Bullying and cyberbullying are major public health issues affecting youth. One potential protective mechanism within schools is positive school climate. We examine how bullying, cyberbullying, and school climate are associated with substance use, emotional problems, and prosocial behavior using data from 5,143 middle school students and 1,584 educators. We found bullying and cyberbullying experiences are associated with all student outcomes, finding a stronger relationship with cyberbullying for some outcomes. Student perceptions of clear school rules and consequences were consistently protective across all outcomes. Educator’s perceptions of school conflict were associated with more substance use and less prosocial behavior. More research is needed to identify aspects of school climate that may be protective and how schools can promote them. © This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

Teen dating violence (TDV) is a significant public health problem that can have lifelong consequences. Using a longitudinal, cluster randomized controlled trial (RCT), this study examines whether the Dating Matters comprehensive prevention model, implemented in middle school, prevented TDV and negative relationship behaviors and promoted positive relationship behaviors in high school (9th-11th grades), when compared with a standard of care intervention. Dating Matters includes programs for sixth to eighth grade youth and their parents, training for school staff, a youth communications program, and policy and data activities implemented in the community. Self-report survey data were collected from students in 46 middle schools that were randomly assigned to condition within site. Students completed two surveys (fall and spring) in each middle school grade and a single survey in the spring of each high school grade. This study examined self-reported TDV perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills in the high school follow-up. While varying patterns emerged, latent panel models demonstrated significant program effects for all outcomes. Dating Matters students reported 19% reduced risk for TDV perpetration, 24% reduced risk for TDV victimization, 7% reduced risk for use of negative conflict strategies, and 3% more use of positive relationship skills, on average across time and cohort, than standard of care students. On average, Dating Matters, implemented in middle school, continued to be more effective at reducing TDV perpetration, TDV victimization, and use of negative conflict resolution strategies in high school than an evidence-based comparison program.Trial Registration: clinicaltrials.gov Identifier: NCT01672541.

This study describes rates of violence victimization, perpetration, and witnessing in 6th-11th grade for a multisite sample (N = 3,466) of predominantly Black and Hispanic middle- and high-school students from urban areas with high rates of crime and economic disadvantage. Students completed surveys in middle and high school assessing teen dating violence, stalking, sexual violence and harassment, bullying, cyberbullying, and physical violence perpetration and victimization, as well as witnessing violence. The highest prevalence rates are observed most often in 8th or 9th grade. Youth reported high rates of witnessing serious assault and severe community violence throughout adolescence. These findings suggest that efforts to prevent violence among youth living in under-resourced communities need to start early and address community-level socioeconomic disparities.

BACKGROUND: Multiple adverse childhood experiences (ACEs) are associated with poor sexual and mental health outcomes in low- and middle-income countries (LMICs). Less well understood is how discrete and gendered clustering of ACEs may influence health. OBJECTIVE: To assess how multiple ACEs co-occur and how dominant patterns of co-occurrence are associated with mental distress, substance use, and sexual risk behaviors among young women and men in Sub-Saharan Africa. PARTICIPANTS AND SETTING: We used pooled data of young men and women aged 19-24 from comparable, nationally representative Violence Against Children and Youth Surveys (VACS) conducted in Cote d'Ivoire, Kenya, Lesotho, Mozambique, and Namibia (n(f) = 7183; n(m) = 2207). METHODS: We estimated sex-disaggregated latent classes of six ACEs among young women and men. We ran Bolck-Croon-Hagenaars (BCH) distal outcome analysis to test the sex-stratified relationships between ACEs latent classes and health outcomes. RESULTS: A six class solution best fit the female data. Classes included witnessing violence and experiencing physical violence (PV); experiencing PV; high ACEs; witnessing community violence; orphanhood; and low ACEs exposure. Among males, the best-fitting three-class solution included experiencing PV and witnessing community violence; high ACEs; and low ACEs exposure. Membership in the high ACEs class was associated with mental distress among females and males, and substance use among males. No differences in sexual risk behavior were identified by class membership among either females or males. CONCLUSIONS: Discrete clusters of co-occurring ACEs are associated with elevated odds of mental distress among females, and mental distress and substance use among males. Preventing ACEs may improve mental health among young women and men in LMICs in Sub-Saharan Africa.

BACKGROUND: Burden of dementia is expected to substantially increase. Early dementia is underdiagnosed in primary care. Given the benefits of active management of dementia, earlier detection in primary care is imperative. The aim of this study was to understand primary care provider (PCP) perceptions of implementing a cognitive assessment toolkit in primary care. METHODS: PCPs in a large health system in the US were recruited to a qualitative study utilizing semi-structured interviews. Interviews captured provider perceptions of options for implementing a cognitive assessment toolkit derived from the Gerontological Society of America (GSA) KAER (Kickstart, Assess, Evaluate, Refer) toolkit, including a workflow and adapted clinical tools. A content analysis approach distinguished themes and exemplary quotes. RESULTS: Ten PCPs were interviewed. They found the toolkit useful, felt the term Kickstart was not specific to dementia care, and stressed that addressing cognitive evaluation would need to be easy to implement in a clinical workflow. Finally, providers knew many resources for referral but were unsure how to help patients navigate options. CONCLUSIONS: Providers stressed simplicity, ease, and efficiency for implementation of a cognitive assessment toolkit. Incorporating these findings into the development of clinical tools and workflows may increase cognitive evaluations conducted by PCPs.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms.

INTRODUCTION: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. METHODS: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. RESULTS: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus. Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections.

Purpose: Social vulnerability in the context of disaster management refers to the sociodemographic characteristics of a population and the physical, social, economic, and environmental factors that increase their susceptibility to adverse disaster outcomes and capacity to anticipate, cope with, resist, and recover from disaster events. Because disasters do not impact people equally, researchers, public health practitioners, and emergency managers need training to meet the complex needs of vulnerable populations. Design/methodology/approach: To address gaps in current education, the CONVERGE initiative, headquartered at the Natural Hazards Center at the University of Colorado Boulder, developed the Social Vulnerability and Disasters Training Module. This free online course draws on decades of research to examine the factors that influence social vulnerability to disasters. Examples of studies and evidence-based programs are included to illuminate common methods for studying social vulnerability and ways that research can guide practice. To evaluate the module, all trainees completed a pre- and post-training questionnaire. Findings: Between July 2019 and September 2021, 1,089 people completed the module. Wilcoxon signed rank tests demonstrated a significant perceived increase in self-rated knowledge, skills, and attitudes (KSA). Students, members of historically underrepresented populations, and those new to or less experienced in the field, had the greatest perceived increase. Practical implications: This training module can help participants understand the specific needs of socially vulnerable populations to help reduce human suffering from disasters. Originality/value: This article describes a novel web-based training and offers evaluation data showing how it can help educate a broad hazards and disaster workforce on an important topic for disaster management. © 2022, Rachel Marie Adams, Candace Evans, Amy Wolkin, Tracy Thomas and Lori Peek.

BACKGROUND: Nasopharyngeal specimens (NPS) are commonly used for SARS-CoV-2 testing but can be uncomfortable for patients. Self-collected saliva or anterior nasal specimens (ANS) for SARS-CoV-2 detection are less invasive but the sensitivity of these specimen types has not been thoroughly evaluated. METHODS: During September-November 2020, 730 adults undergoing SARS-CoV-2 testing at community testing events and homeless shelters in Denver provided self-collected saliva and ANS specimens before NPS collection and answered a short survey about symptoms and specimen preference. Specimens were tested for SARS-CoV-2 by rRT-PCR; viral culture was performed on a subset of specimens positive by rRT-PCR. Sensitivity of saliva and ANS for SARS-CoV-2 detection by rRT-PCR was measured against NPS. Subgroup analyses included test outcomes by symptom status and culture results. RESULTS: Sensitivity for SARS-CoV-2 detection by rRT-PCR appeared higher for saliva than for ANS (85% vs. 80%) and among symptomatic participants than among those without symptoms (94% vs. 29% for saliva; 87% vs. 50% for ANS). Among participants with culture-positive SARS-CoV-2 by any specimen type, sensitivity of saliva and ANS by rRT-PCR was 94% and 100%, respectively. Saliva and ANS were equally preferred by participants; most would undergo NPS again despite being least preferred. CONCLUSIONS: Saliva was slightly more sensitive than ANS for SARS-CoV-2 detection by rRT-PCR. Both saliva and ANS reliably detected SARS-CoV-2 among participants with symptoms. Self-collected saliva and ANS offer practical advantages, are preferred by patients, and might be most useful for testing people with COVID-19 symptoms.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

In late September 2020, the incidence of confirmed COVID-19* in North Dakota began increasing rapidly, from approximately 300 new cases per day to approximately 2,260 cases on November 13, 2020 (1). On October 20, the North Dakota Department of Health reported that contact tracing notification efforts were delayed. Because of the delay, COVID-19 patients were asked to notify their own contacts about potential exposure and encourage them to seek testing for SARS-CoV-2, the virus that causes COVID-19 (2). The Spirit Lake sovereign nation in east central North Dakota is home to approximately 7,500 members of the Spirit Lake Tribe. In response to increasing incidence of COVID-19 on the Spirit Lake Reservation, CDC assisted the Spirit Lake Tribe in building a tribally managed program for comprehensive COVID-19 case investigations, case notification, contact tracing, contact testing, and contact management to ensure timely implementation of these critical epidemic control measures.

Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.

BACKGROUND: With the rapid development of new advanced molecular detection methods, identification of new genetic mutations conferring pathogen resistance to an ever-growing variety of antimicrobial substances will generate massive genomic datasets for public health and clinical laboratories. Keeping up with specialized standard coding for these immense datasets will be extremely challenging. This challenge prompted our effort to create a common molecular resistance Logical Observation Identifiers Names and Codes (LOINC) panel that can be used to report any identified antimicrobial resistance pattern. OBJECTIVE: To develop and utilize a common molecular resistance LOINC panel for molecular drug susceptibility testing (DST) data exchange in the U.S. National Tuberculosis Surveillance System using California Department of Public Health (CDPH) and New York State Department of Health as pilot sites. METHODS: We developed an interface and mapped incoming molecular DST data to the common molecular resistance LOINC panel using Health Level Seven (HL7) v2.5.1 Electronic Laboratory Reporting (ELR) message specifications through the Orion Health™ Rhapsody Integration Engine v6.3.1. RESULTS: Both pilot sites were able to process and upload/import the standardized HL7 v2.5.1 ELR messages into their respective systems; albeit CDPH identified areas for system improvements and has focused efforts to streamline the message importation process. Specifically, CDPH is enhancing their system to better capture parent-child elements and ensure that the data collected can be accessed seamlessly by the U.S. Centers for Disease Control and Prevention. DISCUSSION: The common molecular resistance LOINC panel is designed to be generalizable across other resistance genes and ideally also applicable to other disease domains. CONCLUSION: The study demonstrates that it is possible to exchange molecular DST data across the continuum of disparate healthcare information systems in integrated public health environments using the common molecular resistance LOINC panel.

BACKGROUND: People experiencing homelessness are at increased risk of coronavirus disease 2019 (COVID-19), but little is known about specific risk factors for infection within homeless shelters. METHODS: We performed widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing and collected risk factor information at all homeless shelters in Chicago with at least 1 reported case of COVID-19 (n = 21). Multivariable, mixed-effects log-binomial models were built to estimate adjusted prevalence ratios (aPRs) for SARS-CoV-2 infection for both individual- and facility-level risk factors. RESULTS: During March 1 to May 1, 2020, 1717 shelter residents and staff were tested for SARS-CoV-2; 472 (27%) persons tested positive. Prevalence of infection was higher for residents (431 of 1435, 30%) than for staff (41 of 282, 15%) (prevalence ratio = 2.52; 95% confidence interval [CI], 1.78-3.58). The majority of residents with SARS-CoV-2 infection (293 of 406 with available information about symptoms, 72%) reported no symptoms at the time of specimen collection or within the following 2 weeks. Among residents, sharing a room with a large number of people was associated with increased likelihood of infection (aPR for sharing with >20 people compared with single rooms = 1.76; 95% CI, 1.11-2.80), and current smoking was associated with reduced likelihood of infection (aPR = 0.71; 95% CI, 0.60-0.85). At the facility level, a higher proportion of residents leaving and returning each day was associated with increased prevalence (aPR = 1.08; 95% CI, 1.01-1.16), whereas an increase in the number of private bathrooms was associated with reduced prevalence (aPR for 1 additional private bathroom per 100 people = 0.92; 95% CI, 0.87-0.98). CONCLUSIONS: We identified a high prevalence of SARS-CoV-2 infections in homeless shelters. Reducing the number of residents sharing dormitories might reduce the likelihood of SARS-CoV-2 infection. When community transmission is high, limiting movement of persons experiencing homelessness into and out of shelters might also be beneficial.

BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. RESULTS: Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. CONCLUSION: Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

The Gulf of Mexico (GoM) region is prone to disasters, including recurrent oil spills, hurricanes, floods, industrial accidents, harmful algal blooms, and the current COVID-19 pandemic. The GoM and other regions of the U.S. lack sufficient baseline health information to identify, attribute, mitigate, and facilitate prevention of major health effects of disasters. Developing capacity to assess adverse human health consequences of future disasters requires establishment of a comprehensive, sustained community health observing system, similar to the extensive and well-established environmental observing systems. We propose a system that combines six levels of health data domains, beginning with three existing, national surveys and studies plus three new nested, longitudinal cohort studies. The latter are the unique and most important parts of the system and are focused on the coastal regions of the five GoM States. A statistically representative sample of participants is proposed for the new cohort studies, stratified to ensure proportional inclusion of urban and rural populations and with additional recruitment as necessary to enroll participants from particularly vulnerable or under-represented groups. Secondary data sources such as syndromic surveillance systems, electronic health records, national community surveys, environmental exposure databases, social media, and remote sensing will inform and augment the collection of primary data. Primary data sources will include participant-provided information via questionnaires, clinical measures of mental and physical health, acquisition of biological specimens, and wearable health monitoring devices. A suite of biomarkers may be derived from biological specimens for use in health assessments, including calculation of allostatic load, a measure of cumulative stress. The framework also addresses data management and sharing, participant retention, and system governance. The observing system is designed to continue indefinitely to ensure that essential pre-, during-, and post-disaster health data are collected and maintained. It could also provide a model/vehicle for effective health observation related to infectious disease pandemics such as COVID-19. To our knowledge, there is no comprehensive, disaster-focused health observing system such as the one proposed here currently in existence or planned elsewhere. Significant strengths of the GoM Community Health Observing System (CHOS) are its longitudinal cohorts and ability to adapt rapidly as needs arise and new technologies develop.

Fluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Varying levels of resistance are associated with specific mutations within the Quinolone Resistance Determining Region (QRDR) of gyrA We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PETTS) with baseline (FQ(R)) or acquired FQ resistance (FQ(ACQR)) using the IonTorrent™ Personal Genome Machine to a depth of 10,000x and reported single nucleotide polymorphisms in ≥1% of reads. FQ(R) isolates harbored 15 distinct alleles with 1.3 (max=6) on average per isolate. Eighteen alleles were identified in FQ(ACQR) isolates with an average of 1.6 (max=9) per isolate. Isolates from 78% of FQ(ACQR) individuals had mutant alleles identified within 6 months of treatment initiation. Asp94Gly followed by Ala90Val were the predominant alleles in initial FQ-resistant isolates. Seventy-seven percent (36/47) of FQ(ACQR) group patients had isolates with FQ resistance alleles prior to changes to the FQ component of their treatment. Unlike individuals treated initially with other FQs, none of the 21 individuals treated initially with levofloxacin developed genotypic or phenotypic FQ resistance, although, country of residence is likely a contributing factor since 69% of these individuals were from a single country. Initial detection of phenotypic and genotypic resistance occurred simultaneously for most; however, phenotypic resistance occurred earlier in isolates harboring mixtures of very low-abundance (<1% of reads) alleles while genotypic resistance often occurred earlier for low-level resistance-associated alleles. Understanding factors influencing acquisition and evolution of FQ resistance could reveal strategies for improved treatment success.

On June 3, 2020, a woman aged 73 years (patient A) with symptoms consistent with coronavirus disease 2019 (COVID-19) (1) was evaluated at the emergency department of the Hopi Health Care Center (HHCC, an Indian Health Services facility) and received a positive test result for SARS-CoV-2, the virus that causes COVID-19. The patient's symptoms commenced on May 27, and a sibling (patient B) of the patient experienced symptom onset the following day. On May 23, both patients had driven together and spent time in a retail store in Flagstaff, Arizona. Because of their similar exposures, symptom onset dates, and overlapping close contacts, these patients are referred to as co-index patients. The co-index patients had a total of 58 primary (i.e., direct) and secondary contacts (i.e., contacts of a primary contact); among these, 27 (47%) received positive SARS-CoV-2 test results. Four (15%) of the 27 contacts who became ill were household members of co-index patient B, 14 (52%) had attended family gatherings, one was a child who might have transmitted SARS-CoV-2 to six contacts, and eight (30%) were community members. Findings from the outbreak investigation prompted the HHCC and Hopi Tribe leadership to strengthen community education through community health representatives, public health nurses, and radio campaigns. In communities with similar extended family interaction, emphasizing safe ways to stay in touch, along with wearing a mask, frequent hand washing, and physical distancing might help limit the spread of disease.

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

INTRODUCTION: Etiology studies of severe acute respiratory infections (SARI) in adults are limited. We studied potential etiologies of SARI among adults in six countries using multi-pathogen diagnostics. METHODS: We enrolled both adults with SARI (acute respiratory illness onset with fever and cough requiring hospitalization) and asymptomatic adults (adults hospitalized with non-infectious illnesses, non-household members accompanying SARI patients, adults enrolled from outpatient departments, and community members) in each country. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from both SARI patients and asymptomatic adults. Specimens were tested for presence of 29 pathogens utilizing the Taqman® Array Card platform. We applied a non-parametric Bayesian regression extension of a partially latent class model approach to estimate proportions of SARI caused by specific pathogens. RESULTS: We enrolled 2,388 SARI patients and 1,135 asymptomatic adults from October 2013 through October 2015. We detected ≥1 pathogen in 76% of SARI patients and 67% of asymptomatic adults. Haemophilus influenzae and Streptococcus pneumoniae were most commonly detected (≥23% of SARI patients and asymptomatic adults). Through modeling, etiology was attributed to a pathogen in most SARI patients (range among countries: 57.3-93.2%); pathogens commonly attributed to SARI etiology included influenza A (14.4-54.4%), influenza B (1.9-19.1%), rhino/enterovirus (1.8-42.6%), and RSV (3.6-14.6%). CONCLUSIONS: Use of multi-pathogen diagnostics and modeling enabled attribution of etiology in most adult SARI patients, despite frequent detection of multiple pathogens in the upper respiratory tract. Seasonal flu vaccination and development of RSV vaccine would likely reduce the burden of SARI in these populations.

Sexual violence (SV), including sexual harassment (SH), is a significant public health problem affecting adolescent health and well-being. This study extends prior research by evaluating the effectiveness of a comprehensive teen dating violence prevention model, Dating Matters, on SV and SH perpetration and victimization, inclusive of any victim-perpetrator relationship, among middle school students. Dating Matters includes classroom-delivered programs for youth in 6th, 7th, and 8th grades; community-based programs for parents; a youth communications program; training for educators; and community-level activities. Middle schools in four urban areas in the USA were randomly assigned to receive Dating Matters (DM, N = 22) or a standard-of-care intervention (SC, N = 24) over four consecutive school years (2012-2016). The analytic sample included two cohorts who entered the study in 6th grade and completed 8th grade by the end of the study allowing for full exposure to Dating Matters (DM: N = 1662; SC: N = 1639; 53% female; 50% black, non-Hispanic; 6 waves of data collection for each cohort). Structural equation modeling was employed with multiple imputation to account for missing data. Dating Matters was associated with significant reductions in SV and SH perpetration and victimization scores in most-but not all-sex/cohort groups by the end of 8th grade relative to an evidence-based TDV prevention program. On average, students receiving Dating Matters scored 6% lower on SV perpetration, 3% lower on SV victimization, 4% lower on SH perpetration, and 8% lower on SH victimization by the end of middle school than students receiving an evidence-based violence prevention program. Overall, Dating Matters shows promise for reducing SV and SH, occurring both within and outside dating relationships, through middle school. Clinicaltrials.gov Identifier: NCT01672541.

