Argentina in post-PCV13. This article contains data hosted by Microreact.

      3. Risk of hemolytic uremic syndrome related to treatment of Escherichia coli O157 infection with different antimicrobial classesexternal icon
        Mody RK, Hoekstra RM, Scott MK, Dunn J, Smith K, Tobin-D'Angelo M, Shiferaw B, Wymore K, Clogher P, Palmer A, Comstock N, Burzlaff K, Lathrop S, Hurd S, Griffin PM.
        Microorganisms. 2021 Sep 21;9(9).
        Treatment of Shiga toxin-producing Escherichia coli O157 (O157) diarrhea with antimicrobials might alter the risk of hemolytic uremic syndrome (HUS). However, full characterization of which antimicrobials might affect risk is lacking, particularly among adults. To inform clinical management, we conducted a case-control study of residents of the FoodNet surveillance areas with O157 diarrhea during a 4-year period to assess antimicrobial class-specific associations with HUS among persons with O157 diarrhea. We collected data from medical records and patient interviews. We measured associations between treatment with agents in specific antimicrobial classes during the first week of diarrhea and development of HUS, adjusting for age and illness severity. We enrolled 1308 patients; 102 (7.8%) developed confirmed HUS. Antimicrobial treatment varied by age: <5 years (12.6%), 5-14 (11.5%), 15-39 (45.4%), ≥40 (53.4%). Persons treated with a β-lactam had higher odds of developing HUS (OR 2.80, CI 1.14-6.89). None of the few persons treated with a macrolide developed HUS, but the protective association was not statistically significant. Exposure to "any antimicrobial" was not associated with increased odds of HUS. Our findings confirm the risk of β-lactams among children with O157 diarrhea and extends it to adults. We observed a high frequency of inappropriate antimicrobial treatment among adults. Our data suggest that antimicrobial classes differ in the magnitude of risk for persons with O157 diarrhea.

      4. Detection and characterization of targeted carbapenem-resistant healthcare-associated threats: Findings from the Antibiotic Resistance Laboratory Network, 2017-2019external icon
        Sabour S, Huang JY, Bhatnagar A, Gilbert SE, Karlsson M, Lonsway D, Lutgring JD, Rasheed JK, Halpin AL, Stanton RA, Gumbis S, Elkins CA, Brown AC.
        Antimicrob Agents Chemother. 2021 Sep 27:Aac0110521.
        Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause. To this end, CDC developed the Antibiotic Resistance Laboratory Network (AR Lab Network), in which public health laboratories across all 50 states, several cities, and Puerto Rico characterize clinical isolates of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), and conduct colonization screens to detect the presence of mobile carbapenemase genes. In its first three years, the AR Lab Network tested 76,887 isolates and 31,001 rectal swab colonization screens. Targeted carbapenemase genes (bla(KPC), bla(NDM), bla(OXA-48-like), bla(VIM), or bla(IMP)) were detected by PCR in 35% of CRE, 2% of CRPA, <1% of CRAB, and 8% of colonization screens tested, respectively. bla(KPC) and bla(VIM) were the most common CP-CRE and CP-CRPA, respectively, but regional differences in the frequency of carbapenemase genes detected were apparent. In CRE and CRPA isolates tested for carbapenemase production and the presence of the targeted genes, 97% had concordant results; 3% of CRE and 2% of CRPA were carbapenemase production-positive but PCR-negative for those genes. Isolates harboring bla(NDM) showed the highest frequency of resistance across the carbapenems tested and those harboring bla(IMP) and bla(OXA-48-like) genes showed the lowest frequency of carbapenem resistance. The AR Lab Network provides a national snapshot of rare and emerging carbapenemase genes, delivering data to inform public health actions to limit the spread of these antibiotic resistance threats.

    • Immunity and Immunization
      1. Vaccination information, motivations, and barriers in the context of meningococcal serogroup A conjugate vaccine introduction: A qualitative assessment among caregivers in Burkina Faso, 2018external icon
        Aksnes BN, Walldorf JA, Nkwenkeu SF, Zoma RL, Mirza I, Tarbangdo F, Fall S, Hien S, Ky C, Kambou L, Diallo AO, Aké FH, Hatcher C, Patel JC, Novak RT, Hyde TB, Medah I, Soeters HM, Jalloh MF.
        Vaccine. 2021 Sep 24.
        BACKGROUND: In March 2017, Burkina Faso introduced meningococcal serogroup A conjugate vaccine (MACV) into the Expanded Programme on Immunization. MACV is administered to children aged 15-18 months, concomitantly with the second dose of measles-containing vaccine (MCV2). One year after MACV introduction, we assessed the sources and content of immunization information available to caregivers and explored motivations and barriers that influence their decision to seek MACV for their children. METHODS: Twenty-four focus group discussions (FGDs) were conducted with caregivers of children eligible for MACV and MCV2. Data collection occurred in February-March 2018 in four purposively selected districts, each from a separate geographic region; within each district, caregivers were stratified into groups based on whether their children were unvaccinated or vaccinated with MACV. FGDs were recorded and transcribed. Transcripts were coded and analyzed using qualitative content analysis. RESULTS: We identified many different sources and content of information about MACV and MCV2 available to caregivers. Healthcare workers were most commonly cited as the main sources of information; caregivers also received information from other caregivers in the community. Caregivers' motivations to seek MACV for their children were driven by personal awareness, engagements with trusted messengers, and perceived protective benefits of MACV against meningitis. Barriers to MACV and MCV2 uptake were linked to the unavailability of vaccines, immunization personnel not providing doses, knowledge gaps about the 15-18 month visit, practical constraints, past negative experiences, sociocultural influences, and misinformation, including misunderstanding about the need for MCV2. CONCLUSIONS: MACV and MCV2 uptake may be enhanced by addressing vaccination barriers and effectively communicating vaccination information and benefits through trusted messengers such as healthcare workers and other caregivers in the community. Educating healthcare workers to avoid withholding vaccines, likely due to fear of wastage, may help reduce missed opportunities for vaccination.

      2. The rotavirus vaccine story: From discovery to the eventual control of rotavirus diseaseexternal icon
        Glass RI, Tate JE, Jiang B, Parashar U.
        J Infect Dis. 2021 Sep 30;224(Supplement_4):S331-s342.
        Worldwide, rotavirus is the leading pathogen causing severe diarrhea in children and a major cause of under 5 years mortality. In 1998, the first rotavirus vaccine, RotaShield, was licensed in the United States but a rare adverse event, intussusception, led to its withdrawal. Seven years passed before the next generation of vaccines became available, Rotarix (GSK) and Rotateq (Merck), and 11 years later, 2 additional vaccines from India, Rotavac (Bharat) and Rotasiil (Serum Institute), were recommended by World Health Organization for all children. Today, these vaccines are used in more than 100 countries and have contributed to marked decreases in hospitalizations and deaths from diarrhea. However, these live oral vaccines are less effective in low-income countries with high under 5 years mortality for reasons that are not understood. Efforts to develop new vaccines that avoid the oral route are in progress and will likely be needed to ultimately control rotavirus disease.

      3. Safety monitoring of an additional dose of COVID-19 vaccine - United States, August 12-September 19, 2021external icon
        Hause AM, Baggs J, Gee J, Marquez P, Myers TR, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1379-1384.
        On August 12, 2021, the Food and Drug Administration (FDA) amended Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech and Moderna COVID-19 vaccines to authorize administration of an additional dose after completion of a primary vaccination series to eligible persons with moderate to severe immunocompromising conditions (1,2). On September 22, 2021, FDA authorized an additional dose of Pfizer-BioNTech vaccine ≥6 months after completion of the primary series among persons aged ≥65 years, at high risk for severe COVID-19, or whose occupational or institutional exposure puts them at high risk for COVID-19 (1). Results from a phase 3 clinical trial conducted by Pfizer-BioNTech that included 306 persons aged 18-55 years showed that adverse reactions after receipt of a third dose administered 5-8 months after completion of a 2-dose primary mRNA vaccination series were similar to those reported after receipt of dose 2; these adverse reactions included mild to moderate injection site and systemic reactions (3). CDC developed v-safe, a voluntary, smartphone-based safety surveillance system, to provide information on adverse reactions after COVID-19 vaccination. Coincident with authorization of an additional dose for persons with immunocompromising conditions, the v-safe platform was updated to allow registrants to enter information about additional doses of COVID-19 vaccine received. During August 12-September 19, 2021, a total of 22,191 v-safe registrants reported receipt of an additional dose of COVID-19 vaccine. Most (97.6%) reported a primary 2-dose mRNA vaccination series followed by a third dose of the same vaccine. Among those who completed a health check-in survey for all 3 doses (12,591; 58.1%), 79.4% and 74.1% reported local or systemic reactions, respectively, after dose 3, compared with 77.6% and 76.5% who reported local or systemic reactions, respectively, after dose 2. These initial findings indicate no unexpected patterns of adverse reactions after an additional dose of COVID-19 vaccine; most of these adverse reactions were mild or moderate. CDC will continue to monitor vaccine safety, including the safety of additional doses of COVID-19 vaccine, and provide data to guide vaccine recommendations and protect public health.

      4. Human papillomavirus vaccinesexternal icon
        Markowitz LE, Schiller JT.
        J Infect Dis. 2021 Sep 30;224(Supplement_4):S367-s378.
        Human papillomavirus (HPV) vaccines are among the most effective vaccines available, the first to prevent infection by a mucosatropic sexually transmitted infectious agent and to do so without specific induction of mucosal immunity. Currently available prophylactic HPV vaccines are based on virus-like particles that self-assemble spontaneously from the L1 major capsid protein. The first HPV vaccine was licensed in 2006. All vaccines target HPV-16 and HPV-18, types which cause the majority of HPV-attributable cancers. As of 2020, HPV vaccines had been introduced into national immunization programs in more than 100 countries. Vaccination polices have evolved; most programs target vaccination of young adolescent girls, with an increasing number also including boys. The efficacy and safety found in prelicensure trials have been confirmed by data from national immunization programs. The dramatic impact and effectiveness observed has stimulated interest in ambitious disease reduction goals.

      5. Overview of the United States' immunization programexternal icon
        Roper L, Hall MA, Cohn A.
        J Infect Dis. 2021 Sep 30;224(Supplement_4):S443-s451.
        This manuscript describes the history, background, and current structure of the United States Immunization Program, founded upon public- and private-sector partnerships that include federal agencies, state and local health departments, tribal nations and organizations, healthcare providers, vaccine manufacturers, pharmacies, and a multitude of additional stakeholders. The Centers for Disease Control and Prevention sets the U.S. adult and childhood immunization schedules based on recommendations from the Advisory Committee on Immunization Practices. We review the current immunization schedules; describe the set of surveillance and other systems used to monitor the health impact, coverage levels, and safety of recommended vaccines; and note significant challenges. Vaccines have reduced the incidence of many diseases to historic lows in the US, and have potential to further reduce the burden of respiratory and other infectious diseases in the United States. Though the United States vaccination program has had notable successes in reducing morbidity and mortality from infectious disease, challenges-including disparities in access and vaccine hesitancy-remain. Supporting access to and confidence in vaccines as an essential public health intervention will not only protect individuals from vaccine-preventable diseases; it will also ensure the country is prepared for the next pandemic.

    • Injury and Violence
      1. Testing the nurturing environments framework on youth violence across ethnically and geographically diverse urban and rural samples of adolescentsexternal icon
        Kingston B, Smokowski PR, MacFarland A, Evans CB, Pampel F, Mercado MC, Vagi KJ, Spies EL.
        Youth Soc. 2021 Jul 7;53(5):784-810.
        Although research advocates for comprehensive cross sector youth violence prevention efforts, mobilizing across sectors to translate scientific recommendations into practice has proven challenging. A unifying framework may provide a foundational step towards building a shared understanding of the risk and protective factors that impact youth violence. We conducted two empirical tests of the nurturing environment framework on youth violence across ethnic and geographically diverse rural and urban adolescent samples. Results show that overall the characteristics of nurturing environments are associated with lower levels of aggression and violence. In addition, minimizing exposure to socially toxic conditions had the strongest associations with lower aggression and violence. Findings were supported across both samples, suggesting that this framework may apply in urban and rural, economically disadvantaged contexts.

      2. Effect of parental education and household poverty on recovery after traumatic brain injury in school-aged childrenexternal icon
        Zonfrillo MR, Haarbauer-Krupa J, Wang J, Durbin D, Jaffe KM, Temkin N, Bell M, Tulsky DS, Bertisch H, Yeates KO, Rivara FP.
        Brain Inj. 2021 Sep 16:1-11.
        OBJECTIVE: While prior studies have found parental socioeconomic status (SES) affects the outcomes of pediatric traumatic brain injury (TBI), the longitudinal trajectory of this effect is not well understood. METHODS: This prospective cohort study included children 8-18 years of age admitted to six sites with a complicated mild (n = 123) or moderate-severe TBI (n = 47). We used caregiver education and household poverty level as predictors, and multiple quality of life and health behavior domains as outcomes. Differences at 6, 12, and 24 months from baseline ratings of pre-injury functioning were compared by SES. We examined the association between measures of SES and domains of functioning over the 24 months post-injury in children with a complicated mild or moderate- severe TBI, and determined how this association varied over time. RESULTS: Parental education was associated with recovery among children with complicated mild TBI; outcomes at 6, 12, and 24 months were substantially poorer than at baseline for children with the least educated parents. After moderate-severe TBI, children in households with lower incomes had poorer outcomes compared to baseline across time. IMPLICATIONS: Parental education and household income were associated with recovery trajectories for children with TBI of varying severity.

    • Laboratory Sciences
      1. Development of nucleic-acid lateral flow immunoassay for rapid and accurate detection of Chikungunya virus in Indonesiaexternal icon
        Ajie M, Pascapurnama DN, Prodjosoewojo S, Kusumawardani S, Djauhari H, Handali S, Alisjahbana B, Chaidir L.
        J Microbiol Biotechnol. 2021 Sep 30;31(12).
        Chikungunya fever is an arboviral disease caused by the Chikungunya virus (CHIKV). The disease has similar clinical manifestations with other acute febrile illnesses which complicates differential diagnosis in low-resource settings. We aimed to develop a rapid test for CHIKV detection based on the nucleic acid lateral flow immunoassay technology. The system consisted of a primer set that recognized the E1 region of the CHIKV genome and tagged with FITC/biotin and test strips in an in-housed cassette which detects amplicons labeled with FITC/biotin. Amplification of the viral genome was done using open-source PCR, a low-cost open-source thermal cycler. Assay performance was evaluated using a panel of RNA isolated from patients' blood with confirmed CHIKV (n=8) and dengue virus (n=20) infection. The open-source PCR-NALFIA platform had a limit of detection of 10 RNA copies/ml. The assay had a sensitivity and specificity of 100% (95% CI: 67.56% - 100%) and 100% (95% CI: 83.89% - 100%), respectively, compared to reference standards of any positive virus culture on C6/36 cell lines and/or qRT-PCR. Further evaluation of its performance using a larger sample size may provide important data to extend its usefulness, especially its utilization in the peripheral healthcare facilities with scarce resources and outbreak situations.

      2. Delayed lactose utilization among Shiga toxin-producing Escherichia coli of serogroup O121external icon
        Gill A, McMahon T, Dussault F, Jinneman K, Lindsey R, Martin H, Stoneburg D, Strockbine N, Wetherington J, Feng P.
        Food Microbiol. 2022 ;102.
        Two outbreaks of Shiga toxin-producing Escherichia coli O121:H19 associated with wheat flour, in the United States of America and Canada, involved strains with an unusual phenotype, delayed lactose utilization (DLU). These strains do not ferment lactose when initially cultured on MacConkey agar (MAC), but lactose fermentation occurs following subculture to a second plate of MAC. The prevalence of DLU was determined by examining the β-galactosidase activity of 49 strains of E. coli O121, and of 37 other strains of E. coli. Twenty four of forty three O121:H19 and one O121:NM displayed DLU. Two strains (O121:NM and O145:H34) did not have detectable β-galactosidase activity. β-glucuronidase activity of O121 strains was also determined. All but six DLU strains had normal β-glucuronidase activity. β-glucuronidase activity was suppressed on MAC for 17 of 23 O121 non-DLU strains. Genomic analysis found that DLU strains possessed an insertion sequence, IS600 (1267 bp), between lacZ (β-galactosidase) and lacY (β-galactoside permease), that was not present in strains exhibiting normal lactose utilization. The insert might reduce the expression of β-galactoside permease, delaying import of lactose, resulting in the DLU phenotype. The high probability of DLU should be considered when using lactose-containing media for the isolation of STEC O121. © 2021

      3. Detection of Victoria lineage influenza B viruses with K162 and N163 deletions in the hemagglutinin gene, South Africa, 2018external icon
        Hellferscee O, Treurnicht F, Gaelejwe L, Moerdyk A, Reubenson G, McMorrow M, Tempia S, McAnerney J, Walaza S, Wolter N, von Gottberg A, Cohen C.
        Health Sci Rep. 2021 Sep;4(3):e367.
        BACKGROUND: A group of Victoria lineage influenza B viruses with a two amino acid deletion in the hemagglutinin (HA) at residues K162 and N163, was detected during the 2016 to 2017 Northern Hemisphere influenza season and continues to spread geographically. We describe the first identification of viruses with these deletions from South Africa in 2018. METHODS: Nasopharyngeal samples were obtained from the syndromic surveillance programs. Real-time reverse transcription-polymerase chain reaction was used for virus detection and lineage determination. Influenza genetic characterization was done using next-generation sequencing on the MiSeq platform. The duration of virus circulation was determined using thresholds calculated using the Moving Epidemic Method; duration was used as an indicator of disease transmissibility and impact. RESULTS: In 2018, 42% (426/1015) of influenza-positive specimens were influenza B viruses. Of 426 influenza B-positive samples, 376 (88%) had the lineage determined of which 75% (283/376) were Victoria lineage. The transmissibility of the 2018 South African influenza season was high for a few weeks, although the severity remained moderate through most of the season. The sequenced 2018 South African Victoria lineage influenza B viruses clustered in sub-clade V1A.1 with the 162-163 deletions. CONCLUSIONS: We report the first detection of the 162-163 deletion variant of influenza B/Victoria viruses from South Africa in 2018, and suggest that this deletion variant replaced the previous circulating influenza B/Victoria viruses. These deletions putatively affect the antigenic properties of the viruses because they border an immune-dominant region at the tip of the HA. Therefore, close monitoring of these newly emerging viruses is essential.

      4. Review and meta-analysis of the evidence for choosing between specific pyrethroids for programmatic purposesexternal icon
        Lissenden N, Kont MD, Essandoh J, Ismail HM, Churcher TS, Lambert B, Lenhart A, McCall PJ, Moyes CL, Paine MJ, Praulins G, Weetman D, Lees RS.
        Insects. 2021 Sep 14;12(9).
        Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays were conducted to answer these questions. Evidence suggested that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin, and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide-resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work is needed to examine how this may apply to insecticide resistance management.

      5. The development of insecticide resistance in malaria vectors is of increasing concern in Ethiopia because of its potential implications for vector control failure. To better elucidate the specificity of resistance mechanisms and to facilitate the design of control strategies that minimize the likelihood of selecting for cross-resistance, a whole transcriptomic approach was used to explore gene expression patterns in a multi-insecticide resistant population of Anopheles arabiensis from Oromia Region, Ethiopia. This field population was resistant to the diagnostic doses of malathion (average mortality of 71.9%) and permethrin (77.4%), with pools of survivors and unexposed individuals analyzed using Illumina RNA-sequencing, alongside insecticide susceptible reference strains. This population also demonstrated deltamethrin resistance but complete susceptibility to alpha-cypermethrin, bendiocarb and propoxur, providing a phenotypic basis for detecting insecticide-specific resistance mechanisms. Transcriptomic data revealed overexpression of genes including cytochrome P450s, glutathione-s-transferases and carboxylesterases (including CYP4C36, CYP6AA1, CYP6M2, CYP6M3, CYP6P4, CYP9K1, CYP9L1, GSTD3, GSTE2, GSTE3, GSTE4, GSTE5, GSTE7 and two carboxylesterases) that were shared between malathion and permethrin survivors. We also identified nineteen highly overexpressed cuticular-associated proteins (including CYP4G16, CYP4G17 and chitinase) and eighteen salivary gland proteins (including D7r4 short form salivary protein), which may be contributing to a non-specific resistance phenotype by either enhancing the cuticular barrier or promoting binding and sequestration of insecticides, respectively. These findings provide novel insights into the molecular basis of insecticide resistance in this lesser well-characterized major malaria vector species.

