A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Work-related psychosocial hazards are on the verge of surpassing many other occupational hazards in their contribution to ill-health, injury, disability, direct and indirect costs, and impact on business and national productivity. The risks associated with exposure to psychosocial hazards at work are compounded by the increasing background prevalence of mental health disorders in the working-age population. The extensive and cumulative impacts of these exposures represent an alarming public health problem that merits immediate, increased attention. In this paper, we review the linkage between work-related psychosocial hazards and adverse effects, their economic burden, and interventions to prevent and control these hazards. We identify six crucial societal actions: (1) increase awareness of this critical issue through a comprehensive public campaign; (2) increase etiologic, intervention, and implementation research; (3) initiate or augment surveillance efforts; (4) increase translation of research findings into guidance for employers and workers; (5) increase the number and diversity of professionals skilled in preventing and addressing psychosocial hazards; and (6) develop a national regulatory or consensus standard to prevent and control work-related psychosocial hazards.

INTRODUCTION: Health workers faced overwhelming demands and experienced crisis levels of burnout before the COVID-19 pandemic; the pandemic presented unique challenges that further impaired their mental health. METHODS: Data from the General Social Survey Quality of Worklife Module were analyzed to compare self-reported mental health symptoms among U.S. adult workers from 2018 (1,443 respondents, including 226 health workers) and 2022 (1,952, including 325 health workers). Logistic regression was used to examine associations between health workers' reported perceptions of working conditions and anxiety, depression, and burnout. RESULTS: From 2018 to 2022, health workers reported an increase of 1.2 days of poor mental health during the previous 30 days (from 3.3 days to 4.5 days); the percentage who reported feeling burnout very often (11.6% to 19.0%) increased. In 2022, health workers experienced a decrease in odds of burnout if they trusted management (odds ratio [OR] = 0.40), had supervisor help (OR = 0.26), had enough time to complete work (OR = 0.33), and felt that their workplace supported productivity (OR = 0.38), compared with those who did not. Harassment at work was associated with increased odds of anxiety (OR = 5.01), depression (OR = 3.38), and burnout (OR = 5.83). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health workers continued to face a mental health crisis in 2022. Positive working conditions were associated with less burnout and better mental health. CDC's National Institute for Occupational Safety and Health has developed a national campaign, Impact Wellbeing, to provide employers of health workers with resources to improve the mental health of these workers.

BACKGROUND: COVID-19 screening testing (ST) can detect asymptomatic or pre-symptomatic cases, allowing for prompt identification of cases and close contacts. This study examined parents' and school staffs' knowledge and attitudes toward to a pilot school-based ST program in a school district in southern Arizona. METHODS: In May 2021, online surveys to parents and school staff were administered to examine attitudes toward ST and impacts of the COVID-19 pandemic. Unweighted percent estimates were calculated, and bivariate differences were examined by demographics. Associations were assessed using chi-square tests and logistic regression. RESULTS: The survey had response rates of 10% (606/6085) and 22% (187/849) among parents and staff, respectively. Approximately one-third of responding parents (35%) would or already allow their child to participate in school-based ST, 37% would not participate; 28% were unsure. Among responding staff, 46% would or already participate in ST, 33% would not; 21% were unsure. The top concern (38%) among responding staff was taking job-related leave if testing positive. CONCLUSION: Schools work to balance the needs of students, families, and staff by implementing supportive and flexible policies and practices founded on buy-in and acceptance from their communities.

The present study advances research on the negative consequences of precarious work experiences (PWE), which include perceptions of threats to one's job and financial security as well as a sense of powerlessness and inability to exercise rights in the workplace. Using the COVID-19 pandemic as a backdrop, we examine how PWE relate to sickness presenteeism and worry about work-related COVID-19 exposure. In a 12-week, four-wave study of workers working fully in-person, perceptions of powerlessness and job insecurity were associated with presenteeism (e.g., general presenteeism as well as attending work with known or possible COVID-19 infection) and concerns about disease exposure at work. Whereas powerlessness primarily operated at the between-person level of analysis, job insecurity's effects emerged at both levels of analysis. A sense of powerlessness at work also predicted sending children to school/daycare sick. In sum, the findings suggest that precarity related to being able to keep one's job and a sense of powerlessness at work contribute to concerns about the risk of COVID-19 exposure at work and, simultaneously, behaviors that may contribute to the health risks faced by others. This research provides added support to the argument that precarious work should be addressed in order to improve both worker well-being and public health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Human-aided invasion of alien species across the world sometimes leads to economic, health or environmental burdens. During invasion process, species encounter new environments and partially escape some ecological constrains they faced in their native range, while they face new ones. The Asian tiger mosquito Aedes albopictus is one of the most iconic invasive species that was introduced in every inhabited continent over a short period of time due to international trade. It has also been shown to be infected by a prevalent and yet disregarded gregarine entomoparasite Ascogregarina taiwanensis. In this study, we aimed at deciphering the global dynamics of As. taiwanensis infection in natural Ae. albopictus populations and we further explored factors shaping its distribution. We showed that Ae. albopictus populations are highly colonized by several As. taiwanesis genotypes but recently introduced ones are escaping the parasite. We further performed experiments to explain such pattern. First, we hypothesized that founder effects (i.e. population establishment by a small number of individuals) may influence the parasite dynamics. This was confirmed since experimental increase in mosquitoes' density improves the parasite horizontal transmission to larvae. Furthermore, Ae. albopictus larvae do not exhibit density dependent prophylaxis to control the parasite meaning that infection is not mitigated when larval density increases. Secondly, we hypothesized that unparasitized mosquitoes were more prompt to found new populations through active flight dispersal. This was, however, unlikely since parasitized mosquitoes tend to be more active than their unparasitized relatives. Finally, we hypothesized that mosquito passive dispersal (i.e. often mediated by human-aided transportation of dried eggs) affects the parasite infectiveness. Our results support this hypothesis since parasite infection decreases over time when dry eggs are stored. This study highlights the importance of global trade on parasitism escape in one of the most invasive vector species on earth. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all.

This study's goal was to characterize the utility of symptom screening in staff and students for COVID-19 identification and control of transmission in a school setting. We conducted a secondary analysis of cross-sectional data for staff, students and associated household members in a Georgia school district exposed to COVID-19 cases who received RT-PCR testing and symptom monitoring. Among positive contacts, 30/49 (61%) of students and 1/6 (17%) of staff reported no symptoms consistent with COVID-19. Symptom sensitivity was 30% in elementary students and 42% in middle/high students. Fifty-three percent (10/19) of symptomatic positive contacts had at least one household member test positive for SARS-CoV-2 compared with 50% (10/20) of asymptomatic positive contacts. The absence of symptoms in children is not indicative of a lack of SARS-CoV-2 infection or reduced risk of infection for associated household members. Testing all close contacts of people with COVID-19 in schools is needed to interrupt transmission networks.

A proficiency testing (PT) scheme was prepared for laboratories engaged in bioanalytical testing for synthetic opioid compounds in urine, plasma, and whole blood. Samples were prepared using compounds included in the Opioid Certified Reference Material Kit (Opioid CRM Kit) developed by the U.S. Centers for Disease Control and Prevention. Laboratories received samples during a 2-year project with each year consisting of two PT events 6 months apart. In the first year (pilot test), participants included 10 public health laboratories throughout the United States. In the second year, the group of laboratories expanded to include clinical and forensic drug testing laboratories, and 12 additional participating labs joined the program. In Year 1, overall detection percentages for the compounds present in the PT samples were 95.5% in Event 1% and 97.2% in Event 2. There were 31 apparent false positives reported in Event 1 and four apparent false positives reported in Event 2. Carryover or contamination in laboratory analytical systems were found to be the most significant causes of the false positive results, and none of the laboratories that reported false positives in Event 1 did so in Event 2. In Year 2, overall detection percentages for the compounds present in the PT samples were 89.5% in Event 3% and 94.8% in Event 4. There was one apparent false positive reported in Event 3 and three apparent false positives reported in Event 4. Improvements in drug detection between the two PT events in each year demonstrated the benefit of PT schemes in identifying and addressing potential deficiencies in laboratory systems.

From May 2022 through the end of January 2023, approximately 30,000 cases of monkeypox (mpox) have been reported in the United States and >86,000 cases reported internationally.* JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended for subcutaneous administration to persons at increased risk for mpox (1,2) and has been demonstrated to provide protection against infection (3-5). To increase the total number of vaccine doses available, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) on August 9, 2022, recommending administration of the vaccine intradermally (0.1 mL per dose) for persons aged ≥18 years who are recommended to receive it (6); intradermal administration can generate an equivalent immune response to that achieved through subcutaneous injection using approximately one fifth the subcutaneous dose (7). CDC analyzed JYNNEOS vaccine administration data submitted to CDC from jurisdictional immunization information systems (IIS)(†) to assess the impact of the EUA and to estimate vaccination coverage among the population at risk for mpox. During May 22, 2022-January 31, 2023, a total of 1,189,651 JYNNEOS doses (734,510 first doses and 452,884 second doses)(§) were administered. Through the week of August 20, 2022, the predominant route of administration was subcutaneous, after which intradermal administration became predominant, in accordance with FDA guidance. As of January 31, 2023, 1-dose and 2-dose (full vaccination) coverage among persons at risk for mpox is estimated to have reached 36.7% and 22.7%, respectively. Despite a steady decline in mpox cases from a 7-day daily average of more than 400 cases on August 1, 2022, to five cases on January 31, 2023, vaccination for persons at risk for mpox continues to be recommended (1). Targeted outreach and continued access to and availability of mpox vaccines to persons at risk are important to help prevent and minimize the impact of a resurgence of mpox.

Babesiosis is a tickborne disease caused by intraerythrocytic Babesia parasites. In the United States, most babesiosis cases are caused by Babesia microti, transmitted from bites of blacklegged ticks, Ixodes scapularis, in northeastern and midwestern states. Transmission can also occur through blood transfusions, transplantation of organs from infected donors, or congenital (mother-to-child) transmission (1). Babesia infection can be asymptomatic or cause mild to severe illness that can be fatal. Overall, U.S. tickborne disease cases have increased 25%, from 40,795 reported in 2011 to 50,856 in 2019 (2). Babesiosis trends were assessed in 10 states* where babesiosis was reportable during 2011-2019. Incidence increased significantly in Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Vermont (p<0.001), with the largest increases reported in Vermont (1,602%, from two to 34 cases), Maine (1,422%, from nine to 138), New Hampshire (372%, from 13 to 78), and Connecticut (338%, from 74 to 328). Unlike the other seven states, Maine, New Hampshire, and Vermont, were not included as states with endemic disease in previous CDC babesiosis surveillance summaries. These three states should now be considered to have endemic transmission comparable to that in other high-incidence states; they have consistently identified newly acquired cases every year during 2011-2019 and documented presence of Babesia microti in the associated tick vector (3). Because incidence in Northeastern states, including Maine, New Hampshire, and Vermont, is increasing, tick prevention messaging, provider education, and awareness of infection risk among travelers to these states should be emphasized.

BACKGROUND: The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE). METHODS: Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability. RESULTS: Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high. CONCLUSIONS: Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.

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.

BACKGROUND: Examining workplace psychosocial risk factors for back pain becomes increasingly important because of the changing nature of work and rising healthcare costs. Some psychosocial risk factors for back pain, such as work and family imbalance, exposure to a hostile work environment, and job insecurity, are understudied for the working population in the United States. METHODS: Data used in this study came from the Quality of Work Life Survey (QWL), a supplementary module of the General Social Survey conducted in the United States. Data from the 2002, 2006, 2010, 2014, and 2018 QWL surveys were used in these analyses, giving a total sample size of 6661. Five domains of workplace psychosocial risk factors for back pain were examined, including job strain, low social support, work-family imbalance, exposure to a hostile work environment (harassment and discrimination), and job insecurity. The adjusted odds ratio (aOR) of each psychosocial risk factor for back pain with 95% confidence intervals (CI) was estimated using a multivariable logistic regression model after controlling for job physical factors, occupation, and demographic and socioeconomic characteristics. RESULTS: Significant associations were found between back pain and several psychosocial factors including job strain (aOR 1.19; CI 1.00,1.41), work-family imbalance (aOR,1.42; CI 1.22,1.64), harassment (aOR 1.40; CI 1.15,1.71), and discrimination (aOR 1.20 CI 1.00,1.44). CONCLUSION: This study contributes to the understanding of the relationship between a variety of workplace psychosocial factors and back pain. Our findings suggest directions in future longitudinal research to examine emerging workplace psychosocial factors for back pain.

OBJECTIVE: Globally, COVID-19 has affected how children learn. We evaluated the impact of Test to Stay (TTS) on secondary and tertiary transmission of SARS-CoV-2 and potential impact on in-person learning in four school districts in the United States from September 13-November 19, 2021. METHODS: Implementation of TTS varied across school districts. Data on index cases, school-based close contacts, TTS participation, and testing results were obtained from four school districts in diverse geographic regions. Descriptive statistics, secondary and tertiary attack risk, and a theoretical estimate of impact on in-person learning were calculated. RESULTS: Fifty-one schools in four school districts reported 374 COVID-19 index cases and 2,520 school-based close contacts eligible for TTS. The proportion participating in TTS ranged from 22%-79%. By district, the secondary attack risk (SAR) and tertiary attack risk (TAR) among TTS participants ranged between 2.2%-11.1% and 0%-17.6%, respectively. Nine clusters were identified among secondary cases and two among tertiary cases. The theoretical maximum number of days of in-person learning saved by using TTS was 976-4,650 days across jurisdictions. CONCLUSIONS: TTS preserves in-person learning days. Decisions to participate in TTS may have been influenced by ease of access to testing, communication between schools and families, testing logistics, and school resources. TAR determination became more complicated when numbers of close contacts increased. Minimizing exposure through continued implementation of layered prevention strategies is imperative. To ensure adequate resources for implementation of TTS, community transmission levels should be considered.

BACKGROUND: Daily more than 3,000 children are injured or killed on the road, often along the school route. Road traffic crashes and resulting injuries are preventable. More can be done to reduce injuries and save lives. Traffic Conflict Techniques (TCTs) are simple methods of collecting observational data to evaluate the effectiveness of road safety interventions through counting and analyzing traffic conflicts. A TCT Toolkit was developed and piloted to analyze pedestrian-vehicle traffic conflicts in school zones in low- and middle-income countries. METHODS: Three non-governmental organizations in Ghana, Vietnam, and Mexico applied three TCTs from the TCT Toolkit to collect traffic conflict data before (pre-intervention) and after (post-intervention) road safety intervention implementation. As the number of traffic conflicts was often less than 100, confidence intervals (CIs) based on gamma distributions were calculated for the traffic conflict rate. Using the calculated traffic conflict rate, the difference between pre- and post-intervention rates was assessed by determining overlap of the CIs. When CIs did not overlap, the difference was said to be statistically significant at the 0.05 level. RESULTS: For each method, results indicated a decrease in traffic conflicts between pre- and post-intervention data collection periods. Pre- and post-intervention traffic conflict rates with non-overlapping CIs demonstrated the results were statistically significant, providing evidence that the road safety interventions were effective. CONCLUSIONS: TCTs are relatively low-cost and simple techniques that provide an opportunity to base road safety improvement decisions on real-world data. TCTs are effective in objectively evaluating road safety interventions and can help decision-makers evaluate strategies for improving road safety, preventing injuries and saving lives.

On September 13-14, 2019, the National Institute for Occupational Safety and Health (NIOSH) hosted a national forum entitled "Working hours, sleep and fatigue: Meeting the needs of American workers and employers."The purpose of this inaugural meeting was to discuss current evidence about the broad-based risks and effective countermeasures related to working hours, sleep, and fatigue, with further considerations to tailor solutions for specific industries and worker populations. We aimed to identify the knowledge gaps and needs in this area and future directions for research. We also sought to identify similarities across industries with the goal of sharing lessons learned and successful mitigation strategies across sectors. Participants included an international representation of academics, scientists, government representatives, policymakers, industry leaders, occupational health and safety professionals, and labor representatives.A total of eight manuscripts were developed following stakeholder comments and forum discussions. Six focused on sector-specific approaches (i.e., Agriculture, Forestry & Fishing; Healthcare & Social Assistance; Mining; Oil and Gas Extraction; Public Safety; Transportation, Warehousing & Utilities) to identify unique factors for fatigue-risk and effective countermeasures. Two additional manuscripts addressed topic areas that cut across all industries (disproportionate risks, and economic evaluation).Findings from the Forum highlight that the identification of common risk factors across sectors allows for transfer of information, such as evidence for effective mitigation strategies, from sectors where fatigue risk has been more widely studied to those sectors where it has been less so. Further considerations should be made to improve knowledge translation activities by incorporating different languages and modes of dissemination such that information is accessible for all workers. Additionally, while economic evaluation can be an important decision-making tool for organizational- and policy-level activities, multi-disciplinary approaches combining epidemiology and economics are needed to provide a more balanced approach to economic evaluation with considerations for societal impacts. Although fatigue risk management must be tailored to fit industries, organizations, and individuals, knowledge gained in this forum can be leveraged, modified, and adapted to address these variabilities. Our hope is to continue sharing lessons learned to encourage future innovative, multi-disciplinary, cross-industry collaborations that will meet the needs of workers and employers to mitigate the risks and losses related to workplace fatigue.

BACKGROUND: There is a continuing risk for COVID-19 transmission in school settings while transmission is ongoing in the community, particularly among unvaccinated populations. To ensure that schools continue to operate safely and to inform implementation of prevention strategies, it is imperative to gain better understanding of the risk behaviors of staff and students. This secondary analysis describes the prevalence of COVID-19 risk behaviors in an exposed population of students and school staff in the pre-vaccine era and identifies associations between these behaviors and testing positive for SARS-CoV-2. METHODS: From December 2020-January 2021, school staff and students exposed to confirmed COVID-19 cases in a Georgia school district were tested for SARS-CoV-2 and surveyed regarding risk behaviors in and out of school. Prevalence of risk behaviors was described by age group and school level, and associations with SARS-CoV-2 positivity were identified using chi squared tests. RESULTS: Overall, 717 students and 79 school staff participated in the investigation; SARS-CoV-2 positivity was 9.2%. In the 2 weeks prior to COVID-19 exposure, 24% of participants reported unmasked indoor time at school, 40% attended social gatherings with non-household members, and 71% visited out-of-school indoor locations, including 19% who ate indoors in restaurants. Frequencies of risk behaviors increased by age. Among students, 17% participated in school sports, of whom 86% participated without a mask. SARS-CoV-2 positivity was significantly associated with school sports and unmasked time in sports. Among K-5 students, positivity was associated with exposure to a teacher index case. CONCLUSIONS: This analysis highlights the high prevalence of risk behaviors in an unvaccinated population exposed to COVID-19 in school and identifies an association between student sports participation and SARS-CoV-2 positivity. These findings illustrate the importance of school-level prevention measures to reduce SARS-CoV-2 transmission, including limiting close-contact indoor sports and promoting consistent mask use in unvaccinated individuals. Future research could explore the role of community vaccination programs as a strategy to reduce COVID-19 transmission and introductions into school settings.

To combat the ongoing opioid epidemic, our laboratory has developed and evaluated an approach to detect fentanyl analogs in urine and plasma by screening LC-QTOF MS/MS spectra for ions that are diagnostic of the core fentanyl structure. MS/MS data from a training set of 142 fentanyl analogs were used to select the four product ions and six neutral losses that together provided the most complete coverage (97.2%) of the training set compounds. Furthermore, using the diagnostic ion screen against a set of 49 fentanyl analogs not in the training set resulted in 95.9% coverage of those compounds. With this approach, lower reportable limits for fentanyl and a subset of fentanyl-related compounds range from 0.25 to 2.5 ng/mL in urine and 0.5 to 5.0 ng/mL in plasma. This innovative processing method was applied to evaluate simulated exposure samples of remifentanil and carfentanil in water and their metabolites remifentanil acid and norcarfentanil in urine. This flexible approach enables a way to detect emerging fentanyl analogs in clinical samples.

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI 60-71%) for UTD, 33% (95% CI 18-46%) for 2 doses-not UTD, and 40% (95% CI 27-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI 64-79%) for UTD, 39% (95% CI 10-58%) for 2 doses-not UTD, and 48% (95% CI 25-63%) for 1 dose. VE was higher for vaccination at age <20 than {greater than or equal to}20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10(5), 9.0 × 10(5) or 1.8 × 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10(5) dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2(+)Vγ9(+) T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2(+)Vγ9(+) T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.

Many children with developmental disabilities are not identified before age 3 years of age, preventing them from being able to fully benefit from early intervention services. Early childhood educators, particularly those in Early Head Start (EHS) programs, are important partners in the early identification of children with developmental delays. Learn the Signs. Act Early. (LTSAE) is a program of the U.S. Centers for Disease Control and Prevention that provides free developmental monitoring resources to increase the early identification of children with developmental delays and disabilities. This paper presents findings from the first evaluation of the use of LTSAE resources in EHS, which was conducted across four states and 11 EHS programs from fall 2018 through spring 2019. Surveys (n = 448) and interviews (n = 39) with EHS management, staff, and parents indicated that LTSAE resources were valued and accepted, and their use in EHS considered feasible. Importantly, families and staff reported the LTSAE materials provided shared language to help them more effectively discuss development. These findings inform EHS and other early education programs that wish to enhance developmental monitoring, screening, and referral. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

BACKGROUND: In the United States, HPV vaccination has been recommended since 2011 for males aged 11-12 years, with catch-up vaccination recommended through age 26 years for previously unvaccinated men who have sex with men (MSM). METHODS: During 2016-2018, a cross-sectional study enrolled MSM and transgender women aged 18-26 years in Seattle, Washington. Participants submitted self-collected penile swab specimens for HPV genotyping. HPV vaccination history was self-reported. We compared HPV prevalence among vaccinated participants versus participants with no/unknown vaccination history using log-binomial regression to estimate adjusted prevalence ratios (aPR) and confidence intervals (CI). RESULTS: Among 687 participants, 348 (50.7%) self-reported ever receiving ≥1 HPV vaccine dose; median age at first HPV vaccination was 21 years and median age at first sex was 17 years. Overall, prevalence of penile quadrivalent HPV vaccine (4vHPV)-type HPV was similar in vaccinated participants (12.1%) and participants with no/unknown vaccination (15.6%) (aPR=0.69, 95%CI:0.47-1.01). However, prevalence was significantly lower in participants vaccinated at age ≤18 years than in participants with no/unknown vaccination (aPR=0.15, 95%CI:0.04-0.62), corresponding to a vaccine effectiveness of 85% against 4vHPV-type HPV. CONCLUSIONS: Results suggest HPV vaccination is effective in preventing penile HPV infections in young MSM when administered at age ≤18 years.

BACKGROUND: We assessed sensitivity of self-reported HPV vaccination among young adult men who have sex with men (MSM) with documented HPV vaccination. METHODS: During 2016-2018, MSM and transgender women aged 18-26 years were enrolled in Seattle, Washington. HPV vaccination history was assessed via self-administered survey, clinic electronic medical records (EMR), and the Washington State Immunization Information System (WAIIS). We assessed self-report sensitivity among participants with documented prior HPV vaccination (≥1 dose) in either the EMR or WAIIS, and used logistic regression to compare sensitivity by age, number of doses, and time since first dose. RESULTS: Of 292 participants with ≥1 documented HPV vaccine dose, 243 self-reported ≥1 dose (sensitivity = 83.2%,95%CI:78.4%-87.3%). Compared to participants whose first dose was <1 year ago, likelihood of self-report was lower among those with ≥3 years since first dose (adjusted odds ratio (aOR) = 0.2,95%CI:0.1-0.5). Furthermore, compared to participants with only 1 documented HPV vaccine dose, likelihood of self-reporting ≥1 dose was higher among those with 2 (aOR = 2.4,95%CI:1.0-5.5) or ≥ 3 doses (aOR = 6.2,95%CI:2.7-14.4). Among 115 participants with ≥3 documented doses, sensitivity for recalling ≥3 doses was 69.6% (95%CI:60.3%-77.8%). CONCLUSIONS: Most young adult MSM with a documented history of HPV vaccination self-reported prior HPV vaccination. Although recall was highest in those with ≥3 doses, 30% of this fully-vaccinated subgroup did not correctly recall the number of doses received, highlighting limitations of self-reporting. Furthermore, results indicating reduced recall with ≥3 years since first dose suggest that sensitivity of self-report among young adult MSM may decline over time as adolescent vaccination coverage increases.

OBJECTIVE: Investigate associations between occupational injury to parents and the psychological well-being of their children. METHODS: We used multiple logistic regression to examine effects of occupational injury to parents on measures of psychological well-being among their children using National Health Interview Survey data from 2012 through 2016. RESULTS: Children of injured workers exhibited greater impairment than children of workers who had not sustained injuries for four of five measures of emotional and behavioral functioning that were hypothesized to differentiate these two child groups. A significant group difference was not observed for a sixth behavioral measure that was expected to be insensitive to parent occupational injury. CONCLUSION: Study findings heighten concern over downstream effects of occupational injury and signal need for more expansive investigation of these effects and mitigation strategies among children of injured workers.

BACKGROUND: To inform prevention strategies, we assessed the extent of SARS-CoV-2 transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During December 1, 2020-January 22, 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 RT-PCR testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (e.g., sports, elementary school classroom), index case role (i.e., staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1,119 contacts, 688 (63.1%) of whom received testing. Fifty-nine (8.7%) of 679 contacts tested positive; 15 (17.4%) of 86 index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SAR were in indoor, high-contact sports settings (23.8%, 95% confidence interval [CI] 12.7, 33.3), staff meetings/lunches (18.2%, CI 4.5-31.8), and elementary school classrooms (9.5%, CI 6.5-12.5). SAR was higher for staff (13.1%, CI 9.0-17.2) versus student index cases (5.8%, CI 3.6-8.0) and for symptomatic (10.9%, CI 8.1-13.9) versus asymptomatic index cases (3.0%, CI 1.0-5.5). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include COVID-19 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

In-person learning benefits children and communities (1). Understanding the context in which transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), occurs in schools is critical to improving the safety of in-person learning. During December 1, 2020-January 22, 2021, Cobb and Douglas Public Health (CDPH), the Georgia Department of Public Health (GDPH), and CDC investigated SARS-CoV-2 transmission in eight public elementary schools in a single school district. COVID-19 cases* among educators and students were either self-reported or identified by local public health officials. Close contacts (contacts)(†) of persons with a COVID-19 case received testing. Among contacts who received positive test results, public health investigators assessed epidemiologic links, probable transmission directionality, and the likelihood of in-school transmission.(§) Nine clusters of three or more epidemiologically linked COVID-19 cases were identified involving 13 educators and 32 students at six of the eight elementary schools. Two clusters involved probable educator-to-educator transmission that was followed by educator-to-student transmission and resulted in approximately one half (15 of 31) of school-associated cases. Sixty-nine household members of persons with school-associated cases were tested, and 18 (26%) received positive results. All nine transmission clusters involved less than ideal physical distancing, and five involved inadequate mask use by students. Educators were central to in-school transmission networks. Multifaceted mitigation measures in schools, including promotion of COVID-19 precautions outside of school, minimizing in-person adult interactions at school, and ensuring universal and correct mask use and physical distancing among educators and students when in-person interaction is unavoidable, are important in preventing in-school transmission of SARS-CoV-2. Although not required for reopening schools, COVID-19 vaccination should be considered as an additional mitigation measure to be added when available.

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccination has been recommended for young adult men who have sex with men (MSM) since 2011. METHODS: The Vaccine Impact in Men (VIM) study surveyed MSM and transgender women aged 18-26 years in 3 U.S. cities during 2016-2018. Self-collected anal swab and oral rinse specimens were assessed for 37 types of HPV DNA. We compared HPV prevalence among vaccinated and unvaccinated participants and determined adjusted prevalence ratios (aPR) and confidence intervals (CI). RESULTS: Among 1,767 participants, 704 (39.8%) self-reported receiving HPV vaccine. Median age at vaccination (18.7 years) was older than age at first sex (15.7 years). Quadrivalent vaccine-type HPV was detected in anal or oral specimens from 475 (26.9%) participants. Vaccine-type HPV prevalence was lower among vaccinated (22.9%) compared with unvaccinated (31.6%) participants; aPR for those who initiated vaccination at </=18 years was 0.41 (95% CI: 0.24-0.57) and at >18 years was 0.82 (95% CI: 0.67-0.98). Vaccine effectiveness for at least one HPV vaccine dose at age >/=18 years or >18 years was 59% and 18%, respectively. CONCLUSIONS: Findings suggest real-world effectiveness of HPV vaccination among young adult MSM. This effect was stronger with younger age at vaccination.

Globally, mushroom poisonings cause about 100 human deaths each year, with thousands of people requiring medical assistance. Dogs are also susceptible to mushroom poisonings and require medical assistance. Cyclopeptides, and more specifically amanitins (or amatoxins, here), are the mushroom poison that causes the majority of these deaths. Current methods (predominantly chromatographic, as well as antibody-based) of detecting amatoxins are time-consuming and require expensive equipment. In this work, we demonstrate the utility of the lateral flow immunoassay (LFIA) for the rapid detection of amatoxins in urine samples. The LFIA detects as little as 10 ng/mL of alpha-amanitin (alpha-AMA) or gamma-AMA, and 100 ng/mL of beta-AMA in urine matrices. To demonstrate application of this LFIA for urine analysis, this study examined fortified human urine samples and urine collected from exposed dogs. Urine is sampled directly without the need for any pretreatment, detection from urine is completed in 10 min, and the results are read by eye, without the need for specialized equipment. Analysis of both fortified human urine samples and urine samples collected from intoxicated dogs using the LFIA correlated well with liquid chromatography-mass spectrometry (LC-MS) methods.