Undetected infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) contributes to transmission in nursing homes, settings where large outbreaks with high resident mortality have occurred (1,2). Facility-wide testing of residents and health care personnel (HCP) can identify asymptomatic and presymptomatic infections and facilitate infection prevention and control interventions (3-5). Seven state or local health departments conducted initial facility-wide testing of residents and staff members in 288 nursing homes during March 24-June 14, 2020. Two of the seven health departments conducted testing in 195 nursing homes as part of facility-wide testing all nursing homes in their state, which were in low-incidence areas (i.e., the median preceding 14-day cumulative incidence in the surrounding county for each jurisdiction was 19 and 38 cases per 100,000 persons); 125 of the 195 nursing homes had not reported any COVID-19 cases before the testing. Ninety-five of 22,977 (0.4%) persons tested in 29 (23%) of these 125 facilities had positive SARS-CoV-2 test results. The other five health departments targeted facility-wide testing to 93 nursing homes, where 13,443 persons were tested, and 1,619 (12%) had positive SARS-CoV-2 test results. In regression analyses among 88 of these nursing homes with a documented case before facility-wide testing occurred, each additional day between identification of the first case and completion of facility-wide testing was associated with identification of 1.3 additional cases. Among 62 facilities that could differentiate results by resident and HCP status, an estimated 1.3 HCP cases were identified for every three resident cases. Performing facility-wide testing immediately after identification of a case commonly identifies additional unrecognized cases and, therefore, might maximize the benefits of infection prevention and control interventions. In contrast, facility-wide testing in low-incidence areas without a case has a lower proportion of test positivity; strategies are needed to further optimize testing in these settings.

Candida auris is a difficult to eradicate yeast that has caused outbreaks in healthcare facilities. We report a cluster of five patients in one intensive care unit who were colonized or infected in 2017. The initial two patients were recipients of liver transplants who had cultures that grew C. auris within three days of each other in June 2017 (days 43 and 30 post-transplant). Subsequent screening cultures identified two additional patients with C. auris colonization. Respiratory and urine cultures from a fifth patient yielded C. auris. All isolates were fluconazole-resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from NY/NJ strains, consistent with a separate introduction. However, no source or contact was found. Two of the five patients died. C. auris infection likely contributed to one patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that while severe disease from C. auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C. auris to date.

The national prevalence of employment changes after a cancer diagnosis has not been fully documented. Cancer survivors who worked for pay at or since diagnosis (n = 1,490) were identified from the 2011, 2016 and 2017 Medical Expenditure Panel Survey and Experiences with Cancer Supplements. Analyses characterized employment changes due to cancer and identified correlates of those employment changes. Employment changes were made by 41.3% (95% CI = 38.0% to 44.6%) of cancer survivors, representing over 3.5 million adults in the United States. Of these, 75.4% (95% CI = 71.3 to 79.2%) took extended paid time-off and 46.1% (95% CI = 41.6 to 50.7%) made other changes, including switching to part-time or to a less demanding job. Cancer survivors who were younger, female, non-white or multiple races/ethnicities, and <20 years since last cancer treatment were more likely to make employment changes. Findings highlight the need for patient-provider communication about the effects of cancer and its treatment on employment.

Teen dating violence (TDV) is associated with a variety of delinquent behaviors, such as theft, and health- and delinquency-related risk behaviors, including alcohol use, substance abuse, and weapon carrying. These behaviors may co-occur due to shared risk factors. Thus, comprehensive TDV-focused prevention programs may also impact these other risk behaviors. This study examined the effectiveness of CDC's Dating Matters(R): Strategies to Promote Healthy Teen Relationships (Dating Matters) comprehensive TDV prevention model compared to a standard-of-care condition on health- and delinquency-related risk behaviors among middle school students. Students (N = 3301; 53% female; 50% black, non-Hispanic; and 31% Hispanic) in 46 middle schools in four sites across the USA were surveyed twice yearly in 6th, 7th, and 8th grades. A structural equation modeling framework with multiple imputation to account for missing data was utilized. On average over time, students receiving Dating Matters scored 9% lower on a measure of weapon carrying, 9% lower on a measure of alcohol and substance abuse, and 8% lower on a measure of delinquency by the end of middle school than students receiving an evidence-based standard-of-care TDV prevention program. Dating Matters demonstrated protective effects for most groups of students through the end of middle school. These results suggest that this comprehensive model is successful at preventing risk behaviors associated with TDV. clinicaltrials.gov Identifier: NCT01672541.

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 multi-country prospective cohort study of MDR-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 January 2005-December 2008 from seven 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 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.

Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. We performed analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR-HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR-HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens.