Although humoral immunity is essential for control of SARS-CoV-2, the molecular composition, binding epitopes and effector functions of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following infection are unknown. Proteomic deconvolution of the circulating IgG repertoire (Ig-Seq (1) ) to the spike ectodomain (S-ECD (2) ) in four convalescent study subjects revealed that the plasma response is oligoclonal and directed predominantly (>80%) to S-ECD epitopes that lie outside the receptor binding domain (RBD). When comparing antibodies directed to either the RBD, the N-terminal domain (NTD) or the S2 subunit (S2) in one subject, just four IgG lineages (1 anti-S2, 2 anti-NTD and 1 anti-RBD) accounted for 93.5% of the repertoire. Although the anti-RBD and one of the anti-NTD antibodies were equally potently neutralizing in vitro , we nonetheless found that the anti-NTD antibody was sufficient for protection to lethal viral challenge, either alone or in combination as a cocktail where it dominated the effect of the other plasma antibodies. We identified in vivo protective plasma anti-NTD antibodies in 3/4 subjects analyzed and discovered a shared class of antibodies targeting the NTD that utilize unmutated or near-germline IGHV1-24, the most electronegative IGHV gene in the human genome. Structural analysis revealed that binding to NTD is dominated by interactions with the heavy chain, accounting for 89% of the entire interfacial area, with germline residues uniquely encoded by IGHV1-24 contributing 20% (149 Å (2) ). Together with recent reports of germline IGHV1-24 antibodies isolated by B-cell cloning (3,4) our data reveal a class of shared IgG antibodies that are readily observed in convalescent plasma and underscore the role of NTD-directed antibodies in protection against SARS-CoV-2 infection.

Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

There is widespread recognition that the world of work is changing, and agreement is growing that the occupational safety and health (OSH) field must change to contribute to the protection of workers now and in the future. Discourse on the evolution of OSH has been active for many decades, but formalized support of an expanded focus for OSH has greatly increased over the past 20 years. Development of approaches such as the National Institute for Occupational Safety and Health (NIOSH)'s Total Worker Health(®) concept and the World Health Organization (WHO)'s Healthy Workplace Framework are concrete examples of how OSH can incorporate a new focus with a wider view. In 2019, NIOSH initiated a multi-year effort to explore an expanded focus for OSH. This paper is a report on the outputs of a three-year cooperative agreement between NIOSH and The University of Texas School of Public Health, which led to subject matter expert workshops in 2020 and an international conference of global interest groups in 2021. This article traces the background of these meetings and identifies and assesses the lessons learned. It also reviews ten thematic topics that emerged from the meetings: worker health inequalities; training new OSH professionals; future OSH research and practice; tools to measure well-being of workers; psychosocial hazards and adverse mental health effects; skilling, upskilling and improving job quality; socioeconomic influences; climate change; COVID-19 pandemic influences; and strategic foresight. Cross-cutting these themes is the need for systems and transdisciplinary thinking and operationalization of the concept of well-being to prepare the OSH field for the work of the future.

OBJECTIVE: This study describes characteristics of large tuberculosis (TB) outbreaks in the United States detected using novel molecular surveillance methods during 2014-2016 and followed for 2 years through 2018. METHODS: We developed 4 genotype-based detection algorithms to identify large TB outbreaks of ≥10 cases related by recent transmission during a 3-year period. We used whole-genome sequencing and epidemiologic data to assess evidence of recent transmission among cases. RESULTS: There were 24 large outbreaks involving 518 cases; patients were primarily U.S.-born (85.1%) racial/ethnic minorities (84.1%). Compared with all other TB patients, patients associated with large outbreaks were more likely to report substance use, homelessness, and having been diagnosed while incarcerated. Most large outbreaks primarily occurred within residences among families and nonfamilial social contacts. A source case with a prolonged infectious period and difficulties in eliciting contacts were commonly reported contributors to transmission. CONCLUSION: Large outbreak surveillance can inform targeted interventions to decrease outbreak-associated TB morbidity.

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is often asymptomatic or results in only mild disease.1 Data on the extent of transmission of SARS-CoV-2 from children and adolescents in the household setting, including transmission to older persons who are at increased risk for severe disease, are limited.2 After an outbreak of coronavirus disease 2019 (Covid-19) at an overnight camp,3 we conducted a retrospective cohort study involving camp attendees and their household contacts to assess secondary transmission and factors associated with household transmission (additional details are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2-69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation. Code available at: https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171.

Growth of the information economy and globalization of labor markets will be marked by exponential growth in emerging technologies that will cause considerable disruption of the social and economic sectors that drive the global job market. These disruptions will alter the way we work, where we work, and will be further affected by the changing demographic characteristics and level of training of the available workforce. These changes will likely result in scenarios where existing workplace hazards are exacerbated and new hazards with unknown health effects are created. The pace of these changes heralds an urgent need for a proactive approach to understand the potential effects new and emerging workplace hazards will have on worker health, safety, and well-being. As employers increasingly rely on non-standard work arrangements, research is needed to better understand the work organization and employment models that best support decent work and improved worker health, safety, and well-being. This need has been made more acute by the SARS-CoV-2 global pandemic that has resulted in dramatic changes in employment patterns, millions of lost jobs, an erosion of many economic sectors, and widespread disparities which further challenge occupational safety and health (OSH) systems to ensure a healthy and productive workplace. To help identify new research approaches to address OSH challenges in the future, a virtual workshop was organized in June 2020 with leading experts in the fields of OSH, well-being, research methods, mental health, economics, and life-course analysis. A paradigm shift will be needed for OSH research in the future of work that embraces key stakeholders and thinks differently about research that will improve lives of workers and enhance enterprise success. A more transdisciplinary approach to research will be needed that integrates the skills of traditional and non-traditional OSH research disciplines, as well as broader research methods that support the transdisciplinary character of an expanded OSH paradigm. This article provides a summary of the presentations, discussion, and recommendations that will inform the agenda of the Expanded Focus for Occupational Safety and Health (Ex4OSH) International Conference, planned for December 2021.

The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.

OBJECTIVES: Persons experiencing homelessness (PEH) are disproportionately affected by tuberculosis (TB). We estimate area-specific rates of TB among PEH and characterize the extent to which available data support recent transmission as an explanation of high TB incidence. METHODS: We estimated TB incidence among PEH using National Tuberculosis Surveillance System data and population estimates for the US Department of Housing and Urban Development's Continuums of Care areas. For areas with TB incidence higher than the national average among PEH, we estimated recent transmission using genotyping and a plausible source-case method. For cases with ≥1 plausible source case, we assessed with TB program partners whether available whole-genome sequencing and local epidemiologic data were consistent with recent transmission. RESULTS: During 2011-2016, 3164 TB patients reported experiencing homelessness. National incidence was 36 cases/100,000 PEH. Incidence estimates varied among 21 areas with ≥10,000 PEH (9-150 cases/100,000 PEH); 9 areas had higher than average incidence. Of the 2349 cases with Mycobacterium tuberculosis genotyping results, 874 (37%) had ≥1 plausible source identified. In the 9 areas, 23%-82% of cases had ≥1 plausible source. Of cases with ≥1 plausible source, 63% were consistent and 7% were inconsistent with recent transmission; 29% were inconclusive. CONCLUSIONS: Disparities in TB incidence for PEH persist; estimates of TB incidence and recent transmission vary by area. With a better understanding of the TB risk among PEH in their jurisdictions and the role of recent transmission as a driver, programs can make more informed decisions about prioritizing TB prevention strategies.

OBJECTIVES: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. METHODS: We reviewed medical and public health records, interviewed patients, and reviewed patients' social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. RESULTS: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non-culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. CONCLUSIONS: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient.

INTRODUCTION: Pediatric tuberculosis (TB) cases are sentinel events for Mycobacterium tuberculosis transmission in communities because children, by definition, must have been infected relatively recently. However, these events are not consistently identified by genotype-dependent surveillance alerting methods because many pediatric TB cases are not culture-positive, a prerequisite for genotyping. METHODS: We developed 3 potential indicators of ongoing TB transmission based on identifying counties in the United States with relatively high pediatric (aged <15 years) TB incidence: (1) a case proportion indicator: an above-average proportion of pediatric TB cases among all TB cases; (2) a case rate indicator: an above-average pediatric TB case rate; and (3) a statistical model indicator: a statistical model based on a significant increase in pediatric TB cases from the previous 8-quarter moving average. RESULTS: Of the 249 US counties reporting ≥2 pediatric TB cases during 2009-2017, 240 and 249 counties were identified by the case proportion and case rate indicators, respectively. The statistical model indicator identified 40 counties with a significant increase in the number of pediatric TB cases. We compared results from the 3 indicators with an independently generated list of 91 likely transmission events involving ≥2 pediatric cases (ie, known TB outbreaks or case clusters with reported epidemiologic links). All counties with likely transmission events involving multiple pediatric cases were identified by ≥1 indicator; 23 were identified by all 3 indicators. PRACTICE IMPLICATIONS: This retrospective analysis demonstrates the feasibility of using routine TB surveillance data to identify counties where ongoing TB transmission might be occurring, even in the absence of available genotyping data.

OBJECTIVES: In late June 2020, a large outbreak of coronavirus disease 2019 (COVID-19) occurred at a sleep-away youth camp in Georgia, affecting primarily persons </=21 years. We conducted a retrospective cohort study among campers and staff (attendees) to determine the extent of the outbreak and assess factors contributing to transmission. METHODS: Attendees were interviewed to ascertain demographic characteristics, known exposures to COVID-19 and community exposures, and mitigation measures before, during, and after attending camp. COVID-19 case status was determined for all camp attendees on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results and reported symptoms. We calculated attack rates and instantaneous reproduction numbers and sequenced SARS-CoV-2 viral genomes from the outbreak. RESULTS: Among 627 attendees, the median age was 15 years (interquartile range: 12-16 years); 56% (351 of 627) of attendees were female. The attack rate was 56% (351 of 627) among all attendees. On the basis of date of illness onset or first positive test result on a specimen collected, 12 case patients were infected before arriving at camp and 339 case patients were camp associated. Among 288 case patients with available symptom information, 45 (16%) were asymptomatic. Despite cohorting, 50% of attendees reported direct contact with people outside their cabin cohort. On the first day of camp session, the instantaneous reproduction number was 10. Viral genomic diversity was low. CONCLUSIONS: Few introductions of SARS-CoV-2 into a youth congregate setting resulted in a large outbreak. Testing strategies should be combined with prearrival quarantine, routine symptom monitoring with appropriate isolation and quarantine, cohorting, social distancing, mask wearing, and enhanced disinfection and hand hygiene. Promotion of mitigation measures among younger populations is needed.

Rapid and profound changes anticipated in the future of work will have significant implications for the education and training of occupational safety and health (OSH) professionals and the workforce. As the nature of the workplace, work, and the workforce change, the OSH field must expand its focus to include existing and new hazards (some yet unknown), consider how to protect the health and well-being of a diverse workforce, and understand and mitigate the safety implications of new work arrangements. Preparing for these changes is critical to developing proactive systems that can protect workers, prevent injury and illness, and promote worker well-being. An in-person workshop held on February 3-4, 2020 at The University of Texas Health Science Center (UTHealth) School of Public Health in Houston, Texas, USA, examined some of the challenges and opportunities OSH education will face in both academic and industry settings. The onslaught of the COVID-19 global pandemic reached the United States one month after this workshop and greatly accelerated the pace of change. This article summarizes presentations from national experts and thought leaders across the spectrum of OSH and professionals in the fields of strategic foresight, systems thinking, and industry, and provides recommendations for the field.

Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17-20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21-27, and were joined by 363 campers and three senior staff members on June 21. Camp A adhered to the measures in Georgia's Executive Order* that allowed overnight camps to operate beginning on May 31, including requiring all trainees, staff members, and campers to provide documentation of a negative viral SARS-CoV-2 test ≤12 days before arriving. Camp A adopted most(†) components of CDC's Suggestions for Youth and Summer Camps(§) to minimize the risk for SARS-CoV-2 introduction and transmission. Measures not implemented were cloth masks for campers and opening windows and doors for increased ventilation in buildings. Cloth masks were required for staff members. Camp attendees were cohorted by cabin and engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. On June 23, a teenage staff member left camp A after developing chills the previous evening. The staff member was tested and reported a positive test result for SARS-CoV-2 the following day (June 24). Camp A officials began sending campers home on June 24 and closed the camp on June 27. On June 25, the Georgia Department of Public Health (DPH) was notified and initiated an investigation. DPH recommended that all attendees be tested and self-quarantine, and isolate if they had a positive test result.

Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden. METHODS: Children <5 years old hospitalized for ARI were enrolled through active, prospective, population-based surveillance from November 1, 2015, to June 30, 2016, at 7 US pediatric hospital sites. Clinical information was obtained from parent interviews and medical records. Midturbinate nasal and throat flocked swabs were collected and tested for RSV by using molecular diagnostic assays at each site. We conducted descriptive analyses and calculated population-based rates of RSV-associated hospitalizations. RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSV-positive; 903 (87%) children who were RSV-positive were <2 years old, and 526 (50%) were <6 months old. RSV-associated hospitalization rates were 2.9 per 1000 children <5 years old and 14.7 per 1000 children <6 months old; the highest age-specific rate was observed in 1-month-old infants (25.1 per 1000). Most children who were infected with RSV (67%) had no underlying comorbid conditions and no history of preterm birth. CONCLUSIONS: During the 2015-2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants <6 months. Most children who were RSV-positive had no history of prematurity or underlying medical conditions, suggesting that all young children could benefit from targeted interventions against RSV.

As of April 9, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 1,521,252 cases and 92,798 deaths worldwide, including 459,165 cases and 16,570 deaths in the United States (1,2). Health care personnel (HCP) are essential workers defined as paid and unpaid persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials (3). During February 12-April 9, among 315,531 COVID-19 cases reported to CDC using a standardized form, 49,370 (16%) included data on whether the patient was a health care worker in the United States; including 9,282 (19%) who were identified as HCP. Among HCP patients with data available, the median age was 42 years (interquartile range [IQR] = 32-54 years), 6,603 (73%) were female, and 1,779 (38%) reported at least one underlying health condition. Among HCP patients with data on health care, household, and community exposures, 780 (55%) reported contact with a COVID-19 patient only in health care settings. Although 4,336 (92%) HCP patients reported having at least one symptom among fever, cough, or shortness of breath, the remaining 8% did not report any of these symptoms. Most HCP with COVID-19 (6,760, 90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups; deaths most frequently occurred in HCP aged ≥65 years. These preliminary findings highlight that whether HCP acquire infection at work or in the community, it is necessary to protect the health and safety of this essential national workforce.

Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire-pre- and post-vaccination-and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen.

Background: Human papillomavirus (HPV) vaccine was recommended in 2006 for routine vaccination of US females aged 11-12 years. Most vaccine used through 2014 was quadrivalent vaccine (4vHPV), which prevents HPV-6, -11, -16, and -18 infection. To evaluate vaccine impact, we measured HPV prevalence in the National Health and Nutrition Examination Survey (NHANES). Methods: We analyzed HPV DNA types detected in self-collected cervicovaginal specimens and demographic, sexual behavior, and self-reported vaccination data from females 14-34 years old. We estimated HPV prevalence in the prevaccine (2003-2006) and vaccine eras (2007-2010 and 2011-2014). Results: Among 14- to 19-year-olds, 4vHPV-type prevalence decreased from 11.5% (95% confidence interval [CI], 9.1%-14.4%) in 2003-2006 to 3.3% (95% CI, 1.9%-5.8%) in 2011-2014, when ≥1-dose coverage was 55%. Among 20- to 24-year-olds, prevalence decreased from 18.5% (95% CI, 14.9%-22.8%) in 2003-2006 to 7.2% (95% CI, 4.7%-11.1%) in 2011-2014, when ≥1-dose coverage was 43%. Compared to 2003-2006, 4vHPV prevalence in sexually active 14- to 24-year-olds in 2011-2014 decreased 89% among those vaccinated and 34% among those unvaccinated. Vaccine effectiveness was 83%. Conclusions: Within 8 years of vaccine introduction, 4vHPV-type prevalence decreased 71% among 14- to 19-year-olds and 61% among 20- to 24-year-olds. Estimated vaccine effectiveness was high. The decrease in 4vHPV-type prevalence among unvaccinated females suggests herd protection.

BACKGROUND: Incarcerated persons are disproportionately diagnosed with tuberculosis (TB). California has the second highest inmate population in the United States, but reports the highest number of cases. OBJECTIVE: To describe the TB epidemiology among incarcerated patients in California. METHODS : Trends in incidence were assessed using Poisson regression, and trends in percentage were assessed using weighted linear regression. Demographic and clinical characteristics were compared using v2 or Mann-Whitney U tests. RESULTS: During 1993-2013, of the 64 090 TB cases reported, 2323 (4%) were correctional facility residents. Incidence in correctional facilities decreased until 2006 (annual per cent change [APC] -12.3%, 95%CI -14.4 to -10.1), but has since stabilized (APC 4.4%, 95%CI -2.1 to 11.4). Compared with state prisoners, federal prisoners were more likely to be male (98%, P<0.03), persons arriving in the United States within 5 years of diagnosis (62%, P< 0.001), and born in Mexico (88%, P=0.02), whereas local jail inmates were more likely to have a history of substance use (75%, P<0.001) and homelessness (35%, P< 0.001). CONCLUSIONS: TB incidence in correctional facilities had steadily declined over the last two decades, but has recently leveled out. To promote further reduction in incidence among diverse incarcerated populations, health departments and correctional facilities should strengthen collaboration by conducting TB risk-based assessments.

Although previous reports indicate that exercise improves cognitive function in normoxia, the influence of exercise on cognitive function in hypoxia is unknown. The purpose of this study was to determine if the impaired cognitive function in hypoxia can be restored by low to moderate intensity exercise. Sixteen young healthy men completed the ANAM versions of the Go/No-Go task (GNT) and Running Memory Continuous Performance Task (RMCPT) in normoxia to serve as baseline (B-Norm) (21% O2). Following 60 minutes of exposure to normobaric hypoxia (B-Hypo) (12.5% O2), these tests were repeated at rest and during cycling exercise at 40% and 60% of adjusted Vo2max. At B-Hypo, the % correct (p≤0.001) and throughput score (p≤0.001) in RMCPT were significantly impaired compared to B-Norm. During exercise at 40% (p=0.023) and 60% (p=0.006) of adjusted Vo2max, the throughput score in RMCPT improved compared to B-Hypo, and there was no significant difference in throughput score between the two exercise intensities. Mean reaction time also improved at both exercise intensities compared to B-Hypo (p≤0.028). Both peripheral oxygen saturation (Spo2) and regional cerebral oxygen saturation (rSo2) significantly decreased during B-Hypo (p≤0.001) and further decreased at 40% (p≤0.05) and 60% (p≤0.039) exercise. There was no significant difference in Spo2 or rSo2 between two exercise intensities. These data indicate that low to moderate exercise (i.e., 40%-60% adjusted Vo2max) may attenuate the risk of impaired cognitive function that occurs in hypoxic conditions.

We report principles and guidelines (Supplementary Note) that were developed by the Next-Generation Sequencing: Standardization of Clinical Testing II (Nex-StoCT II) informatics workgroup, which was first convened on October 11–12, 2012, in Atlanta, Georgia, by the US Centers for Disease Control and Prevention (CDC; Atlanta, GA). We present here recommendations for the design, optimization and implementation of an informatics pipeline for clinical next-generation sequencing (NGS) to detect germline sequence variants in compliance with existing regulatory and professional quality standards1. The workgroup, which included informatics experts, clinical and research laboratory professionals, physicians with experience in interpreting NGS results, NGS test platform and software developers and participants from US government agencies and professional organizations, also discussed the use of NGS in testing for cancer and infectious disease. A typical NGS analytical process and selected workgroup recommendations are summarized in Table 1, and detailed in the guidelines presented in the Supplementary Note.

Human salmonellosis linked to contact with live poultry is an increasing public health concern. In 2012, eight unrelated outbreaks of human salmonellosis linked to live poultry contact resulted in 517 illnesses. In July 2012, PulseNet, a national molecular surveillance network, reported a multistate cluster of a rare strain of Salmonella Braenderup infections which we investigated. We defined a case as infection with the outbreak strain, determined by pulsed-field gel electrophoresis, with illness onset from 25 July 2012-27 February 2013. Ill persons and mail-order hatchery (MOH) owners were interviewed using standardized questionnaires. Traceback and environmental investigations were conducted. We identified 48 cases in 24 states. Twenty-six (81%) of 32 ill persons reported live poultry contact in the week before illness; case-patients named 12 different MOHs from eight states. The investigation identified hatchery D as the ultimate poultry source. Sampling at hatchery D yielded the outbreak strain. Hatchery D improved sanitation procedures and pest control; subsequent sampling failed to yield Salmonella. This outbreak highlights the interconnectedness of humans, animals, and the environment and the importance of industry knowledge and involvement in solving complex outbreaks. Preventing these infections requires a 'One Health' approach that leverages expertise in human, animal, and environmental health.

On September 16, 2013, the North Carolina Division of Public Health was notified of an elemental (metallic and liquid) mercury spill on a school bus. An elementary student boarded the bus with approximately 1 pound (454 g) of elemental mercury contained in a film canister, which the student had taken from an adult relative who had found it in a neighbor's shed. The canister was handled by several students before the contents spilled on the bus floor. Ten passengers aboard the bus were exposed, including eight students and two staff members. Although elemental mercury is not readily absorbed from skin contact or ingestion, it does vaporize at room temperatures and inhalation of the vapor can be harmful. The bus driver promptly notified school officials. Firefighters and a local hazardous materials team directed decontamination procedures (i.e., changing clothes and washing hands and shoes) for the 10 exposed passengers. The bus was immediately taken out of service and sent for disposal because of its age and the cost of decontamination.

