Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (∼70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.

For more than a decade, the U.S. Department of Housing and Urban Development (HUD) and the National Center for Health Statistics (NCHS) have partnered to link NCHS national health survey data with HUD administrative records on persons participating in federal public and assisted housing programs. This study used 2015-18 National Health Interview Survey (NHIS)-HUD linked data to examine women 18-44 years old with children and renting their home who were receiving HUD assistance (n=852) and a comparison population of women of the same age with children, who were low-income renters but did not link to HUD records at the time of their NHIS interview (n=894). The population of HUD-assisted women differed from the comparison group on key sociodemographic characteristics and health indicators. HUD-assisted women were more likely to report their health as fair or poor and to being a current smoker. HUD-assisted women also were less likely to be uninsured and more likely to have a regular source of care. The findings in this article are exploratory but demonstrate how the NCHS-HUD-linked data can be a resource for researchers and policymakers in further examining housing status as an important social determinant of health.

The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories. IMPORTANCE: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.

BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections.

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

PURPOSE: Although smoking cessation reduces the risk of all-cause mortality, evidence-based cessation treatments are underused. This study examined healthcare provider knowledge of evidence-based cessation treatments and associations between knowledge and clinical practice characteristics. DESIGN: Cross-sectional survey. SETTING: 2020 DocStyles. SUBJECTS: 1480 U.S. healthcare providers. MEASURES: Provider knowledge of availability of tobacco use disorder diagnostic criteria, clinical practice guideline availability, treatment efficacy, evidence-based counseling modalities, and medications approved by the U.S. Food and Drug Administration (FDA). ANALYSIS: Adjusted odds ratios (aORs), adjusted for personal and clinical practice characteristics. RESULTS: Less than half of respondents demonstrated high knowledge of availability of diagnostic criteria (36.8%), cessation treatment efficacy (33.2%), evidence-based counseling modalities (5.6%), and FDA-approved medications (40.1%). Significant differences were found between specialties: compared to internists, family physicians were less likely to have low knowledge of medications (aOR = .69, 95% CI = .53, .90) and obstetricians/gynecologists were more likely to have low knowledge of medications (aOR = 2.62, 95% CI = 1.82, 3.76). Overall, few associations between knowledge and clinical practice characteristics were identified. CONCLUSION: Most providers had low knowledge of the topics of interest, with little variation across clinical practice characteristics, indicating room for improvement. Efforts to improve provider knowledge of evidence-based treatments are an important component of a comprehensive approach to improving delivery and use of cessation interventions and increasing tobacco cessation.

Tenofovir disoproxil fumarate and emtricitabine are used for HIV treatment and pre-exposure prophylaxis. Previously, we found that topical rectal application of tenofovir 1% gel caused many gene expression changes. