Volume 13, Issue 18, May 18, 2021

CDC Science Clips: Volume 13, Issue 18, May 18, 2021

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions.

  1. Top Articles of the Week
    Selected weekly by a senior CDC scientist from the standard sections listed below.
    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • Unequal Local Progress Towards Healthy People 2020 Objectives for Stroke and Coronary Heart Disease Mortalityexternal icon
        Woodruff RC, Casper M, Loustalot F, Vaughan AS.
        Stroke. 2021 May 6:Strokeaha121034100.
        BACKGROUND AND PURPOSE: Healthy People establishes objectives to monitor the nation's health. Healthy People 2020 included objectives to reduce national stroke and coronary heart disease (CHD) mortality by 20% (to 34.8 and 103.4 deaths per 100 000, respectively). Documenting the proportion and geographic distribution of counties meeting neither the Healthy People 2020 target nor an equivalent proportional reduction can help identify high-priority geographic areas for future intervention. METHODS: County-level mortality data for stroke (International Classification of Diseases, Tenth Revision codes I60-I69) and CHD (I20-I25) and bridged-race population estimates were used. Bayesian spatiotemporal models estimated age-standardized county-level death rates in 2007 and 2017 which were used to calculate and map the proportion and 95% credible interval of counties achieving neither the national Healthy People 2020 target nor a 20% reduction in mortality. RESULTS: In 2017, 45.8% of counties (credible interval, 42.9-48.3) met neither metric for stroke mortality. These counties had a median stroke death rate of 42.2 deaths per 100 000 in 2017, representing a median 12.8% decline. For CHD mortality, 26.1% (credible interval, 25.0-27.8) of counties met neither metric. These counties had a median CHD death rate of 127.1 deaths per 100 000 in 2017, representing a 10.2% decline. For both outcomes, counties achieving neither metric were not limited to counties with traditionally high stroke and CHD death rates. CONCLUSIONS: Recent declines in stroke and CHD mortality have not been equal across US counties. Focusing solely on high mortality counties may miss opportunities in the prevention and treatment of cardiovascular disease and in learning more about factors leading to successful reductions in mortality.

    • Communicable Diseases
      • Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosisexternal icon
        Dorman SE, Nahid P, Kurbatova EV, Phillips PP, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE.
        N Engl J Med. 2021 May 6;384(18):1705-1718.
        BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 number, NCT02410772.).

      • BACKGROUND: The fungus Aspergillus fumigatus (A. fumigatus) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use. OBJECTIVES: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates. DISCUSSION: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992-2005 but increased  > 4-fold during 2006-2016 to 2.9 million kg in 2016. During 1992-2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance.

    • Disease Reservoirs and Vectors
      • Anopheles stephensi Mosquitoes as Vectors of Plasmodium vivax and falciparum, Horn of Africa, 2019external icon
        Tadesse FG, Ashine T, Teka H, Esayas E, Messenger LA, Chali W, Meerstein-Kessel L, Walker T, Wolde Behaksra S, Lanke K, Heutink R, Jeffries CL, Mekonnen DA, Hailemeskel E, Tebeje SK, Tafesse T, Gashaw A, Tsegaye T, Emiru T, Simon K, Bogale EA, Yohannes G, Kedir S, Shumie G, Sabir SA, Mumba P, Dengela D, Kolaczinski JH, Wilson A, Churcher TS, Chibsa S, Murphy M, Balkew M, Irish S, Drakeley C, Gadisa E, Bousema T.
        Emerg Infect Dis. 2021 Feb;27(2):603-607.
        Anopheles stephensi mosquitoes, efficient vectors in parts of Asia and Africa, were found in 75.3% of water sources surveyed and contributed to 80.9% of wild-caught Anopheles mosquitoes in Awash Sebat Kilo, Ethiopia. High susceptibility of these mosquitoes to Plasmodium falciparum and vivax infection presents a challenge for malaria control in the Horn of Africa.

    • Health Disparities
      • Geographic Disparities in Late-Stage Breast Cancer Diagnosis Rates and Their Persistence Over Timeexternal icon
        Mobley LR, Tangka FK, Berkowitz Z, Miller J, Hall IJ, Wu M, Sabatino SA.
        J Womens Health (Larchmt). 2021 Apr 29.
        Background: Other than skin cancer, breast cancer is the most common cancer in the United States. Lower uptake of mammography screening is associated with higher rates of late-stage breast cancers. This study aims to show geographic patterns in the United States, where rates of late-stage breast cancer are high and persistent over time, and examines factors associated with these patterns. Materials and Methods: We examined all primary breast cancers diagnosed among all counties in 43 U.S. states with available data. We used spatial cluster analysis to identify hot spots (i.e., spatial clusters with above average late-stage diagnosis rates among counties). Demographic and socioeconomic characteristics were compared between persistent hot spots and those counties that were never hot spots. Results: Of the 2,599 counties examined in 43 states, 219 were identified as persistent hot spots. Counties with persistent hot spots (compared with counties that were never hot spots) were located in more deprived areas with worse housing characteristics, lower socioeconomic status, lower levels of health insurance, worse access to mammography, more isolated American Indian/Alaska Native, Black, or Hispanic neighborhoods, and larger income disparity. In addition, persistent hot spots were significantly more likely to be observed among poor, rural, African American, or Hispanic communities, but not among poor, rural, White communities. This analysis includes a broader range of socioeconomic conditions than those included in previous literature. Conclusion: We found geographic disparities in late-stage breast cancer diagnosis rates, with some communities experiencing persistent disparities over time. Our findings can guide public health efforts aimed at reducing disparities in stage of diagnosis for breast cancer.

    • Health Economics
      • BACKGROUND: An estimated 862,000 to 2.4 million people have chronic hepatitis B infection (CHB). Left undiagnosed and untreated CHB increases risk of death from liver cirrhosis or liver cancer. Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk, but diagnosis rates remain low with only 33% of people with CHB aware of their infection.. This study aimed to assess the cost-effectiveness of universal adult screening for CHB. METHODS: We used a Markov model to calculate the costs, population health impact and cost-effectiveness of one-time universal screening and CHB monitoring and treatment compared to current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-savings or cost-effectiveness based on willinness-to-pay of $50,000/QALY . The analysis assumed testing would be performed during routine healthcare visits, and generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates. RESULTS: At an estimated 0.24% prevalence of undiagnosed CHB, universal HBsAg screening in adults 18-69 years old is cost-saving compared with current practice if antiviral treatment drug costs remain below $894 per year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 HBV related deaths at a savings of $263,000 per 100,000 adults screened. CONCLUSION: Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared to current CHB screening recommendations.

    • Immunity and Immunization
      • US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021external icon
        See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, Streiff MB, Rao AK, Wheeler AP, Beavers SF, Durbin AP, Edwards K, Miller E, Harrington TA, Mba-Jonas A, Nair N, Nguyen DT, Talaat KR, Urrutia VC, Walker SC, Creech CB, Clark TA, DeStefano F, Broder KR.
        Jama. 2021 Apr 30.
        IMPORTANCE: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. OBJECTIVE: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. DESIGN, SETTING, AND PARTICIPANTS: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). EXPOSURES: Receipt of Ad26.COV2.S vaccine. MAIN OUTCOMES AND MEASURES: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. RESULTS: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). CONCLUSIONS AND RELEVANCE: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

    • Laboratory Sciences
      • Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopesexternal icon
        Voss WN, Hou YJ, Johnson NV, Delidakis G, Kim JE, Javanmardi K, Horton AP, Bartzoka F, Paresi CJ, Tanno Y, Chou CW, Abbasi SA, Pickens W, George K, Boutz DR, Towers DM, McDaniel JR, Billick D, Goike J, Rowe L, Batra D, Pohl J, Lee J, Gangappa S, Sambhara S, Gadush M, Wang N, Person MD, Iverson BL, Gollihar JD, Dye J, Herbert A, Finkelstein IJ, Baric RS, McLellan JS, Georgiou G, Lavinder JJ, Ippolito GC.
        Science. 2021 May 4.
        The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.

    • Maternal and Child Health
      • Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settingsexternal icon
        Dolk H, Leke AZ, Whitfield P, Moore R, Karnell K, Barišić I, Barlow-Mosha L, Botto LD, Garne E, Guatibonza P, Godfred-Cato S, Halleux CM, Holmes LB, Moore CA, Orioli I, Raina N, Valencia D.
        Birth Defects Res. 2021 May 5.
        BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The "basic" version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The "surveillance" version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The "basic" version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance" version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care.

    • Occupational Safety and Health
      • Association of Parent Workplace Injury With Emotional and Behavioral Problems in Childrenexternal icon
        Asfaw A, Sauter SL, Swanson N, Beach CM, Sauter DL.
        J Occup Environ Med. 2021 Apr 30.
        OBJECTIVE: Investigate associations between occupational injury to parents and the psychological well-being of their children. METHODS: We used multiple logistic regression to examine effects of occupational injury to parents on measures of psychological well-being among their children using National Health Interview Survey data from 2012 through 2016. RESULTS: Children of injured workers exhibited greater impairment than children of workers who had not sustained injuries for four of five measures of emotional and behavioral functioning that were hypothesized to differentiate these two child groups. A significant group difference was not observed for a sixth behavioral measure that was expected to be insensitive to parent occupational injury. CONCLUSION: Study findings heighten concern over downstream effects of occupational injury and signal need for more expansive investigation of these effects and mitigation strategies among children of injured workers.

    • Veterinary Medicine
      • Antimicrobial Resistance Creates Threat to Chimpanzee Health and Conservation in the Wildexternal icon
        Parsons MB, Travis DA, Lonsdorf EV, Lipende I, Elchoufi D, Gilagiza B, Collins A, Kamenya S, Tauxe RV, Gillespie TR.
        Pathogens. 2021 Apr 14;10(4).
        Infectious disease is recognized as the greatest threat to the endangered chimpanzees made famous by the groundbreaking work of Dr. Jane Goodall at Gombe National Park (GNP), Tanzania. The permeable boundary of this small protected area allows for regular wildlife-human and wildlife-domestic animal overlap, which may facilitate cross-species transmission of pathogens and antimicrobial resistance. Few studies have examined the prevalence of antimicrobial resistance in wild ape populations. We used molecular techniques to investigate the presence of genes conferring resistance to sulfonamides (often used to treat diarrheal illness in human settings in this region) and tetracycline (used in the past-though much less so now) in fecal specimens from humans, domestic animals, chimpanzees, and baboons in and around GNP. We also tested stream water used by these groups. Sulfonamide resistance was common in humans (74%), non-human primates (43%), and domestic animals (17%). Tetracycline resistance was less common in all groups: humans (14%), non-human primates (3%), and domestic animals (6%). Sul resistance genes were detected from 4/22 (18%) of streams sampled. Differences in sul gene frequencies did not vary by location in humans nor in chimpanzees.

    • Zoonotic and Vectorborne Diseases

  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. BACKGROUND: Various professional organizations have issued recommendations on use of the PSA test to screen for prostate cancer in different age groups. AIMS: Using Medicare claims databases, we aimed to determine rates of PSA testing in the context of screening recommendations during 1999-2015 for US men age ≥65, stratified by age group and census regions, after excluding claims relating to all prostate-related conditions. METHODS AND RESULTS: Medicare claims databases encompassed 9.71-11.12 million men for the years under study. PSA testing rate was the proportion of men with ≥1 test(s) per 12 months of continuous enrollment. Men diagnosed with any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 1999-2015, annual testing rate was 10.1%-23.1%, age ≥85; 16.6%-31.0%, age 80-84; 23.8%-35.8%, age 75-79; 28.3%-36.9%, age 70-74; and 26.4%-33.6%, age 65-69. From 1999 to 2015, PSA testing rate decreased 40.7%, 29.9%, 13.9%, and 2.9%, respectively, for men age ≥85, 80-84, 75-79, and 70-74. For men age 65-69, test use increased by 0.3%. Significant APC trends were: APC(1999-2002) = +8.1%, P = .029 and APC(2008-2015) = -9.0%, P < .001 for men age ≥85; APC(2008-2015) = -7.1%, P = .001 for men age 80-84; APC(2001-2015) = -2.5%, P < .001 for men age 75-79; APC(2008-2015) = -3.3%, P = .007 for men age 70-74; and APC(2010-2015) = -5.2%, P = .014 for men age 65-69. COCLUSION: Although decreased from 1999 to 2015, PSA testing rates remained high for men age ≥70. Further research could help understand why PSA testing continues inconsistent with recommendations.

      2. BACKGROUND: Given the public health relevance of PSA-based screening, various professional organizations have issued recommendations on the use of the PSA test to screen for prostate cancer in different age groups. AIM: Using a large commercial claims database, we aimed to determine the most recent rates of PSA testing for privately insured men age 30 to 64 in the context of screening recommendations. METHODS AND RESULTS: Data from employer plans were from MarketScan commercial claims database. Annual PSA testing rate was the proportion of men with ≥1 paid test(s) per 12 months of continuous enrollment. Men with diagnosis of any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 2011 to 2017, annual testing rate encompassing 5.02 to 5.53 million men was approximately 1.4%, age 30 to 34; 3.4% to 4.1%, age 35 to 39; 11% to 13%, age 40 to 44; 18% to 21%, age 45 to 49; 31% to 33%, age 50 to 54; 35% to 37%, age 55 to 59; and 38% to 41%, age 60 to 64. APC for 2011 to 2017 was -0.5% (P = .11), age 30 to 34; -3.0% (P = .001), age 35-39; -3.1% (P < .001), age 40 to 44; -2.4% (P = .001), age 45 to 49; -0.2% (P = .66), age 50 to 54; 0.0% (P = .997), age 55 to 59; and -3.3% (P = .054) from 2011 to 2013 and 1.2% (P = .045) from 2013 to 2017, age 60 to 64. PSA testing rate decreased from 2011 to 2017 for age groups between 35 and 49 by 13.4% to 16.9%. CONCLUSIONS: Based on these data, PSA testing rate has modestly decreased from 2011 to 2017. These results, however, should be considered in view of the limitation that MarketScan claims data may not be equated to actual PSA testing practices in the entire U.S. population age 30 to 64. Future research should be directed to understand why clinicians continue ordering PSA test for men younger than 50.

      3. Older Adult Willingness to Use Fully Autonomous Vehicle (FAV) Ride Sharingexternal icon
        Siegfried AL, Bayne A, Beck LF, Freund K.
        Geriatrics (Basel). 2021 Apr 29;6(2).
        In the United States, older adults (age 65 and older) rely on private automobiles for transportation. For those who stop driving, access to alternative modes of transportation is important for health, wellbeing, mobility, and independence. This paper explores older adult willingness to use fully autonomous vehicle (FAV) ride sharing and the features or services of FAV ride sharing that would make them willing to take a ride. These data were gathered as part of a larger qualitative research study designed to explore the factors affecting older adult use of ride share services. For the larger study, we conducted 68 telephone interviews with older adults, and 10 in-person focus groups with 56 older adults, including individuals who both used and never used ride share services. We used a convenience sample recruited by study partners, including ride share and transportation services and a recruitment firm. The predominant thematic findings of the qualitative analysis included a desire for a proven safety record in terms of performance and technology, followed by dependability and accuracy of FAV ride sharing. Older adults' concerns about FAV ride sharing included safety concerns and preferences for social interaction with drivers. Ride share services that use FAVs in the future may need to tailor transportation offerings for older adults to increase their willingness to use FAVS to support their mobility and social needs.

    • Communicable Diseases
      1. Scale-up of antiretroviral treatment access among people living with HIV in Rivers State, Nigeria, 2019--2020external icon
        Boyd AT, Ogbanufe O, Onyenuobi C, Mgbakor I, Bachanas P, Olupitan O, Umeh C, Adegboye A, Owhonda G, Odafe S, Jahun I, Dakum P, Mensah C, Gwamna J, Onotu D, Dirlikov E, Williams-Sherlock M, Okolo C, Verinumbe T, Idakwo S, Kumtap MU, Ellerbrock T, Swaminathan M.
        Aids. 2021 Jun 1;35(7):1127-1134.
        OBJECTIVE: The aim of this study was to describe and evaluate the impact of the programme intervention of the Rivers State Antiretroviral Treatment (ART) Surge, a collaboration between the US President's Emergency Plan for AIDS Relief (PEPFAR) and the State Ministry of Health, to increase HIV case-finding and ART access in Rivers State, the state with the largest ART gap among people living with HIV (PWH) in Nigeria. DESIGN: During April 2019-September 2020, the intervention included six specific strategies: using local government area-level ART gap analysis to guide case-finding; expanding targeted community testing; tailoring comprehensive key population HIV services; engaging HIV treatment programme stakeholders; synchronizing team efforts; and using near real-time data for programme action. METHODS: Weekly reported facility and community data on tests conducted, PWH diagnosed, and PWH initiated on ART were aggregated. The total number of PWH maintained on ART was reported quarterly. RESULTS: During May 2019-September 2020, the weekly number of newly diagnosed PWH initiated on ART supported by PEPFAR in Rivers State increased from 82 to 1723. During October 2019-September 2020, the monthly number of people screened for HIV testing eligibility in the community increased from 44 000 to 360 000. During April 2019-September 2020, the total number of PWH on ART supported by PEPFAR statewide increased by 3.8 times, from 26 041 to 99 733. CONCLUSION: The strategies applied by HIV program stakeholders contributed to scale-up of PWH identification and ART linkage within the Rivers State ART Surge. Continued gains through time indicate the importance of the application of a quality improvement approach to maintain programme flexibility and effectiveness.

      2. Collect Once, Use Many Times: Attaining Unified Metrics for Tuberculosis Preventive Treatment for People Living With HIVexternal icon
        Fukunaga R, Lowrance D, MacNeil A, Al-Samarrai T, Cavanaugh J, Baddeley A, Nichols C, Peterson M, Ahmedov S, Singh V, Edwards CG, Jain S, Date A, Maloney SA.
        JMIR Public Health Surveill. 2021 Apr 30;7(4):e27013.
        The World Health Organization (WHO) recommends providing tuberculosis preventive treatment (TPT) to all persons living with HIV and to all household contacts of persons with bacteriologically confirmed pulmonary tuberculosis disease. Regrettably, the absence of a harmonized data collection and management approach to TPT indicators has contributed to programmatic challenges at local, national, and global levels. However, in April 2020, the WHO launched the Consolidated HIV Strategic Information Guidelines, with an updated set of priority indicators. These guidelines recommend that Ministries of Health collect, report, and use data on TPT completion in addition to TPT initiation. Both indicators are reflected in the WHO's list of 15 core indicators for program management and are also required by the US President's Emergency Plan for AIDS Relief's Monitoring, Evaluation, and Reporting (MER) guidance. Although not perfectly harmonized, both frameworks now share essential indicator characteristics. Aligned indicators are necessary for robust strategic and operational planning, resource allocation, and data communication. "Collect once, use many times" is a best practice for strategic information management. Building harmonized and sustainable health systems will enable countries to successfully maintain essential HIV, tuberculosis, and other health services while combatting new health threats.

      3. SARS-CoV-2 B.1.1.7 variant of concern detected in a pet dog and cat after exposure to a person with COVID-19, USAexternal icon
        Hamer SA, Ghai RR, Zecca IB, Auckland LD, Roundy CM, Davila E, Busselman RE, Tang W, Pauvolid-Corrêa A, Killian ML, Jenkins-Moore M, Torchetti MK, Robbe Austerman S, Lim A, Akpalu Y, Fischer RS, Barton Behravesh C, Hamer GL.
        Transbound Emerg Dis. 2021 May 6.
        As part of a longitudinal household transmission study of pets living with persons with COVID-19 in Texas, two pets were confirmed to be infected with the SARS-CoV-2 B.1.1.7 variant of concern (VOC). The pets were a dog and a cat from the same household, sampled two days after their owner tested positive for COVID-19. The oral, nasal, and fur swabs for both pets tested positive for SARS-CoV-2 by qRT-PCR and consensus whole genome sequences from the dog and cat were 100 % identical and matched the B.1.1.7 VOC. Virus was isolated from the cat's nasal swab. One month after initial detection of infection, the pets were re-tested twice at which time only the fur swabs (both pets) and oral swab (dog only) remained positive, and neutralizing antibodies for SARS-CoV-2 were present in both animals. Sneezing by both pets was noted by the owner in the weeks between initial and follow-up testing. This study documents the first detection of B.1.1.7. in companion animals in the United States, and the first genome recovery and isolation of B.1.1.7 variant of concern globally in any animal.

      4. Changes in Emergency Medical Services before and during COVID-19 in the United States, January 2018-December 2020external icon
        Handberry M, Bull-Otterson L, Dai M, Mann CN, Chaney E, Ratto J, Horiuchi K, Siza C, Kulkarni A, Gundlapalli AV, Boehmer TK.
        Clin Infect Dis. 2021 May 6.
        BACKGROUND: As a result of the continuing surge of COVID-19, many patients have delayed or missed routine screening and preventive services. Medical conditions, such as coronary heart disease, mental health issues, and substance use disorder, may be identified later, leading to increases in patient morbidity and mortality. METHODS: The National Emergency Medical Services Information System (NEMSIS) data were used to assess 911 Emergency Medical Services (EMS) activations during 2018-2020. For specific activation types, the percentage of total activations was calculated per week and joinpoint analysis was used to identify changes over time. RESULTS: Since March 2020, the number of 911 emergency medical services (EMS) activations has decreased, while the percentages of on-scene death, cardiac arrest, and opioid use/overdose EMS activations were higher than pre-pandemic levels. During the early pandemic period, percentages of total EMS activations increased for on-scene death (from 1.3% to 2.4% during weeks 11-15), cardiac arrest (from 1.3% to 2.2% during weeks 11-15), and opioid use/overdose (from 0.6% to 1.1% during weeks 8-18); the percentages then declined, but remained above pre-pandemic levels through calendar week 52. CONCLUSIONS: The COVID-19 pandemic has indirect consequences, such as relative increases in EMS activations for cardiac events and opioid use/overdose, possibly linked to disruptions is healthcare access and health-seeking behaviors. Increasing telehealth visits or other opportunities for patient-provider touch points for chronic disease and substance use disorders that emphasize counseling, preventive care, and expanded access to medications can disrupt delayed care-seeking during the pandemic and potentially prevent premature death.

      5. A remote household-based approach to influenza self-testing and antiviral treatmentexternal icon
        Heimonen J, McCulloch DJ, O'Hanlon J, Kim AE, Emanuels A, Wilcox N, Brandstetter E, Stewart M, McCune D, Fry S, Parsons S, Hughes JP, Jackson ML, Uyeki TM, Boeckh M, Starita LM, Bedford T, Englund JA, Chu HY.
        Influenza Other Respir Viruses. 2021 May 3.
        BACKGROUND: Households represent important settings for transmission of influenza and other respiratory viruses. Current influenza diagnosis and treatment relies upon patient visits to healthcare facilities, which may lead to under-diagnosis and treatment delays. This study aimed to assess the feasibility of an at-home approach to influenza diagnosis and treatment via home testing, telehealth care, and rapid antiviral home delivery. METHODS: We conducted a pilot interventional study of remote influenza diagnosis and treatment in Seattle-area households with children during the 2019-2020 influenza season using pre-positioned nasal swabs and home influenza tests. Home monitoring for respiratory symptoms occurred weekly; if symptoms were reported within 48 hours of onset, participants collected mid-nasal swabs and used a rapid home-based influenza immunoassay. An additional home-collected swab was returned to a laboratory for confirmatory influenza RT-PCR testing. Baloxavir antiviral treatment was prescribed and delivered to symptomatic and age-eligible participants, following a telehealth encounter. RESULTS: 124 households comprising 481 individuals self-monitored for respiratory symptoms, with 58 home tests administered. 12 home tests were positive for influenza, of which eight were true positives confirmed by RT-PCR. The sensitivity and specificity of the home influenza test were 72.7% and 96.2%, respectively. There were eight home deliveries of baloxavir, with 7 (87.5%) occurring within 3 hours of prescription and all within 48 hours of symptom onset. CONCLUSIONS: We demonstrate the feasibility of self-testing combined with rapid home delivery of influenza antiviral treatment. This approach may be an important control strategy for influenza epidemics and pandemics.

      6. National HIV testing campaigns to support UNAIDS 90-90-90 agenda: A lesson from KENYAexternal icon
        Koros DK, Ondondo RO, Junghae M, Oluoch P, Chesang K.
        East Afr Med J. 2020 ;97(12):3295-3302.

      7. Assessment of the tuberculosis case-finding and prevention cascade among people living with HIV in Zambia - 2018: a cross-sectional cluster surveyexternal icon
        Melgar M, Shiraishi RW, Tende C, Mwanza S, Mulenga J, Khondowe S, Mwakazanga D, Kapungu K, Tembo M, Nota A, Lungu P, Moore B, Podewils LJ.
        BMC Public Health. 2021 May 4;21(1):859.
        BACKGROUND: The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia. METHODS: In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation. RESULTS: We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training. CONCLUSIONS: TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV.

      8. Modeling the Transmission of Covid-19: Impact of Mitigation Strategies in Prekindergarten-Grade 12 Public Schools, United States, 2021external icon
        Miller GF, Greening B, Rice KL, Arifkhanova A, Meltzer MI, Coronado F.
        J Public Health Manag Pract. 2021 Apr 30.
        BACKGROUND: Schools are an integral part of the community; however, congregate settings facilitate transmission of SARS-CoV-2, presenting a challenge to school administrators to provide a safe, in-school environment for students and staff. METHODS: We adapted the Centers for Disease Control and Prevention's COVIDTracer Advanced tool to model the transmission of SARS-CoV-2 in a school of 596 individuals. We estimate possible reductions in cases and hospitalizations among this population using a scenario-based analysis that accounts for (a) the risk of importation of infection from the community; (b) adherence to key Centers for Disease Control and Prevention-recommended mitigation strategies: mask wearing, cleaning and disinfection, hand hygiene, and social distancing; and (c) the effectiveness of contact tracing interventions at limiting onward transmission. RESULTS: Low impact and effectiveness of mitigation strategies (net effectiveness: 27%) result in approximately 40% of exposed staff and students becoming COVID-19 cases. When the net effectiveness of mitigation strategies was 69% or greater, in-school transmission was mostly prevented, yet importation of cases from the surrounding community could result in nearly 20% of the school's population becoming infected within 180 days. The combined effects of mitigation strategies and contact tracing were able to prevent most onward transmission. Hospitalizations were low among children and adults (<0.5% of the school population) across all scenarios examined. CONCLUSIONS: Based on our model, layering mitigation strategies and contact tracing can limit the number of cases that may occur from transmission in schools. Schools in communities with substantial levels of community spread will need to be more vigilant to ensure adherence of mitigation strategies to minimize transmission. Our results show that for school administrators, teachers, and parents to provide the safest environment, it is important to utilize multiple mitigation strategies and contract tracing that reduce SARS CoV-2 transmission by at least 69%. This will require training, reinforcement, and vigilance to ensure that the highest level of adherence is maintained over the entire school term.

      9. Delayed Tuberculosis Diagnoses During the COVID-19 Pandemic in 2020 - King County, Washingtonexternal icon
        Narita M, Hatt G, Toren KG, Vuong K, Pecha M, Jereb JA, Goswami ND.
        Clin Infect Dis. 2021 May 6.

      10. Global progress and gaps in tuberculosis screening and treatment among people with HIV: experience from 32 countriesexternal icon
        Peterson M, Sarita Shah N, Smith-Jeffcoat SE, Nichols C, Fukunaga R, Al-Samarrai T, MacNeil A.
        Aids. 2021 Jun 1;35(7):1154-1156.

      11. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021external icon
        Rao AK, Sobel J, Chatham-Stephens K, Luquez C.
        MMWR Recomm Rep. 2021 May 7;70(2):1-30.
        Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.

      12. Investigation of a Suspect SARS-CoV-2 and Influenza A Mixed Outbreak: Lessons Learned for Long-Term Care Facilities Nationwideexternal icon
        Schrodt CA, Malenfant JH, Hunter JC, Slifka KJ, Campbell A, Stone N, Whitehouse ER, Wittry B, Christensen B, Barnes JR, Brammer L, Hemarajata P, Green NM, Civen R, Gounder PP, Rao AK.
        Clin Infect Dis. 2021 May 6.
        A suspected outbreak of influenza A and SARS-CoV-2 at a long-term care facility in Los Angeles County was months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow CDC guidelines that specifically address infection control challenges.

      13. Racial and geographical disparities exist in HIV infections in the USA. The highest burden of HIV diagnoses remains among Black/African American persons and is concentrated in the Southern region. This paper describes within-race changes in HIV diagnoses among heterosexually active Black/African American persons in seven states with the highest rates/100,000 population of HIV diagnoses in the South, during 2014-2018. The total number of diagnoses among Black males and females with infection attributed to heterosexual contact decreased in 2018 compared to 2014. Diagnoses decreased among Black males and females in Louisiana and among Black females in Texas. While the declines indicate progress, Black males and females in the South remain disproportionately affected by HIV. Results support a need for the development, implementation, and evaluation of evidence-based HIV prevention interventions and strategies for heterosexually active persons in jurisdictions that have not seen decreases in HIV diagnoses.

      14. Surveillance to Track Progress Toward Polio Eradication - Worldwide, 2019-2020external icon
        Tuma JN, Wilkinson AL, Diop OM, Jorba J, Gardner T, Snider CJ, Anand A, Ahmed J.
        MMWR Morb Mortal Wkly Rep. 2021 May 7;70(18):667-673.
        When the Global Polio Eradication Initiative (GPEI) was established in 1988, an estimated 350,000 poliomyelitis cases were reported worldwide. In 2020, 140 wild poliovirus (WPV) cases were confirmed, representing a 99.99% reduction since 1988. WPV type 1 transmission remains endemic in only two countries (Pakistan and Afghanistan), but outbreaks of circulating vaccine-derived poliovirus (cVDPV) occurred in 33 countries during 2019-2020 (1,2). Poliovirus transmission is detected primarily through syndromic surveillance for acute flaccid paralysis (AFP) among children aged <15 years, with confirmation by laboratory testing of stool specimens. Environmental surveillance supplements AFP surveillance and plays an increasingly important role in detecting poliovirus transmission. Within 2 weeks of COVID-19 being declared a global pandemic (3), GPEI recommended continuing surveillance activities with caution and paused all polio supplementary immunization activities (4). This report summarizes surveillance performance indicators for 2019 and 2020 in 42 priority countries at high risk for poliovirus transmission and updates previous reports (5). In 2020, 48% of priority countries* in the African Region, 90% in the Eastern Mediterranean Region, and 40% in other regions met AFP surveillance performance indicators nationally. The number of priority countries rose from 40 in 2019 to 42 in 2020.(†) Analysis of 2019-2020 AFP surveillance data from 42 countries at high risk for poliovirus transmission indicates that national and subnational nonpolio AFP rates and stool specimen adequacy declined in many priority countries, particularly in the African Region, suggesting a decline in surveillance sensitivity and quality. The findings in this report can be used to guide improvements to restore a sensitive surveillance system that can track poliovirus transmission and provide evidence of interruption of transmission.

      15. Building a Virtual Global Knowledge Network during COVID-19: The Infection Prevention and Control Global Webinar Seriesexternal icon
        Wilson K, Dennison C, Struminger B, Armistad A, Osuka H, Montoya E, Padoveze MC, Arora S, Park B, Lessa FC.
        Clin Infect Dis. 2021 May 6.
        INTRODUCTION: The 2019 coronavirus (COVID-19) pandemic has been an unprecedented global health challenge. Traditional modes of knowledge dissemination have not been feasible. A rapid solution was needed to share guidance and implementation examples among the global Infection Prevention and Control (IPC) community. We designed the IPC Global Webinar Series to bring together subject matter experts and IPC professionals in the fight against COVID-19. METHODS: The Extension for Community Healthcare Outcomes (ECHO) model was adapted to create an interactive global knowledge network. Speakers and panelists provided presentations and answers to questions from participants. The webinars were simultaneously interpreted to five languages and recorded for later access. RESULTS: Thirteen webinar sessions were completed from May 14 through August 6, 2020. On average, 634 participants attended each session (range: 393 - 1,181). Each session was represented by participants from an average of over 100 countries; sessions 1-3 had participation from approximate 120 countries, and sessions 6 and 12 had participation from approximately 80 countries. DISCUSSION: The IPC Global Webinar Series shared critical information and promoted peer-to-peer learning during the COVID-19 pandemic response. The webinar sessions reached a broader audience than many in-person events. The webinar series was rapidly scaled and can be rapidly re-activated as needed. Our lessons learned in designing and implementing the series can inform design of other global health virtual knowledge networks. The continued and expanded use of adapted virtual communities of practice and other learning networks for the IPC community can serve as a valuable tool for addressing COVID-19 and other infectious disease threats.

    • Disaster Control and Emergency Services
      1. BACKGROUND: Urgent care centers (UCCs) have become frontline healthcare facilities for individuals with acute infectious diseases. Additionally, UCCs could potentially support the healthcare system response during a public health emergency. Investigators sought to assess NYC UCCs' implementation of nationally-recommended IPC and EP practices. METHODS: Investigators identified 199 eligible UCCs based on criteria defined by the Urgent Care Association of America. Multiple facilities under the same ownership were considered a network. As part of a cross-sectional analysis, an electronic survey was sent to UCC representatives assessing their respective facilities' IPC and EP practices. Representatives of urgent care networks responded on behalf of all UCCs within the network if all sites within the network used the same policies and procedures. RESULTS: Of the respondents, 18 representing 144 UCCs completed the survey. Of these, 8 of them (44.4% of the respondents) represented more than 1 facility that utilized standardized practices (range = 2-60 facilities). Overall, 81.3% have written IPC policies, 75.0% have EP policies, 80.6% require staff to train on IPC, and 75.7% train staff on EP. CONCLUSION: Most UCCs reported implementation of IPC and EP practices; however, the comprehensiveness of these activities varied across UCCs. Public health can better prepare the healthcare system by engaging UCCs in planning and executing of IPC and EP-related initiatives.

    • Disease Reservoirs and Vectors
      1. Two abundant species of aggressive ticks commonly feed on humans in Georgia: the Gulf Coast tick (Amblyomma maculatum) and the Lone Star tick (A. americanum). A. maculatum is the primary host of Rickettsia parkeri, "Candidatus Rickettsia andeanae," and a Francisella-like endosymbiont (AmacFLE), whereas A. americanum is the primary host for R. amblyommatis, Ehrlichia chaffeensis, E. ewingii, and a Coxiella-like endosymbiont (AamCLE). Horizontal transmission of R. parkeri from A. maculatum to A. americanum by co-feeding has been described, and R. amblyommatis has been found infrequently in A. maculatum ticks. We assessed the prevalence of these agents and whether exchange of tick-associated bacteria is common between A. maculatum and A. americanum collected from the same field site. Unengorged ticks were collected May-August 2014 in west-central Georgia from a 4.14 acre site by flagging and from humans and canines traversing that site. All DNA samples were screened with quantitative PCR assays for the bacteria found in both ticks, and the species of any Rickettsia detected was identified by species-specific TaqMan assays or sequencing of the rickettsial ompA gene. Only R. amblyommatis (15) and AamCLE (39) were detected in 40 A. americanum, while the 74 A. maculatum only contained R. parkeri (30), "Candidatus Rickettsia andeanae" (3), and AmacFLE (74). Neither tick species had either Ehrlichia species. Consequently, we obtained no evidence for the frequent exchange of these tick-borne agents in a natural setting despite high levels of carriage of each agent and the common observance of infestation of both ticks on both dogs and humans at this site. Based on these data, exchange of these Rickettsia, Coxiella, and Francisella agents between A. maculatum and A. americanum appears to be an infrequent event.

      2. Borrelia miyamotoi is a hard tick-associated relapsing fever spirochete that is geographically widespread in Ixodes spp. (Acari: Ixodidae) ticks, but typically occurs at low prevalence. Genetic variability has been described among strains derived from Asia, Europe, and North America, and among tick species that carry the infection, but little variability has been described within foci or tick species. Capitalizing on access to B. miyamotoi nucleic acid extracted from host-seeking Ixodes scapularis Say or Ixodes pacificus Cooley & Kohls from 16 states, we explored genetic variability based on sequence analysis of four amplicons described herein. Consistent with previous studies, we detected significant genetic differences between strains derived from I. scapularis (eastern United States) and I. pacificus (western United States) and identified two distinct sequences in the western United States (Am-West-1 and Am-West-2). Unique to this study, we identified two distinct sequences in the eastern United States (Am-East-1 and Am-East-2). Based on the 161 samples we analyzed, Am-East-1 was the only type represented in 50 B. miyamotoi-infected ticks collected from the Northeast (Vermont, Maine, New York, Connecticut, and Rhode Island), whereas ticks collected from the North-Central and Mid-Atlantic states harbored B. miyamotoi comprised of both Am-East-1 and Am-East-2. Further studies are needed to better characterize the phylogeography of B. miyamotoi and to discern if there are biologically meaningful differences among sequence types. To facilitate further exploration, we developed a polymerase chain reaction (PCR) assay designed to differentiate Am-East-1, Am-East-2, and Am-West sequence types without having to sequence the amplicon.

    • Environmental Health
      1. CATMoS: Collaborative Acute Toxicity Modeling Suiteexternal icon
        Mansouri K, Karmaus AL, Fitzpatrick J, Patlewicz G, Pradeep P, Alberga D, Alepee N, Allen TE, Allen D, Alves VM, Andrade CH, Auernhammer TR, Ballabio D, Bell S, Benfenati E, Bhattacharya S, Bastos JV, Boyd S, Brown JB, Capuzzi SJ, Chushak Y, Ciallella H, Clark AM, Consonni V, Daga PR, Ekins S, Farag S, Fedorov M, Fourches D, Gadaleta D, Gao F, Gearhart JM, Goh G, Goodman JM, Grisoni F, Grulke CM, Hartung T, Hirn M, Karpov P, Korotcov A, Lavado GJ, Lawless M, Li X, Luechtefeld T, Lunghini F, Mangiatordi GF, Marcou G, Marsh D, Martin T, Mauri A, Muratov EN, Myatt GJ, Nguyen DT, Nicolotti O, Note R, Pande P, Parks AK, Peryea T, Polash AH, Rallo R, Roncaglioni A, Rowlands C, Ruiz P, Russo DP, Sayed A, Sayre R, Sheils T, Siegel C, Silva AC, Simeonov A, Sosnin S, Southall N, Strickland J, Tang Y, Teppen B, Tetko IV, Thomas D, Tkachenko V, Todeschini R, Toma C, Tripodi I, Trisciuzzi D, Tropsha A, Varnek A, Vukovic K, Wang Z, Wang L, Waters KM, Wedlake AJ, Wijeyesakere SJ, Wilson D, Xiao Z, Yang H, Zahoranszky-Kohalmi G, Zakharov AV, Zhang FF, Zhang Z, Zhao T, Zhu H, Zorn KM, Casey W, Kleinstreuer NC.
        Environ Health Perspect. 2021 Apr;129(4):47013.
        BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets ( The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made.

    • Epidemiology and Surveillance

    • Food Safety
      1. Notes from the Field: An Outbreak of Escherichia coli O157:H7 Infections Linked to Romaine Lettuce Exposure - United States, 2019external icon
        Hoff C, Higa J, Patel K, Gee E, Wellman A, Vidanes J, Holland A, Kozyreva V, Zhu J, Mattioli M, Roundtree A, McFadden K, Whitlock L, Wise M, Gieraltowski L, Schwensohn C.
        MMWR Morb Mortal Wkly Rep. 2021 May 7;70(18):689-690.

    • Health Disparities
      1. CONTEXT: Social and structural determinants of health (SDOH) have become part of the public health and health care landscape. The need to address SDOH is reinforced by morbidity and mortality trends, including a recent multiyear decrease in life expectancy and persistent health disparities. Leadership on SDOH-related efforts has come from public health, health care, private philanthropy, and nongovernmental entities. STRATEGY: The Centers for Disease Control and Prevention (CDC) has been addressing SDOH through both disease- or condition-specific programs and crosscutting offices. Guidance from public health partners in the field has led the CDC to consider more strategic approaches to incorporating SDOH into public health activities. IMPLEMENTATION: The CDC's crosscutting SDOH Workgroup responded to external recommendations to develop a specific vision and plan that aims to integrate SDOH into the agency's infrastructure. The group also sponsors CDC forums for sharing research and trainings on embedding SDOH in programs. The group created a Web site to centralize CDC SDOH research, data sources, practice tools, programs, and policies. PROGRESS: The CDC has shown strong leadership in prioritizing SDOH in recent years. Individual programs and crosscutting offices have developed various models aimed at ensuring that public health research and practice address SDOH. DISCUSSION: Building sustainable SDOH infrastructures in public health institutions that reach across multiple health topics and non-health organizations could increase chances of meeting public health morbidity and mortality reduction goals, including decreasing health disparities. Although public health priorities and socioeconomic trends will change over time, experience suggests that social and structural factors will continue to influence the public's health. The CDC and state, tribal, local, and territorial public health institutions have played important leadership roles in the system of community and service organizations that interface with communities they mutually serve to address SDOH. Continued capacity-building could help grow and sustain an SDOH infrastructure that advances this work.

      2. OBJECTIVES: By race/ethnicity and socioeconomic position (SEP), to estimate and examine changes over time in (1) mortality rate, (2) mortality disparities and (3) excess mortality risk attributed to diagnosed diabetes (DM). DESIGN: Population-based cohort study using National Health Interview Survey data linked to mortality status from the National Death Index from survey year up to 31 December 2015 with 5 years person-time. PARTICIPANTS: US adults aged ≥25 years with (31 586) and without (332 451) DM. PRIMARY OUTCOME: Age-adjusted all-cause mortality rate for US adults with DM in each subgroup of SEP (education attainment and income-to-poverty ratio (IPR)) and time (1997-2001, 2002-2006 and 2007-2011). RESULTS: Among adults with DM, mortality rates fell from 23.5/1000 person-years (p-y) in 1997-2001 to 18.1/1000 p-y in 2007-2011 with changes of -5.2/1000 p-y for non-Hispanic whites; -5.2/1000 p-y for non-Hispanic blacks; and -5.4/1000 p-y for Hispanics. Rates significantly declined within SEP groups, measured as education attainment (<high school=-5.7/1000 p-y; high school graduate=-4.2/1000 p-y; and >high school=-4.8/1000 p-y) and IPR group (poor=-7.9/1000 p-y; middle income=-4.7/1000 p-y; and high income=-6.2/1000 p-y; but not for near poor). For adults with DM, statistically significant all-cause mortality disparity showed greater mortality rates for the lowest than the highest SEP level (education attainment and IPR) in each time period. However, patterns in mortality trends and disparity varied by race/ethnicity. The excess mortality risk attributed to DM significantly decreased from 1997-2001 to 2007-2011, within SEP levels, and among Hispanics and non-Hispanic whites; but no statistically significant changes among non-Hispanic blacks. CONCLUSIONS: There were substantial improvements in all-cause mortality among US adults. However, we observed SEP disparities in mortality across race/ethnic groups or for adults with and without DM despite targeted efforts to improve access and quality of care among disproportionately affected populations.

    • Health Economics
      1. Cognitive ability in childhood is positively associated with economic productivity in adulthood. Expected gains in economic output from interventions that protect cognitive function can be incorporated in benefit-cost and cost-effectiveness analyses conducted from a societal perspective. This review summarizes estimates from high-income countries of the association of general cognitive ability, standardized as intelligence quotient (IQ), with annual and lifetime earnings among adults. Estimates of the association of adult earnings with cognitive ability assessed in childhood or adolescence vary from 0.5% to 2.5% per IQ point. That range reflects differences in data sources and analytic methods. We take a conservative published estimate of a 1.4% difference in market productivity per IQ point in the United States from a recent study that controlled for confounding by family background and behavioral attributes. Using that estimate and the present value of lifetime earnings calculated using a 3% discount rate, the implied lifetime monetary valuation of an IQ point in the United States is USD 10,600-13,100. Despite uncertainty and the exclusion of non-market productivity, incorporation of such estimates could lead to a fuller assessment of the benefits of public health and clinical interventions that protect the developing brains of fetuses, infants, and young children.

