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Volume 12, Issue 22, July 7, 2020

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CDC Science Clips: Volume 12, Issue 22, July 7, 2020

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!

The report consists of these components:

  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
      • Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention-sponsored summitexternal icon
        Gupta S, Coronado GD, Argenbright K, Brenner AT, Castaneda SF, Dominitz JA, Green B, Issaka RB, Levin TR, Reuland DS, Richardson LC, Robertson DJ, Singal AG, Pignone M.
        CA Cancer J Clin. 2020 Jun 25.
        Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.

    • Communicable Diseases
      • BACKGROUND: Improving management of and treatment within sanitation waste streams could slow the development and transmission of antimicrobial-resistant organisms, but the magnitude of impact has not been quantified. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are a major cause of antimicrobial-resistant infections and are frequently detected in faecal waste streams, making them model indicators of the distribution of antimicrobial-resistant organisms that are transmitted through the faecal-oral route. We aimed to estimate the mass of faeces containing ESBL-producing E coli entering different levels of the sanitation ladder globally and by WHO region to determine the global scale at which sanitation infrastructure serves as a vehicle for dissemination of antimicrobial-resistant organisms. METHODS: In this global and regional analysis, we used publicly available sanitation coverage data from the WHO/UNICEF Joint Monitoring Programme and most recent available scientific literature on human faecal production (2018) and carriage of ESBL-producing E coli by healthy individuals (2016) to estimate the quantity of faeces that has been discharged that contains ESBL-producing E coli for 2015 and projected for 2030. We estimated the mass of faeces containing ESBL-producing E coli by WHO region and at different levels of the Sustainable Development Goal sanitation ladder-ie, into at-least basic (ie, safely managed or basic) systems, limited systems, and unimproved systems, and via open defecation. We modelled three scenarios in which the proportion of ESBL-producing E coli among all E coli that was excreted by carriers varied on the basis of the scientific literature: 100% (scenario A), 10% (scenario B), or 1% (scenario C). FINDINGS: Under scenario B, we estimated that approximately 19 billion kg of faeces carrying ESBL-producing E coli was excreted in 2015 globally. Approximately 65.8% (1.2-120 billion kg depending on modelled scenario) of this faecal biomass was managed in at-least basic sanitation systems, 8.4% (160 million-16 billion kg) in limited sanitation systems, 14.4% (270 million-27 billion kg) in unimproved sanitation systems, and 11.4% (220 million-22 billion kg) was openly defecated. The regions with the highest proportion of openly defecated faeces containing ESBL-producing E coli were the South-East Asia (29.4%) and African (21.8%) regions. The South-East Asia, Western Pacific, and African regions produced 524 billion kg (63%) of the total global human faecal biomass, but 16.9 billion kg (90%) of faeces containing ESBL-producing E coli under scenario B. By 2030, estimates under scenario B will have approximately doubled to 37.6 billion kg of faeces carrying ESBL-producing E coli under the most conservative projections. INTERPRETATION: At-least basic sanitation does not guarantee effective removal or inactivation of antimicrobial-resistant organisms from faecal biomass. However, our findings indicate the need for mitigating transport of antimicrobial-resistant organisms via sanitation systems that are not safely managed, including open defecation, which might result in direct environmental discharge and subsequent risk of transmission back to humans. FUNDING: None.

      • Model-based cost-effectiveness of state-level latent tuberculosis interventions in California, Florida, New York and Texasexternal icon
        Jo Y, Shrestha S, Gomes I, Marks S, Hill A, Asay G, Dowdy D.
        Clin Infect Dis. 2020 Jun 25.
        BACKGROUND: Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) is a recommended strategy to accelerate TB reductions and further tuberculosis elimination in the United States (US). Evidence on cost-effectiveness of TTT for key populations can help advance this goal. METHODS: We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-gamma release assay (IGRA) and treated for LTBI with three months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, HIV-positive, homeless or incarcerated in California, Florida, New York, and Texas - states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), thirty-year reductions in TB incidence, and incremental cost effectiveness (cost per quality-adjusted life year [QALY] gained) for TTT in each modeled population. RESULTS: The projected cost effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among the non-US-born. TTT was most cost-effective among persons living with HIV (from $2,828/QALY gained in Florida to $11,265/QALY gained in New York) and least cost-effective among people with diabetes (from $223,041/QALY gained in California to $817,753 /QALY in New York). CONCLUSIONS: The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people living with HIV, moderate among people who are non-US-born, incarcerated, or homeless, and least cost-effective among people living with diabetes.

      • The articles in this supplement address key questions on syphilis diagnostics, provide reference tables of test performances, and discuss optimal specimens and knowledge gaps. Laboratory-developed genetic direct detection tests could be most useful at the point of care and add to the currently available serologic methods of nontreponemal and treponemal tests.

      • In vitro inhibition of mumps virus replication by Favipiravir (T-705)external icon
        Lawson B, Suppiah S, Rota PA, Hickman CJ, Latner DR.
        Antiviral Res. 2020 Jun 14:104849.
        During the last decade multiple mumps outbreaks have occurred in the U.S. despite high two dose MMR coverage with most cases detected among two dose MMR vaccine recipients. Waning immunity, the evolution of wild-type virus strains, and settings with intense exposure have contributed to the resurgence of mumps. Typically, mumps virus infections resolve without serious clinical sequelae; however, serious complications may occur among unvaccinated or severely immunocompromised individuals. Favipiravir (T-705) has been shown to have in vitro anti-viral activity against a broad range of positive and negative strand RNA viruses. Here, we demonstrate that T-705 inhibits the growth of wildtype and vaccine strains of mumps virus in vitro at low micro-molar concentrations (EC50 8-10muM). We did not observe the development of resistance after five subsequent passages at low concentrations of drug. Both viral RNA and protein synthesis were selectively reduced compared to host mRNA and protein synthesis. Antiviral treatment options for mumps virus infection may be valuable, especially for areas with a high disease burden or for cases with severe complications. These results presented here suggest that further studies are warranted.

      • US CDC real-time reverse transcription PCR panel for detection of severe acute respiratory syndrome coronavirus 2external icon
        Lu X, Wang L, Sakthivel SK, Whitaker B, Murray J, Kamili S, Lynch B, Malapati L, Burke SA, Harcourt J, Tamin A, Thornburg NJ, Villanueva JM, Lindstrom S.
        Emerg Infect Dis. 2020 May 12;26(8).
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10(-1.5) 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel.

      • Increasing pediatric HIV testing positivity rates through focused testing in high-yield points of service in health facilities-Nigeria, 2016-2017external icon
        Odafe S, Onotu D, Fagbamigbe JO, Ene U, Rivadeneira E, Carpenter D, Omoigberale AI, Adamu Y, Lawal I, James E, Boyd AT, Dirlikov E, Swaminathan M.
        PLoS One. 2020 ;15(6):e0234717.
        BACKGROUND: In 2017, UNAIDS estimated that 140,000 children aged 0-14 years are living with HIV in Nigeria, but only 35% have been diagnosed and are receiving antiretroviral therapy. Children are tested primarily in outpatient clinics, which show low HIV-positive rates. To demonstrate efficient facility-based HIV testing among children aged 0-14 years, we evaluated pediatric HIV-positivity rates in points of service in select health facilities in Nigeria. METHODS: We conducted a retrospective analysis of HIV testing and case identification among children aged 0-14 years at all points of service at nine purposively sampled hospitals (November 2016-March 2017). Points of service included family index testing, pediatric outpatient department (POPD), tuberculosis (TB) clinics, immunization clinics, and pediatric inpatient ward. Eligibility for testing at POPD was done using a screening tool while all children with unknown status were eligible for HIV test at other points of service. The main outcome was HIV positivity rates stratified by the testing point of service and by age group. Predictors of an HIV-positive result were assessed using logistic regression. All analyses were done using Stata 15 statistical software. RESULTS: Of 2,180 children seen at all facility points of service with unknown HIV status, 1,822 (83.6%) were tested for HIV, of whom 43 (2.4%) tested HIV positive. The numbers of children tested by age group were <1 years = 230 (12.6%); 1-4 years = 752 (41.3%); 5-9 years = 520 (28.5%); and 10-14 years = 320 (17.6%). The number of children tested by point of service were POPD = 906 (49.7%); family index testing = 693 (38.0%); pediatric inpatient ward = 192 (10.5%); immunization clinic = 16 (0.9%); and TB clinic = 15 (0.8%). HIV positivity rates by point of service were TB clinic = 6.7% (95% Confidence Interval (CI): 0.9-35.2%); pediatric inpatient ward = 4.7% (95%CI: 2.5-8.8%); family index testing = 3.5% (95%CI: 2.3-5.1%); POPD = 1.0% (95%CI: 0.5-1.9%); and immunization clinic = 0%. The percentage contribution to total HIV positive children found by point of services was: family index testing = 55.8% (95%CI: 40.9-69.8%); POPD = 20.9% (95%CI: 11.3-35.6%); inpatient ward = 20.9 (95%CI: 11.3-35.6%) and TB Clinic = 2.3% (95%CI: 0.3-14.8%). Compared with the POPD, the adjusted odds ratio (95% CI) for finding an HIV positive child by point of service were TB clinic = 7.2 (95% CI: 0.9-60.9); pediatric inpatient ward = 4.9 (95% CI: 1.9-12.8); and family index testing = 3.7 (95% CI: 1.5-8.8). HIV-positivity rates did not significantly differ by age group. CONCLUSION: In Nigeria, to improve facility-based HIV positivity rates among children aged 0-14 years, an increased focus on HIV testing among children seeking care in pediatric inpatient wards, through family index testing, and perhaps TB clinics is appropriate.


    • Health Disparities
      • Importance: Screening for breast, cervical, and colorectal cancers in the United States has remained below the Healthy People 2020 goals, with evidence indicating that persistent screening disparities still exist. The US Department of Health and Human Services has emphasized cross-sectoral collaboration in aligning social determinants of health with public health and medical services. Examining the economics of intervening through these novel methods in the realm of cancer screening can inform program planners, health care providers, implementers, and policy makers. Objective: To conduct a systematic review of economic evaluations of interventions leveraging social determinants of health to improve screening for breast, cervical, and colorectal cancer to guide implementation. Evidence Review: A systematic literature search for economic evidence was performed in MEDLINE, Embase, PsycINFO, Cochrane Library, Global Health, Scopus, Academic Search Complete, Business Source Complete, EconLit, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ERIC (Education Resources Information Center), and Sociological Abstracts from January 1, 2004, to November 25, 2019. Included studies intervened on social determinants of health to improve breast, cervical, and colorectal cancer screening in the United States and reported intervention cost, incremental cost per additional person screened, and/or incremental cost per quality-adjusted life-year (QALY). Risk of bias was assessed along with qualitative assessment of quality to ensure complete reporting of economic measures, data sources, and analytic methods. In addition, included studies with modeled outcomes had to define structural elements and sources for input parameters, distinguish between programmatic and literature-derived data, and assess uncertainty. Findings: Thirty unique articles with 94 706 real and 4.21 million simulated participants satisfied our inclusion criteria and were included in the analysis. The median intervention cost per participant was $123.87 (interquartile interval [IQI], $24.44-$313.19; 34 estimates). The median incremental cost per additional person screened was $250.37 (IQI, $44.67-$609.38; 17 estimates). Studies that modeled final economic outcomes had a median incremental cost per person of $122.96 (IQI, $46.96-$124.80; 5 estimates), a median incremental screening rate of 15% (IQI, 14%-20%; 5 estimates), and a median incremental QALY per person of 0.04 years (IQI, 0.006-0.06 year; 5 estimates). The median incremental cost per QALY gained of $3120.00 (IQI, $782.59-$33600.00; 5 estimates) was lower than $50000, an established, conservative threshold of cost-effectiveness. Conclusions and Relevance: Interventions focused on social determinants of health to improve breast, cervical, and colorectal cancer screening appear to be cost-effective for underserved, vulnerable populations in the United States. The increased screening rates were associated with earlier diagnosis and treatment and in improved health outcomes with significant gains in QALYs. These findings represent the latest economic evidence to guide implementation of these interventions, which serve the dual purpose of enhancing health equity and economic efficiency.

    • Healthcare Associated Infections
      • High prevalence of multidrug-resistant organism colonization in 28 nursing homes: An "iceberg effect"external icon
        McKinnell JA, Miller LG, Singh RD, Gussin G, Kleinman K, Mendez J, Laurner B, Catuna TD, Heim L, Saavedra R, Felix J, Torres C, Chang J, Estevez M, Mendez J, Tchakalian G, Bloomfield L, Ceja S, Franco R, Miner A, Hurtado A, Hean R, Varasteh A, Robinson PA, Park S, Tam S, Tjoa T, He J, Agrawal S, Yamaguchi S, Custodio H, Nguyen J, Bittencourt CE, Evans KD, Mor V, McConeghy K, Weinstein RA, Hayden MK, Stone ND, Steinberg K, Beecham N, Montgomery J, DeAnn W, Peterson EM, Huang SS.
        J Am Med Dir Assoc. 2020 Jun 15.
        OBJECTIVE: Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). DESIGN: Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. SETTING: Twenty-eight NHs in Southern California from 2016 to 2017. PARTICIPANTS: NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. METHODS: Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). RESULTS: A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. CONCLUSIONS AND IMPLICATIONS: In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization.

    • Laboratory Sciences
      • Massively multiplexed nucleic acid detection with Cas13external icon
        Ackerman CM, Myhrvold C, Thakku SG, Freije CA, Metsky HC, Yang DK, Ye SH, Boehm CK, Kosoko-Thoroddsen TF, Kehe J, Nguyen TG, Carter A, Kulesa A, Barnes JR, Dugan VG, Hung DT, Blainey PC, Sabeti PC.
        Nature. 2020 Jun;582(7811):277-282.
        The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples(1-3) while simultaneously testing for many pathogens(4-6). Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents(7) self-organize in a microwell array(8) to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health(9-11).

    • Zoonotic and Vectorborne Diseases
      • BACKGROUND: Dengue, chikungunya, and Zika viruses are increasingly important public health problems. Burning vegetation, leaves, and other plant products have been shown to be effective mosquito repellents for their vector, Aedes spp., but there has been scant research on whether firewood cooking smoke in households influences mosquito populations or mosquito-borne diseases. About 2.9 billion people worldwide use biomass fuel for household cooking and heating, resulting in an estimated 1.6 million deaths annually from household air pollution (HAP)-related diseases. Global health agencies now encourage households to transition from biomass to clean fuels, but it is unclear whether such interventions may actually increase risk for mosquito-borne diseases. This retrospective case-control study evaluated associations between arboviral infections and cooking with firewood in Santa Rosa, Guatemala. METHOD: Vigilancia Integrada Comunitaria (VICo) was a prospective public health surveillance system for bacterial, parasitic, and viral causes of diarrheal, neurological, respiratory, and febrile illnesses in hospitals and clinics in the department of Santa Rosa, Guatemala. Enrolled VICo in-patients and out-patients during 2011-2018 were interviewed using standardized questionnaires on demographics and household characteristics. Blood and stool specimens were collected and tested to identify the etiologies presenting symptoms. Cases were defined as laboratory-positive for dengue, chikungunya, or Zika virus infections. Controls were laboratory-positive for bacterial and viral diarrheal illnesses (e.g., Salmonella, Shigella, Campylobacter, Escherichia coli, rotavirus, norovirus, sapovirus, or astrovirus). Cooking with firewood, kitchen location, stove type, and firewood cooking frequency were the independent exposure variables. Logistic regression models were used to analyze unadjusted and adjusted associations between arboviral infections and exposures of interest. RESULT: There were 311 arboviral cases and 1,239 diarrheal controls. Arboviral infections were inversely associated with cooking with firewood in the main house (AOR: 0.22; 95% CI: 0.08-0.57), cooking with firewood on an open hearth (AOR: 0.50; 95% CI: 0.33-0.78), and cooking with firewood >/=5 times per week (AOR: 0.54; 95% CI: 0.36-0.81), adjusting for age, sex, ethnicity, socioeconomic status index, number of people per household, community population density, community elevation, recruitment location, season, and admission year. CONCLUSION: Several primary determinants of HAP exposure were inversely associated with arboviral infections. Additional studies are needed to understand whether interventions to reduce HAP might actually increase risk for mosquito-borne infectious diseases, which would warrant improved education and mosquito control efforts in conjunction with fuel interventions.


  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. Disparities in dental use and untreated caries prevalence by incomeexternal icon
        Griffin SO, Thornton-Evans G, Wei L, Griffin PM.
        JDR Clin Trans Res. 2020 Jun 25.
        INTRODUCTION: Untreated dental caries (UC), although preventable, is the most prevalent disease in the United States. UC diminishes quality of life and lowers productivity for millions of Americans and is notably higher among lower-income compared to higher-income persons. OBJECTIVE: This study examines changes in disparities by income in past-year dental use (DU) and UC in 4 life stages (2-5, 6-19, 20-64, and >/=65 y) between 1999-2004 and 2011-2016. We also examined changes in dental safety net policies during this time. METHODS: We obtained data on dependent variables, UC and DU, from cross-sectional, nationally representative surveys for 1999-2004 and 2011-2016. We used multivariable regression models with 3 main-effect explanatory variables: income (<200% or >/=200% federal poverty level), life stage, and survey period (1999-2004 or 2011-2016) and sociodemographic variables. We included 2-way interaction terms among main-effect variables to test whether disparities had changed over time in each life stage and a 3-way term to test changes in disparities differed across life stages. RESULTS: Model-adjusted disparities in DU decreased for both preschool-age and school-age children, and disparities in UC decreased for school-age children. Changes in DU and UC disparities were not detectable for working-age adults and increased for retirement-age adults. Changes in DU and UC among preschool and school-age children were not significantly different from one another and were significantly different from changes among retirement-age adults. Compared to working-age adults, changes in disparities for DU and UC were significantly different for school-age children, and changes in DU were significantly different for preschool-age children. Between surveys, the dental safety net was expanded for youth but remained largely unchanged for adults. CONCLUSIONS: Expanding the dental safety net for youth could have contributed to increased access to dental care among children relative to adults and contributed to the decrease in disparities in DU and UC among youth. Knowledge Transfer Statement: Between 1999-2004 and 2011-2016, the dental safety net was expanded for youth but remained largely unchanged for adults. Using national survey data to compare changes in disparities in past-year dental use and untreated dental caries by income between adults and youth sheds light on the potential impact of expanding the dental safety net.

      2. Accelerating use of self-measured blood pressure monitoring (SMBP) through clinical-community care modelsexternal icon
        Meador M, Hannan J, Roy D, Whelihan K, Sasu N, Hodge H, Lewis JH.
        J Community Health. 2020 Jun 20.
        Self-measured blood pressure monitoring (SMBP), the regular measurement of blood pressure by a patient outside the clinical setting, plus additional support, is a proven, cost-effective but underutilized strategy to improve hypertension outcomes. To accelerate SMBP use, the Centers for Disease Control and Prevention (CDC) funded the National Association of Community Health Centers, the YMCA of the USA, and Association of State and Territorial Health Officials to develop cross-sector care models to offer SMBP to patients with hypertension. The project aimed to increase the use of SMBP through the coordinated action of health department leaders, community organizations and clinical providers. From 1/31/2017 to 6/30/2018, nine health centers in Kentucky, Missouri, and New York partnered with seven local Y associations (local Y) and their local health departments to design and implement care models that adapted existing primary care SMBP practices by leveraging capacities and resources in community and public health organizations. Nine collaborative care models emerged, shaped by available community assets, strategic priorities, and organizational culture. Overall, 1421 patients were recommended for SMBP; of those, 795 completed at least one cycle of SMBP (BP measurements morning and evening for at least three consecutive days). Of those recommended for SMBP, 308 patients were referred to a local Y to receive additional SMBP and healthy lifestyle support. Community and public health organizations can be brought into the health care delivery process and can play valuable roles in supporting patients in SMBP.

      3. PURPOSE AND OBJECTIVES: Since 2005 the Centers for Disease Control and Prevention (CDC) has funded organizations across the United States to promote screening for colorectal cancer (CRC) to detect early CRC or precancerous polyps that can be treated to avoid disease progression and death. The objective of this study was to describe how findings from economic evaluation approaches of a subset of these awardees and their implementation sites (n = 9) can drive decision making and improve program implementation and diffusion. INTERVENTION APPROACH: We described the framework for the implementation economics evaluation used since 2016 for the Colorectal Cancer Control Program (CRCCP) Learning Collaborative. EVALUATION METHODS: We compared CRC interventions implemented across health systems, changes in screening uptake, and the incremental cost per person of implementing an intervention. We also analyzed data on how implementation costs changed over time for a CRC program that conducted interventions in a series of rounds. RESULTS: Implementation of the interventions, which included provider and patient reminders, provider assessment and feedback, and incentives, resulted in increases in screening uptake ranging from 4.9 to 26.7 percentage points. Across the health systems, the incremental cost per person screened ranged from $18.76 to $144.55. One awardee's costs decreased because of a reduction in intervention development and start-up costs. IMPLICATIONS FOR PUBLIC HEALTH: Health systems, CRCCP awardees, and CDC can use these findings for quality improvement activities, incorporation of information into trainings and support activities, and future program design.

    • Communicable Diseases
      1. Concurrent advanced HIV disease and viral load suppression in a high-burden setting: Findings from the 2015-6 ZIMPHIA surveyexternal icon
        Balachandra S, Rogers JH, Ruangtragool L, Radin E, Musuka G, Oboho I, Paulin H, Parekh B, Birhanu S, Takarinda KC, Hakim A, Apollo T.
        PLoS One. 2020 ;15(6):e0230205.
        BACKGROUND: As Zimbabwe approaches epidemic control of HIV, programs now prioritize viral load over CD4 monitoring, making it difficult to identify persons living with HIV (PLHIV) suffering from advanced disease (AD). We present an analysis of cross-sectional ZIMPHIA data, highlighting PLHIV with AD and concurrent viral load suppression (VLS). METHODS: ZIMPHIA collected blood specimens for HIV testing from 22,501 consenting adults (ages 15 years and older); 3,466 PLHIV had CD4 and VL results. Household HIV testing used the national serial algorithm, and those testing positive then received point-of-care CD4 enumeration with subsequent VL testing. We used logistic regression analysis to explore factors associated with concurrent AD and VLS (<1000 copies/mL). All analyses were weighted to account for complex survey design. RESULTS: Of the 3,466 PLHIV in the survey with CD4 and VL results, 17% were found to have AD (CD4<200cells/mm3). Of all AD patients, 30% had VLS. Concurrent AD and VLS was associated with male sex (aOR 2.45 95%CI 1.61-3.72), older age (35-49 years [aOR 2.46 95%CI 1.03-5.91] and 50+ years [aOR 4.82 95%CI 2.02-11.46] vs 15-24 years), and ART duration (<6 months [aOR 0.46 95%CI 0.29-0.76] and 6-24 months [aOR 2.07 95%CI 1.35-3.17] vs more than 2 years). The relationship between sex and AD is driven by age with significant associations among men aged 25-34, (aOR 3.37 95%CI 1.35-8.41), 35-49 (aOR 5.13 95%CI 2.16-12.18), and 50+ (aOR 12.56 95%CI 4.82-32.72) versus men aged 15-24. CONCLUSIONS: The percentage of PLHIV with AD and VLS illustrates the conundrum of decreased support for CD4 monitoring, as these patients may not receive appropriate clinical services for advanced HIV disease. In high-prevalence settings such as Zimbabwe, CD4 monitoring support warrants further consideration to differentiate care appropriately for the most vulnerable PLHIV. Males may need to be prioritized, given their over-representation in this sub-population.

      2. Screening for SARS-CoV-2 infection within a psychiatric hospital and considerations for limiting transmission within residential psychiatric facilities - Wyoming, 2020external icon
        Callaghan AW, Chard AN, Arnold P, Loveland C, Hull N, Saraiya M, Saydah S, Dumont W, Frakes LG, Johnson D, Peltier R, Van Houten C, Trujillo AA, Moore J, Rose DA, Honein MA, Carrington D, Harrist A, Hills SL.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):825-829.
        In the United States, approximately 180,000 patients receive mental health services each day at approximately 4,000 inpatient and residential psychiatric facilities (1). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly within congregate residential settings (2-4), including psychiatric facilities. On April 13, 2020, two patients were transferred to Wyoming's state psychiatric hospital from a private psychiatric hospital that had confirmed COVID-19 cases among its residents and staff members (5). Although both patients were asymptomatic at the time of transfer and one had a negative test result for SARS-CoV-2 at the originating facility, they were both isolated and received testing upon arrival at the state facility. On April 16, 2020, the test results indicated that both patients had SARS-CoV-2 infection. In response, the state hospital implemented expanded COVID-19 infection prevention and control (IPC) procedures (e.g., enhanced screening, testing, and management of new patient admissions) and adapted some standard IPC measures to facilitate implementation within the psychiatric patient population (e.g., use of modified face coverings). To assess the likely effectiveness of these procedures and determine SARS-CoV-2 infection prevalence among patients and health care personnel (HCP) (6) at the state hospital, a point prevalence survey was conducted. On May 1, 2020, 18 days after the patients' arrival, 46 (61%) of 76 patients and 171 (61%) of 282 HCP had nasopharyngeal swabs collected and tested for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction. All patients and HCP who received testing had negative test results, suggesting that the hospital's expanded IPC strategies might have been effective in preventing the introduction and spread of SARS-CoV-2 infection within the facility. In congregate residential settings, prompt identification of COVID-19 cases and application of strong IPC procedures are critical to ensuring the protection of other patients and staff members. Although standard guidance exists for other congregate facilities (7) and for HCP in general (8), modifications and nonstandard solutions might be needed to account for the specific needs of psychiatric facilities, their patients, and staff members.

      3. Incidence, etiology, and severity of acute gastroenteritis among prospectively enrolled patients in 4 Veterans Affairs hospitals and outpatient centers, 2016-18external icon
        Cardemil CV, Balachandran N, Kambhampati A, Grytdal S, Dahl RM, Rodriguez-Barradas MC, Vargas B, Beenhouwer DO, Evangelista KV, Marconi VC, Meagley KL, Brown ST, Perea A, Lucero-Obusan C, Holodniy M, Browne H, Gautam R, Bowen MD, Vinje J, Parashar UD, Hall AJ.
        Clin Infect Dis. 2020 Jun 25.
        BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well-characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston and Los Angeles), collectively serving >320,000 patients annually. METHODS: From July 1, 2016-June 30, 2018, we actively identified AGE inpatient cases and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatient cases through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens via multiplex gastrointestinal PCR panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatient cases, 394 controls, and 506 outpatient cases. Clostridioides difficile and norovirus were most frequently detected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<0.01 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%). Incidence per 100,000 population was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >/=65 years old (AGE: 459; C. difficile: 91; norovirus: 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/EIEC cases. Overall, 12% of AGE inpatient cases had ICU stays and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US Veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

      4. Shigellosis among gay and bisexual men: A qualitative assessment to examine knowledge, attitudes, and practicesexternal icon
        Caruso E, Wright ER, Respress ET, Evener SL, Jacobson K, Bowen A, Kachur R, Garcia-Williams A.
        Sex Transm Dis. 2020 Jun 18.
        BACKGROUND: Shigellosis is a highly contagious enteric bacterial disease transmitted through the fecal-oral route. It is primarily transmitted through person-to-person contact, and via contaminated food and water. Outbreaks of shigellosis among men who have sex with men (MSM) attributed to sexual person-to-person contact have been reported. These outbreaks are of concern because they are often caused by multidrug-resistant strains of Shigella. Little is known about shigellosis-related knowledge, attitudes, and practices (KAPs) among gay, bisexual, and other MSM. METHODS: Six focus groups were conducted among self-identified gay or bisexual men in Atlanta, GA in Fall 2017. Participants were asked about shigellosis-related KAPs. Focus groups were audio recorded and the transcribed audio was analyzed using inductive and deductive thematic coding. RESULTS: Among the 24 focus group participants, most perceived that diarrheal illness was caused by contaminated food. Knowledge of shigellosis and Shigella was low, with most never having heard of the disease or bacteria. Participants did not perceive shigellosis to be a serious health concern, especially when compared with HIV; however, they did perceive gay and bisexual men to be at risk for Shigella infection. Participants reported mixed intentions to change sexual behaviors to prevent shigellosis or talk with sexual partners about diarrhea. CONCLUSION: Health communication and education efforts could be used to increase knowledge about shigellosis and shift perceptions about the severity of shigellosis among gay, bisexual, and other MSM. Additional work is needed to identify effective ways to promote shigellosis-related prevention behaviors among gay, bisexual, and other MSM.

      5. Investigation and serologic follow-up of contacts of early confirmed case-patient with COVID-19, United Statesexternal icon
        Chu VT, Freeman-Ponder B, Lindquist S, Spitters C, Kawakami V, Dyal JW, Clark S, Bruce H, Duchin JS, DeBolt C, Podczervinski S, D'Angeli M, Pettrone K, Zacks R, Vahey G, Holshue ML, Lang M, Burke RM, Rolfes MA, Marlow M, Midgley CM, Lu X, Lindstrom S, Hall AJ, Fry AM, Thornburg NJ, Gerber SI, Pillai SK, Biggs HM.
        Emerg Infect Dis. 2020 May 29;26(8).
        We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected approximately 6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

      6. Isoniazid and rifampin-resistance mutations associated with resistance to second-line drugs and with sputum culture conversionexternal icon
        Click ES, Kurbatova EV, Alexander H, Dalton TL, Chen MP, Posey JE, Ershova J, Cegielski JP.
        J Infect Dis. 2020 Jun 11;221(12):2072-2082.
        BACKGROUND: Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. METHODS: In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. RESULTS: In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). CONCLUSIONS: Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.

      7. Loss of taste and smell as distinguishing symptoms of COVID-19external icon
        Dawson P, Rabold EM, Laws RL, Conners EE, Gharpure R, Yin S, Buono SA, Dasu T, Bhattacharyya S, Westergaard RP, Pray IW, Ye D, Nabity SA, Tate JE, Kirking HL.
        Clin Infect Dis. 2020 Jun 21.
        In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42; 62%) among COVID-19 case-patients and had the highest positive predictive value (83%; 95% CI: 55-95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.

      8. Predicting the impact of sexual behavior change on adolescent STI in the US and New York State: a case study of the teen-SPARC toolexternal icon
        Goodreau SM, Pollock ED, Wang LY, Barrios LC, Dunville RL, Aslam MV, Katz DA, Hart-Malloy R, Rosenthal EM, Trigg M, Fields M, Hamilton DT, Rosenberg ES.
        Ann Epidemiol. 2020 ;47:13-18.
        Purpose: Adolescents aged 13–18 years bear a large burden of sexually transmitted infections (STIs) and changing adolescent sexual risk behavior is a key component of reducing this burden. We demonstrate a novel publicly available modeling tool (teen-SPARC) to help state and local health departments predict the impact of behavioral change on gonorrhea, chlamydia, and HIV burden among adolescents. Methods: Teen-SPARC is built in Excel for familiarity and ease and parameterized using data from CDC's Youth Risk Behavior Surveillance System. We present teen-SPARC's methods, including derivation of national parameters and instructions to obtain local parameters. We model multiple scenarios of increasing condom use and estimate the impact on gonorrhea, chlamydia, and HIV incidence, comparing national and New York State (NYS) results. Results: A 1% annual increase in condom use (consistent with Healthy People 2020 goals) could prevent nearly 10,000 cases of STIs nationwide. Increases in condom use of 17.1%, 2.2%, and 25.5% in NYS would be necessary to avert 1000 cases of gonorrhea, 1000 cases of chlamydia, and 10 cases of HIV infection, respectively. Additional results disaggregate outcomes by age, sex, partner sex, jurisdiction, and pathogen. Conclusion: Teen-SPARC may be able to assist health departments aiming to tailor behavioral interventions for STI prevention among adolescents.

      9. Cryptococcal meningitis: a review of cryptococcal antigen screening programs in Africaexternal icon
        Greene G, Lawrence D, Jordan A, Chiller T, Jarvis JN.
        Expert Rev Anti Infect Ther. 2020 Jun 22.
        INTRODUCTION: Cryptococcal meningitis remains a significant contributor to AIDS-related mortality despite widened access to antiretroviral therapy. Cryptococcal antigen (CrAg) can be detected in the blood prior to the development of meningitis. The development of highly sensitive and specific rapid diagnostic CrAg tests has helped facilitate the adoption of CrAg screening programs in 19 African countries. AREAS COVERED: The biological rationale for CrAg screening and the programmatic strategies that have been adopted are reviewed. We describe the approach to the investigation of patients with cryptococcal antigenemia and the importance of lumbar puncture to identify individuals who may have cryptococcal meningitis in the absence of symptoms. The limitations of current treatment recommendations and the potential role of newly defined combination antifungal therapies are discussed. A literature review was conducted using a broad database search for cryptococcal antigen screening and related terms in published journal articles dating up to December 2019. Conference abstracts, publicly available guidelines and project descriptions were also incorporated. EXPERT OPINION: As we learn more about the risks of cryptococcal antigenemia, it has become clear that the current management paradigm is inadequate. More intensive investigation and management are required to prevent the development of cryptococcal meningitis and reduce mortality associated with cryptococcal antigenemia.

      10. Background: Globally, mental health problems are more common among people living with human immunodeficiency virus (PLHIV) than among the general population. Mental health problems affect human immunodeficiency virus (HIV) treatment adherence and retention. To address this challenge, partners used a task-sharing approach among lay healthcare works and clinicians to integrate mental health services into HIV services at pilot hospitals in the Amhara and Tigray regions of Ethiopia. In this model, trained lay healthcare workers proactively screened patients using a mental health screening tool and subsequently linked potential clients with trained clinicians working at HIV clinics for further diagnosis and treatment.

      11. Population prevalence of sexually transmitted infections in a high HIV burden district in KwaZulu-Natal, South Africa: Implications for HIV epidemic controlexternal icon
        Kharsany AB, McKinnon LR, Lewis L, Cawood C, Khanyile D, Maseko DV, Goodman TC, Beckett S, Govender K, George G, Ayalew KA, Toledo C.
        Int J Infect Dis. 2020 Jun 17.
        BACKGROUND: Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known. METHODS: A total of 9812 participants aged 15-49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs. RESULTS: Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR = 1.49, 95% CI 1.02-2.19) among males and syphilis (aPR = 2.54, 95% CI 1.32-4.86), N. gonorrhoeae (aPR = 2.39, 95% CI 1.62-3.52), T. vaginalis (aPR = 1.70, 95% CI 1.43-2.01) and M. genitalium (aPR = 1.60, 95% CI 1.15-2.22) among females. HIV viral load >/=400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR = 1.91, 95% CI 1.36-2.70), C. trachomatis (aPR = 1.52, 95% CI 1.12-2.05) and M. genitalium (aPR = 1.83, 95% CI 1.27-2.63). CONCLUSIONS: The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden.

      12. A mathematical model to estimate the state-specific impact of the Health Resources and Services Administration's Ryan White HIV/AIDS Programexternal icon
        Klein PW, Cohen SM, Uzun Jacobson E, Li Z, Clark G, Fanning M, Sterling R, Young SR, Sansom S, Hauck H.
        PLoS One. 2020 ;15(6):e0234652.
        BACKGROUND: Access to and engagement in high-quality HIV medical care and treatment is essential for ending the HIV epidemic. The Health Resources and Services Administration's (HRSA) Ryan White HIV/AIDS Program (RWHAP) plays a critical role in ensuring that people living with diagnosed HIV (PLWH) are linked to and consistently engaged in high quality care and receive HIV medication in a timely manner. State variation in HIV prevalence, the proportion of PLWH served by the RWHAP, and local health care environments could influence the state-specific impact of the RWHAP. This analysis sought to measure the state-specific impact of the RWHAP on the HIV service delivery system and health outcomes for PLWH, and presents template language to communicate this impact for state planning and stakeholder engagement. METHODS AND FINDINGS: The HRSA's HIV/AIDS Bureau (HAB) and the Centers for Disease Control and Prevention's Division of HIV/AIDS Prevention (CDC DHAP) have developed a mathematical model to estimate the state-specific impact of the RWHAP. This model was parameterized using RWHAP data, HIV surveillance data, an existing CDC model of HIV transmission and disease progression, and parameters from the literature. In this study, the model was used to analyze the hypothetical scenario of an absence of the RWHAP and to calculate the projected impact of this scenario on RWHAP clients, RWHAP-funded providers, mortality, new HIV cases, and costs compared with the current state inclusive of the RWHAP. To demonstrate the results of the model, we selected two states, representing high HIV prevalence and low HIV prevalence areas. These states serve to demonstrate the functionality of the model and how state-specific results can be translated into a state-specific impact statement using template language. CONCLUSIONS: In the example states presented, the RWHAP provides HIV care, treatment, and support services to a large proportion of PLWH in each state. The absence of the RWHAP in these states could result in substantially more deaths and HIV cases than currently observed, resulting in considerable lifetime HIV care and treatment costs associated with additional HIV cases. State-specific impact statements may be valuable in the development of state-level HIV prevention and care plans or for communications with planning bodies, state health department leadership, and other stakeholders. State-specific impact statements will be available to RWHAP Part B recipients upon request from HRSA's HIV/AIDS Bureau.