PROBLEM/CONDITION: An estimated 55,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2010. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. REPORTING PERIOD COVERED: 2010. DESCRIPTION OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, supplementary homicide reports, hospital data, and crime laboratory data). NVDRS data collection began in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in 2005, and two in 2010 (Ohio and Michigan), for a total of 19 states. This report includes data from 16 states that collected statewide data in 2010; data from California are not included in this report because data were not collected after 2009. Ohio and Michigan were excluded because data collection, which began in 2010, did not occur statewide until 2011. RESULTS: For 2010, a total of 15,781 fatal incidents involving 16,186 deaths were captured by NVDRS in the 16 states included in this report. The majority (62.8%) of deaths were suicides, followed by homicides and deaths involving legal intervention (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force, excluding legal executions) (24.4%), deaths of undetermined intent (12.2%), and unintentional firearm deaths (0.7%). Suicides occurred at higher rates among males, non-Hispanic whites, American Indians/Alaska Natives, and persons aged 45-54 years. Suicides most often occurred in a house or apartment and involved the use of firearms. Suicides were preceded primarily by a mental health or intimate partner problem, a crisis during the previous 2 weeks, or a physical health problem. Homicides occurred at higher rates among males and persons aged 20-24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm and occurred in a house or apartment or on a street/highway. Homicides were precipitated primarily by arguments and interpersonal conflicts or in conjunction with another crime. INTERPRETATION: This report provides a detailed summary of data from NVDRS for 2010. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected persons aged <55 years, males, and certain minority populations. For homicides and suicides, relationship problems, interpersonal conflicts, mental health problems, and recent crises were among the primary precipitating factors. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. PUBLIC HEALTH ACTION: For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. NVDRS data have been used to enhance prevention programs. Examples include use of linked NVDRS data and adult protective service data to better target elder maltreatment prevention programs and improve staff training to identify violent death risks for older adults in North Carolina, use of Oklahoma VDRS homicide data to help evaluate the effectiveness of a new police and advocate intervention at domestic violence incident scenes, and data-informed changes in primary care practice in Oregon to more effectively address older adult suicide prevention. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal impacts of violence. Further efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

According to 1981-2009 data, homicide accounts for 16,000-26,000 deaths annually in the United States and ranks within the top four leading causes of death among U.S. residents aged 1-40 years. Homicide can have profound long-term emotional consequences on families and friends of victims and on witnesses to the violence, as well as cause excessive economic costs to residents of affected communities. For years, homicide rates have been substantially higher among certain populations. Previous reports have found that homicides are higher among males, adolescents and young adults, and certain racial/ethnic groups, such as non-Hispanic blacks, non-Hispanic American Indian/Alaska Natives (AI/ANs), and Hispanics. The 2011 CDC Health Disparities and Inequalities Report (CHDIR) described similar findings for the year 2007. For example, the 2011 report showed that the 2007 homicide rate was highest among non-Hispanic blacks (23.1 deaths per 100,000), followed by AI/ANs (7.8 deaths per 100,000), Hispanics (7.6 deaths per 100,000), non-Hispanic whites (2.7 deaths per 100,000), and Asian/Pacific Islanders (A/PIs) (2.4 deaths per 100,000). In addition, non-Hispanic black men aged 20-24 years were at greatest risk for homicide in 2007, with a rate that exceeded 100 deaths per 100,000 population. Other studies have reported that community factors such as poverty and economic inequality and individual factors such as unemployment and involvement in criminal activities can play a substantial role in these persistent disparities in homicide rates. Public health strategies are needed in communities at high risk for homicide to prevent violence and save lives.

Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens.

We examined the circumstances that precipitated suicide among 1,046 youth aged 10-17 years in 16 U.S. states from 2005 to 2008. The majority of deaths were among male subjects (75.2%), non-Hispanic whites (69.3%), those aged 16-17 years (58.1%), those who died by hanging/strangulation/suffocation (50.2%) and those who died in a house or an apartment (82.5%). Relationship problems, recent crises, mental health problems, and intimate partner and school problems were the most common precipitating factors and many differed by sex. School problems were reported for 25% of decedents, of which 30.3% were a drop in grades and 12.4% were bullying related. Prevention strategies directed toward relationship-building, problem-solving, and increasing access to treatment may be beneficial for this population.