      6. AIMS: Growing evidence suggests that Gulf War Illness (GWI) is the result of underlying neuroimmune dysfunction. For example, previously we found that several GWI-relevant organophosphate acetylcholinesterase inhibitors produce heightened neuroinflammatory responses following subchronic exposure to stress hormone as a mimic of high physiological stress. The goal of the current study was to evaluate the potential for the β-adrenergic receptor inhibitor and anti-inflammatory drug, propranolol, to treat neuroinflammation in a novel long-term mouse model of GWI. MAIN METHODS: Adult male C57BL/6J mice received a subchronic exposure to corticosterone (CORT) at levels mimicking high physiological stress followed by exposure to the sarin surrogate, diisopropyl fluorophosphate (DFP). These mice were then re-exposed to CORT every other week for a total of five weeks, followed by a systemic immune challenge with lipopolysaccharide (LPS). Animals receiving the propranolol treatment were given a single dose (20 mg/kg, i.p.) either four or 11 days prior to the LPS challenge. The potential anti-neuroinflammatory effects of propranolol were interrogated by analysis of cytokine mRNA expression. KEY FINDINGS: We found that our long-term GWI model produces a primed neuroinflammatory response to subsequent immune challenge that is dependent upon GWI-relevant organophosphate exposure. Propranolol treatment abrogated the elaboration of inflammatory cytokine mRNA expression in the brain instigated in our model, having no treatment effects in non-DFP exposed groups. SIGNIFICANCE: Our results indicate that propranolol may be a promising therapy for GWI with the potential to treat the underlying neuroinflammation associated with the illness.

      7. Comparison of three Coxiella burnetii infectious routes in miceexternal icon
        Miller HK, Priestley RA, Kersh GJ.
        Virulence. 2021 Dec;12(1):2562-2570.
        Evidence suggests that Coxiella burnetii, which is shed in the milk, urine, feces, and birth products of infected domestic ruminants, can lead to Q fever disease following consumption of unpasteurized dairy products; however, C. burnetii is not believed to be a major gastrointestinal pathogen. Most infections are associated with inhalation of aerosols generated from the excreta of domestic ruminants. We recently demonstrated that C. burnetii delivered by oral gavage (OG) resulted in dissemination and an immune response; however, it is unclear how infection via the oral route compares to other well-established routes. Therefore, we delivered three strains of C. burnetii (representing three pertinent sequence types in the United States, such as ST16, ST20, and ST8) to immunocompetent mice in four doses via aerosol challenge (AC), intraperitoneal injection (IP), or OG. Low dose (10^5) of ST16 by OG was insufficient to cause infection, yet doses 1,000- or 100-fold lower by IP or AC, respectively, induced a robust immune response and dissemination. Despite being able to induce an immune response in a dose-dependent manner, administration of C. burnetii via OG is the least efficient route tested. Not only were the immune responses and bacterial loads diminished in mice exposed by OG relative to AC or IP, the efficiency of transmission was also inferior. High doses (10^8) were not sufficient to ensure transmission to 100% of the ST20 or ST8 cohorts. These results may provide some basis for why ingestion of C. burnetii as a mode of Q fever transmission is not often reported.

      8. Feasibility and performance of self-collected nasal swabs for detection of influenza virus, respiratory syncytial virus, and human metapneumovirusexternal icon
        Suntarattiwong P, Mott JA, Mohanty S, Sinthuwattanawibool C, Srisantiroj N, Patamasingh Na Ayudhaya O, Klungthong C, Fernandez S, Kim L, Hunt D, Hombroek D, Brummer T, Chotpitayasunondh T, Dawood FS, Kittikraisak W.
        J Infect Dis. 2021 Sep 1;224(5):831-838.
        BACKGROUND: We assessed performance of participant-collected midturbinate nasal swabs compared to study staff-collected midturbinate nasal swabs for the detection of respiratory viruses among pregnant women in Bangkok, Thailand. METHODS: We enrolled pregnant women aged ≥18 years and followed them throughout the 2018 influenza season. Women with acute respiratory illness self-collected midturbinate nasal swabs at home for influenza viruses, respiratory syncytial viruses (RSV), and human metapneumoviruses (hMPV) real-time RT-PCR testing and the study nurse collected a second midturbinate nasal swab during home visits. Paired specimens were processed and tested on the same day. RESULTS: The majority (109, 60%) of 182 participants were 20-30 years old. All 200 paired swabs had optimal specimen quality. The median time from symptom onsets to participant-collected swabs was 2 days and to staff-collected swabs was also 2 days. The median time interval between the 2 swabs was 2 hours. Compared to staff-collected swabs, the participant-collected swabs were 93% sensitive and 99% specific for influenza virus detection, 94% sensitive and 99% specific for RSV detection, and 100% sensitive and 100% specific for hMPV detection. CONCLUSIONS: Participant-collected midturbinate nasal swabs were a valid alternative approach for laboratory confirmation of influenza-, RSV-, and hMPV-associated illnesses among pregnant women in a community setting.

