BACKGROUND: With accumulating evidence of single-dose human papillomavirus (HPV) vaccine efficacy in young women, we conducted a community vaccine effectiveness study comparing HPV single-dose and 2-dose regimens (0 and 6 months) of a bivalent HPV vaccine among grade 8 schoolgirls (aged 13-14 years) in Thailand. METHODS: In 2018, eligible grade 8 schoolgirls in Udon Thani (single dose) and Buri Ram (2 doses) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey for measuring baseline HPV prevalence was conducted in grade 10 (n = 2600) and grade 12 unvaccinated schoolgirls (n = 2000) in each province. HPV infection was assessed in first-void urine samples, tested by DNA polymerase chain reaction on the cobas 4800 system (Roche Molecular Diagnostics, Pleasanton, CA). All samples positive on the cobas system and an equal number of negative samples were also tested by Anyplex II HPV28 Detection (Seegene, Seoul, South Korea). The surveys were repeated in 2020 and 2022, when vaccinated grade 8 schoolgirls reached grade 10, and then subsequently grade 12, respectively. Vaccine effectiveness was estimated by comparing the weighted prevalence of HPV-16 or HPV-18 between grade-matched unvaccinated schoolgirls on the baseline survey (2018) and vaccinated schoolgirls in the year-2 (2020) and year-4 (2022) surveys. Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the noncontemporaneous comparison. RESULTS: The prevalence of HPV-16 and HPV-18 on the baseline survey among unvaccinated grade 10/grade 12 schoolgirls was 2.90% (95% confidence interval [CI] = 2.54% to 3.31%)/3.98% (95% CI = 3.52% to 4.49%) for Udon Thani and 3.87% (95% CI = 3.46% to 4.34%)/6.13% (95% CI = 5.56% to 6.75%) for Buri Ram. On the year-2 survey, the prevalence among vaccinated grade 10 schoolgirls was 0.57% (95% CI = 0.42% to 0.77%) for Udon Thani and 0.31% (95% CI = 0.21% to 0.47%) for Buri Ram. The 2-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 80.4% (95% CI = 73.9% to 86.9%), and for the 2-dose regimen at 91.9% (95% CI = 88.5% to 95.4%). On the year-4 survey, the prevalence among vaccinated grade 12 schoolgirls was 0.37% (95% CI = 0.25% to 0.56%) for Udon Thani and 0.28% (95% CI = 0.18% to 0.45%) for Buri Ram. Four-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 90.6% (95% CI = 86.6% to 94.6%) and for the 2-dose regimen was estimated at 95.4% (95% CI = 93.2% to 97.6%). All adjustment methods minimally affected vaccine effectiveness for the single-dose and 2-dose regimens. At 4 years after vaccination, the difference in crude vaccine effectiveness between the single-dose and 2-dose regimens was ‒4.79% (95% CI = ‒9.32% to ‒0.25%), meeting the study's noninferiority criteria. CONCLUSIONS: Our study demonstrated that both single-dose and 2-dose HPV vaccination significantly decreased HPV-16/18 point prevalence 2 years and 4 years after vaccination. Crude vaccine effectiveness at 4 years after vaccination was greater than 90% for both the single-dose and 2-dose regimens; the single-dose regimen was not inferior to the 2-dose regimen. These data show that a single dose of HPV vaccine provides high levels of protection when administered to schoolgirls younger than 15 years of age.

PURPOSE: Research has shown that cancer genetic risk is often not well understood by patients undergoing genetic testing and counseling. We describe the barriers to understanding genetic risk and the needs of high-risk persons and cancer survivors who have undergone genetic testing. METHODS: Using data from an internet survey of adults living in the USA who responded 'yes' to having ever had a genetic test to determine cancer risk (N = 696), we conducted bivariate analyses and multivariable logistic regression models to evaluate associations between demographic, clinical, and communication-related variables by our key outcome of having vs. not having enough information about genetics and cancer to speak with family. Percentages for yes and no responses to queries about unmet informational needs were calculated. Patient satisfaction with counseling and percentage disclosure of genetic risk status to family were also calculated. RESULTS: We found that a lack of resources provided by provider to inform family members and a lack of materials provided along with genetic test results were strongly associated with not having enough information about genetics and cancer (OR 4.54 95% CI 2.40-8.59 and OR 2.19 95% CI 1.16-4.14 respectively). Among participants undergoing genetic counseling, almost half reported needing more information on what genetic risk means for them and their family and how genetic testing results might impact future screening. CONCLUSION: High levels of satisfaction with genetic counseling may not give a full picture of the patient-provider interaction and may miss potential unmet needs of the patient. Accessible resources and ongoing opportunities for updating family history information could reinforce knowledge about genetic risk.

OBJECTIVE: To examine population-level scrotal cancer incidence rates and trends among adult men in the United States. METHODS: Data from the United States Cancer Statistics, covering approximately 96% of the United States population, were analyzed to calculate age-standardized incidence rates of scrotal cancer among men aged 18 years and older from 1999 to 2020. Trends in incidence rates were evaluated by age, race and ethnicity, Census region, and histology using joinpoint regression. RESULTS: Overall, 4669 men were diagnosed with scrotal cancer (0.20 per 100,000). Incidence rates were highest among men aged 70 years and older (0.82 per 100,000). Rates were higher among non-Hispanic Asian or Pacific Islander men (0.31 per 100,000) compared to other race and ethnicity groups. The most common histologic subtypes were squamous cell carcinoma (35.9%), extramammary Paget disease (20.8%), and sarcoma (20.5%). Incidence rates decreased by 2.9% per year from 1999 to 2019 for non-Hispanic Asian or Pacific Islander men, decreased by 8.1% per year from 1999 to 2006 for basal cell carcinomas, and increased by 1.8% per year from 1999 to 2019 for extramammary Paget disease; otherwise, rates remained stable for all other variables examined. CONCLUSION: While scrotal cancer incidence rates were higher than previously reported, rates were still low and stable over time.

BACKGROUND: Shigellosis is diarrheal disease caused by highly infectious Shigella bacteria. Shigella can spread in multiple ways, including sexual contact. Gay, bisexual, and other men who have sex with men are particularly at risk for shigellosis. METHODS: To evaluate the acceptability of three CDC-developed behavioral recommendations for the prevention of sexually transmitted shigellosis, virtual in-depth interviews were conducted among twenty-six gay or bisexual men in March-May 2021. RESULTS: Participants had a median age of 25; 65% were Non-Hispanic White, 12% were Hispanic White, 12% Asian, 4% Hispanic Black, and 8% multiracial/other. Respondents indicated willingness to engage in certain prevention behaviors (e.g., washing hands, genitals, and anus before and after sex), but were less willing to engage in behaviors that were viewed as outside social norms or difficult to practice (e.g., dental dams for oral-anal contact; latex gloves for fingering or fisting). Respondents thought recommendations may be more feasible if knowledge of shigellosis was greater; however, some perceived that the severity of shigellosis is low and did not warrant the effort of engaging in prevention behaviors. CONCLUSIONS: Educational efforts to increase awareness of shigellosis and other enteric diseases spread through sexual contact are needed and public health practitioners should consider the acceptability of how realistic it is for individuals to engage in certain prevention behaviors. Rather than recommending behaviors that do not have buy-in, it may be more efficacious to focus recommendations on adopting behaviors reported as acceptable to the target audience.

INTRODUCTION: Scrotal squamous cell carcinomas (SCCs) are rare malignancies that are not considered to be associated with the human papillomavirus (HPV) by the International Agency for Research on Cancer. However, recent studies have detected HPV in these cancers. We sought to determine the presence of HPV types among scrotal cancer cases identified through population-based cancer registries. METHODS: Primary scrotal SCCs diagnosed from 2014 to 2015 were identified, and tissue sections from formalin-fixed, paraffin-embedded tissue blocks were obtained for laboratory testing. A pathology review was performed to confirm morphology. HPV testing was performed using L1 consensus polymerase chain reaction analysis. Immunohistochemistry was used to evaluate p16INK4a (p16) expression. RESULTS: Five cases of scrotal SCC were identified from 1 cancer registry. Age at diagnosis ranged from 34 to 75 years (median, 56 years). Four cases were non-Hispanic White, and 1 was non-Hispanic Black. The morphologic subtype of 4 cases was keratinizing (usual), and 1 case was verrucous (warty) histologic subtype. Two of the usual cases of SCC were HPV-negative and p16-negative, and 2 were positive for HPV16 and p16. The verrucous (warty) SCC subtype case was HPV6-positive and p16-negative. CONCLUSIONS: The presence of HPV16 and p16 overexpression in the examined tissue specimens lends additional support for the role of HPV in the etiology of scrotal SCC.

Associations between antenatal SARS-CoV-2 infection and pregnancy outcomes have been conflicting and the role of the immune system is currently unclear. This prospective cohort study investigated the interaction of antenatal SARS-CoV-2 infection, changes in cytokine and HS-CRP levels, birthweight and gestational age at birth. 2352 pregnant participants from New York City (2020-2022) were included. Plasma levels of interleukin (IL)-1β, IL-6, IL-17A and high-sensitivity C-reactive protein (HS-CRP) were quantified in blood specimens obtained across pregnancy. Quantile and linear regression models were conducted to 1) assess the impact of antenatal SARS-CoV-2 infection, overall and by timing of detection of SARS-CoV-2 positivity (< 20 weeks versus ≥ 20 weeks), on birthweight and gestational age at delivery; 2) examine the relationship between SARS-CoV-2 infection and maternal immune changes during pregnancy. All models were adjusted for maternal demographic and obstetric factors and pandemic timing. Birthweight models were additionally adjusted for gestational age at delivery and fetal sex. Immune marker models were also adjusted for gestational age at specimen collection and multiplex assay batch. 371 (15.8%) participants were infected with SARS-CoV-2 during pregnancy, of which 98 (26.4%) were infected at < 20 weeks gestation. Neither SARS-CoV-2 infection in general nor in early or late pregnancy was associated with lower birthweight nor earlier gestational age at delivery. Further, we did not observe cytokine or HS-CRP changes in response to SARS-CoV-2 infection and thus found no evidence to support a potential association between immune dysregulation and the diversity in pregnancy outcomes following infection.

BACKGROUND: Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in pncA, encoding an enzyme that converts pyrazinamide into its active form. METHODS: We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features. RESULTS: The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in pncA derived from 24 231 clinical isolates. CONCLUSIONS: This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs.

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases.

Leptospirosis, the most widespread zoonotic disease in the world, is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 266 sampled opportunistically from other California regions and species. In the five target species seroprevalences ranged from 5 to 60%, and infection prevalences ranged from 0.8 to 15.2% in all except fox squirrels (0%). Leptospira phylogenomics and patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas.

Background In May-July 2020 in the New York City area, up to 16% of pregnant women had reportedly been infected with SARS-CoV-2. Prior studies found associations between SARS-CoV-2 infection during pregnancy and certain adverse outcomes (e.g., preterm birth, cesarean delivery). These studies relied on reverse transcription polymerase chain reaction (RT-PCR) testing to establish SARS-CoV-2 infection. This led to overrepresentation of symptomatic or acutely ill cases in scientific studies.Objective To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology and stage of infection, by using serological tests to measure IgG antibody levels.Study Design The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant women receiving obstetrical care at the Mount Sinai Hospital and Mount Sinai West Hospital from April 20, 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before August 15, 2020. Blood was drawn as part of routine clinical care; for each woman, we tested the latest sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labor and delivery. Pregnancy outcomes of interest (i.e., gestational age at delivery, birth weight, mode of delivery, Apgar score, ICU/NICU admission, and neonatal hospital length of stay) and covariates were extracted from electronic medical records. Among all Generation C participants who had given birth by August 15, 2020 (n=708), we established the SARS-CoV-2 seroprevalence. Excluding women who tested RT-PCR positive at delivery, we conducted crude and adjusted linear and logistic regression models to compare antibody positive women without RT-PCR positivity at delivery with antibody negative women without RT-PCR positivity at delivery. We stratified analyses by race/ethnicity to examine potential effect modification.Results The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (n=116, 95% CI 13.7-19.3). Twelve women (1.7%) were SARS-CoV-2 RT-PCR positive at delivery (11 of these women were seropositive). Seropositive women were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative women. SARS-CoV-2 seropositivity without RT-PCR positivity at delivery was associated with decreased odds of caesarean delivery (aOR 0.48, 95%CI 0.27; 0.84) compared with seronegative women without RT-PCR positivity at delivery. Stratified by race/ethnicity, the association between seropositivity and decreased odds of caesarean delivery remained for non-Hispanic Black/African-American and Hispanic women, but not for non-Hispanic White women. No other pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity.Conclusion Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery, suggesting that infection occurred earlier during pregnancy, was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample of women from New York City. While non-Hispanic Black and Latina women in our cohort had a higher rate of SARS-CoV-2 seropositivity compared with non-Hispanic White women, we found no increase in adverse maternal or neonatal outcomes among these groups due to infection.Competing Interest StatementMount Sinai has licensed serological assays to commercial entities and has filed for patent protection for serological assays. D.S and F.K. are listed as inventors on the pending patent application. The other authors have nothing to report.Funding StatementThis study is partially funded (contract 75D30120C08186) by the US Centers for Disease Control and Prevention (CDC), who also provided technical assistance related to analysis and interpretation of data and writing the report. The find ngs and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Initial assay development work in the Krammer laboratory was partially supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C (FK, for reagent generation), Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (FK, for reagent generation), and the generous support of the JPB foundation, the Open Philanthropy Project (#2020-215611) and other philanthropic donations. These funding sources were not involved in the current study.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All participants provided informed consent per the institutional review board (IRB)-approved study protocol (IRB at the Icahn School of Medicine at Mount Sinai, protocol IRB-20-03352, April 15, 2020).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData not publicly available. Please contact the corresponding author for data requests.

BACKGROUND Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODS Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTS SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (&lt;14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%–97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants.CONCLUSIONS Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.Competing Interest StatementAllison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work. Kurt T. Hegmann serves at the Editor of the American College of Occupational and Environmental Medicine evidence-based practice guidelines. Matthew S. These reported grants and personal fees from Reed Group and the American College of Occupational and Environmental Medicine, outside the submitted work. Other authors have reported no conflicts of interest.Funding StatementFunding provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was reviewed and approved by the University of Arizona IRB as the single IRB for this studyAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesSummary data will be available once all study objectives are met.

Leptospirosis is the most widespread zoonotic disease in the world, yet it is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), Northern raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 260 sampled opportunistically from other regions and species. In the five target species, seroprevalences ranged from 5-60% and active infection prevalences ranged from 0.8-15.2% in all except fox squirrels (0%). Patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Objective: Dysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels. Study design: We conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured. Result(s): Individual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy. Conclusion(s): Our findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Introduction: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. Method(s): We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. Result(s): The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (>=37 weeks), and gestational age at delivery did not differ between the SARSCoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. Discussion(s): SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

This article presented a new product development tool for adults with intellectual and developmental disabilities (IDD) developed by the Centers for Disease Control and Prevention (CDC). People with IDD who also have extreme low literacy (ELL) have unique communication needs; public health communicators often face challenges developing effective communication materials for this audience. To support CDC communication specialists with the development of communication products for adults with IDD/ELL, CDC, with its partners RTI International and CommunicateHealth, created a product development tool for this audience through literature review, expert input, and interviews with adults with IDD/ELL and caregivers of adults with IDD/ELL. To build evidence around the principles described in the tool, RTI conducted interviewer-administered surveys with 100 caregivers who support people with IDD/ELL. During the interviews, we presented caregivers with stimuli (portions of a communication product) that either did or did not apply a single principle and asked which would be easier for the person they support to understand. Across all 14 principles tested, the caregiver respondents indicated that the principle-based version would be easier for the person they support to understand compared with the non-principle-based version(s). These findings provide additional evidence to support the principles included in CDC's Tool for Developing Products for People with IDD/ELL.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are drinking water contaminants. Tools to assess the potential body burden associated with drinking PFAS-contaminated water may be helpful for public health assessment of exposed communities. METHODS: We implemented a suite of one-compartment toxicokinetic models using extensively calibrated toxicokinetic parameters (half-life and volume of distribution). We implemented the models both in the R programming language for research purposes, and as a web estimator for the general public (built in typescript.js). These models simulate exposure to PFAS water concentrations for individuals with varying characteristics such as age, sex, weight, and breastfeeding history. The models account for variability and uncertainty in parameter inputs to produce Monte Carlo-based estimates of serum concentration. For children, the models additionally account for gestational exposure, lactational exposure, and potential exposure through formula feeding. For adults who have borne children, the models account for clearance through birth and breastfeeding. We ran simulations of individuals with known PFAS water and serum concentrations to evaluate the model. We then compared the predicted serum PFAS concentrations to measured data. RESULTS: The models accurately estimate individual-level serum levels for each PFAS for most adults within ½ order of magnitude. We found that the models somewhat overestimated serum concentrations for children in the tested locations, and that these overestimates are generally within an order of magnitude. DISCUSSION: This paper presents scientifically robust models that allow users to estimate serum PFAS concentrations based on known PFAS water concentrations and physiologic information. However, accuracy in historical water concentration inputs, exposure from non-drinking water sources, and life-history characteristics of individuals present a complex problem for individual estimation. Additional refinements to the model suite to improve the prediction of individual results may consist of including duration of exposure and additional life-history characteristics.

BACKGROUND: Since 2012, the Lower Anogenital Squamous Terminology (LAST) Project recommended a 2-tiered nomenclature, low-grade and high-grade squamous intraepithelial lesion (LSIL and HSIL), to replace the 3-tiered cervical intraepithelial neoplasia (CIN) system for HPV-associated lesions. Prior to 2019, preinvasive cervical lesions classified as CIN3, severe dysplasia, carcinoma in situ (CIS), and adenocarcinoma in situ (AIS) were considered reportable to the Louisiana Tumor Registry for a CIN3 project funded by the Centers for Disease Control and Prevention (CDC); but lesions classified exclusively as high-grade/HSIL based on the 2-tiered system were not considered reportable. Due to the terminology changes, we wanted to know whether pre-2019 reportable criteria need to be modified to capture all reportable precancerous cervical cases diagnosed in 2019 forward. OBJECTIVES: To evaluate the utilization of LAST 2-tiered classification, low-grade and high-grade squamous intraepithelial lesion, and p16 immunohistochemistry (IHC) testing on cervical biopsy/surgical specimens, assess the search criteria needed to identify high-grade lesions for the CDC-funded CIN3 project, and assess the impact of underreporting cervical lesions caused by terminology changes. METHODS: An equal number of abnormal/precancerous and normal cervical findings from biopsy pathology reports received in 2015 were randomly selected by an artificial intelligence (AI) search engine developed by Artificial Intelligence in Medicine Inc (AIM) using pre2019 search criteria. Selected pathology reports were reflagged for the reportability by AIM audit software based on 2019 search criteria and manually reviewed for the use of reportable terms including CIN3, severe dysplasia, CIS, AIS, highgrade/HSIL terminology, and CIN2 or CIN2-3 with positive p16 IHC testing. Cohen's kappa statistic was used to assess the agreement between AIM auto-coding and manual review. Positive predictive values (PPV) and sensitivity tests were computed to evaluate the reportable terms. RESULTS: Six out of 9 surveyed laboratories used 2-tiered terminology on cervical biopsy pathology reports and 7 performed p16 IHC tests. Of 1,974 randomly selected reports from 5 laboratories, 987 were flagged as precancer by AI using pre-2019 search criteria. After adding the high-grade/HSIL term into pre-2019 search criteria, precancerous reports increased by 29%. After manual review, 41.6% of these cases were reportable precancerous cervical cases with a PPV of 0.65 (95% CI, 0.62-0.67) and 13.6% had p16 IHC performed. CONCLUSIONS: Both the 2-tiered and 3-tiered nomenclature are needed to ensure complete identification of all reportable high-grade cervical lesions.

BACKGROUND AND AIMS: Rectal squamous cell carcinoma (SCC) is a rare malignancy, and the causal role of human papillomavirus (HPV) in these cancers is thought to be similar to anal cancer. We compared type-specific prevalence of HPV in rectal SCC to anal cancer. In rectal SCC, we evaluated the agreement between HPV prevalence and positivity for p16, a marker of oncogenic activity. METHODS: A stratified random sample of rectal SCCs and anal cancers diagnosed between 2014 and 2015 were identified from 3 statewide cancer registries in Iowa, Kentucky, and Louisiana. HPV testing was performed at the HPV laboratory at the Centers for Disease Control and Prevention. HPV types were described using hierarchical attribution to HPV16 and other oncogenic types, weighted for sampling design. In rectal SCC, we computed concordance and Cohen's kappa coefficient (κ) between HPV status and p16 positivity. RESULTS: A total of 39 rectal and 72 anal cancers were analyzed. HPV16 was the most common type in both rectal and anal cancer and did not differ significantly between sites (71.4% vs 82.1%; P = .32). Concordance between the presence of any HPV type and p16 positivity in rectal SCC was 92% with κ = 0.77. CONCLUSIONS: Rectal SCC and anal cancer have similar type-specific HPV prevalence, with HPV16 found most frequently. Substantial agreement between p16 and HPV status in rectal SCC lends additional support for the etiologic role of HPV in both anal and rectal cancer. Larger studies could be conducted to replicate these findings.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

OBJECTIVE: The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. METHODS: Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-Pee(Ⓡ) device from November 2018 to February 2019. The samples were initially tested using Cobas(Ⓡ) 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by Anyplex(Ⓡ) assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. RESULTS: Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. CONCLUSION: A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.

Tap water is not sterile, and its use in home medical devices can result in infections from waterborne pathogens. However, many participants in a recent survey in the United States said tap water could safely be used for home medical devices. These results can inform communication materials to reduce the high consequence of infections.

From July-November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values &lt;30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (β = 12.42 g [-90.5, 114.8]), gestational age (β = 0.2 days [-1.1, 1.5]), blood loss (β = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

BACKGROUND: Handwashing with soap and water is an important way to prevent transmission of viruses and bacteria and worldwide it is estimated handwashing can prevent 1 in 5 viral respiratory infections. Frequent handwashing is associated with a decreased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Using a hand sanitizer with at least 60% alcohol when handwashing is not feasible can also help prevent the transmission of viruses and bacteria. OBJECTIVE: Since early 2020, the public has been encouraged to handwash frequently with soap and water and use alcohol-based hand sanitizer when soap and water are not available to reduce COVID-19 transmission. This study's objectives were to assess U.S. adults' perceptions of components of the Capability, Opportunity, Motivation and Behavior (COM-B) Model in relation to these two hand hygiene behaviors and to identify relationships between these components and hand hygiene behaviors. METHODS: Items assessing capability, opportunity, motivation, and hand hygiene behaviors were included in FallStyles, a survey completed by 3,625 adults in the fall of 2020 through an online panel representative of the U.S. POPULATION: We calculated composite capability, opportunity, and motivation measures and descriptive statistics for all measures. Finally, we conducted multiple logistic regressions to identify predictors of handwashing and hand sanitizer use. RESULTS: Most respondents reported frequently washing hands with soap and water (89%) and using alcohol-based hand sanitizer (72%) to prevent coronavirus. For capability, over 90% of respondents said that neither behavior takes a lot of effort, but fewer agreed that they knew when, or how, they should engage in handwashing (67%; 74%) and hand sanitizer use (62%; 64%). For opportunity, over 95% of respondents said lack of time didn't make it hard to engage in either behavior; fewer said visual cues reminded them to engage in the behaviors (handwashing: 30%; sanitizer use: 48%). For motivation, the majority believed the two behaviors were good ways to prevent coronavirus illness (handwashing: 76%; sanitizer use: 59%). Regressions indicated that capability, opportunity, and particularly motivation were positively associated with both hand hygiene behaviors. CONCLUSIONS: The COM-B model was a helpful framework for increasing understanding of hand hygiene behavior; it identified capability, opportunity, and motivation as predictors of both handwashing and hand sanitizer use.

BACKGROUND: Setting health-protective standards for poly- and perfluoroalkyl substances (PFAS) exposure requires estimates of their population toxicokinetics, but existing studies have reported widely varying PFAS half-lives (T()) and volumes of distribution (V(d)). OBJECTIVES: We combined data from multiple studies to develop harmonized estimates of T() and V(d), along with their interindividual variability, for four PFAS commonly found in drinking water: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). METHODS: We identified published data on PFAS concentrations in human serum with corresponding drinking water measurements, separated into training and testing data sets. We fit training data sets to a one-compartment model incorporating interindividual variability, time-dependent drinking water concentrations, and background exposures. Use of a hierarchical Bayesian approach allowed us to incorporate informative priors at the population level, as well as at the study level. We compared posterior predictions to testing data sets to evaluate model performance. RESULTS: Posterior median (95% CI) estimates of T() (in years) for the population geometric mean were 3.14 (2.69, 3.73) for PFOA, 3.36 (2.52, 4.42) for PFOS, 2.35 (1.65, 3.16) for PFNA, and 8.30 (5.38, 13.5) for PFHxS, all of which were within the range of previously published values. The extensive individual-level data for PFOA allowed accurate estimation of population variability, with a population geometric standard deviation of 1.57 (95% CI: 1.42, 1.73); data from other PFAS were also consistent with this degree of population variability. V(d) estimates ranged from 0.19 to 0.43 L/kg across the four PFAS, which tended to be slightly higher than previously published estimates. DISCUSSION: These results have direct application in both risk assessment (quantitative interspecies extrapolation and uncertainty factors for interindividual variability) and risk communication (interpretation of monitoring data). In addition, this study provides a rigorous methodology for further refinement with additional data, as well as application to other PFAS. https://doi.org/10.1289/EHP10103.

Zoonotic transmission of SARS-CoV-2 from infected humans to other animals has been documented around the world, most notably in mink farming operations in Europe and the United States. Outbreaks of SARS-CoV-2 on Utah mink farms began in late July 2020 and resulted in high mink mortality. An investigation of these outbreaks revealed active and past SARS-CoV-2 infections in free-roaming and in feral cats living on or near several mink farms. Cats were captured using live traps, were sampled, fitted with GPS collars, and released on the farms. GPS tracking of these cats show they made frequent visits to mink sheds, moved freely around the affected farms, and visited surrounding residential properties and neighborhoods on multiple occasions, making them potential low risk vectors of additional SARS-CoV-2 spread in local communities.

Background | One in four American adults reports having at least one disability. The COVID-19 pandemic has disproportionately impacted people with disabilities and widened already-existing health disparities and inequities. For many people with intellectual and developmental disabilities (IDD), these disparities are compounded by literacy limitations that make it challenging to access, understand, and act upon critical COVID-19 prevention information. | Methods | Using a design thinking framework, we conducted interviews with 27 caregivers of adults with IDD who also have extreme low literacy (ELL) to assess COVID-19 information needs and recommendations for how health care providers could best provide COVID-19 information. Based on our findings, we developed a draft tip sheet to help health care providers communicate with adults with IDD/ELL about COVID-19. We then tested the tip sheet with six health care providers via a focus group discussion. We refined and finalized the tip sheet based on our focus group findings. | Results | Caregivers noted the importance of visual aids, repetition, empathy and addressing the person with IDD/ELL directly when discussing COVID-19. Many health care providers indicated that the tip sheet would be most helpful for those with limited experience with patients with IDD/ELL and specific instructions for implementing the tips would be important. | Conclusions | We developed an evidence-informed tip sheet to facilitate communication between health care providers and adults with IDD/ELL and their caregivers, particularly around COVID-19.

Environmental health affects everyone. The air we breathe, the food we eat, the water we drink, and other aspects of the environment in which we live, work, and play all have a direct impact on our health. The Environmental Health Nexus (EH Nexus) from the Centers for Disease Control and Prevention (CDC) is a new communication network for sharing information about environmental public health topics. | | The network was created to help CDC actively communicate about environmental public health with interested members of the public and public health colleagues whose work involves environmental health concerns. This month's column highlights the EH Nexus and its four pillars: webinars and conferences, newsletters, communication partners, and expanded outreach activities.

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.