We reviewed the available evidence on psychosocial treatments for disruptive behaviors in children, as an update to Kaminski and Claussen (2017), focusing on children up to age 12 years. Search strategies, study inclusion, and treatment classification followed the procedures developed by Southam-Gerow and Prinstein (2014). Of the 44 included studies from 2016 to 2021, only 9 impacted previous results, either by increasing the level of evidence (for two treatment families) or documenting evidence for a new treatment family (four new treatment families). All three treatment families classified as Level 1: Well Established are parent-focused and now include Group parent behavior therapy + group child behavior therapy (previously classified as Probably Efficacious), in addition to Group parent behavior therapy and Individual parent behavior therapy with child participation (already classified as Well Established). Fifteen treatment families were classified as Level 2: Probably Efficacious, eight were classified as Level 3: Possibly Efficacious. Given the variability of programs in each treatment family, the evidence is for the overall treatment approach and may not apply to each program with those characteristics. Data were insufficient to examine outcomes in relation to participant characteristics. The information can be used to improve dissemination, implementation, and uptake of effective treatment, and inform research on improving access barriers.

Adolescent mental health and suicide risk remain substantial public health concerns. High pre-COVID rates of poor mental health and suicide-related behaviors have continued to rise, highlighting the need to identify factors that might foster positive mental health outcomes and reduce suicide-related behaviors at population levels. Using CDC's 2023 Youth Risk Behavior Survey, CDC analyzed the prevalence of mental health and suicide risk indicators and their associations with individual-, family-, and school- or community-level protective factors. Prevalence estimates were calculated for each of the mental health and suicide risk indicators by demographic characteristic. Prevalence ratios adjusted for sex, sexual identity, grade, and race and ethnicity were calculated to examine the association between protective factors and mental health and suicide risk indicators. Overall, 39.7% of students experienced persistent feelings of sadness and hopelessness, 28.5% experienced poor mental health, 20.4% seriously considered attempting suicide, and 9.5% had attempted suicide. Mental health and suicide risk indicators differed by sex, sexual identity, grade, and race and ethnicity. All protective factors were associated with lower prevalence of one or more risk indicators. Findings from this report can serve as a foundation for the advancement of research on protective factors and for the development and implementation of programs, practices, and policies that protect and promote mental health and emotional well-being among youth.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.

Youths have experienced disruptions to school and home life since the COVID-19 pandemic began in March 2020. During January-June 2021, CDC conducted the Adolescent Behaviors and Experiences Survey (ABES), an online survey of a probability-based, nationally representative sample of U.S. public- and private-school students in grades 9-12 (N = 7,705). ABES data were used to estimate the prevalence of disruptions and adverse experiences during the pandemic, including parental and personal job loss, homelessness, hunger, emotional or physical abuse by a parent or other adult at home, receipt of telemedicine, and difficulty completing schoolwork. Prevalence estimates are presented for all students and by sex, race and ethnicity, grade, sexual identity, and difficulty completing schoolwork. Since the beginning of the pandemic, more than half of students found it more difficult to complete their schoolwork (66%) and experienced emotional abuse by a parent or other adult in their home (55%). Prevalence of emotional and physical abuse by a parent or other adult in the home was highest among students who identified as gay, lesbian, or bisexual (74% emotional abuse and 20% physical abuse) and those who identified as other or questioning (76% and 13%) compared with students who identified as heterosexual (50% and 10%). Overall, students experienced insecurity via parental job loss (29%), personal job loss (22%), and hunger (24%). Disparities by sex and by race and ethnicity also were noted. Understanding health disparities and student disruptions and adverse experiences as interconnected problems can inform school and community initiatives that promote adolescent health and well-being. With community support to provide coordinated, cross-sector programming, schools can facilitate linkages to services that help students address the adverse experiences that they faced during the ongoing COVID-19 pandemic. Public health and health care professionals, communities, schools, families, and adolescents can use these findings to better understand how students' lives have been affected during the pandemic and what challenges need to be addressed to promote adolescent health and well-being during and after the pandemic.

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June-September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

CONTEXT: Public health policy can play an important role in improving public health outcomes. Accordingly, there has been an increasing emphasis by policy makers on identifying and implementing evidence-informed public health policy interventions. PROGRAM OR POLICY: Growth and refinement of the field of research assessing the impact of legal interventions on health outcomes, known as legal epidemiology, prompted this review of studies on the relationship between laws and health or economic outcomes. IMPLEMENTATION: Authors systematically searched 8 major literature databases for all English language journal articles that assessed the effect of a law on health and economic outcomes published between January 1, 2009, and September 18, 2019. This search generated 12 570 unique articles 177 of which met inclusion criteria. The team conducting the systematic review was a multidisciplinary team that included health economists and public health policy researchers, as well as public health lawyers with expertise in legal epidemiological research methods. The authors identified and assessed the types of methods used to measure the laws' health impact. EVALUATION: In this review, the authors examine how legal epidemiological research methods have been described in the literature as well as trends among the studies. Overall, 3 major themes emerged from this study: (1) limited variability in the sources of the health data across the studies, (2) limited differences in the methodological approaches used to connect law to health outcomes, and (3) lack of transparency surrounding the source and quality of the legal data relied upon. DISCUSSION: Through highlighting public health law research methodologies, this systematic review may inform researchers, practitioners, and lawmakers on how to better examine and understand the impacts of legal interventions on health and economic outcomes. Findings may serve as a source of suggested practices in conducting legal epidemiological outcomes research and identifying conceptual and method-related gaps in the literature.

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naϊeve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets. In this paper, we present fast and scalable k-mer-based framework to perform such sequence similarity queries efficiently, which specifically targets data produced by deep sequencing of heterogeneous populations such as viruses. The tool is freely available for download at https://github.com/vyacheslav-tsivina/signature-sj

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply(†) (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.(§) To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men(¶) aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection(††) (5).

On May 17, 2022, the Massachusetts Department of Health announced the first suspected case of monkeypox associated with the global outbreak in a U.S. resident. On May 23, 2022, CDC launched an emergency response (1,2). CDC's emergency response focused on surveillance, laboratory testing, medical countermeasures, and education. Medical countermeasures included rollout of a national JYNNEOS vaccination strategy, Food and Drug Administration (FDA) issuance of an emergency use authorization to allow for intradermal administration of JYNNEOS, and use of tecovirimat for patients with, or at risk for, severe monkeypox. During May 17-October 6, 2022, a total of 26,384 probable and confirmed* U.S. monkeypox cases were reported to CDC. Daily case counts peaked during mid-to-late August. Among 25,001 of 25,569 (98%) cases in adults with information on gender identity,(†) 23,683 (95%) occurred in cisgender men. Among 13,997 cisgender men with information on recent sexual or close intimate contact,(§) 10,440 (75%) reported male-to-male sexual contact (MMSC) ≤21 days preceding symptom onset. Among 21,211 (80%) cases in persons with information on race and ethnicity,(¶) 6,879 (32%), 6,628 (31%), and 6,330 (30%) occurred in non-Hispanic Black or African American (Black), Hispanic or Latino (Hispanic), and non-Hispanic White (White) persons, respectively. Among 5,017 (20%) cases in adults with information on HIV infection status, 2,876 (57%) had HIV infection. Prevention efforts, including vaccination, should be prioritized among persons at highest risk within groups most affected by the monkeypox outbreak, including gay, bisexual, and other men who have sex with men (MSM); transgender, nonbinary, and gender-diverse persons; racial and ethnic minority groups; and persons who are immunocompromised, including persons with advanced HIV infection or newly diagnosed HIV infection.

The Centers for Disease Control and Prevention's (CDC) Division of Adolescent and School Health (DASH) works with local decision makers, schools, youth-serving organizations, and parents across the nation to equip youth with knowledge, skills, and resources needed for healthy adolescence and adulthood. Aligned with this effort, DASH maintains high-quality surveillance systems to understand youth health behaviors and assess school health programs and policies. The Youth Risk Behavior Surveillance System (YRBSS) is a system of surveys administered every other year to high school students. In addition to the national Youth Risk Behavior Survey conducted by CDC, YRBSS features Youth Risk Behavior Surveys (YRBS) conducted by state, territorial, and local education and health agencies and tribal governments across the nation.1 Local decision makers collaborate with partners to develop questionnaires for their respective YRBS, then coordinate data dissemination and utilization. Since its inception in 1991, YRBSS has collected data from more than 5 million high school students in approximately 2200 separate surveys across the United States.1 The School Health Profiles (Profiles) is a system of surveys conducted by state, territorial, and local education and health agencies and tribal governments. These surveys collect data every other year from principals and lead health education teachers to assess school-implemented health programs and policies.2 Since 1994, Profiles data have helped evaluate health programs and informed professional development needs for educators in middle and high schools.2 Together, YRBSS and Profiles offer metrics to inform public health needs, which are then translated into evidence-based programs to protect youth.

Human monkeypox is caused by Monkeypox virus (MPXV), an Orthopoxvirus, previously rare in the United States (1). The first U.S. case of monkeypox during the current outbreak was identified on May 17, 2022 (2). As of September 28, 2022, a total of 25,341 monkeypox cases have been reported in the United States.* The outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexposure prophylaxis (PEP) for persons with known exposures to MPXV began in May 2022. A U.S. national vaccination strategy(†) for expanded PEP, announced on June 28, 2022, recommended subcutaneous vaccination of persons with known or presumed exposure to MPXV, broadening vaccination eligibility. FDA emergency use authorization (EUA) of intradermal administration of 0.1 mL of JYNNEOS on August 9, 2022, increased vaccine supply (5). As of September 28, 2022, most vaccine has been administered as PEP or expanded PEP. Because of the limited amount of time that has elapsed since administration of initial vaccine doses, as of September 28, 2022, relatively few persons in the current outbreak have completed the recommended 2-dose series.(§) To examine the incidence of monkeypox among persons who were unvaccinated and those who had received ≥1 JYNNEOS vaccine dose, 5,402 reported monkeypox cases occurring among males(¶) aged 18-49 years during July 31-September 3, 2022, were analyzed by vaccination status across 32 U.S. jurisdictions.** Average monkeypox incidence (cases per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine ≥14 days earlier. Monitoring monkeypox incidence by vaccination status in timely surveillance data might provide early indications of vaccine-related protection that can be confirmed through other well-controlled vaccine effectiveness studies. This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series.

Lesbian, gay, and bisexual (LGB) adolescents are often at higher risk than their heterosexual peers for adverse sexual health, violence, mental health, and substance use outcomes. Schools are a vital resource for enhancing protective behaviors and reducing risk behaviors. Sixteen school districts selected schools to implement a sexual health program (exposed) or usual programming (unexposed). We analyzed LGB student health outcomes using 2015 and 2017 Youth Risk Behavior Surveys. Analyses compared LGB student health outcomes by exposure status across time points using a multilevel approach. Program exposure was associated with decreased odds of ever having sex, ever testing for HIV, and using effective hormonal birth control, and an increased odds of condom use. There were no significant findings among secondary violence, mental health, and substance use outcomes. This evaluation highlights the potential for schools to reduce sexual risk behaviors among LGB youth, and opportunities to improve access to health services.

INTRODUCTION: Improving access to naloxone is an important public health strategy in the U.S. This study examines the state-level trends in naloxone dispensing from 2012 to 2019 for all 50 states and the District of Columbia. METHODS: Data from IQVIA Xponent were used to examine the trends and geographic inequality in annual naloxone dispensing rates and the number of naloxone prescriptions dispensed per high-dose opioid prescription from 2012 to 2019 and from 2016 to 2019 to correspond with the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain release. Annual percentage change was estimated using linear regression. Analyses were conducted in 2020. RESULTS: Naloxone dispensing rates and the number of naloxone prescriptions per 100 high-dose opioid prescriptions increased from 2012 to 2019 across all states and the District of Columbia. Average state-level naloxone dispensing rates increased from 0.55 per 100,000 population in 2012 to 45.60 in 2016 and 292.31 in 2019. Similarly, the average number of naloxone prescriptions per 100 high-dose opioid prescriptions increased from 0.002 in 2012 to 0.24 in 2016 and 3.04 in 2019. Across both measures of naloxone dispensing, the geographic inequality gap increased during the study period. In 2019, the number of naloxone prescriptions dispensed per 100 high-dose opioid prescriptions ranged from 1.04 to 16.64 across states. CONCLUSIONS: Despite increases in naloxone dispensing across all states, dispensing rates remain low, with substantial variation and increasing disparities over time at the state level. This information may be helpful in efforts to improve naloxone access and in designing state-specific intervention programs.

Violence is a leading cause of death for youths aged 10 to 24 years in the United States.1 Consequently, violence among youths presents urgent challenges for communities. To address these, it can help to interrogate researchers’ understanding of interpersonal violence and how it influences the levers of change we identify when developing community-level violence-prevention strategies. In practice, this requires a shift in focus, from the individual behaviors traditionally recognized as violence to the social and structural determinants underlying interpersonal violence.2,3 Youth voices critically inform this process. In addition to assessing the youth perspective, it is vital to meaningfully engage youths in violence prevention and evaluate such efforts. | | For 20 years, the Centers for Disease Control and Prevention’s (CDC’s) Youth Violence Prevention Centers (YVPCs; https://bit.ly/36WRDgU) have engaged in academic–community collaborations for youth violence prevention. Currently focused on community-level strategies, these efforts have benefitted from youths who are from communities affected by violence. As they work alongside researchers as well as community, government and business leaders, YVPC-engaged youths provide expertise derived from their lived experience and other skillsets to develop violence-prevention strategies. They have been instrumental in shifting narratives about violence, leading equitable youth engagement, and influencing power entities to protect and uplift their communities.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions(†) (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need(§) (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs(¶) to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.

Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management.

The zoonotic disease anthrax is endemic to most continents. It is a disease of herbivores that incidentally infects humans through contact with animals that are ill or have died from anthrax or through contact with Bacillus anthracis-contaminated byproducts. In the United States, human risk is primarily associated with handling carcasses of hoofstock that have died of anthrax; the primary risk for herbivores is ingestion of B. anthracis spores, which can persist in suitable alkaline soils in a corridor from Texas through Montana. The last known naturally occurring human case of cutaneous anthrax associated with livestock exposure in the United States was reported from South Dakota in 2002. Texas experienced an increase of animal cases in 2019 and consequently higher than usual human risk. We describe the animal outbreak that occurred in southwest Texas beginning in June 2019 and an associated human case. Primary prevention in humans is achieved through control of animal anthrax.

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (beta-D-N(4)-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

From July 2009 to June 2018, the rates of multiple-victim, school-associated homicides in the United States fluctuated substantially, with evidence of a significant increase in recent years (1). Data on the effects of such incidents on students' school attendance and perceptions of safety and connectedness are limited (2,3) but important. This study used data from a neighboring within-district school before and after a multiple-fatality shooting at Marjory Stoneman Douglas High School in Parkland, Florida, on February 14, 2018. Self-administered questionnaires were completed by one group of students on February 14 just before the shooting (575) and another group during February 15-21 (502); demographics for these groups appeared similar. Linear and logistic regression analyses controlling for demographic characteristics explored differences between groups for safety-related perceptions or experiences, school connectedness, and absenteeism. Compared with students surveyed before the shooting, students surveyed in the days immediately following the shooting had lower odds of feeling safe at school, higher odds of absenteeism, and higher school connectedness scores. Findings suggest the shooting had an immediate, sizeable effect on safety perceptions and absenteeism among students in a neighboring school. Findings also suggest higher school connectedness following the shooting. Further study of school connectedness, including how to enhance and sustain it, might help schools and communities better respond to traumatic events in the community.

As evidence-based interventions (EBIs) to prevent mental, emotional, and behavioral health problems continue to become available, approaches for implementation in systems and settings, at scale, are needed. The article, Scaling-up Evidence-based Interventions in U.S. Public Systems to Prevent Behavioral Health Problems: Challenges and Opportunities (Fagan et al. 2019) examines five large, complex public systems (behavioral health, child welfare, education, juvenile justice, and public health) that have adopted and implemented EBIs in various ways and presents common factors that support scale-up in these systems. This commentary builds on the authors' strategic approach to offer a few additional considerations-issues of sustainability, ways of thinking about knowledge creation, and use of systems science/modeling approaches-to address scale-up in public systems. Moreover, the focus on public systems provides an opportunity to consider how the implementation and sustainment of EBIs might more directly address social determinants of health that are relevant across policy areas and public systems.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis was used to qualitatively and quantitatively assess the distribution of permethrin insecticide on the surfaces and interiors of Olyset long-lasting insecticidal net (LLIN) fibers. Total insecticide content in LLINs has been established using many analytical methods. However, it is important to quantify the bioavailable portion residing on the fiber surfaces for incorporated LLINs. ToF-SIMS is a very surface sensitive technique and can directly image the spatial distribution of permethrin insecticide on the surface of Olyset fibers. Surface permethrin appeared as patchy deposits which were easily removed by acetone and reappeared after several days as interior permethrin migrated (bloomed) from the fiber interior. After a wash/incubation cycle, permethrin deposits were more diffuse and less concentrated than those on the as-received fibers. ToF-SIMS is particularly sensitive to detect the Cl- ion, which is the characteristic ion of permethrin. Ion implantation and quantification of dopants using SIMS is well established in the semiconductor industry. In this study, quantitative depth profiling was carried out using 35Cl- ion implantation to correlate secondary ion yield with permethrin concentration, yielding a limit of detection of 0.051 wt% for permethrin. In some cases, surface concentration differed greatly from the fiber interior (>1 mum below the surface). Two- and three-dimensional mapping of Cl at sub-micrometer resolution showed permethrin to be dissolved throughout the fiber, with about 2 vol% residing in disperse, high-concentration domains. This suggests that these fibers fall into the class of monolithic sustained-release devices. It is expected that ToF-SIMS can be a valuable tool to provide insight into the insecticide release behavior of other LLIN products, both current and future.

BACKGROUND: Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naieve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets. RESULTS: In this paper, we present fast and scalable k-mer-based framework to perform such sequence similarity queries efficiently, which specifically targets data produced by deep sequencing of heterogeneous populations such as viruses. It shows better filtering quality and time performance when comparing to other tools. The tool is freely available for download at https://github.com/vyacheslav-tsivina/signature-sj CONCLUSION: The proposed tool allows for efficient detection of genetic relatedness between genomic samples produced by deep sequencing of heterogeneous populations. It should be especially useful for analysis of relatedness of genomes of viruses with unevenly distributed variable genomic regions, such as HIV and HCV. For the future we envision, that besides applications in molecular epidemiology the tool can also be adapted to immunosequencing and metagenomics data.

BACKGROUND: Molecular surveillance and outbreak investigation are important for elimination of hepatitis C virus (HCV) infection in the United States. A web-based system, Global Hepatitis Outbreak and Surveillance Technology (GHOST), has been developed using Illumina MiSeq-based amplicon sequence data derived from the HCV E1/E2-junction genomic region to enable public health institutions to conduct cost-effective and accurate molecular surveillance, outbreak detection and strain characterization. However, as there are many factors that could impact input data quality to which the GHOST system is not completely immune, accuracy of epidemiological inferences generated by GHOST may be affected. Here, we analyze the data submitted to the GHOST system during its pilot phase to assess the nature of the data and to identify common quality concerns that can be detected and corrected automatically. RESULTS: The GHOST quality control filters were individually examined, and quality failure rates were measured for all samples, including negative controls. New filters were developed and introduced to detect primer dimers, loss of specimen-specific product, or short products. The genotyping tool was adjusted to improve the accuracy of subtype calls. The identification of "chordless" cycles in a transmission network from data generated with known laboratory-based quality concerns allowed for further improvement of transmission detection by GHOST in surveillance settings. Parameters derived to detect actionable common quality control anomalies were incorporated into the automatic quality control module that rejects data depending on the magnitude of a quality problem, and warns and guides users in performing correctional actions. The guiding responses generated by the system are tailored to the GHOST laboratory protocol. CONCLUSIONS: Several new quality control problems were identified in MiSeq data submitted to GHOST and used to improve protection of the system from erroneous data and users from erroneous inferences. The GHOST system was upgraded to include identification of causes of erroneous data and recommendation of corrective actions to laboratory users.

Human immunodeficiency virus (HIV) infection is rising as a leading cause of morbidity and mortality among hepatitis C virus (HCV)-infected patients. Both viruses interact in co-infected hosts, which may affect their intra-host evolution, potentially leading to differing genetic composition of viral populations in co-infected (CIP) and mono-infected (MIP) patients. Here, we investigate genetic differences between intra-host variants of the HCV hypervariable region 1 (HVR1) sampled from CIP and MIP. Nucleotide (nt) sequences of intra-host HCV HVR1 variants (N=28,622) obtained from CIP (N=112) and MIP (n=176) were represented using 148 physical-chemical (PhyChem) indexes of DNA nt dimers. Significant (p<.0001) differences in the means and frequency distributions of 7 PhyChem properties were found between HVR1 variants from both groups. Linear projection analysis of 29 PhyChem features extracted from such PhyChem properties showed that the CIP and MIP HVR1 variants have a distinct distribution in the modeled 2D-space, with only ~1.3% of PhyChem profiles (N=6782), shared by all HVR1 variants, being found in both groups. Probabilistic neural network (PNN) and naive Bayesian (NB) classifiers trained on the PhyChem features accurately classified HVR1 variants by the group in cross-validation experiments (AUROC>/=0.96). Similarly, both models showed a high accuracy (AUROC>/=0.95) when evaluated on a test dataset of HVR1 sequences obtained from 10 patients, data from whom were not used for model building. Both models performed at the expected lower accuracy on randomly labeled datasets in cross-validation experiments (AUROC=0.50). The random-label trained PNN showed a similar drop in accuracy on the test dataset (AUROC=0.48), indicating that the detected associations were unlikely due to random correlations. Marked differences in genetic composition of HCV HVR1 variants sampled from CIP and MIP suggest differing intra-host HCV evolution in the presence of HIV infection. PhyChem features identified here may be used for detection of HIV infection from intra-host HCV variants alone in co-infected patients, thus facilitating monitoring for HIV introduction to high-risk populations with high HCV prevalence.

BACKGROUND: Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections associated with unsafe injection practices, drug diversion, and other exposures to blood are difficult to detect and investigate. Effective HCV outbreak investigation requires comprehensive surveillance and robust case investigation. We previously developed and validated a methodology for the rapid and cost-effective identification of HCV transmission clusters. Global Hepatitis Outbreak and Surveillance Technology (GHOST) is a cloud-based system enabling users, regardless of computational expertise, to analyze and visualize transmission clusters in an independent, accurate and reproducible way. RESULTS: We present and explore performance of several GHOST implemented algorithms using next-generation sequencing data experimentally obtained from hypervariable region 1 of genetically related and unrelated HCV strains. GHOST processes data from an entire MiSeq run in approximately 3 h. A panel of seven specimens was used for preparation of six repeats of MiSeq libraries. Testing sequence data from these libraries by GHOST showed a consistent transmission linkage detection, testifying to high reproducibility of the system. Lack of linkage among genetically unrelated HCV strains and constant detection of genetic linkage between HCV strains from known transmission pairs and from follow-up specimens at different levels of MiSeq-read sampling indicate high specificity and sensitivity of GHOST in accurate detection of HCV transmission. CONCLUSIONS: GHOST enables automatic extraction of timely and relevant public health information suitable for guiding effective intervention measures. It is designed as a virtual diagnostic system intended for use in molecular surveillance and outbreak investigations rather than in research. The system produces accurate and reproducible information on HCV transmission clusters for all users, irrespective of their level of bioinformatics expertise. Improvement in molecular detection capacity will contribute to increasing the rate of transmission detection, thus providing opportunity for rapid, accurate and effective response to outbreaks of hepatitis C. Although GHOST was originally developed for hepatitis C surveillance, its modular structure is readily applicable to other infectious diseases. Worldwide availability of GHOST for the detection of HCV transmissions will foster deeper involvement of public health researchers and practitioners in hepatitis C outbreak investigation.

BACKGROUND: Black persons have an excess burden of cardiovascular disease (CVD) compared with white persons. This burden persists after adjustment for socioeconomic status and other known CVD risk factors. This study evaluated the CVD burden and the socioeconomic gradient of CVD among black participants in the JHS (Jackson Heart Study). METHODS AND RESULTS: CVD burden was evaluated by comparing the observed prevalence of myocardial infarction, stroke, and hypertension in the JHS at baseline (2000-2004) with the expected prevalence according to US national surveys during a similar time period. The socioeconomic gradient of CVD was evaluated using logistic regression models. Compared with the national data, the JHS age- and sex-standardized prevalence ratios for myocardial infarction, stroke, and hypertension were 1.07 (95% CI, 0.90-1.27), 1.46 (95% CI, 1.18-1.78), and 1.51 (95% CI, 1.42-1.60), respectively, in men and 1.50 (95% CI, 1.27-1.76), 1.33 (95% CI, 1.12-1.57), and 1.43 (95% CI, 1.37-1.50), respectively, in women. A significant and inverse relationship was observed between socioeconomic status and CVD within the JHS cohort. The strongest and most consistent socioeconomic correlate after adjusting for age and sex was income for myocardial infarction (odds ratio: 3.53; 95% CI, 2.31-5.40) and stroke (odds ratio: 3.73; 95% CI, 2.32-5.97), comparing the poor and affluent income categories. CONCLUSIONS: Except for myocardial infarction in men, CVD burden in the JHS cohort was higher than expected. A strong inverse socioeconomic gradient of CVD was also observed within the JHS cohort.

BACKGROUND: Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections associated with unsafe injection practices, drug diversion, and other exposures to blood are difficult to detect and investigate. Molecular analysis has been frequently used in the study of HCV outbreaks and transmission chains; helping identify a cluster of sequences as linked by transmission if their genetic distances are below a previously defined threshold. However, HCV exists as a population of numerous variants in each infected individual and it has been observed that minority variants in the source are often the ones responsible for transmission, a situation that precludes the use of a single sequence per individual because many such transmissions would be missed. The use of Next-Generation Sequencing immensely increases the sensitivity of transmission detection but brings a considerable computational challenge because all sequences need to be compared among all pairs of samples. METHODS: We developed a three-step strategy that filters pairs of samples according to different criteria: (i) a k-mer bloom filter, (ii) a Levenhstein filter and (iii) a filter of identical sequences. We applied these three filters on a set of samples that cover the spectrum of genetic relationships among HCV cases, from being part of the same transmission cluster, to belonging to different subtypes. RESULTS: Our three-step filtering strategy rapidly removes 85.1% of all the pairwise sample comparisons and 91.0% of all pairwise sequence comparisons, accurately establishing which pairs of HCV samples are below the relatedness threshold. CONCLUSIONS: We present a fast and efficient three-step filtering strategy that removes most sequence comparisons and accurately establishes transmission links of any threshold-based method. This highly efficient workflow will allow a faster response and molecular detection capacity, improving the rate of detection of viral transmissions with molecular data.