      9. BACKGROUND: Plasmodium spp. sporozoite rates in mosquitoes are used to better understand malaria transmission intensity, the relative importance of vector species and the impact of interventions. These rates are typically estimated using an enzyme-linked immunosorbent assay (ELISA) utilizing antibodies against the circumsporozoite protein of Plasmodium falciparum, Plasmodium vivax VK210 (P. vivax210) or P. vivax VK247 (P. vivax247), employing assays that were developed over three decades ago. The ELISA method requires a separate assay plate for each analyte tested and can be time consuming as well as requiring sample volumes not always available. The bead-based multiplex platform allows simultaneous measurement of multiple analytes and may improve the lower limit of detection for sporozoites. METHODS: Recombinant positive controls for P. falciparum, P. vivax210 and P. vivax247 and previously developed circumsporozoite (cs) ELISA antibodies were used to optimize conditions for the circumsporozoite multiplex bead assay (csMBA) and to determine the detection range of the csMBA. After optimizing assay conditions, known amounts of sporozoites were used to determine the lower limit of detection for the csELISA and csMBA and alternate cut-off measures were applied to demonstrate how cut-off criteria can impact lower limits of detection. Sporozoite rates from 1275 mosquitoes collected in Madagascar and 255 mosquitoes collected in Guinea were estimated and compared using the established csELISA and newly optimized csMBA. All mosquitoes were tested (initial test), and those that were positive were retested (retest). When sufficient sample volume remained, an aliquot of homogenate was boiled and retested (boiled retest), to denature any heat-unstable cross-reactive proteins. RESULTS: Following optimization of the csMBA, the lower limit of detection was 25 sporozoites per mosquito equivalent for P. falciparum, P. vivax210 and P. vivax247 whereas the lower limits of detection for csELISA were found to be 1400 sporozoites for P. falciparum, 425 for P. vivax210 and 1650 for P. vivax247. Combined sporozoite rates after re-testing of samples that initially tested positive for Madagascar mosquitoes by csELISA and csMBA were 1.4 and 10.3%, respectively, and for Guinea mosquitoes 2% by both assays. Boiling of samples followed by csMBA resulted in a decrease in the Madagascar sporozoite rate to 2.8-4.4% while the Guinea csMBA sporozoite rate remained at 2.0%. Using an alternative csMBA cut-off value of median fluorescence intensity (MFI) of 100 yielded a sporozoite rate after confirmational testing of 3.7% for Madagascar samples and 2.0% for Guinea samples. Whether using csMBA or csELISA, the following steps may help minimize false positives: specimens are appropriately stored and bisected anterior to the thorax-abdomen junction, aliquots of homogenate are boiled and retested following initial testing, and an appropriate cut-off value is determined. CONCLUSIONS: The csMBA is a cost-comparable and time saving alternative to the csELISA and may help eliminate false negatives due to a lower limit of detection, thus increasing sensitivity over the csELISA. The csMBA expands the potential analyses that can be done with a small volume of sample by allowing multiplex testing where analytes in addition to P. falciparum, P. vivax210 and P. vivax247 can be added following optimization.

      10. Comparison of four enzymatic library preparation kits for sequencing Shiga toxin-producing Escherichia coli for surveillance and outbreak detectionexternal icon
        Truong J, Poates A, Joung YJ, Sabol A, Griswold T, Williams-Newkirk AJ, Lindsey R, Trees E.
        J Microbiol Methods. 2021 Sep 22;190:106329.
        Four enzymatic DNA library preparation kits were compared for sequencing Shiga toxin-producing E. coli. All kits produced high quality sequence data which performed equally well in the downstream analyses for surveillance and outbreak detection. Important differences were noted in the workflow user-friendliness and per sample cost.

      11. Development of a new peptide-bead coupling method for an all peptide-based Luminex multiplexing assay for detection of Plasmodium falciparum antibody responsesexternal icon
        Wakeman BS, Shakamuri P, McDonald MA, Weinberg J, Svoboda P, Murphy MK, Kariuki S, Mace K, Elder E, Rivera H, Qvarnstrom Y, Pohl J, Shi YP.
        J Immunol Methods. 2021 Sep 21:113148.
        Using a recombinant protein antigen for antibody testing shows a sum of antibody responses to multiple different immune epitopes existing in the protein antigen. In contrast, the antibody testing to an immunogenic peptide epitope reflects a singular antibody response to the individual peptide epitope. Therefore, using a panel of peptide epitopes provides an advantage for profiling multiple singular antibody responses with potential to estimate recent malaria exposure in human infections. However, transitioning from malaria immune epitope peptide-based ELISA to an all peptide bead-based multiplex Luminex assay presents some challenges including variation in the ability of different peptides to bind beads. The aim of this study was to develop a peptide coupling method while demonstrating the utility of these peptide epitopes from multiple stage antigens of Plasmodium falciparum for measuring antibodies. Successful coupling of peptide epitopes to beads followed three steps: 1) development of a peptide tag appended to the C-terminus of each peptide epitope consisting of beta-alanine-lysine (x 4)--cysteine, 2) bead modification with a high concentration of adipic acid dihydrazide, and 3) use of the peptide epitope as a blocker in place of the traditional choice, bovine serum albumin (BSA). This new method was used to couple 12 peptide epitopes from multiple stage specific antigens of P. falciparum, 1 Anopheles mosquito salivary gland peptide, and 1 Epstein-Barr virus peptide as an assay control. The new method was applied to testing of IgG in pooled samples from 30 individuals with previously repeated malaria exposure in western Kenya and IgM and IgG in samples from 37 U.S. travelers with recent exposure to malaria. The new peptide-bead coupling method and subsequent multiplex Luminex assay showed reliable detection of IgG to all 14 peptides in Kenyan samples. Among 37 samples from U.S. travelers recently diagnosed with malaria, IgM and IgG to the peptide epitopes were detected with high sensitivity and variation. Overall, the U.S. travelers had a much lower positivity rates of IgM than IgG to different peptide epitopes, ranging from a high of 62.2% positive for one epitope to a low of only 5.4% positive for another epitope. In contrast, the travelers had IgG positive rates from 97.3% to 91.9% to various peptide epitopes. Based on the different distribution in IgM and IgG positivity to overall number of peptide epitopes and to the number of pre-erythrocytic, erythrocytic, gametocytic, and salivary stage epitopes at the individual level, four distinct patterns of IgM and IgG responses among the 37 samples from US travelers were observed. Independent peptide-bead coupling and antibody level readout between two different instruments also showed comparable results. Overall, this new coupling method resolves the peptide-bead coupling challenge, is reproducible, and can be applied to any other immunogenic peptide epitopes. The resulting all peptide bead-based multiplex Luminex assay can be expanded to include other peptide epitopes of P. falciparum, different malaria species, or other diseases for surveillance, either in US travelers or endemic areas.

      12. Use of real-time PCR as an alternative to conventional genotyping methods for the laboratory detection of lymphogranuloma venereum (LGV)external icon
        Woodson EN, Katz SS, Mosley SS, Danavall DC, Bowden KE, Chi KH, Raphael BH.
        Diagn Microbiol Infect Dis. 2021 Aug 27;101(4):115532.
        Lymphogranuloma venereum (LGV) can be differentiated from non-LGV chlamydial infection using Sanger sequencing or molecular assays, including those that are commercially-available internationally. Here, we describe the performance of a rapid real-time PCR (RT-PCR)-based strategy in differentiating Chlamydia trachomatis infections associated with LGV or non-LGV serovars. One hundred three rectal swabs, previously genotyped using Sanger sequencing of the ompA gene as a reference method, were tested in the RT-PCR assays. All non-LGV specimens were correctly identified, but the RT-PCR failed to detect 1 LGV specimen, resulting in a sensitivity of 87.5% for the non-LGV/LGV RT-PCR assay. Additional performance characteristics (e.g., specificity, accuracy, and reproducibility) were all between 93% and 100% with a limit of detection ≤100 copies/reaction. Thus, this rapid RT-PCR method for LGV detection in clinical specimens is comparable to the reference method.

      13. Confirmation of Rickettsia conorii subspecies indica infection by next-generation sequencing, Shandong, Chinaexternal icon
        Xu N, Gai W, Zhang Y, Wang W, Wang G, Dasch GA, Eremeeva ME.
        Emerg Infect Dis. 2021 Oct;27(10):2691-2694.
        We describe 3 similar cases of rickettsial disease that occurred after tick bites in a mountainous rural area of Shandong Province, China. Next-generation sequencing indicated the etiologic agent of 1 patient was Rickettsia conorii subspecies indica. This agent may be more widely distributed across China than previously thought.

    • Maternal and Child Health
      1. Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) networkexternal icon
        Breiman RF, Blau DM, Mutevedzi P, Akelo V, Mandomando I, Ogbuanu IU, Sow SO, Madrid L, El Arifeen S, Garel M, Thwala NB, Onyango D, Sitoe A, Bassey IA, Keita AM, Alemu A, Alam M, Mahtab S, Gethi D, Varo R, Ojulong J, Samura S, Mehta A, Ibrahim AM, Rahman A, Vitorino P, Baillie VL, Agaya J, Tapia MD, Assefa N, Chowdhury AI, Scott JA, Gurley ES, Kotloff KL, Jambai A, Bassat Q, Tippett-Barr BA, Madhi SA, Whitney CG.
        PLoS Med. 2021 Sep 30;18(9):e1003814.
        BACKGROUND: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. METHODS AND FINDINGS: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. CONCLUSIONS: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

    • Nutritional Sciences
      1. Lower diet quality is a leading preventable risk factor for obesity and chronic diseases. This study assesses differences in the nutritional quality of at-home food purchases, using the Healthy Eating Index (HEI)-2015 and its components, among households with and without a member reporting type 2 diabetes (T2D), cardiovascular disease (CVD), obesity, and/or smoking. We use the 2015 IRI Consumer Network nationally representative household food purchase scanner data, combined with the IRI MedProfiler and the USDA's Purchase-to-Plate Crosswalk datasets. For each/multiple condition(s), the difference in mean HEI score adjusted for covariates is tested for equivalence with the respective score against households without any member with the condition(s). The HEI score is higher for households without a member with reported T2D (2.4% higher), CVD (3.2%), obesity (3.3%), none of the three conditions (6.1%, vs. all three conditions), and smoking (10.5%) than for those with a member with the respective condition. Households with a member with T2D score better on the added sugar component than those with no member reporting T2D. We found that the average food purchase quality is lower than the recommended levels, especially for households with at least one member reporting a chronic condition(s).

    • Occupational Safety and Health
      1. Persistence of SARS-Co-V-2 on N95 filtering facepiece respirators: implications for reuseexternal icon
        Fisher EM, Kuhlman MR, Choi YW, Jordan TL, Sunderman M.
        J Occup Environ Hyg. 2021 Sep 27:1-11.
        In response to the shortage of N95 filtering facepiece respirators for healthcare workers during the COVID-19 pandemic, the Centers for Disease Control and Prevention issued guidance for extended use and limited reuse of N95 FFRs to conserve supply. Previously worn N95 filtering facepiece respirators can serve as a source of pathogens, which can be transferred to the wearer while doffing and donning a respirator when practicing reuse. When practicing limited filtering facepiece respirators reuse, to reduce the risk of self-contamination, the Centers for Disease Control and Prevention recommends storing filtering facepiece respirators for five days between uses to allow for the decay of viable pathogens including SARS-CoV-2. This study assesses the persistence of the SARS-CoV-2 strain USA-WA1/2020 on N95 filtering facepiece respirators under controlled storage conditions for up to five days to inform the Centers for Disease Control and Prevention guidance. Coupons excised from six N95 filtering facepiece respirator models and glass slide coverslips were inoculated with the virus in a defined culture medium and in human saliva and stored at 20 °C and 20%, 45%, and 75% relative humidity. Statistically significant differences in SARS-CoV-2 half-lives were measured among the tested humidity levels with half-lives decreasing from an average of approximately 30 hours at 20% relative humidity to approximately 2 hours at 75% relative humidity. Significant differences in virus half-lives were also observed between the culture medium and saliva suspension media at 20% and 45% relative humidity with half lives up to 2.9 times greater when the virus was suspended in cell culture medium. The five-day storage strategy, assessed in this study, resulted in a minimum of 93.4% reduction in viable virus for the most challenging condition (20% relative humidity, cell culture medium) and exceeding 99% reduction in virus at all other conditions.

      2. Impact of occupational heat stress on worker productivity and economic costexternal icon
        Morrissey MC, Brewer GJ, Williams WJ, Quinn T, Casa DJ.
        Am J Ind Med. 2021 Sep 29.
        Heat stress is a growing concern in the occupational setting as it endangers worker health, safety, and productivity. Heat-related reductions in physical work capacity and missed workdays directly and indirectly cause productivity losses and may substantially affect the economic wellbeing of the organization. This review highlights the physiological, physical, psychological, and financial harms of heat stress on worker productivity and proposes strategies to quantify heat-related productivity losses. Heat stress produces a vicious-cycle feedback loop that result in adverse outcomes on worker health, safety, and productivity. We propose a theoretical model for implementing an occupational heat safety plan that disrupts this loop, preventing heat-related productivity losses while improving worker health and safety.

      3. Work has become increasingly technologically driven and fast paced, with long work hours, new/emerging hazards, and rising health care costs. Threats to worker safety, health, and well-being including non-traditional work arrangements and practices, precarious work, uncertain hazardous exposures, and work organization issues, such as heavy workloads, design of work, uneven work hours, and difficult interpersonal relationships among workers and managers are apparent. Furthermore, the relationship between personal health risk factors and workplace risks and exposures has drawn increased attention and concern. As employer economic pressures continue to build, it is anticipated that ethical dilemmas for practitioners will become increasingly complex. A review of relevant Total Worker Health (TWH) literature, related ethical constructs and competencies, an examination of codes of ethics for occupational safety and health and health promotion/education disciplines was conducted. A case study for TWH utilizing an ethical decision-making model for the analysis of key ethical issues and solutions was completed. TWH approaches to protecting safety, promoting health, and advancing well-being are increasingly being adopted. These approaches can reveal ethical dilemmas, and ethical constructs are needed to guide decision-making. A core set of proposed ethical competencies for TWH professionals are identified as a transdisciplinary framework to support workplace ethical culture. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

    • Parasitic Diseases
      1. Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopiaexternal icon
        Feleke SM, Reichert EN, Mohammed H, Brhane BG, Mekete K, Mamo H, Petros B, Solomon H, Abate E, Hennelly C, Denton M, Keeler C, Hathaway NJ, Juliano JJ, Bailey JA, Rogier E, Cunningham J, Aydemir O, Parr JB.
        Nat Microbiol. 2021 Oct;6(10):1289-1299.
        In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.