      13. State trends in HIV testing among US adults aged 18-64 years, 2011-2017external icon
        Krueger A, Johnson C, Heitgerd J, Patel D, Harris N.
        Public Health Rep. 2020 Jun 24.
        OBJECTIVES: HIV testing identifies persons living with HIV and can lead to treatment, decreased risk behaviors, and reduced transmission. The objective of our study was to describe state-level trends in HIV testing in the general US adult population aged 18-64 years, for both ever tested for HIV and tested for HIV in the previous 12 months. METHODS: Using 2011-2017 Behavioral Risk Factor Surveillance System data, we estimated the percentage of the state population, plus the District of Columbia, aged 18-64 years ever tested for HIV and tested for HIV in the previous 12 months. The 50 states and the District of Columbia were grouped according to the estimated prevalence of HIV in 2011. We used orthogonal contrasts to calculate P values for linear trends. RESULTS: The percentage of the population ever tested for HIV increased significantly in 23 states during 2011-2017, whereas the percentage tested for HIV in the previous 12 months increased significantly in 8 states. In 2017, the mean percentage ever tested for HIV in states with a high prevalence of HIV was 8.6 percentage points higher than the mean percentage in states with a low prevalence of HIV (48.5% vs 39.9%); the mean increase in the percentage ever tested was highest (11.4%) in states with a low prevalence of HIV. CONCLUSION: Enhanced efforts by states to make HIV testing simple, accessible, and routine are needed to reduce the number of persons who are not aware of their infection.

      14. Exposures before issuance of stay-at-home orders among persons with laboratory-confirmed COVID-19 - Colorado, March 2020external icon
        Marshall K, Vahey GM, McDonald E, Tate JE, Herlihy R, Midgley CM, Kawasaki B, Killerby ME, Alden NB, Staples JE.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):847-849.
        On March 26, 2020, Colorado instituted stay-at-home orders to reduce community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). To inform public health messaging and measures that could be used after reopening, persons with laboratory-confirmed COVID-19 during March 9-26 from nine Colorado counties comprising approximately 80% of the state's population(dagger) (Adams, Arapahoe, Boulder, Denver, Douglas, El Paso, Jefferson, Larimer, and Weld) were asked about possible exposures to SARS-CoV-2 before implementation of stay-at-home orders. Among 1,738 persons meeting the inclusion criteria( section sign) in the Colorado Electronic Disease Surveillance System, 600 were randomly selected and interviewed using a standardized questionnaire by telephone. Data collection during April 10-30 included information about demographic characteristics, occupations, and selected activities in the 2 weeks preceding symptom onset. During the period examined, SARS-CoV-2 molecular testing was widely available in Colorado; community transmission was documented before implementation of the stay-at-home order. At least three attempts were made to contact all selected patients or their proxy (for deceased patients, minors, and persons unable to be interviewed [e.g., those with dementia]) on at least 2 separate days, at different times of day. Data were entered into a Research Electronic Data Capture (version 9.5.13; Vanderbilt University) database, and descriptive analyses used R statistical software (version 3.6.3; The R Foundation).

      15. Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United Statesexternal icon
        Martines RB, Ritter JM, Matkovic E, Gary J, Bollweg BC, Bullock H, Goldsmith CS, Silva-Flannery L, Seixas JN, Reagan-Steiner S, Uyeki T, Denison A, Bhatnagar J, Shieh WJ, Zaki SR, Covid-Pathology Working Group .
        Emerg Infect Dis. 2020 May 21;26(9).
        An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.

      16. Serial laboratory testing for SARS-CoV-2 infection among incarcerated and detained persons in a correctional and detention facility - Louisiana, April-May 2020external icon
        Njuguna H, Wallace M, Simonson S, Tobolowsky FA, James AE, Bordelon K, Fukunaga R, Gold JA, Wortham J, Sokol T, Haydel D, Tran H, Kim K, Fisher KA, Marlow M, Tate JE, Doshi RH, Curran KG.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):836-840.
        Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by asymptomatic and presymptomatic persons poses important challenges to controlling spread of the disease, particularly in congregate settings such as correctional and detention facilities (1). On March 29, 2020, a staff member in a correctional and detention facility in Louisiana developed symptoms(dagger) and later had a positive test result for SARS-CoV-2. During April 2-May 7, two additional cases were detected among staff members, and 36 cases were detected among incarcerated and detained persons at the facility; these persons were removed from dormitories and isolated, and the five dormitories that they had resided in before diagnosis were quarantined. On May 7, CDC and the Louisiana Department of Health initiated an investigation to assess the prevalence of SARS-CoV-2 infection among incarcerated and detained persons residing in quarantined dormitories. Goals of this investigation included evaluating COVID-19 symptoms in this setting and assessing the effectiveness of serial testing to identify additional persons with SARS-CoV-2 infection as part of efforts to mitigate transmission. During May 7-21, testing of 98 incarcerated and detained persons residing in the five quarantined dormitories (A-E) identified an additional 71 cases of SARS-CoV-2 infection; 32 (45%) were among persons who reported no symptoms at the time of testing, including three who were presymptomatic. Eighteen cases (25%) were identified in persons who had received negative test results during previous testing rounds. Serial testing of contacts from shared living quarters identified persons with SARS-CoV-2 infection who would not have been detected by symptom screening alone or by testing at a single time point. Prompt identification and isolation of infected persons is important to reduce further transmission in congregate settings such as correctional and detention facilities and the communities to which persons return when released.

      17. The traditional or reverse algorithm for diagnosis of syphilis: Pros and consexternal icon
        Ortiz DA, Shukla MR, Loeffelholz MJ.
        Clin Infect Dis. 2020 Jun 24;71(Supplement_1):S43-s51.
        We reviewed relevant syphilis diagnostic literature to address the question "What diagnostic considerations should be taken into account when screening for syphilis using the traditional or reverse algorithm?" Improved laboratory diagnosis of syphilis is an important element of the effort to reduce syphilis rates. Screening for syphilis is performed using either a nontreponemal or treponemal test (part of the traditional or reverse algorithm, respectively). Both syphilis algorithms are used by laboratories. However, there are limited data on the performance and cost-effectiveness of the algorithms. An expert panel generated "key questions" in the laboratory diagnosis of syphilis. This paper pertains to the key factors that should be considered when deciding whether to screen for syphilis using either the traditional or the reverse algorithm. A systematic literature review was performed, and tables of evidence were created to address this question.

      18. Sensitivity and specificity of treponemal-specific tests for the diagnosis of syphilisexternal icon
        Park IU, Tran A, Pereira L, Fakile Y.
        Clin Infect Dis. 2020 Jun 24;71(Supplement_1):S13-s20.
        We conducted a systematic review of relevant syphilis diagnostic literature to address the question, "What is the sensitivity and specificity of the treponemal tests currently approved by the Food and Drug Administration (FDA) for the diagnosis of syphilis (by stage)?" There were 16 treponemal assays evaluated: 13 immunoassays and 3 manual assays (fluorescent treponemal antibody absorbed test [FTA-ABS], microhemagglutination assay for Treponema pallidum antibodies [MHA-TP], Treponema pallidum particle agglutination assay [TP-PA]). MHA-TP and FTA-ABS were less sensitive in primary and secondary syphilis than TP-PA; TP-PA is the most specific manual treponemal assay. There is insufficient evidence to recommend one particular treponemal immunoassay (eg, enzyme immunoassays, chemiluminescence immunoassays, microbead immunoassays) over another based on published performance data. For diagnosis of neurosyphilis, cerebrospinal fluid (CSF) TP-PA has similar performance to CSF FTA-ABS in studies with patients with definitive or presumptive neurosyphilis. However, CSF treponemal testing has limitations in its sensitivity and specificity and should be interpreted within the context of the clinical scenario, additional CSF test results and syphilis prevalence.

      19. Clinical characteristics of patients hospitalized with coronavirus disease, Thailandexternal icon
        Pongpirul WA, Mott JA, Woodring JV, Uyeki TM, MacArthur JR, Vachiraphan A, Suwanvattana P, Uttayamakul S, Chunsuttiwat S, Chotpitayasunondh T, Pongpirul K, Prasithsirikul W.
        Emerg Infect Dis. 2020 Jul;26(7):1580-1585.
        Among 11 patients in Thailand infected with severe acute respiratory syndrome coronavirus 2, we detected viral RNA in upper respiratory specimens a median of 14 days after illness onset and 9 days after fever resolution. We identified viral co-infections and an asymptomatic person with detectable virus RNA in serial tests. We describe implications for surveillance.

      20. SARS-CoV-2 infections in children - multi-center surveillance, United States, January-March 2020external icon
        Rha B, Lively JY, Englund JA, Staat MA, Weinberg GA, Selvarangan R, Halasa NB, Williams JV, Boom JA, Sahni LC, Michaels MG, Stewart LS, Harrison CJ, Szilagyi PG, McNeal MM, Klein EJ, Strelitz B, Lacombe K, Schlaudecker E, Moffatt ME, Schuster JE, Pahud BA, Weddle G, Hickey RW, Avadhanula V, Wikswo ME, Hall AJ, Curns AT, Gerber SI, Langley G.
        J Pediatric Infect Dis Soc. 2020 Jun 18.
        Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January-March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.

      21. Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance predictionexternal icon
        Sena AC, Bachmann L, Johnston C, Wi T, Workowski K, Hook EW, Hocking JS, Drusano G, Unemo M.
        Lancet Infect Dis. 2020 Jun 19.
        Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial resistance and clinical outcomes; (2) systematic pharmacokinetic and pharmacodynamic evaluations to ensure resistance suppression and bacterial eradication at all sites of infection; (3) development of novel, affordable antimicrobials; and (4) advancements in new molecular and point-of-care tests to detect antimicrobial resistance determinants. Antimicrobial resistance among STIs is a global public health crisis. Continuous efforts to develop novel antimicrobials will be essential, in addition to other public health interventions to reduce the global STI burden. Apart from prevention through safer sexual practices, the development of STI vaccines to prevent transmission is a crucial research priority.

      22. Characteristics of adult outpatients and inpatients with COVID-19 - 11 academic medical centers, United States, March-May 2020external icon
        Tenforde MW, Billig Rose E, Lindsell CJ, Shapiro NI, Files DC, Gibbs KW, Prekker ME, Steingrub JS, Smithline HA, Gong MN, Aboodi MS, Exline MC, Henning DJ, Wilson JG, Khan A, Qadir N, Stubblefield WB, Patel MM, Self WH, Feldstein LR, CDC COVID-19 Response Team .
        MMWR Morb Mortal Wkly Rep. 2020 Jul 3;69(26):841-846.
        Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged >/=18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).

      23. Spatial characteristics of men who have sex with men and transgender women attending HIV voluntary counselling and testing in Bangkok, Thailand, 2005-2015external icon
        Weiss K, Karuchit S, Pattanasin S, Chitwarakorn A, Wimonsate W, Suksamosorn J, Visavakum P, Sukwicha W, Ungsedhapand C, Dunne EF, Holtz TH.
        Geospat Health. 2020 Jun 15;15(1).
        Spatiotemporal analyses can support Human Immuno-deficiency Virus (HIV) prevention programmes by identifying locations of at-risk populations in space and time, and their proximity to HIV testing and prevention services. We assessed residential proximity to HIV testing venues for Men who have Sex with Men (MSM) and Transgender Women (TGW) attending Voluntary Counselling and Testing (VCT) at a large urban MSM clinic in Bangkok, Thailand in the period 2005-2015. We mapped clientprovided spatial data and HIV testing venues, calculating distance from residence to venues for VCT clients between i) September 2005-December 2009; ii) January 2010-September 2013; and iii) October 2013-May 2015. We assessed spatial characteristics across times, evaluating autocorrelation of HIV prevalence and visit density using Moran's I. Among 8,758 first-time VCT clients reporting geographic information from 2005-2015 (by period: 2737, 3917, 2104), 1329 (15.2%) lived in postal codes </=5 km from the clinic. Over time, the proportion living in areas covered by Bangkok postal codes </=2 km from any MSM HIV testing venue increased from 12.6% to 41.0% (p<0.01). The proportion living </=5 km from the clinic decreased from 16.6% to 13.0% (p<0.01). HIV prevalence and clinic visit density demonstrated statistically significant non-random spatial patterning. Significant non-random patterning of prevalent infection and client visits highlighted Bangkok's urban HIV epidemic, clinic proximity to clients, and geographic reach. Clients lived closer to testing venues, yet farther from the urban MSM clinic, over time. Spatiotemporal characteristics of VCT clients can help assess service accessibility and guide targeted prevention planning.

    • Disaster Control and Emergency Services
      1. In August 2014, the World Health Organization declared the Ebola virus disease epidemic in West Africa a public health emergency of international concern. After 2 imported cases of the disease were identified in the United States in autumn 2014, the Centers for Disease Control and Prevention recommended that all jurisdictions begin active monitoring of travelers at risk of developing Ebola virus disease for 21 days from the last day of a potential exposure to minimize the risk of disease transmission. Here we describe the infrastructure development, monitoring processes, total planned expenditures, and effects on the public health system in Georgia associated with active monitoring and illness response of all travelers from Ebola-affected West African countries from October 2014 to March 2016. We conducted qualitative interviews with Georgia Department of Public Health (GDPH) staff. We identified state active monitoring and illness response infrastructure investments and monitoring activities and state and federal funds spent in both areas. And, we evaluated whether active monitoring and illness response enhanced Georgia's ability to respond to future infectious disease outbreaks. Developing the infrastructure to support the monitoring and response required investment in information technology, training of public health and medical personnel, increasing laboratory capacity, and securing personal protective equipment. Estimated total expenditures were $8.25 million, with 76% spent on infrastructure and 17% on daily monitoring. The GDPH leveraged internal resources and partnerships to implement active monitoring and illness response. Infrastructure investment increased surveillance capacity, strengthened relationships between the GDPH and medical providers, and led to the creation of infectious disease transport and hospital networks. Active monitoring and illness response increased outbreak preparedness, but it warrants comparison with other possible responses to determine its overall value.

    • Environmental Health
      1. The Fire and Tree Mortality Database, for empirical modeling of individual tree mortality after fireexternal icon
        Cansler CA, Hood SM, Varner JM, van Mantgem PJ, Agne MC, Andrus RA, Ayres MP, Ayres BD, Bakker JD, Battaglia MA, Bentz BJ, Breece CR, Brown JK, Cluck DR, Coleman TW, Corace RG, Covington WW, Cram DS, Cronan JB, Crouse JE, Das AJ, Davis RS, Dickinson DM, Fitzgerald SA, Fule PZ, Ganio LM, Grayson LM, Halpern CB, Hanula JL, Harvey BJ, Kevin Hiers J, Huffman DW, Keifer M, Keyser TL, Kobziar LN, Kolb TE, Kolden CA, Kopper KE, Kreitler JR, Kreye JK, Latimer AM, Lerch AP, Lombardero MJ, McDaniel VL, McHugh CW, McMillin JD, Moghaddas JJ, O'Brien JJ, Perrakis DD, Peterson DW, Prichard SJ, Progar RA, Raffa KF, Reinhardt ED, Restaino JC, Roccaforte JP, Rogers BM, Ryan KC, Safford HD, Santoro AE, Shearman TM, Shumate AM, Sieg CH, Smith SL, Smith RJ, Stephenson NL, Stuever M, Stevens JT, Stoddard MT, Thies WG, Vaillant NM, Weiss SA, Westlind DJ, Woolley TJ, Wright MC.
        Sci Data. 2020 Jun 22;7(1):194.
        Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research.

    • Epidemiology and Surveillance
      1. Public health surveillance during Simhastha Kumbh, a religious mass gathering in Ujjain district, Madhya Pradesh, India, 2016external icon
        Goel P, Dhuria M, Yadav R, Khasnobis P, Meena S, Venkatesh S.
        Indian J Public Health. 2020 Apr-Jun;64(2):198-200.
        A daily surveillance for disease detection and response at the Simhastha Kumbh Mela, in Ujjain, Madhya Pradesh, April-May 2016, was established. Existing weekly reporting of the Integrated Disease Surveillance Programme (IDSP) was modified to report 17 diseases or events from 22 public hospitals and three private hospitals in Ujjain. Water samples were also tested for fecal contamination in areas reporting diarrhea. We identified 56,600 ill persons (92% from government hospitals and 8% from private hospitals): 33% had fever, 28% acute respiratory infection, and 26% acute diarrheal diseases. There were 15 deaths (12 injury and 3 drowning). We detected two diarrhea outbreaks (Mahakaal Zone with 9 cases and Dutta Akhara Zone with 42 cases). Among 26 water samples, eight showed fecal contamination. This was a large implementation of daily disease surveillance in a religious mass gathering in India by IDSP. We recommended laboratory confirmation for diseases and similar daily surveillance in future mass gatherings in India.

      2. Initial findings from a novel population-based child mortality surveillance approach: a descriptive studyexternal icon
        Taylor AW, Blau DM, Bassat Q, Onyango D, Kotloff KL, Arifeen SE, Mandomando I, Chawana R, Baillie VL, Akelo V, Tapia MD, Salzberg NT, Keita AM, Morris T, Nair S, Assefa N, Seale AC, Scott JA, Kaiser R, Jambai A, Barr BA, Gurley ES, Ordi J, Zaki SR, Sow SO, Islam F, Rahman A, Dowell SF, Koplan JP, Raghunathan PL, Madhi SA, Breiman RF.
        Lancet Glob Health. 2020 Jul;8(7):e909-e919.
        BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5.9 million under-5 deaths and 77% of 2.6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhica, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation.

    • Genetics and Genomics
      1. The effect of variant interference on de novo assembly for viral deep sequencingexternal icon
        Castro CJ, Marine RL, Ramos E, Ng TF.
        BMC Genomics. 2020 Jun 22;21(1):421.
        BACKGROUND: Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approaches have surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. RESULTS: Our results from > 15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This "variant interference" (VI) is highly consistent and reproducible by ten commonly-used de novo assemblers, and occurs over a range of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the "rescue" of full viral genomes from fragmented contigs. CONCLUSIONS: These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.

    • Global Health
      1. Health challenges in refugee resettlement: An innovative multi-sector partnership to improve the continuum of care for resettled refugeesexternal icon
        Mann EM, Klosovsky A, Yen C, Olson AP, Hoffman SJ, Mamo B, Frerich EA, Weinberg M, Mayali H, McCoy M, Prasad S, Dunlop SJ, Stauffer WM.
        J Travel Med. 2020 Jun 24.

      2. Research ethics and refugee health: a review of reported considerations and applications in published refugee health literature, 2015-2018external icon
        Seagle EE, Dam AJ, Shah PP, Webster JL, Barrett DH, Ortmann LW, Cohen NJ, Marano NN.
        Confl Health. 2020 ;14:39.
        Introduction: Public health investigations, including research, in refugee populations are necessary to inform evidence-based interventions and care. The unique challenges refugees face (displacement, limited political protections, economic hardship) can make them especially vulnerable to harm, burden, or undue influence. Acute survival needs, fear of stigma or persecution, and history of trauma may present challenges to ensuring meaningful informed consent and establishing trust. We examined the recently published literature to understand the application of ethics principles in investigations involving refugees. Methods: We conducted a preliminary review of refugee health literature (research and non-research data collections) published from 2015 through 2018 available in PubMed. Article inclusion criteria were: participants were refugees, topic was health-related, and methods used primary data collection. Information regarding type of investigation, methods, and reported ethics considerations was abstracted. Results: We examined 288 articles. Results indicated 33% of investigations were conducted before resettlement, during the displacement period (68% of these were in refugee camps). Common topics included mental health (48%) and healthcare access (8%). The majority (87%) of investigations obtained consent. Incentives were provided less frequently (23%). Most authors discussed the ways in which community stakeholders were engaged (91%), yet few noted whether refugee representatives had an opportunity to review investigational protocols (8%). Cultural considerations were generally limited to gender and religious norms, and 13% mentioned providing some form of post-investigation support. Conclusions: Our analysis is a preliminary assessment of the application of ethics principles reported within the recently published refugee health literature. From this analysis, we have proposed a list of best practices, which include stakeholder engagement, respect for cultural norms, and post-study support. Investigations conducted among refugees require additional diligence to ensure respect for and welfare of the participants. Development of a refugee-specific ethics framework with ethics and refugee health experts that addresses the need for stakeholder involvement, appropriate incentive use, protocol review, and considerations of cultural practices may help guide future investigations in this population.

    • Immunity and Immunization
      1. Risk for subdeltoid bursitis after influenza vaccination: A population-based cohort studyexternal icon
        Hesse EM, Navarro RA, Daley MF, Getahun D, Henninger ML, Jackson LA, Nordin J, Olson SC, Zerbo O, Zheng C, Duffy J.
        Ann Intern Med. 2020 Jun 23.
        BACKGROUND: Subdeltoid bursitis has been reported as an adverse event after intramuscular vaccination in the deltoid muscle. Most published case reports involved influenza vaccine. OBJECTIVE: To estimate the risk for subdeltoid bursitis after influenza vaccination. DESIGN: Retrospective cohort study. SETTING: The Vaccine Safety Datalink, which contains health encounter data for 10.2 million members of 7 U.S. health care organizations. PATIENTS: Persons who received an inactivated influenza vaccine during the 2016-2017 influenza season. MEASUREMENTS: Potential incident cases were identified by searching administrative data for persons with a shoulder bursitis diagnostic code within 180 days after receiving an injectable influenza vaccine in the same arm. The date of reported bursitis symptom onset was abstracted from the medical record. A self-controlled risk interval analysis was used to calculate the incidence rate ratio of bursitis in a risk interval of 0 to 2 days after vaccination versus a control interval of 30 to 60 days, which represents the background rate. The attributable risk was also estimated. RESULTS: The cohort included 2 943 493 vaccinated persons. Sixteen cases of symptom onset in the risk interval and 51 cases of symptom onset in the control interval were identified. The median age of persons in the risk interval was 57.5 years (range, 24 to 98 years), and 69% were women. The incidence rate ratio was 3.24 (95% CI, 1.85 to 5.68). The attributable risk was 7.78 (CI, 2.19 to 13.38) additional cases of bursitis per 1 million persons vaccinated. LIMITATION: The results may not be generalizable to vaccinations done in other types of health care settings. CONCLUSION: Although an increased risk for bursitis after vaccination was present, the absolute risk was small. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

      2. Projected population benefit of increased effectiveness and coverage of influenza vaccination on influenza burden in the United Statesexternal icon
        Hughes MM, Reed C, Flannery B, Garg S, Singleton JA, Fry AM, Rolfes MA.
        Clin Infect Dis. 2020 Jun 10;70(12):2496-2502.
        BACKGROUND: Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC). METHODS: For 3 influenza seasons (2011-12, 2015-16, and 2017-18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC. RESULTS: During the 2017-18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18-64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations. CONCLUSIONS: Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18-49 years.

      3. Global vaccine action plan lessons learned I: Recommendations for the next decadeexternal icon
        MacDonald N, Mohsni E, Al-Mazrou Y, Kim Andrus J, Arora N, Elden S, Madrid MY, Martin R, Mahmoud Mustafa A, Rees H, Salisbury D, Zhao Q, Jones I, Steffen CA, Hombach J, O'Brien KL, Cravioto A.
        Vaccine. 2020 May 5.
        The Global Vaccine Action Plan 2011-2020 (GVAP) was developed to realize the ambitions of the Decade of Vaccines - that all individuals and communities enjoy lives free from vaccine-preventable diseases. It included a comprehensive monitoring and evaluation/accountability framework to assess progress towards global targets with recommendations for corrective actions. While many of the GVAP targets are very unlikely to be met by the end of 2020, substantial progress has nevertheless been made, establishing a strong foundation for a successor global immunization strategy, the Immunization Agenda 2030 (IA2030). The Strategic Advisory Group of Experts on immunization has made a series of recommendations to ensure that the lessons learned from GVAP inform the development and implementation of IA2030.

      4. A randomized controlled trial of antibody response to 2018-19 cell-based vs. egg-based quadrivalent inactivated influenza vaccine in childrenexternal icon
        Moehling KK, Zimmerman RK, Nowalk MP, Jeng Lin C, Martin JM, Alcorn JF, Susick M, Burroughs A, Holiday C, Flannery B, Levine MZ.
        Vaccine. 2020 Jun 21.
        BACKGROUND: Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial. METHODS: Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax(R)]; n = 85); or in egg medium (IIV4 [Fluzone (R)]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio >/= 4 with day 28 titer >/= 40). Secondary outcomes were elevated titers (day 28 HI titer >/= 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment. RESULTS: In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients. CONCLUSION: In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses. CLINICAL TRIALS NO: NCT03614975.

      5. Building immunization decision-making capacity within the World Health Organization European Regionexternal icon
        Mosina L, Sankar Datta S, Shefer A, Cavallaro KF, Henaff L, Steffen CA, Jacques-Carroll L.
        Vaccine. 2020 Jun 17.
        A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provides evidence-based recommendations to policy-makers, assisting them in making sound immunization policy and programme decisions. The World Health Organization (WHO) Regional Office for Europe is working to strengthen the capacity of newly-established NITAGs and has targeted efforts on low- and middle-income countries. The Regional Office, in collaboration with WHO Headquarters and USA Centers for Disease Control and Prevention (CDC), developed a new training strategy and held training workshops to improve NITAGs' functioning and ability to make evidence-based recommendations. Feedback from countries that participated in trainings indicated that the updated training materials and interactive approach with follow-up technical support enabled them to align their NITAG charters and processes with WHO recommendations. To ensure continued progress, global and regional partners such as WHO and CDC should continue providing technical support to recently established NITAGs.

      6. Prevention of hepatitis A virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020external icon
        Nelson NP, Weng MK, Hofmeister MG, Moore KL, Doshani M, Kamili S, Koneru A, Haber P, Hagan L, Romero JR, Schillie S, Harris AM.
        MMWR Recomm Rep. 2020 Jul 3;69(5):1-38.
        Hepatitis a is a vaccine-preventable, communicable disease of the liver caused by the hepatitis a virus (hav). The infection is transmitted via the fecal-oral route, usually from direct person-to-person contact or consumption of contaminated food or water. Hepatitis a is an acute, self-limited disease that does not result in chronic infection. Hav antibodies (immunoglobulin g [igg] anti-hav) produced in response to hav infection persist for life and protect against reinfection; igg anti-hav produced after vaccination confer long-term immunity. This report supplants and summarizes previously published recommendations from the advisory committee on immunization practices (acip) regarding the prevention of hav infection in the united states. Acip recommends routine vaccination of children aged 12-23 months and catch-up vaccination for children and adolescents aged 2-18 years who have not previously received hepatitis a (hepa) vaccine at any age. Acip recommends hepa vaccination for adults at risk for hav infection or severe disease from hav infection and for adults requesting protection against hav without acknowledgment of a risk factor. These recommendations also provide guidance for vaccination before travel, for postexposure prophylaxis, in settings providing services to adults, and during outbreaks.

    • Injury and Violence
      1. Characteristics of diagnosed concussions in children aged 0 to 4 years presenting to a large pediatric healthcare networkexternal icon
        Podolak OE, Chaudhary S, Haarbauer-Krupa J, Metzger KB, Curry AE, Kessler RS, Pfeiffer MR, Breiding MJ, Master CL, Arbogast KB.
        Pediatr Emerg Care. 2020 Jun 16.
        OBJECTIVE: The aim of the study was to comprehensively describe the natural history of concussion in early childhood between 0 and 4 years. METHODS: Retrospective cohort study of 329 patients aged 0 to 4 years, with an International Classification of Diseases, Ninth Revision, concussion diagnosis in the Children's Hospital of Philadelphia healthcare network from October 1, 2013, to September 30, 2015. Clinical data were abstracted from the Children's Hospital of Philadelphia electronic health record, which captured all clinical care visits and injury characteristics. RESULTS: Nearly 9 (86.6%) of 10 patients sought care in the emergency department or urgent care setting, most commonly on the day of injury (56.2%) and as a result of a fall (64.4%). More than two-thirds (64.4%) of patients or their parent/caregiver reported somatic symptoms (ie, vomiting or headache), whereas close to half (49.2%) reported sleep issues. One of 5 patients identified emotional symptoms (21.9%) or visio-vestibular dysfunction (20.4%). Many patients also experienced symptoms not included in standard assessment tools including personality changes (34.0%) and change in appetite (12.8%). CONCLUSIONS: These results provide insight into the clinical characteristics of concussion in early childhood up to 4 years of age. Because assessment in this group relies heavily on parent/caregiver symptom reporting, rather than patient self-report, these results will aid clinicians with the challenge of diagnosing concussions in this population. These findings highlight the need to develop additional tools to adequately and systematically assess common signs and symptoms of concussion in early childhood that may not be included in standard assessment scales routinely used in older adolescents and adults.

    • Laboratory Sciences
      1. Segregation of respirable dust for chemical and toxicological analysesexternal icon
        Barone TL, Lee T, Cauda EG, Mazzella AL, Stach R, Mizaikoff B.
        Arch Environ Occup Health. 2020 Jun 18:1-11.
        Respirable dust can pass beyond ciliated airways of the respiratory tract and influence adverse health effects. Health effects can be studied using samples generated from bulk dust segregation. Because previous segregation methods diverge from size-selection criteria of the international convention for respirable particles (ICRP), a method was developed to approximate the ICRP. The method was compared to an ideal sampler by measuring the sample collection bias. The comparison shows that the uncertainty due to the bias was 0.10 based on European Standard EN13205:2014 criteria, which indicates that the segregator effectively follows the ICRP. Respirable particle size distributions were confirmed by an aerodynamic particle sizer and by computer-controlled scanning electron microscopy. Consequently, a systematic way to generate respirable powders for health effects studies and chemical analyses was developed.

      2. Durable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodiesexternal icon
        Garber DA, Adams DR, Guenthner P, Mitchell J, Kelley K, Schoofs T, Gazumyan A, Nason M, Seaman MS, McNicholl J, Nussenzweig MC, Heneine W.
        Nat Commun. 2020 Jun 24;11(1):3195.
        Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 mug ml(-1) correlated with >/=99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.

      3. Performance evaluation of culture-independent SYBR Green Candida auris qPCR diagnostics on anterior nares surveillance swabsexternal icon
        Georgacopoulos O, Nunnally NS, Le N, Lysen C, Welsh RM, Kordalewska M, Perlin DS, Berkow EL, Sexton DJ.
        J Clin Microbiol. 2020 Jun 24.
        Early identification of Candida auris is important for timely implementation of infection prevention and control actions. Here, we evaluated performance of the C. auris-specific SYBR Green qPCR assay on a panel of 70 anterior nares swabs. Enrichment broth culture was used as "gold standard". After performing a receiver operating curve (ROC) to optimize signal threshold, we found perfect agreement between culture and qPCR. Additionally, we found no indication of inhibitors in the anterior nares swabs.

      4. Diagnosis of prion diseases by RT-QuIC results in improved surveillanceexternal icon
        Rhoads DD, Wrona A, Foutz A, Blevins J, Glisic K, Person M, Maddox RA, Belay ED, Schonberger LB, Tatsuoka C, Cohen ML, Appleby BS.
        Neurology. 2020 Jun 22.
        OBJECTIVE: We present the National Prion Disease Pathology Surveillance Center's (NPDPSC) experience using cerebrospinal fluid (CSF) real time quaking induced conversion (RT-QuIC) as a diagnostic test, examine factors associated with false negative RT-QuIC results, and investigate RT-QuIC's impact on prion disease surveillance. METHODS: Between May 2015-April 2018, the NPDPSC received 10,498 CSF specimens that were included in the study. Sensitivity and specificity analyses were performed using 567 autopsy verified cases. Prion disease type, demographic characteristics, specimen color, and time variables were examined for association with RT-QuIC results. The effect of including positive RT-QuIC cases in prion disease surveillance was examined. RESULTS: The diagnostic sensitivity and specificity of RT-QuIC across all prion diseases was 90.3% and 98.5%, respectively. Diagnostic sensitivity was lower for fatal familial insomnia, Gerstmann-Straussler-Scheinker disease, sporadic fatal insomnia, variably protease sensitive prionopathy, and the VV1 and MM2 subtypes of sCJD. Individuals with prion disease and negative RT-QuIC results were younger, had elevated tau levels, and non-elevated 14-3-3 levels compared to RT-QuIC positive cases. Sensitivity was high throughout the disease course. Some cases that initially tested RT-QuIC negative had a subsequent specimen test positive. Including positive RT-QuIC cases in surveillance statistics increased laboratory-based case ascertainment of prion disease by 90% over autopsy alone. CONCLUSIONS: RT-QuIC has high sensitivity and specificity for diagnosing prion diseases. Sensitivity limitations are associated with prion disease type, age, and related CSF diagnostic results. RT-QuIC greatly improves laboratory-based prion disease ascertainment for surveillance purposes. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that 2(nd) generation real time quaking-induced conversion (RT-QuIC) identifies prion disease with sensitivity of 90.3% and specificity of 98.5%, among patients being screened for these diseases due to concerning symptoms.

      5. Direct detection methods for Treponema pallidum include dark-field microscopy (DFM), direct fluorescence antibody (DFA) testing, immunohistochemistry (IHC), and nucleic acid amplification tests (NAATs). Here, we reviewed the relevant syphilis diagnostic literature to address 2 main questions with respect to T. pallidum direct detection techniques: "What are the performance characteristics for each direct detection test for T. pallidum and what are the optimal specimen types for each test?" and "What options are available for T. pallidum molecular epidemiology?" To answer these questions, we searched 5 electronic databases (OVID Medline, OVID Embase, CINAHL, Cochrane Library, and Scopus) from 1964 to 2017 using relevant search terms and identified 1928 articles, of which 37 met our inclusion criteria. DFM and DFA sensitivities ranged from 73% to 100% in cases of primary syphilis; and while sensitivity using silver stain histopathology for T. pallidum was generally low (0%-41%), higher performance characteristics were observed for T. pallidum-specific IHC (49-92%). Different genes have been targeted by T. pallidum-specific NAATs, with the majority of studies indicating that sensitivity is primarily dependent on the type of collected biological sample, with highest sensitivity observed in primary lesion exudate (75-95%). Given the rising incidence of syphilis, the development of direct, Food and Drug Administration-cleared T. pallidum NAATs should be considered an immediate priority.

      6. Syphilis laboratory guidelines: Performance characteristics of nontreponemal antibody testsexternal icon
        Tuddenham S, Katz SS, Ghanem KG.
        Clin Infect Dis. 2020 Jun 24;71(Supplement_1):S21-s42.
        We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960-2017, and for data related to the venereal disease research laboratory test from 1940-1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed.

      7. Genome-wide transcriptome architecture in a mouse model of Gulf War illnessexternal icon
        Xu F, Ashbrook DG, Gao J, Starlard-Davenport A, Zhao W, Miller DB, O'Callaghan JP, Williams RW, Jones BC, Lu L.
        Brain Behav Immun. 2020 Jun 20.
        Gulf War Illness (GWI) is thought to be a chronic neuroimmune disorder caused by in-theater exposure during the 1990-1991 Gulf War. There is a consensus that the illness is caused by exposure to insecticides and nerve agent toxicants. However, the heterogeneity in both development of disease and clinical outcomes strongly suggests a genetic contribution. Here, we modeled GWI in 30 BXD recombinant inbred strains with a combined treatment of corticosterone (CORT) and diisopropyl fluorophosphate (DFP). We quantified transcriptomes from 409 prefrontal cortex samples. Compared to the untreated and DFP treated controls. The combined treatment significantly activated pathways such as cytokine-cytokine receptor interaction and TNF signaling pathway. Protein-protein interaction analysis defined 6 subnetworks for CORT+DFP, with the key regulators being Cxcl1, Il6, Ccnb1, Tnf, Agt, and Itgam. We also identified 21 differentially expressed genes having significant QTLs related to CORT+DFP, but without evidence for untreated and DFP treated controls, suggesting regions of the genome specifically involved in the response to CORT+DFP. We identified Adamts9 as a potential contributor to response to CORT+DFP and found links to symptoms of GWI. Furthermore, we observed a significant effect of CORT+DFP treatment on the relative proportion of myelinating oligodendrocytes, with a QTL on Chr5. We highlight three candidates, Magi2, Sema3c, and Gnai1, based on their high expression in the brain and oligodendrocyte. In summary, our results show significant genetic effects of the CORT+DFP treatment, which mirrors gene and protein expression changes seen in GWI sufferers, providing insight into the disease and a testbed for future interventions.

      8. Nanoceria distribution and effects are mouse-strain dependentexternal icon
        Yokel RA, Tseng MT, Butterfield DA, Hancock ML, Grulke EA, Unrine JM, Stromberg AJ, Dozier AK, Graham UM.
        Nanotoxicology. 2020 Jun 18:1-20.
        Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO2 nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1beta, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. Electron microscopy showed intracellular nanoceria particles bioprocessed to form crystalline cerium phosphate nanoneedles. Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. Nanoceria uptake, initiation of bioprocessing, and crystalline cerium phosphate nanoneedle formation were rapid. Ferritin greatly increased with a macrophage phenotype-dependent distribution. Further study will be needed to understand the mechanisms underlying the observed differences.

    • Maternal and Child Health
      1. Mapping the relationship between dysmorphology and cognitive, behavioral, and developmental outcomes in children with autism spectrum disorderexternal icon
        Tian LH, Wiggins LD, Schieve LA, Yeargin-Allsopp M, Dietz P, Aylsworth AS, Elias ER, Hoover-Fong JE, Meeks NJ, Souders MC, Tsai AC, Zackai EH, Alexander AA, Dowling NF, Shapira SK.
        Autism Res. 2020 Jun 22.
        Previous studies investigating the association between dysmorphology and cognitive, behavioral, and developmental outcomes among individuals with autism spectrum disorder (ASD) have been limited by the binary classification of dysmorphology and lack of comparison groups. We assessed the association using a continuous measure of dysmorphology severity (DS) in preschool children aged 2-5 years (322 with ASD and intellectual disability [ID], 188 with ASD without ID, and 371 without ASD from the general population [POP]). In bivariate analyses, an inverse association between DS and expressive language, receptive language, fine motor, and visual reception skills was observed in children with ASD and ID. An inverse association of DS with fine motor and visual reception skills, but not expressive language and receptive language, was found in children with ASD without ID. No associations were observed in POP children. These results persisted after exclusion of children with known genetic syndromes or major morphologic anomalies. Quantile regression models showed that the inverse relationships remained significant after adjustment for sex, race/ethnicity, maternal education, family income, study site, and preterm birth. DS was not associated with autistic traits or autism symptom severity, behaviors, or regression among children with ASD with or without ID. Thus, DS was associated with a global impairment of cognitive functioning in children with ASD and ID, but only with fine motor and visual reception deficits in children with ASD without ID. A better understanding is needed for mechanisms that explain the association between DS and cognitive impairment in children with different disorders. LAY SUMMARY: We examined whether having more dysmorphic features (DFs) was related to developmental problems among children with autism spectrum disorder (ASD) with or without intellectual disability (ID), and children without ASD from the general population (POP). Children with ASD and ID had more language, movement, and learning issues as the number of DFs increased. Children with ASD without ID had more movement and learning issues as the number of DFs increased. These relationships were not observed in the POP group. Implications are discussed.

    • Nutritional Sciences
      1. Healthier food and beverage interventions in schools: Four Community Guide systematic reviewsexternal icon
        Wethington HR, Finnie RK, Buchanan LR, Okasako-Schmucker DL, Mercer SL, Merlo C, Wang Y, Pratt CA, Ochiai E, Glanz K.
        Am J Prev Med. 2020 Jul;59(1):e15-e26.
        CONTEXT: Healthy eating during childhood is important for optimal growth and helps reduce the risk of obesity, which has potentially serious health consequences. Changing the school food environment may offer one way to improve students' dietary intake. This manuscript reports 4 Community Guide systematic reviews examining the effectiveness of interventions in schools promoting healthy eating and weight. EVIDENCE ACQUISITION: School obesity prevention programs aiming to improve diet were identified from a 2013 Agency for Health Care Research and Quality systematic review and an updated search (August 2012-January 4, 2017). In 2017-2018, Community Guide systematic review methods were used to assess effectiveness as determined by dietary behavior and weight changes. EVIDENCE SYNTHESIS: Interventions improving school meals or offering fruits and vegetables (n=27 studies) are considered effective. Evidence is insufficient to determine the effectiveness of interventions supporting healthier snack foods and beverages outside of school meal programs given inconsistent findings (n=13 studies). Multicomponent interventions to increase availability of healthier foods and beverages are considered effective. These interventions must include 1 component from school meals or fruit and vegetable programs and interventions supporting healthier snack foods and beverages (n=12 studies). There is insufficient evidence to determine the effectiveness of interventions to increase water access because only 2 studies met inclusion criteria. CONCLUSIONS: A total of 2 school-based dietary interventions have favorable effects for improving dietary habits and modest effects for improving or maintaining weight. More evidence is needed regarding interventions with insufficient findings. These reviews may inform researchers and school administrators about healthy eating and obesity prevention interventions.

    • Occupational Safety and Health
      1. Field or laboratory data collected for work-related musculoskeletal disorder (WMSD) risk assessment in construction often becomes unreliable as a large amount of data go missing due to technology-induced errors, instrument failures or sometimes at random. Missing data can adversely affect the assessment conclusions. This study proposes a method that applies Canonical Polyadic Decomposition (CPD) tensor decomposition to fuse multiple sparse risk-related datasets and fill in missing data by leveraging the correlation among multiple risk indicators within those datasets. Two knee WMSD risk-related datasets—3D knee rotation (kinematics) and electromyography (EMG) of five knee postural muscles—collected from previous studies were used for the validation and demonstration of the proposed method. The analysis results revealed that for a large portion of missing values (40%), the proposed method can generate a fused dataset that provides reliable risk assessment results highly consistent (70%–87%) with those obtained from the original experimental datasets. This signified the usefulness of the proposed method for use in WMSD risk assessment studies when data collection is affected by a significant amount of missing data, which will facilitate reliable assessment of WMSD risks among construction workers. In the future, findings of this study will be implemented to explore whether, and to what extent, the fused dataset outperforms the datasets with missing values by comparing consistencies of the risk assessment results obtained from these datasets for further investigation of the fusion performance.

      2. Associations of sleep measures with retinal microvascular diameters among police officersexternal icon
        Ma CC, Gu JK, Andrew ME, Fekedulegn D, Violanti JM, Klein B, Tinney-Zara C, Charles LE.
        Ophthalmic Epidemiol. 2020 Jun 24:1-11.
        PURPOSE: We examined cross-sectional associations of sleep measures with central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) and investigated whether sex and race/ethnicity modified these associations. METHODS: Participants (N = 202; 78% white; 71% men) were enrolled in the Buffalo Cardio-metabolic Occupational Police Stress study (2011-2014). Wrist actigraphy was used to assess sleep measures including sleep duration, sleep efficiency, sleep onset latency, wake after sleep onset, number of awakenings, and longest wake episode. CRAE and CRVE were obtained from fundus photography of retina and were averaged from both eyes per officer. RESULTS: We observed significant associations between sleep efficiency and CRVE (beta = -2.81 microm; P= .046), and between longest wake episode and CRVE (beta = 3.24 microm; P= .021). Adjustments for demographics, lifestyles, and physical and psychological factors attenuated these associations. Sex modified the independent associations of sleep onset latency and longest wake episode with CRVE. One standard deviation (SD) increase in sleep onset latency was associated with 4.81 microm larger CRVE (P= .028) (P-interaction = 0.098), and one SD increase in longest wake episode was associated with 4.62 microm larger CRVE (P= .032) (P-interaction = 0.115) among men. Race/ethnicity also modified the association between longest wake episode and CRVE (P-interaction = 0.088). A significant association was observed only among white officers (beta = 4.96 microm; P= .025). CONCLUSIONS: We found that poor sleep quality, measured by longest wake episode, was positively and independently associated with retinal venular diameter among white and male officers. Longitudinal studies are warranted to assess whether poor sleep quality is a risk factor for retinal diameter changes.

      3. Asthma and chronic obstructive pulmonary disease (COPD) are respiratory conditions associated with a significant economic cost among U.S. adults (1,2), and up to 44% of asthma and 50% of COPD cases among adults are associated with workplace exposures (3). CDC analyzed 2011-2015 Medical Expenditure Panel Survey (MEPS) data to determine the medical expenditures attributed to treatment of asthma and COPD among U.S. workers aged >/=18 years who were employed at any time during the survey year. During 2011-2015, among the estimated 166 million U.S. workers, 8 million had at least one asthma-related medical event,* and 7 million had at least one COPD-related medical event. The annualized total medical expenditures, in 2017 dollars, were $7 billion for asthma and $5 billion for COPD. Private health insurance paid for 61% of expenditures attributable to treatment of asthma and 59% related to COPD. By type of medical event, the highest annualized per-person asthma- and COPD-related expenditures were for inpatient visits: $8,238 for asthma and $27,597 for COPD. By industry group, the highest annualized per-person expenditures ($1,279 for asthma and $1,819 for COPD) were among workers in public administration. Early identification and reduction of risk factors, including workplace exposures, and implementation of proven interventions are needed to reduce the adverse health and economic impacts of asthma and COPD among workers.

      4. Psychosocial factors and low back pain outcomes in a pooled analysis of low back pain studiesexternal icon
        Thiese MS, Lu ML, Merryweather A, Tang R, Ferguson SA, Malloy EJ, Marras WS, Hegmann KT, Kapellusch J.
        J Occup Environ Med. 2020 Jun 16.
        OBJECTIVE: Assessment of possible relationships between work-related psychosocial measures and self-reported low back pain (LBP) outcomes in a large pooled dataset of 1,929 participants from 82 facilities in the United States. METHODS: Pooled data from 3 prospective cohort studies were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for relationships between psychosocial factors and the LBP outcomes. Personal and occupational confounders were controlled for in adjusted Logistic regression models. RESULTS: Supervisor support and job satisfaction were significantly (p < 0.05) related to all three LBP outcomes. Other psychosocial factors were significantly (p < 0.05) associated with at least one of the LBP outcomes. Adjusted ORs ranged from approximately 1.50 to 3.50 for most associations. CONCLUSIONS: There is a significant relationship between work-related psychosocial measures and LBP outcomes.

    • Parasitic Diseases
      1. Monitoring the durability of the long-lasting insecticidal nets MAGNet and Royal Sentry in three ecological zones of Mozambiqueexternal icon
        Abilio AP, Obi E, Koenker H, Babalola S, Saifodine A, Zulliger R, Swamidoss I, Ponce de Leon G, Alfai E, Blaufuss S, Olapeju B, Harig H, Kilian A.
        Malar J. 2020 Jun 17;19(1):209.
        BACKGROUND: Malaria prevention with long-lasting insecticidal nets (LLINs) has seen a tremendous scale-up in sub-Saharan Africa in the last decade. To sustain this success, it is important to understand how long LLINs remain in the households and continue to protect net users, which is termed durability. This information is needed to decide the appropriate timing of LLIN distribution and also to identify product(s) that may be underperforming relative to expectations. Following guidance from the U.S. President's Malaria Initiative, durability monitoring of polyethylene 150-denier LLIN (Royal Sentry((R)) and MAGNet((R))) distributed during a 2017 mass campaign in Mozambique was implemented in three ecologically different sites: Inhambane, Tete, and Nampula. METHODS: This was a prospective cohort study in which representative samples of households from each district were recruited at baseline, 1 to 6 months after the mass campaign. All campaign LLINs in these households were labelled and followed up over a period of 36 months. The primary outcome was the "proportion of LLINs surviving in serviceable condition" based on attrition and integrity measures and the median survival in years. The outcome for insecticidal durability was determined by bio-assay from subsamples of campaign LLINs. RESULTS: A total of 998 households (98% of target) and 1998 campaign LLIN (85% of target) were included in the study. Definite outcomes could be determined for 80% of the cohort LLIN in Inhambane, 45% in Tete, and 72% in Nampula. The highest all-cause attrition was seen in Nampula with 74% followed by Inhambane at 56% and Tete at 50%. Overall, only 2% of campaign LLINs were used for other purposes. Estimated survival in serviceable condition of campaign LLINs after 36 months was 57% in Inhambane, 43% in Tete, and 33% in Nampula, corresponding to median survival of 3.0, 2.8, and 2.4 years, respectively. Factors that were associated with better survival were exposure to social and behavioural change communication, a positive net care attitude, and folding up the net during the day. Larger household size negatively impacted survival. Insecticidal performance was optimal up to 24 months follow-up, but declined at 36 months when only 3% of samples showed optimal effectiveness in Inhambane, 11% in Tete and 29% in Nampula. However, 96% of LLIN still had minimal effectiveness at 36 months. CONCLUSIONS: Differences in median survival could be attributed at least in part to household environment and net care and repair behaviours. This means that in two of the three sites the assumption of a three-year cycle of campaign distributions holds, while in the Nampula site either continuous distribution channels could be expanded or more intense or targeted social and behaviour change activities to encourage net care and retention could be considered.