    • Immunity and Immunization
      1. Vaccinations and Vaccinators' Tracking System in Island Settlements: CHAD 2017-2018external icon
        Atagbaza A, Okeibunor J, Amadou F, Kalilou S, Esanga AM, Bagayoko AN, Bohoussou P, Igweonu O, Seid MM, Aliyu AJ, Ntezayabo EB, Traore MA, Nzioki M, Olaleye A, Aluma AD, Sedick DA, Seid AM, Tahir MS, de Medeiros N, Rabenarivo B, Diomande F, Mkanda P.
        J Immunol Sci. 2021 Apr 12;Spec Issue(2):1116.
        INTRODUCTION: Chad is a country within the Lake Chad sub region, currently at risk for poliovirus infection. The Lake Chad Task Team on polio eradication in this sub region made significant efforts to reduce the risk of polio transmission in Chad by tacking immunization teams in the Island Settlement using a Geographic Information System (GIS) technology. This article demonstrates the application of GIS technology to track vaccination teams to monitor immunization coverage in the Island settlements, reduce the number of missed settlements, to provide evidence for vaccination implementation and accountability and improve team performance. METHODS: In each district where tracking was conducted, global positioning system-enabled Android phones were given to each team on a daily basis and were used to record team tracks. These tracks were uploaded to a dashboard to show the level of coverage and identify areas missed by the teams. RESULTS: In 2018, tracking covered 30 immunization days, in six rounds. Approximately average of 1173 Island settlements were tracked and covered in each of the six rounds. A total of 806,999 persons aged 0-10 years were immunized, out of which 4273 were zero dose cases at the point of their immunization. Tracking activities were conducted. There was an improvement in the geographic coverage of settlements and an overall reduction in the number of missed settlements. CONCLUSIONS: The tracking of vaccination teams and Island settlements ensured useful information for planning and implementation of polio campaigns and enabled supervisors to evaluate performance of vaccination teams.

      2. Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Projectexternal icon
        Deloria Knoll M, Bennett JC, Garcia Quesada M, Kagucia EW, Peterson ME, Feikin DR, Cohen AL, Hetrich MK, Yang Y, Sinkevitch JN, Ampofo K, Aukes L, Bacci S, Bigogo G, Brandileone MC, Bruce MG, Camilli R, Castilla J, Chan G, Chanto Chacón G, Ciruela P, Cook H, Corcoran M, Dagan R, Danis K, de Miguel S, De Wals P, Desmet S, Galloway Y, Georgakopoulou T, Hammitt LL, Hilty M, Ho PL, Jayasinghe S, Kellner JD, Kleynhans J, Knol MJ, Kozakova J, Kristinsson KG, Ladhani SN, Lara CS, León ME, Lepp T, Mackenzie GA, Mad'arová L, McGeer A, Mungun T, Mwenda JM, Nuorti JP, Nzoyikorera N, Oishi K, De Oliveira LH, Paragi M, Pilishvili T, Puentes R, Rafai E, Saha SK, Savrasova L, Savulescu C, Scott JA, Scott KJ, Serhan F, Setchanova LP, Sinkovec Zorko N, Skoczyńska A, Swarthout TD, Valentiner-Branth P, van der Linden M, Vestrheim DF, von Gottberg A, Yildirim I, Hayford K, The Pserenade T.
        Microorganisms. 2021 Apr 2;9(4).
        Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

      3. Anxiety-Related Adverse Event Clusters After Janssen COVID-19 Vaccination - Five U.S. Mass Vaccination Sites, April 2021external icon
        Hause AM, Gee J, Johnson T, Jazwa A, Marquez P, Miller E, Su J, Shimabukuro TT, Shay DK.
        MMWR Morb Mortal Wkly Rep. 2021 May 7;70(18):685-688.
        On April 7, 2021, after 5 weeks' use of the Janssen COVID-19 vaccine under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA), CDC received reports of clusters of anxiety-related events after administration of Janssen COVID-19 vaccine from five mass vaccination sites, all in different states. To further investigate these cases, CDC interviewed vaccination site staff members to gather additional information about the reported events and vaccination site practices. Four of the five sites temporarily closed while an investigation took place. Overall, 64 anxiety-related events, including 17 reports of syncope (fainting), an anxiety-related event, among 8,624 Janssen COVID-19 vaccine recipients, were reported from these sites for vaccines administered during April 7-9. As a follow-up to these interviews, CDC analyzed reports of syncope shortly after receipt of Janssen COVID-19 vaccine to the Vaccine Adverse Event Reporting System (VAERS), the vaccine safety monitoring program managed by CDC and FDA. To compare the occurrence of these events with those reported after receipt of other vaccines, reports of syncopal events after influenza vaccine administered in the 2019-20 influenza season were also reviewed. Syncope after Janssen COVID-19 vaccination was reported to VAERS (8.2 episodes per 100,000 doses). By comparison, after influenza vaccination, the reporting rate of syncope was 0.05 episodes per 100,000 doses. Anxiety-related events can occur after any vaccination. It is important that vaccination providers are aware that anxiety-related adverse events might be reported more frequently after receipt of the Janssen COVID-19 vaccine than after influenza vaccination and observe all COVID-19 vaccine recipients for any adverse reactions for at least 15 minutes after vaccine administration.

      4. Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?external icon
        Malosh RE, Petrie JG, Callear A, Truscon R, Johnson E, Evans R, Bazzi L, Cheng C, Thompson MS, Martin ET, Monto AS.
        Clin Infect Dis. 2021 May 5.
        BACKGROUND: The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort. METHODS: Using longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households. RESULTS: The pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (-6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccination coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VE was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households. CONCLUSION: Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.

      5. Safety Monitoring of the Janssen (Johnson & Johnson) COVID-19 Vaccine - United States, March-April 2021external icon
        Shay DK, Gee J, Su JR, Myers TR, Marquez P, Liu R, Zhang B, Licata C, Clark TA, Shimabukuro TT.
        MMWR Morb Mortal Wkly Rep. 2021 May 7;70(18):680-684.
        On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Janssen (Ad.26.COV2.S) COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson) (1). The Janssen COVID-19 vaccine, the third COVID-19 vaccine authorized for use in the United States, uses a replication-incompetent human adenoviral type 26 vector platform* (2) and is administered as a single intramuscular dose, whereas the first two authorized vaccines use an mRNA platform and require 2 doses. On February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for use of Janssen COVID-19 vaccine among persons aged ≥18 years (3). During April 13-23, CDC and FDA recommended a pause in use of Janssen vaccine after reports of six cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia (platelet count <150,000/μL of blood) among Janssen vaccine recipients (4). Similar thrombotic events, primarily among women aged <60 years, have been described in Europe after receipt of the AstraZeneca COVID-19 vaccine, which uses a replication-incompetent chimpanzee adenoviral vector (5-7). The U.S. CVST cases that prompted the pause in Janssen vaccination, as well as subsequently detected CVST cases, are described elsewhere (8). This report summarizes adverse events among Janssen vaccine recipients, including non-CVST cases of thrombosis with thrombocytopenia syndrome (TTS), reported to the Vaccine Adverse Events Reporting System (VAERS), a passive surveillance system, and through v-safe, an active monitoring system. As of April 21, 2021, 7.98 million doses of the Janssen COVID-19 vaccine had been administered. Among 13,725 VAERS reports reviewed, 97% were classified as nonserious and 3% as serious,(†) including three reports among women of cases of thrombosis in large arteries or veins accompanied by thrombocytopenia during the second week after vaccination. These three cases and the previously detected CVST cases are consistent with 17 cases of TTS,(§) a newly defined condition. Approximately 338,700 Janssen COVID-19 vaccine recipients completed at least one v-safe survey during the week after vaccination; 76% reported a systemic reaction, 61% reported a local reaction, and 34% reported a health impact.(¶) Fatigue and pain were commonly reported symptoms in both VAERS and v-safe. The overall safety profile is consistent with preauthorization clinical trials data. Prompt review of U.S. vaccine safety data detected three additional cases of non-CVST TTS, in addition to the previously recognized CVST cases that initiated the pause in use of the Janssen COVID-19 vaccine. Ongoing monitoring of adverse events after COVID-19 vaccination, including vaccination with the Janssen single-dose vaccine, is essential for evaluating the risks and benefits of each vaccine.

      6. Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years - United States, January-March 2021external icon
        Tenforde MW, Olson SM, Self WH, Talbot HK, Lindsell CJ, Steingrub JS, Shapiro NI, Ginde AA, Douin DJ, Prekker ME, Brown SM, Peltan ID, Gong MN, Mohamed A, Khan A, Exline MC, Files DC, Gibbs KW, Stubblefield WB, Casey JD, Rice TW, Grijalva CG, Hager DN, Shehu A, Qadir N, Chang SY, Wilson JG, Gaglani M, Murthy K, Calhoun N, Monto AS, Martin ET, Malani A, Zimmerman RK, Silveira FP, Middleton DB, Zhu Y, Wyatt D, Stephenson M, Baughman A, Womack KN, Hart KW, Kobayashi M, Verani JR, Patel MM.
        MMWR Morb Mortal Wkly Rep. 2021 May 7;70(18):674-679.
        Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination(†) with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

    • Injury and Violence
      1. Epidemiology of Chronic Effects of Traumatic Brain Injuryexternal icon
        Haarbauer-Krupa J, Pugh MJ, Prager EM, Harmon N, Wolfe J, Yaffe KC.
        J Neurotrauma. 2021 May 5.
        Although many patients diagnosed with traumatic brain injury (TBI), particularly mild TBI, recover from their symptoms within a few weeks, a small but meaningful subset experience symptoms that persist for months or years after injury and significantly impact quality of life for the individual and their family. The factors associated with an increased likelihood of negative TBI outcomes include not only characteristics of the injury and injury mechanism, but also the individual's age, pre-injury status, comorbid conditions, environment, and propensity for resilience. In this article, as part of the Brain Trauma Blueprint: TBI State of the Science framework, we examine the epidemiology of long-term outcomes of TBI, including incidence, prevalence, and risk factors. We identify the need for increased longitudinal, global, standardized, and validated assessments on incidence, recovery, and treatments, as well as standardized assessments of the influence of genetics, race, ethnicity, gender, and environment on TBI outcomes. By identifying how epidemiological factors contribute to TBI outcomes in different groups of people and potentially impact differential disease progression, we can guide investigators and clinicians towards more precise patient diagnosis along with tailored management and improve clinical trial designs, data evaluation and patient selection criteria.

      2. Approximately 60,000 older adults (aged ≥65 years) die from unintentional injuries each year; in 2019 these included 34,000 fall deaths, 8,000 traffic-related motor vehicle crash deaths, and 3,000 drug poisoning deaths (1). In addition, >9,000 suicide deaths occur among older adults each year (1). Deaths among older adults account for 33% of these unintentional injury deaths and 19% of suicide deaths among all age groups (1). Nonfatal injuries from these causes are more common in this age group and can lead to long-term health consequences, such as brain injury and loss of independence. This study included 2018 data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project (HCUP) to determine the prevalence of selected nonfatal injuries among older adults treated in emergency departments (EDs) and hospitals. Injury mechanisms among the leading causes of injury death in older adults were studied, including unintentional falls, unintentional traffic-related motor vehicle crashes, unintentional opioid overdoses, and self-harm (suicidal and nonsuicidal by any mechanism). In 2018, an estimated 2.4 million ED visits and >700,000 hospitalizations from these injuries occurred among adults aged ≥65 years. Unintentional falls accounted for >90% of the selected ED visits and hospitalizations. Injuries among older adults can be prevented (2). Educational campaigns, such as CDC's Still Going Strong* awareness campaign, that use positive messages can encourage older adults to take steps to prevent injuries. Health care providers can help prevent injuries by recommending that older patients participate in effective interventions, including referrals to physical therapy and deprescribing certain medications.(†).

    • Laboratory Sciences
      1. The feasibility of modified HIV and antiretroviral drug testing using self-collected dried blood spots from men who have sex with menexternal icon
        Luo W, Sullivan V, Chavez PR, Wiatrek SE, Zlotorzynska M, Martin A, Rossetti R, Sanchez T, Sullivan P, MacGowan RJ, Owen SM, Masciotra S.
        BMC Infect Dis. 2021 May 5;21(1):423.
        BACKGROUND: In the US, one in six men who have sex with men (MSM) with HIV are unaware of their HIV infection. In certain circumstances, access to HIV testing and viral load (VL) monitoring is challenging. The objective of this study was to evaluate the feasibility of conducting laboratory-based HIV and antiretroviral (ARV) drug testing, and VL monitoring as part of two studies on self-collected dried blood spots (DBS). METHODS: Participants were instructed to collect DBS by self-fingerstick in studies that enrolled MSM online. DBS from the first study (N = 1444) were tested with HIV serological assays approved by the Food and Drug Administration (FDA). A subset was further tested with laboratory-modified serological and VL assays, and ARV levels were measured by mass spectrometry. DBS from the second study (N = 74) were only tested to assess VL monitoring. RESULTS: In the first study, the mail back rate of self-collected DBS cards was 62.9%. Ninety percent of DBS cards were received at the laboratory within 2 weeks from the day of collection, and 98% of the cards had sufficient spots for one assay. Concordance between FDA-approved and laboratory-modified protocols was high. The samples with undetectable ARV had higher VL than samples with at least one ARV drug. In the second study, 70.3% participants returned self-collected DBS cards, and all had sufficient spots for VL assay. High VL was observed in samples from participants who reported low ARV adherence. CONCLUSIONS: In these studies, MSM were able to collect and provide adequate DBS for HIV testing. The FDA-approved and laboratory-modified testing algorithms performed similarly. DBS collected at home may be feasible for HIV testing, ARV measurement, and monitoring viral suppression.

      2. Implementing reference systems for thyroid function tests - A collaborative effortexternal icon
        Vesper HW, Van Uytfanghe K, Hishinuma A, Raverot V, Patru MM, Danilenkko U, van Herwaarden AE, Shimizu E.
        Clin Chim Acta. 2021 Apr 29.
        Measurements of thyroid stimulating hormone (TSH) and free thyroxine (fT4) are critical for the early detection of thyroid diseases and for monitoring treatment. The IFCC Committee for Standardization of Thyroid Function Tests (C-STFT) established reference systems for TSH harmonization and FT4 standardization, and is now working national partners on implementing these reference systems. These implementation activities include the maintenance of the reference systems, their use to standardize and harmonize assays, and educational activities to inform stakeholders about anticipated changes in measurement values as a result of standardization and harmonization. The IFCC C-STFT formed a network of reference laboratories for FT4 and is creating a new harmonization panel for TSH. The U.S. Centers for Disease Control and Prevention is a member of the reference laboratory network and is launching a formal standardization program for FT4. In Japan, national organizations successfully implemented TSH harmonization and established harmonized reference intervals for TSH. The C-STFT made available on its website research findings about potential concerns, communication needs and benefits of FT4 standardization and is assisting local organizations with communicating changes related to these standardization and harmonization efforts. Implementation of fT4 standardization and TSH harmonization is a complex, continuous task that requires collaboration with IVD manufacturers, laboratories, physicians and health care providers. C-STFT is working successfully with national organizations and local groups on improving FT4 and TSH measurements.

    • Maternal and Child Health
      1. OBJECTIVE: The objective of this article was to assess the impact on behavioral and socioemotional development, 2 to 6 years postintervention (depending on the curriculum), of Legacy for Children, a public health approach to improve child developmental outcomes among families living in poverty. METHODS: Mothers who were recruited prenatally or at the time of childbirth participated in a set of Legacy parallel design randomized control trials between 2001 and 2009 in Miami, Florida, or Los Angeles, California. Of the initial 574 mother-child dyads, 364 completed at least 1 behavioral or socioemotional outcome measure at the third-grade follow-up. Intention-to-treat analyses compared Legacy and comparison groups on behavioral and socioemotional outcomes. RESULTS: Children of Legacy mothers in Los Angeles were at lower risk for externalizing behaviors and poor adaptive skills than children whose mothers did not participate in the intervention. No significant outcome differences by group assignment were found in Miami. CONCLUSION: Group-based positive parenting interventions such as Legacy may have a sustained impact on children's behavioral and socioemotional development several years after intervention completion.

      2. Individuals aged 1-64 years with documented congenital heart defects at healthcare encounters, five U.S. surveillance sites, 2011-2013external icon
        Glidewell MJ, Farr SL, Book WM, Botto L, Li JS, Soim AS, Downing KF, Riehle-Colarusso T, D'Ottavio AA, Feldkamp ML, Khanna AD, Raskind-Hood CL, Sommerhalter KM, Crume TL.
        Am Heart J. 2021 May 2.
        BACKGROUND: Many individuals born with CHD survive to adulthood. However, population estimates of CHD beyond early childhood are limited in the U.S. OBJECTIVES: To estimate the percentage of individuals aged 1-to-64 years at five U.S. sites with CHD documented at a healthcare encounter during a three-year period and describe their characteristics. METHODS: Sites conducted population-based surveillance of CHD among 1 to 10-year-olds (three sites) and 11 to 64-year-olds (all five sites) by linking healthcare data. Eligible cases resided in the population catchment areas and had one or more healthcare encounters during the surveillance period (1/1/11-12/31/13) with a CHD-related ICD-9-CM code. Site-specific population census estimates from the same age groups and time period were used to assess percentage of individuals in the catchment area with a CHD-related ICD-9-CM code documented at a healthcare encounter (hereafter referred to as CHD cases). Severe and non-severe CHD were based on an established mutually exclusive anatomic hierarchy. RESULTS: Among 42,646 CHD cases, 23.7% had severe CHD and 51.5% were male. Percentage of CHD cases among 1 to 10-year olds, was 6.36/1,000 (range: 4.33 to 9.96/1,000) but varied by CHD severity [severe: 1.56/1,000 (range: 1.04 to 2.64/1,000); non-severe: 4.80/1,000 (range: 3.28 to 7.32/1,000)]. Percentage of cases across all sites in 11 to 64-year-olds was 1.47/1,000 (range: 1.02 to 2.18/1,000) and varied by CHD severity [severe: 0.34/1,000 (range: 0.26 to 0.49/1,000); non-severe: 1.13/1,000 (range: 0.76 to 1.69/1,000)]. Percentage of CHD cases decreased with age until 20-44 years and, for non-severe CHD only, increased slightly for ages 45-64 years. CONCLUSION: CHD cases varied by site, CHD severity, and age. These findings will inform planning for the needs of this growing population.

      3. Effect of Delays in Maternal Access to Healthcare on Neonatal Mortality in Sierra Leone: A Social Autopsy Case-Control Study at a Child Health and Mortality Prevention Surveillance (CHAMPS) Siteexternal icon
        Preslar JP, Worrell MC, Kaiser R, Cain CJ, Samura S, Jambai A, Raghunathan PL, Clarke K, Goodman D, Christiansen-Lindquist L, Webb-Girard A, Kramer M, Breiman R.
        Matern Child Health J. 2021 May 4.
        INTRODUCTION: In low-resource settings, a social autopsy tool has been proposed to measure the effect of delays in access to healthcare on deaths, complementing verbal autopsy questionnaires routinely used to determine cause of death. This study estimates the contribution of various delays in maternal healthcare to subsequent neonatal mortality using a social autopsy case-control design. METHODS: This study was conducted at the Child Health and Mortality Prevention Surveillance (CHAMPS) Sierra Leone site (Makeni City and surrounding rural areas). Cases were neonatal deaths in the catchment area, and controls were sex- and area-matched living neonates. Odds ratios for maternal barriers to care and neonatal death were estimated, and stratified models examined this association by neonatal age and medical complications. RESULTS: Of 53 neonatal deaths, 26.4% of mothers experienced at least one delay during pregnancy or delivery compared to 46.9% of mothers of stillbirths and 18.6% of control mothers. The most commonly reported delay among neonatal deaths was receiving care at the facility (18.9%). Experiencing any barrier was weakly associated (OR 1.68, CI 0.77, 3.67) and a delay in receiving care at the facility was strongly associated (OR 19.15, CI 3.90, 94.19) with neonatal death. DISCUSSION: Delays in healthcare are associated with neonatal death, particularly delays experienced at the healthcare facility. Heterogeneity exists in the prevalence of specific delays, which has implications for local public health policy. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

    • Medicine
      1. Despite advances in transfusion safety, concerns with safety of platelet transfusions remain including platelet-related sepsis and higher reaction rates observed among patients receiving apheresis platelets (APLTs). National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) data were analyzed to quantify the burden and severity of adverse reactions occurring from APLTs and whole blood-derived platelets (WBD-PLTs). Facilities participating in NHSN HM during 2010-2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for APLTs and WBD-PLTs stratified by severity, use of platelet additive solution (PAS), and pathogen reduction technology (PRT). Chi-square tests were used to compare rates. During the study interval, 2,000,589 platelets were transfused: 1,435,154 APLTs; 525,902 WBD-PLTs; and among APLTs, 39,533 PRT-APLTs. APLT adverse reaction rates were higher (478 vs 70/ 100,000, P< .01) and more often serious (34 vs 6/100,000; P< .01) compared with WBD-PLTs. Adverse reactions were higher among PRT-APLTs (572/100,000) and were less often serious (18/100,000) compared with non-PRT-APLTs (35/100,000) although this association was not statistically significant. Among components implicated in adverse reactions, 92% of APLTs were suspended in plasma. Compared with PRT-APLTs stored in PAS, rates were higher among units stored in plasma (760 vs 525/100,000). Most serious reactions (75%) were allergic. No transfusion-transmitted infections were reported among PRT-APLTs. APLTs were associated with a 6-fold and 2-fold higher serious adverse reaction risks compared with WBD-PLTs and PRT-APLTs, respectively. These findings demonstrate the importance of monitoring transfusion-related adverse reactions to track the safety of platelet transfusions and quantify the impact of mitigation strategies through national hemovigilance systems.

    • Occupational Safety and Health
      1. Perceptions of Safety Climate and Fatigue Related to ACGME Residency Duty Hour Restrictions in Otolaryngology Residentsexternal icon
        Carr MM, Friedel JE, Foreman AM, O'Brien DC, Wirth O.
        Otolaryngol Head Neck Surg. 2021 May 4:1945998211010108.
        OBJECTIVE: To compare otolaryngology residents' perceptions of safety climate with respect to duty hour compliance and self-perceived fatigue. STUDY DESIGN: Cross-sectional study. SETTING: Forty-one otolaryngology residencies distributed across the United States. METHODS: A national sample of otolaryngology residents was surveyed electronically in 2019. The survey included demographic details, on-call descriptors, an 18-point Safety Climate Survey (SCS) modified to measure perceptions of program attitudes and practices around resident duty hour compliance, and the 33-point Chalder Fatigue Questionnaire (CFQ). RESULTS: Of 397 surveyed residents, 205 (51.6%) responded. The mean modified SCS score was 11.29 out of 18 (95% CI, 10.76-11.81). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME [Accreditation Council for Graduate Medical Education] duty hour restrictions," where 100 (48.8%) disagreed or strongly disagreed. The mean CFQ score was 15.99 of 33 (95% CI, 15.17-16.81). As the modified SCS score improved, CFQ scores decreased, indicating an inverse relationship between duty hour safety climate and fatigue. Having a protected postcall day off and having the program director, chief resident, or senior resident decide that a resident should take a postcall day off were all associated with higher modified SCS scores. CONCLUSION: Otolaryngology residents perceived a safety climate that is suboptimal with regard to duty hour restriction issues. Additionally, an inverse relationship between fatigue and modified SCS scores suggests that fatigue among residents may be lower in programs where residents perceive that ACGME duty hour compliance is more important.

    • Parasitic Diseases
      1. No Serological Evidence of Trachoma or Yaws Among Residents of Registered Camps and Makeshift Settlements in Cox's Bazar, Bangladeshexternal icon
        Cooley GM, Feldstein LR, Bennett SD, Estivariz CF, Weil L, Bohara R, Vandenent M, Mainul Hasan A, Akhtar MS, Uzzaman MS, Billah MM, Conklin L, Ehlman DC, Asiedu K, Solomon AW, Alamgir A, Flora MS, Martin DL.
        Am J Trop Med Hyg. 2021 May 3.
        Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

      2. BACKGROUND: The Plasmodium falciparum antigen histidine rich protein 2 (HRP2) is a preferred target for malaria rapid diagnostic tests (RDTs) because of its abundant production by the parasite and thermal stability. As a result, a majority of RDTs procured globally target this antigen. However, previous reports from South America and recent reports from sub-Saharan Africa and Asia indicate that certain P. falciparum parasites have deletions of the gene coding for HRP2. The HRP2 antigen is paralogous to another P. falciparum antigen HRP3 and some antibodies to HRP2 cross-react with HRP3. Multiple parasites have been described with deletions of one or both hrp2 and hrp3 genes. It is unclear how the various combinations of hrp2 and hrp3 deletion genotypes affect clinical sensitivity of HRP2-based RDTs. METHODS: Cross-reactivity between HRP2 and HRP3 was tested on malaria RDTs using culture-adapted P. falciparum parasites with both hrp2 and hrp3 intact or with one or both genes deleted. Ten-fold serial dilutions of four culture-adapted P. falciparum parasites [3D7 (hrp2+/hrp3+), Dd2 (hrp2-/hrp3+), HB3 (hrp2+/hrp3-) and 3BD5 (hrp2-/hrp3-)] ranging from 100,000 to 0.01 parasites/µL were prepared. HRP2, Plasmodium lactate dehydrogenase (pLDH) and aldolase concentrations were determined for the diluted samples using a multiplex bead assay. The samples were subsequently tested on three RDT products designed to detect P. falciparum by HRP2 alone or in combination with pLDH. RESULTS: At parasite densities of approximately 1000 parasites/µL, parasites that expressed either hrp2 or hrp3 were detected by all three RDTs. Multiplex based antigen measurement using HRP2- conjugated beads demonstrated higher antigen concentration when both hrp2 and hrp3 genes were intact (3D7 parasites, 47.9 ng/ml) compared to HB3 (3.02 ng/mL) and Dd2 (0.20 ng/mL) strains that had one gene deleted. 3D7 at 10 parasites/µL (0.45 ng/mL) was reactive on all three RDT products whereas none of the other parasites were reactive at that density. CONCLUSIONS: Above a certain antigen threshold, HRP3 cross-reactivity on HRP2-based RDTs is sufficient to mask the effects of deletions of hrp2 only. Studies of hrp2 deletion and its effects on HRP2-based RDTs must be studied alongside hrp3 deletions and include clinical sample reactivity on HRP2-based tests.

      3. Targeted deep amplicon sequencing of antimalarial resistance markers in Plasmodium falciparum isolates from Cameroonexternal icon
        L'Episcopia M, Kelley J, Dongho BG, Patel D, Schmedes S, Ravishankar S, Perrotti E, Modiano D, Lucchi NW, Russo G, Talundzic E, Severini C.
        Int J Infect Dis. 2021 Apr 30.
        BACKGROUND: Recent studies show the first emergence of the R561H artemisinin-associated resistance marker in Africa, which highlights the importance of continued molecular surveillance to assess the selection and spread of this and other drug resistance markers in the region. METHOD: In this study, we used targeted deep amplicon sequencing (TADS) of 116 isolates collected in two areas of Cameroon to genotype the major drug resistance genes k13, crt, mdr1, dhfr, dhps, and the cytochrome b (cytb) in P. falciparum. RESULTS: No confirmed or associated artemisinin resistance markers were observed in Pfk13. In comparison, both major and minor alleles associated with drug resistance were found in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. Notably, a high frequency of other non-synonymous mutations was observed across all the genes, except Pfcytb, suggesting continued selection pressure. CONCLUSIONS: The results from this study support the continued use of artemisinin combination therapy (ACT) for treatment and administration of sulphadoxine-pyrimethamine for intermittent preventive therapy in pregnant women and for seasonal chemoprevention in these study sites in Cameroon.

    • Reproductive Health
      1. Postpartum Care Utilization Among Women with Medicaid-Funded Live Births in Oregonexternal icon
        Robbins CL, Deputy NP, Patel R, Tong VT, Oakley LP, Yoon J, Bui LN, Luck J, Harvey SM.
        Matern Child Health J. 2021 Apr 29.
        INTRODUCTION: Postpartum care is an important strategy for preventing and managing chronic disease in women with pregnancy complications (i.e., gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP)). METHODS: Using a population-based, cohort study among Oregon women with Medicaid-financed deliveries (2009-2012), we examined Medicaid-financed postpartum care (postpartum visits, contraceptive services, and routine preventive health services) among women who retained Medicaid coverage for at least 90 days after delivery (n = 74,933). We estimated postpartum care overall and among women with and without GDM and/or HDP using two different definitions: 1) excluding care provided on the day of delivery, and 2) including care on the day of delivery. Pearson chi-square tests were used to assess differential distributions in postpartum care by pregnancy complications (p < .05), and generalized estimating equations were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Of Oregon women who retained coverage through 90 days after delivery, 56.6-78.1% (based on the two definitions) received any postpartum care, including postpartum visits (26.5%-71.8%), contraceptive services (30.7-35.6%), or other routine preventive health services (38.5-39.1%). Excluding day of delivery services, the odds of receiving any postpartum care (aOR 1.26, 95% CI 1.08-1.47) or routine preventive services (aOR 1.32, 95% CI 1.14-1.53) were meaningfully higher among women with GDM and HDP (reference = neither). DISCUSSION: Medicaid-financed postpartum care in Oregon was underutilized, it varied by pregnancy complications, and needs improvement. Postpartum care is important for all women and especially those with GDM or HDP, who may require chronic disease risk assessment, management, and referrals.

      2. Bias in Self-reported Prepregnancy Weight Across Maternal and Clinical Characteristicsexternal icon
        Sharma AJ, Bulkley JE, Stoneburner AB, Dandamudi P, Leo M, Callaghan WM, Vesco KK.
        Matern Child Health J. 2021 Apr 30.
        OBJECTIVES: Prepregnancy body mass index (BMI) and gestational weight gain (GWG) are known determinants of maternal and child health; calculating both requires an accurate measure of prepregnancy weight. We compared self-reported prepregnancy weight to measured weights to assess reporting bias by maternal and clinical characteristics. METHODS: We conducted a retrospective cohort study among pregnant women using electronic health records (EHR) data from Kaiser Permanente Northwest, a non-profit integrated health care system in Oregon and southwest Washington State. We identified women age ≥ 18 years who were pregnant between 2000 and 2010 with self-reported prepregnancy weight, ≥ 2 measured weights between ≤ 365-days-prior-to and ≤ 42-days-after conception, and measured height in their EHR. We compared absolute and relative difference between self-reported weight and two "gold-standards": (1) weight measured closest to conception, and (2) usual weight (mean of weights measured 6-months-prior-to and ≤ 42-days-after conception). Generalized-estimating equations were used to assess predictors of misreport controlling for covariates, which were obtained from the EHR or linkage to birth certificate. RESULTS: Among the 16,227 included pregnancies, close agreement (± 1 kg or ≤ 2%) between self-reported and closest-measured weight was 44% and 59%, respectively. Overall, self-reported weight averaged 1.3 kg (SD 3.8) less than measured weight. Underreporting was higher among women with elevated BMI category, late prenatal care entry, and pregnancy outcome other than live/stillbirth (p < .05). Using self-reported weight, BMI was correctly classified for 91% of pregnancies, but ranged from 70 to 98% among those with underweight or obesity, respectively. Results were similar using usual weight as gold standard. CONCLUSIONS FOR PRACTICE: Accurate measure of prepregnancy weight is essential for clinical guidance and surveillance efforts that monitor maternal health and evaluate public-health programs. Identification of characteristics associated with misreport of self-reported weight can inform understanding of bias when assessing the influence of prepregnancy BMI or GWG on health outcomes.

    • Substance Use and Abuse
      1. Biomarkers of Potential Harm among Adult Cigarette and Smokeless Tobacco Users in the PATH Study Wave 1 (2013-2014): A Cross-Sectional Analysisexternal icon
        Chang JT, Vivar JC, Tam J, Hammad HT, Christensen CH, van Bemmel DM, Das B, Danilenko U, Chang CM.
        Cancer Epidemiol Biomarkers Prev. 2021 May 4.
        BACKGROUND: While smokeless tobacco (ST) is causes oral cancer and is associated with cardiovascular diseases, less is known about how its effects differ from other tobacco use. Biomarkers of potential harm (BOPH) can measure short-term health effects such as inflammation and oxidative stress. METHOD: We compared BOPH concentrations (interleukin-6 [IL-6], high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and F2-isoprostane) across 3,460 adults in Wave 1 of the Population Assessment of Tobacco and Health Study (2013-2014) by tobacco use groups: primary ST users (current exclusive ST use among never smokers), secondary ST users (current exclusive ST use among former smokers), exclusive cigarette smokers, dual users of ST and cigarettes, former smokers, and never tobacco users. We estimated geometric mean ratios (GMRs) using never tobacco users, cigarette smokers, and former smokers as referents, adjusting for demographic and health conditions, creatinine (for F2-isoprostane), and pack-years in smoker referent models. RESULTS: BOPH levels among primary ST users were similar to both never tobacco users and former smokers. Most BOPH levels were lower among ST users compared to current smokers. Compared to never tobacco users, dual users had significantly higher sICAM-1, IL-6 and F2-isoprostane. However, compared to smokers, dual users had similar biomarker levels. Former smokers and secondary ST users had similar levels of all five biomarkers. CONCLUSIONS: ST users have lower levels of inflammatory and oxidative stress biomarkers than smokers. IMPACT: ST use alone and in combination with smoking may result in different levels of inflammatory and oxidative stress levels.

      2. Trends and correlates of cocaine use among adults in the United States, 2006-2019external icon
        Mustaquim D, Jones CM, Compton WM.
        Addict Behav. 2021 Apr 20;120:106950.
        BACKGROUND: Cocaine is the most commonly reported illicit stimulant used in the U.S., yet limited research has examined recent changes in cocaine use patterns and co-occurring substance use and mental health characteristics among adults using cocaine. METHODS: Self-report data from adults (age 18 years or older) participating in the 2006 to 2019 National Surveys on Drug Use and Health (NSDUH) were used to estimate trends in prevalence of past-year cocaine use by demographic characteristics, cocaine use disorder, cocaine injection, frequency of use. For 2018-2019, prevalence of co-occurring past-year use of other illicit and prescription substances and mental health characteristics were estimated. Multivariable logistic regression examined demographic, substance use, and mental health characteristics associated with past-year cocaine use in 2018-2019. RESULTS: The annual average estimated prevalence of past-year cocaine use among adults was highest in 2006-2007 (2.51%), declined to 1.72% in 2010-2011, and then increased to 2.14% in 2018-2019. The annual average estimated prevalence of past-year cocaine use disorder was highest in 2006-2007 (0.71%) and declined to 0.37% in 2018-2019. Characteristics associated with higher adjusted odds of past-year cocaine use included: males; ages 18-49; Hispanic ethnicity; income <$20,000; large or small metro counties; use of other substances (nicotine, alcohol, marijuana, sedative/tranquilizers, prescription opioids, prescription stimulants, heroin, and methamphetamine); and serious psychological distress and suicidal ideation or attempt. CONCLUSION: Additional efforts to support prevention and response capacity in communities, expand linkages to care and retention for substance use and mental health, and enhance collaborations between public health and public safety are needed.

    • Veterinary Medicine
      1. Clinical, diagnostic, and epidemiological features of a community-wide outbreak of canine leptospirosis in a low-prevalence region (Maricopa County, Arizona)external icon
        Iverson SA, Levy C, Yaglom HD, Venkat HL, Artus A, Galloway R, Guagliardo SA, Reynolds L, Kretschmer MJ, LaFerla Jenni ME, Woodward P, Reindel AA, Tarrant S, Sylvester T, Klein R, Mundschenk P, Sunenshine R, Schafer IJ.
        J Am Vet Med Assoc. 2021 Mar 15;258(6):616-629.
        OBJECTIVE: To describe clinical, diagnostic, and epidemiological features of an outbreak of leptospirosis in dogs in Maricopa County, Ariz, from January 2016 through June 2017. ANIMALS: 71 case and 281 control dogs. PROCEDURES: Cases were classified as confirmed, probable, suspect, or not a case on the basis of medical record data that fulfilled clinical, diagnostic, and epidemiological criteria. Potential exposures were assessed by owner survey. For the case-control investigation, control dogs were recruited through owner completion of a July 2017 survey. Summary statistics and ORs for case dog lifestyle factors were reported. RESULTS: 54 dogs were classified as confirmed and 17 as probable cases. For 4 dogs of a household cluster (5 confirmed and 3 probable), the highest microscopic agglutination titer was for serovar Djasiman (Leptospira kirschneri detected by PCR assay), and for 13 dogs of a community outbreak (49 confirmed and 14 probable cases), the highest titer was for serovar Canicola (Leptospira interrogans detected by PCR assay). The 44 case dogs included in the case-control investigation were 7.7 (95% CI, 3.5 to 16.7) and 2.9 times (95% CI, 1.3 to 6.6) as likely as control dogs to have visited dog daycare or to have been kenneled overnight at a boarding facility, respectively, 30 days prior to the onset of clinical signs or diagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic and epidemiological findings indicated 2 outbreaks. Transmission where dogs congregated likely propagated the community outbreak. Outbreaks of leptospiral infections can occur in regions of low prevalence, and a dog's exposure to areas where dogs congregate should be considered when making Leptospira vaccination recommendations.

    • Zoonotic and Vectorborne Diseases
      1. Educational Approach to Prevent the Burden of Vaccinia Virus Infections in a Bovine Vaccinia Endemic Area in Brazilexternal icon
        Barbosa Costa G, Silva de Oliveira J, Townsend MB, Carson WC, Borges IA, McCollum AM, Kroon EG, Satheshkumar PS, Reynolds MG, Nakazawa YJ, de Souza Trindade G.
        Pathogens. 2021 Apr 23;10(5).
        Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonotic disease characterized by exanthematous lesions on the teats of dairy cows and the hands of milkers, and is an important public health issue in Brazil and South America. BV also results in economic losses to the dairy industry, being a burden to the regions involved in milk production. In the past 20 years, much effort has been made to increase the knowledge regarding BV epidemiology, etiologic agents, and interactions with the hosts and the environment. In the present study, we evaluated milking practices that could be associated with VACV infections in an endemic area in Brazil and proposed an educational tool to help prevent VACV infections. In our survey, 124 individuals (51.7%) from a total of 240 had previously heard of BV, 94 of which knew about it through BV outbreaks. Although most individuals involved in dairy activities (n = 85/91) reported having good hygiene practices, only 29.7% used adequate disinfecting products to clean their hands and 39.5% disinfected cows' teats before and after milking. Furthermore, 46.7% of individuals reported having contact with other farm and domestic animals besides dairy cattle. We also evaluated the presence of IgG and IgM antibodies in the surveyed population. Overall, 6.1% of likely unvaccinated individuals were positive for anti-Orthopoxvirus IgG antibodies, and 1.7% of all individuals were positive for IgM antibodies. Based on our findings, we proposed educational materials which target individuals with permanent residence in rural areas (mainly farmers and milkers), providing an overview and basic information about preventive measures against VACV infections that could enhance BV control and prevention efforts, especially for vulnerable populations located in endemic areas.

      2. Epidemiology, Ecology and Prevention of Plague in the West Nile Region of Uganda: The Value of Long-Term Field Studiesexternal icon
        Eisen RJ, Atiku LA, Enscore RE, Mpanga JT, Acayo S, Mead PS, Apangu T, Yockey BM, Borchert JN, Beard CB, Gage KL.
        Am J Trop Med Hyg. 2021 May 3.
        Plague, a fleaborne rodent-associated zoonosis, is a neglected disease with most recent cases reported from east and central Africa and Madagascar. Because of its low incidence and sporadic occurrence, most of our knowledge of plague ecology, prevention, and control derives from investigations conducted in response to human cases. Long-term studies (which are uncommon) are required to generate data to support plague surveillance, prevention, and control recommendations. Here we describe a 15-year, multidisciplinary commitment to plague in the West Nile region of Uganda that led to significant advances in our understanding of where and when persons are at risk for plague infection and how to reduce morbidity and mortality. These findings provide data-driven support for several existing recommendations on plague surveillance and prevention and may be generalizable to other plague foci.

      3. Zika Prevention Behaviors Among Women of Reproductive Age in Puerto Rico, 2016external icon
        Ellington SR, Simeone RM, Serrano-Rodriguez RA, Bertolli J, Swartzendruber A, Goldberg HI, Mercado AS, Jamieson DJ, Honein MA, Cordero JF, Shapiro-Mendoza CK.
        Am J Prev Med. 2021 May 2.
        INTRODUCTION: Zika virus is primarily transmitted through mosquito bites. Because Zika virus infection during pregnancy can cause serious birth defects, reproductive-aged women need protection from Zika virus infection. This report describes Zika virus prevention behaviors among women aged 18-49 years and assesses whether pregnancy status and healthcare provider counseling increases Zika virus prevention behaviors. METHODS: A population-based cell phone survey of women aged 18-49 years living in Puerto Rico was conducted in July-November 2016. Data were analyzed in 2018-2019. Prevalence estimates and 95% CIs were calculated for Zika virus prevention behaviors. Adjusted prevalence ratios were estimated to examine the association of pregnancy status with healthcare provider counseling on Zika virus prevention behaviors, controlling for age, education, and health insurance status. RESULTS: Most women reported using screens on open doors/windows (87.7%) and eliminating standing water in/around their homes (92.3%). Other Zika virus prevention behaviors were less common (<33%). In adjusted analysis, pregnant women were more likely than women not at risk for unintended pregnancy to report using mosquito repellent every/most days (adjusted prevalence ratio=1.44, 95% CI=1.13, 1.85). Healthcare provider counseling was associated with receiving professional spraying/larvicide treatment (adjusted prevalence ratio=1.42, 95% CI=1.17, 1.74), sleeping under a bed net (adjusted prevalence ratio=2.37, 95% CI=1.33, 4.24), using mosquito repellent (adjusted prevalence ratio=1.57, 95% CI=1.40, 1.77), and wearing long sleeves/pants (adjusted prevalence ratio=1.32, 95% CI=1.12, 1.55). CONCLUSIONS: Receipt of healthcare provider counseling was more consistently associated with Zika virus prevention behaviors than pregnancy status. Healthcare provider counseling is an important strategy for increasing the uptake of Zika virus prevention behaviors among women aged 18-49 years.

      4. Ocular Findings and Visual Function in Children Examined during the Zika Health Brigade in the US Virgin Islands, March 2018external icon
        Prakalapakorn SG, Bonafede L, Lawrence L, Lattin D, Kim N, House RD, Hillman B, de Wilde L, Harrison C, Fehrenbach N, Godfred-Cato S, Reynolds MR, Ellis EM.
        Trop Med Infect Dis. 2021 Apr 29;6(2).
        Among children born with laboratory-confirmed Zika virus (ZIKV) infection, visual impairment (VI) can occur despite normal ocular structure. The objective of this report is to describe ocular findings and visual function among children examined during the Department of Health Zika Health Brigade (ZHB) in the United States Virgin Islands in March 2018. This analysis is based on a retrospective chart review of children eligible to participate in the ZHB (i.e., part of the US Zika Pregnancy and Infant Registry) and who were examined by ophthalmologists. Eighty-eight children attended the ZHB. This report includes 81 children [48 (59.3%) males] whose charts were located [average gestational age = 37.6 weeks (range: 27.6-41.3) and average adjusted age at examination = 9.1 months (range: 0.9-21.9)]. Of those examined, 5/81 (6.2%) had microcephaly at birth, 2/81 (2.5%) had a structural eye abnormality, and 19/72 (26.4%) had VI. Among children with normal ocular structure and neurologic examination, 13/51 (25.5%) had VI. Despite a low incidence of abnormal ocular structure and microcephaly, about a quarter of children examined had VI. Our findings emphasize that ophthalmological examinations should be performed in all children with suspicion for antenatal ZIKV infection, even children with normal ocular structure and neurologic examination.

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