      2. Mass drug administration for malariaexternal icon
        Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M.
        Cochrane Database Syst Rev. 2021 Sep 29;9(9):Cd008846.
        BACKGROUND: Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published. OBJECTIVES: Primary objectives To assess the sustained effect of MDA with antimalarial drugs on: - the reduction in malaria transmission in moderate- to high-transmission settings; - the interruption of transmission in very low- to low-transmission settings. Secondary objective To summarize the risk of drug-associated adverse effects following MDA. SEARCH METHODS: We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) and non-randomized studies comparing MDA to no MDA with balanced co-interventions across study arms and at least two geographically distinct sites per study arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no-MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster-randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coefficient. We assessed the certainty of the evidence using the GRADE approach. For non-randomized controlled before-and-after (CBA) studies, we summarized the data using difference-in-differences (DiD) analyses. MAIN RESULTS: Thirteen studies met our criteria for inclusion. Ten were cRCTs and three were CBAs. Cluster-randomized controlled trials Moderate- to high-endemicity areas (prevalence ≥ 10%) We included data from two studies conducted in The Gambia and Zambia.  At one to three months after MDA, the Plasmodium falciparum (hereafter, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no effect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low-certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate-certainty evidence); and confirmed malaria illness incidence may be substantially lower,  but the CIs included no effect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low-certainty evidence).  At four to six months after MDA, MDA showed little or no effect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate-certainty evidence) and, no persisting effect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low- to low-endemicity areas (prevalence < 10%) Seven studies from Cambodia, Laos, Myanmar (two studies), Vietnam, Zambia, and Zanzibar evaluated the effects of multiple rounds of MDA on P falciparum. Immediately following MDA (less than one month after MDA), parasitaemia prevalence was reduced (RR 0.12, 95% CI 0.03 to 0.52; one study; low-certainty evidence). At one to three months after MDA, there was a reduction in both parasitaemia incidence (rate ratio 0.37, 95% CI 0.21 to 0.55; 1 study; moderate-certainty evidence) and prevalence (RR 0.25, 95% CI 0.15 to 0.41; 7 studies; low-certainty evidence). For confirmed malaria incidence, absolute rates were low, and it is uncertain whether MDA had an effect on this outcome (rate ratio 0.58, 95% CI 0.12 to 2.73; 2 studies; very low-certainty evidence).  For P falciparum prevalence, the relative differences declined over time, from RR 0.63 (95% CI 0.36 to 1.12; 4 studies) at four to six months after MDA, to RR 0.86 (95% CI 0.55 to 1.36; 5 studies) at 7 to 12 months after MDA. Longer-term prevalence estimates showed overall low absolute risks, and relative effect estimates of the effect of MDA on prevalence varied from RR 0.82 (95% CI 0.20 to 3.34) at 13 to 18 months after MDA, to RR 1.25 (95% CI 0.25 to 6.31) at 31 to 36 months after MDA in one study. Five studies from Cambodia, Laos, Myanmar (2 studies), and Vietnam evaluated the effect of MDA on Plasmodium vivax (hereafter, P vivax). One month following MDA, P vivax prevalence was lower (RR 0.18, 95% CI 0.08 to 0.40; 1 study; low-certainty evidence). At one to three months after MDA, there was a reduction in P vivax prevalence (RR 0.15, 95% CI 0.10 to 0.24; 5 studies; low-certainty evidence). The immediate reduction on P vivax prevalence was not sustained over time, from RR 0.78 (95% CI 0.63 to 0.95; 4 studies) at four to six months after MDA, to RR 1.12 (95% CI 0.94 to 1.32; 5 studies) at 7 to 12 months after MDA. One of the studies in Myanmar provided estimates of longer-term effects, where overall absolute risks were low, ranging from RR 0.81 (95% CI 0.44 to 1.48) at 13 to 18 months after MDA, to RR 1.20 (95% CI 0.44 to 3.29) at 31 to 36 months after MDA. Non-randomized studies Three CBA studies were conducted in moderate- to high-transmission areas in Burkina Faso, Kenya, and Nigeria. There was a reduction in P falciparum parasitaemia prevalence in MDA groups compared to control groups during MDA (DiD range: -15.8 to -61.4 percentage points), but the effect varied at one to three months after MDA (DiD range: 14.9 to -41.1 percentage points).  AUTHORS' CONCLUSIONS: In moderate- to high-transmission settings, no studies reported important effects on P falciparum parasitaemia prevalence within six months after MDA. In very low- to low-transmission settings, parasitaemia prevalence and incidence were reduced initially for up to three months for both P falciparum and P vivax; longer-term data did not demonstrate an effect after four months, but absolute risks in both intervention and control groups were low. No studies provided evidence of interruption of malaria transmission.

    • Physical Activity
      1. BACKGROUND: Understanding how participation is changing across domains of physical activity is important for monitoring progress and informing promotion efforts. The authors examined changes in physical activity participation in the National Health and Nutrition Examination Survey 2007/2008 to 2017/2018. METHODS: The prevalence of inactivity, insufficient activity, and meeting the aerobic physical activity guideline in multidomain physical activity and each domain (leisure time, occupational/household, and transportation) was estimated for each cycle and stratified by selected characteristics. The authors tested trends over time and overall changes (2017/2018 vs 2007/2008). RESULTS: For multidomain physical activity, the prevalence of inactivity decreased linearly; meeting the aerobic guideline increased nonmonotonically, and the 2017/2018 prevalence (68.1%) was higher than 2007/2008 (64.1%). Similar findings were observed for adults aged ≥65 years, non-Hispanic Blacks, Hispanics, high school graduates, and adults with obesity. Domain-specific results varied, but decreasing trends in inactivity and increasing trends in meeting the guideline were consistently observed across subgroups for occupational/household activity. Meeting the guideline through transportation activity was rare. CONCLUSIONS: Increases in meeting the guideline and decreases in inactivity in multidomain activity and selected domains are encouraging results, especially among subgroups historically reporting low activity participation. Activity promotion efforts are important to maintain progress, and the transportation domain may be an underutilized source of physical activity.

    • Substance Use and Abuse
      1. Methamphetamine use in the United States: epidemiological update and implications for prevention, treatment, and harm reductionexternal icon
        Jones CM, Houry D, Han B, Baldwin G, Vivolo-Kantor A, Compton WM.
        Ann N Y Acad Sci. 2021 Sep 24.
        Recent attention has focused on the growing role of psychostimulants, such as methamphetamine in overdose deaths. Methamphetamine is an addictive and potent stimulant, and its use is associated with a range of physical and mental health harms, overdose, and mortality. Adding to the complexity of this resurgent methamphetamine threat is the reality that the increases in methamphetamine availability and harms are occurring in the midst of and intertwined with the ongoing opioid overdose crisis. Opioid involvement in psychostimulant-involved overdose deaths increased from 34.5% of overdose deaths in 2010 to 53.5% in 2019-an increase of more than 50%. This latest evolution of the nation's overdose epidemic poses novel challenges for prevention, treatment, and harm reduction. This narrative review synthesizes what is known about changing patterns of methamphetamine use with and without opioids in the United States, other characteristics associated with methamphetamine use, the contributions of the changing illicit drug supply to use patterns and overdose risk, motivations for couse of methamphetamine and opioids, and awareness of exposure to opioids via the illicit methamphetamine supply. Finally, the review summarizes illustrative community and health system strategies and research opportunities to advance prevention, treatment, and harm reduction policies, programs, and practices.

      2. Notes from the field: E-cigarette use among middle and high school students - National Youth Tobacco Survey, United States, 2021external icon
        Park-Lee E, Ren C, Sawdey MD, Gentzke AS, Cornelius M, Jamal A, Cullen KA.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 1;70(39):1387-1389.

    • Veterinary Medicine
      1. Low SARS-CoV-2 seroprevalence and no active infections among dogs and cats in animal shelters with laboratory-confirmed COVID-19 human cases among employeesexternal icon
        Cossaboom CM, Medley AM, Spengler JR, Kukielka EA, Goryoka GW, Baird T, Bhavsar S, Campbell S, Campbell TS, Christensen D, Condrey JA, Dawson P, Doty JB, Feldpausch A, Gabel J, Jones D, Lim A, Loiacono CM, Jenkins-Moore M, Moore A, Noureddine C, Ortega J, Poulsen K, Rooney JA, Rossow J, Sheppard K, Sweet E, Stoddard R, Tell RM, Wallace RM, Williams C, Barton Behravesh C.
        Biology (Basel). 2021 Sep 11;10(9).
        Human-to-animal and animal-to-animal transmission of SARS-CoV-2 has been documented; however, investigations into SARS-CoV-2 transmission in congregate animal settings are lacking. We investigated four animal shelters in the United States that had identified animals with exposure to shelter employees with laboratory-confirmed COVID-19. Of the 96 cats and dogs with specimens collected, only one dog had detectable SARS-CoV-2 neutralizing antibodies; no animal specimens had detectable viral RNA. These data indicate a low probability of human-to-animal transmission events in cats and dogs in shelter settings with early implementation of infection prevention interventions.

      2. One Health investigation of SARS-CoV-2 infection and seropositivity among pets in households with confirmed human COVID-19 cases-Utah and Wisconsin, 2020external icon
        Goryoka GW, Cossaboom CM, Gharpure R, Dawson P, Tansey C, Rossow J, Mrotz V, Rooney J, Torchetti M, Loiacono CM, Killian ML, Jenkins-Moore M, Lim A, Poulsen K, Christensen D, Sweet E, Peterson D, Sangster AL, Young EL, Oakeson KF, Taylor D, Price A, Kiphibane T, Klos R, Konkle D, Bhattacharyya S, Dasu T, Chu VT, Lewis NM, Queen K, Zhang J, Uehara A, Dietrich EA, Tong S, Kirking HL, Doty JB, Murrell LS, Spengler JR, Straily A, Wallace R, Barton Behravesh C.
        Viruses. 2021 Sep 12;13(9).
        Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pets during a COVID-19 household transmission investigation. Pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April-May 2020. We enrolled 37 dogs and 19 cats from 34 households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog's fur swabs (2%) tested positive by rRT-PCR at the first sampling. Among 47 pets with serological results, eight (17%) pets (four dogs, four cats) from 6/30 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40-100%) compared to households with no seropositive pet (median 37%; range: 13-100%) (p = 0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 h) with the index patient before the person's COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the index patient after diagnosis and none were seropositive; of the 19 (58%) pets with continued contact, four (21%) were seropositive. Seropositive pets likely acquired infection after contact with people with COVID-19. People with COVID-19 should restrict contact with pets and other animals.

    • Zoonotic and Vectorborne Diseases
      1. Rickettsial diseases (RDs) are transmitted to humans by ectoparasites, including ticks and fleas. Symptoms range from mild febrile illness, to severe disease or death. Doxycycline is the treatment of choice for patients of all ages; early treatment based on clinical diagnosis is critical to prevent severe outcomes. We conducted a descriptive analysis using insurance claims data captured by IBM MarketScan(®) research databases to describe demographics, treatment patterns, and outcomes of patients diagnosed with RDs in the United States during 2005-2017. Overall, 14,830 patients had a RD diagnosis during 2005-2017; 7,517 (50.7%) spotted fever rickettsiosis (SFR), 4,571 ( 30.8%) ehrlichiosis, 1,362 (9.2%) typhus group rickettsiosis (TGR), and 1,193 (8.0%) other rickettsial diseases. Among all patients diagnosed, 53.1% received doxycycline. Prescription rates varied by diagnosis and age; 24.1% of TGR and 61.1% of SFR patients received doxycycline; 23.9% of persons < 8 years received doxycycline, compared with 47.7% for 8-17 years, and 55.4% for ≥ 18 years. RDs are frequently diagnosed in the outpatient population; however, providers prescribed the recommended treatment to about half of patients. Continued education of treatment recommendations is critical to prevent severe outcomes.

      2. Post-treatment Lyme borreliosis in context: Advancing the science and patient careexternal icon
        Marx GE, Hinckley AF, Mead PS.
        Lancet Reg Health Eur. 2021 Jul;6:100153.

      3. Effects of COVID-19 pandemic on reported Lyme disease, United States, 2020external icon
        McCormick DW, Kugeler KJ, Marx GE, Jayanthi P, Dietz S, Mead P, Hinckley AF.
        Emerg Infect Dis. 2021 Oct;27(10):2715-2717.
        Surveys indicate US residents spent more time outdoors in 2020 than in 2019, but fewer tick bite-related emergency department visits and Lyme disease laboratory tests were reported. Despite ongoing exposure, Lyme disease case reporting for 2020 might be artificially reduced due to coronavirus disease-associated changes in healthcare-seeking behavior.

      4. Human infection with avian influenza A(H9N2) virus, Cambodia, February 2021external icon
        Um S, Siegers JY, Sar B, Chin S, Patel S, Bunnary S, Hak M, Sor S, Sokhen O, Heng S, Chau D, Sothyra T, Khalakdina A, Mott JA, Olsen SJ, Claes F, Sovann L, Karlsson EA.
        Emerg Infect Dis. 2021 Oct;27(10):2742-2745.
        In February 2021, routine sentinel surveillance for influenza-like illness in Cambodia detected a human avian influenza A(H9N2) virus infection. Investigations identified no recent H9N2 virus infections in 43 close contacts. One chicken sample from the infected child's house was positive for H9N2 virus and genetically similar to the human virus.

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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