      2. BACKGROUND: Despite available control strategies, malaria morbidity and mortality, especially in infants and young children in sub-Saharan Africa, remain intractable. Malaria vaccination could substantially reduce malaria episodes and deaths. One vaccine candidate is the whole sporozoite PfSPZ Vaccine, consisting of irradiated cryopreserved sporozoites administered by direct venous inoculation (DVI). DVI may be less acceptable than more familiar administration routes, particularly intramuscular. As part of a PfSPZ Vaccine trial among infants in western Kenya, a qualitative study was conducted to explore caregiver and community perceptions of the malaria vaccine trial, including the unique DVI administration procedure. METHODS: Twelve focus groups and 28 in-depth interviews explored perceptions of the DVI procedure in infants, factors influencing trial acceptability, and barriers to sustained trial participation. Purposively sampled participants included mothers of enrolled children, fathers and mothers who withdrew their children from the trial, village elders, and study clinicians from two trial enrollment sites. An iterative, multi-stage analytic approach, adapted from the Framework Method, was used to synthesize and interpret textual data. RESULTS: Desires to prevent malaria and participation incentives (e.g., free consultations and medication) motivated caregivers to enroll their children in the trial. However, numerous factors also demotivated trial participation. Family members' (i.e., fathers') objections to required blood draws were cited most frequently as drivers of early trial withdrawal, in many cases prior to receiving any vaccine. Among mothers whose children received PfSPZ Vaccine (or placebo), many spoke favourably of DVI administration, describing improved tolerability relative to intramuscularly administered immunizations. Other trial-related challenges cited by caregivers included negative interactions with study clinicians and perceived delays in administering trial procedures. CONCLUSIONS: Despite high acceptance of DVI among caregivers whose children received PfSPZ Vaccine (or placebo), objections to trial procedures from other non-sensitized household and family members prompted early trial withdrawal and inhibited successful completion of trial procedures for some infants. Implications for future trials include targeting heads of household during sensitization and recruitment activities, as well as equipping trial staff to effectively respond to participant and community concerns regarding trial procedures.

      3. Efficacy and safety of artesunate-amodiaquine and artemether-lumefantrine and prevalence of molecular markers associated with resistance, Guinea: an open-label two-arm randomised controlled trialexternal icon
        Beavogui AH, Camara A, Delamou A, Diallo MS, Doumbouya A, Kourouma K, Bouedouno P, Guilavogui T, Dos Santos Souza S, Kelley J, Talundzic E, Fofana A, Plucinski MM.
        Malar J. 2020 Jun 24;19(1):223.
        BACKGROUND: Anti-malarial resistance is a threat to recent gains in malaria control. This study aimed to assess the efficacy and safety of artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) in the management of uncomplicated malaria and to measure the prevalence of molecular markers of resistance of Plasmodium falciparum in sentinel sites in Maferinyah and Labe Health Districts in Guinea in 2016. METHODS: This was a two-arm randomised controlled trial of the efficacy of AL and ASAQ among children aged 6-59 months with uncomplicated Plasmodium falciparum malaria in two sites. Children were followed for 28 days to assess clinical and parasitological response. The primary outcome was the Kaplan-Meier estimate of Day 28 (D28) efficacy after correction by microsatellite-genotyping. Pre-treatment (D0) and day of failure samples were assayed for molecular markers of resistance in the pfk13 and pfmdr1 genes. RESULTS: A total of 421 participants were included with 211 participants in the Maferinyah site and 210 in Labe. No early treatment failure was observed in any study arms. However, 22 (5.3%) participants developed a late treatment failure (8 in the ASAQ arm and 14 in the AL arm), which were further classified as 2 recrudescences and 20 reinfections. The Kaplan-Meier estimate of the corrected efficacy at D28 was 100% for both AL and ASAQ in Maferinyah site and 99% (95% Confidence Interval: 97.2-100%) for ASAQ and 99% (97.1-100%) for AL in Labe. The majority of successfully analysed D0 (98%, 380/389) and all day of failure (100%, 22/22) samples were wild type for pfk13. All 9 observed pfk13 mutations were polymorphisms not associated with artemisinin resistance. The NFD haplotype was the predominant haplotype in both D0 (197/362, 54%) and day of failure samples (11/18, 61%) successfully analysed for pfmdr1. CONCLUSION: This study observed high efficacy and safety of both ASAQ and AL in Guinea, providing evidence for their continued use to treat uncomplicated malaria. Continued monitoring of ACT efficacy and safety and molecular makers of resistance in Guinea is important to detect emergence of parasite resistance and to inform evidence-based malaria treatment policies.

      4. Associations between schistosomiasis and HIV-1 acquisition risk in four prospective cohorts: a nested case-control analysisexternal icon
        Bochner AF, Baeten JM, Secor WE, van Dam GJ, Szpiro AA, Njenga SM, Corstjens P, Newsam A, Mugo NR, Celum C, Mujugira A, McClelland RS, Barnabas RV.
        J Int AIDS Soc. 2020 Jun;23(6):e25534.
        INTRODUCTION: Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub-Saharan Africa. Schistosomiasis is hypothesized to increase HIV-1 acquisition risk, and multiple cross-sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. METHODS: We conducted nested case-control analyses within three longitudinal cohorts of heterosexual HIV-1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow-up from 1993 to 2014. Cases HIV-1 seroconverted during prospective follow-up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. RESULTS: We included 245 HIV-1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV-1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV-1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species-specific effects, there was no statistically significant association between HIV-1 acquisition risk and Schistosoma mansoni (serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) or Schistosoma haematobium (serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. CONCLUSIONS: Schistosomiasis was not a strong risk factor for HIV-1 acquisition in these four prospective studies. S. mansoni was responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis that S. mansoni infection is associated with increased HIV-1 acquisition risk. S. haematobium infection was associated with a point estimate of elevated HIV-1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts.

      5. Programmatic options for monitoring malaria in elimination settings: easy access group surveys to investigate Plasmodium falciparum epidemiology in two regions with differing endemicity in Haitiexternal icon
        Druetz T, Stresman G, Ashton RA, van den Hoogen LL, Joseph V, Fayette C, Monestime F, Hamre KE, Chang MA, Lemoine JF, Drakeley C, Eisele TP.
        BMC Med. 2020 Jun 23;18(1):141.
        BACKGROUND: As in most eliminating countries, malaria transmission is highly focal in Haiti. More granular information, including identifying asymptomatic infections, is needed to inform programmatic efforts, monitor intervention effectiveness, and identify remaining foci. Easy access group (EAG) surveys can supplement routine surveillance with more granular information on malaria in a programmatically tractable way. This study assessed how and which type of venue for EAG surveys can improve understanding malaria epidemiology in two regions with different transmission profiles. METHODS: EAG surveys were conducted within the departments of Artibonite and Grand'Anse (Haiti), in regions with different levels of transmission intensity. Surveys were conducted in three venue types: primary schools, health facilities, and churches. The sampling approach varied accordingly. Individuals present at the venues at the time of the survey were eligible whether they presented malaria symptoms or not. The participants completed a questionnaire and were tested for Plasmodium falciparum by a highly sensitive rapid diagnostic test (hsRDT). Factors associated with hsRDT positivity were assessed by negative binomial random-effects regression models. RESULTS: Overall, 11,029 individuals were sampled across 39 venues in Artibonite and 41 in Grand'Anse. The targeted sample size per venue type (2100 in Artibonite and 2500 in Grand'Anse) was reached except for the churches in Artibonite, where some attendees left the venue before they could be approached or enrolled. Refusal rate and drop-out rate were < 1%. In total, 50/6003 (0.8%) and 355/5026 (7.1%) sampled individuals were hsRDT positive in Artibonite and Grand'Anse, respectively. Over half of all infections in both regions were identified at health facilities. Being male and having a current or reported fever in the previous 2 weeks were consistently identified with increased odds of being hsRDT positive. CONCLUSIONS: Surveys in churches were problematic because of logistical and recruitment issues. However, EAG surveys in health facilities and primary schools provided granular information about malaria burden within two departments in Haiti. The EAG surveys were able to identify residual foci of transmission that were missed by recent national surveys. Non-care seeking and/or asymptomatic malaria infections can be identified in this alternative surveillance tool, facilitating data-driven decision-making for improved targeting of interventions.

      6. Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysisexternal icon
        Roh ME, Kuile FO, Rerolle F, Glymour MM, Shiboski S, Gosling R, Gutman J, Kakuru A, Desai M, Kajubi R, L'Ianziva A, Kamya MR, Dorsey G, Chico RM.
        Lancet Glob Health. 2020 Jul;8(7):e942-e953.
        BACKGROUND: Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine. METHODS: We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). We quantified the relative effect of treatment on birthweight (primary outcome) attributed to preventing placental malaria infection (mediator). We estimated antimalarial (indirect) and non-malarial (direct) effects of IPTp on birth outcomes using causal mediation analyses, accounting for confounders. We used two-stage individual participant data meta-analyses to calculate pooled-effect sizes. FINDINGS: Overall, birthweight was higher among neonates of women randomly assigned to sulfadoxine-pyrimethamine compared with women assigned to dihydroartemisinin-piperaquine (mean difference 69 g, 95% CI 26 to 112), despite placental malaria infection being lower in the dihydroartemisinin-piperaquine group (relative risk [RR] 0.64, 95% CI 0.39 to 1.04). Mediation analyses showed sulfadoxine-pyrimethamine conferred a greater non-malarial effect than did dihydroartemisinin-piperaquine (mean difference 87 g, 95% CI 43 to 131), whereas dihydroartemisinin-piperaquine conferred a slightly larger antimalarial effect than did sulfadoxine-pyrimethamine (8 g, -9 to 26), although more frequent dosing increased the antimalarial effect (31 g, 3 to 60). INTERPRETATION: IPTp with sulfadoxine-pyrimethamine appears to have potent non-malarial effects on birthweight. Further research is needed to evaluate monthly dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine (or another compound with non-malarial effects) to achieve greater protection against malarial and non-malarial causes of low birthweight. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation, and Worldwide Antimalarial Resistance Network.

    • Physical Activity
      1. Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemiaexternal icon
        Hall KS, Hyde ET, Bassett DR, Carlson SA, Carnethon MR, Ekelund U, Evenson KR, Galuska DA, Kraus WE, Lee IM, Matthews CE, Omura JD, Paluch AE, Thomas WI, Fulton JE.
        Int J Behav Nutr Phys Act. 2020 Jun 20;17(1):78.
        BACKGROUND: Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. METHODS: A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults >/=18 years old; and non-patient populations. RESULTS: Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. CONCLUSIONS: Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.

    • Substance Use and Abuse
      1. Since the ratification of the World Health Organization Framework Convention on Tobacco Control in 2004, Pakistan has made modest but continued progress in implementing various tobacco control measures. By 2014, substantial progress was achieved in areas of monitoring, mass media antitobacco campaigns, and advertising bans. However, the findings from the 2014 Global Adult Tobacco Survey of Pakistan show significant differences in antitobacco campaign exposure among individuals of different educational attainment. Given this large variation in noticing antitobacco information, this paper analyzes how heterogeneity in treatment exposure may differentially impact tobacco-use prevalence across household groups. Household-level tobacco-use prevalence in 2014 was, respectively, 56% and 48% for the low- and high-education households. The gap in tobacco-use prevalence between the two educational groups further widens post 2014. We find that, on average, individuals with higher than primary education are 14 percentage points and 6 percentage points more likely to notice anticigarette and antismokeless tobacco information in 2014, respectively. Subsequently, in 2016, high-education households experienced a 3.6 percentage point higher reduction in tobacco-use prevalence compared to the low-education households. These findings motivate policies to enhance the outreach of tobacco control measures across different educational groups.

      2. Cigarette and electronic vapor product use among high school students in Georgia, 2015-2018external icon
        Ingels JB, Thapa K, Shrestha S, Rajbhandari-Thapa J.
        Prev Med Rep. 2020 ;19.
        Adolescent use of electronic vapor products (EVP) is increasing; however, changes in EVP use in the context of cigarette smoking is less certain. We analyzed trends in EVP and cigarette use among high school students in the state of Georgia. We used self-reported EVP and cigarette use from the annual Georgia Student Health Survey 2.0 for 2015 to 2018 (N = 1,405,108). Users were categorized as exclusive EVP users, exclusive cigarette users, or dual users. We assessed current (≥1 day in past 30 days) use of EVPs, cigarettes, and dual users of both products, as well as number of days the products were used among current users. We compared current users, as well as number of days used, across adjacent years using tests for proportion and Wilcoxon t-tests, respectively. The proportion of current exclusive EVP users and dual users increased during 2017–2018 (4.2% to 6.9% and 1.6% to 3.7%, p < 0.001, respectively) after declining during 2015–2017, while the proportion of exclusive cigarette users declined during 2015–2018 (2.0% to 1.0%, p < 0.001). Similarly, the mean number of days of EVP use increased among exclusive EVP and dual users, and mean number of days of cigarette use increased among dual users during 2017–2018 (p < 0.001). These findings reinforce the importance of continued efforts to reduce all forms of tobacco products use among Georgia high school students.


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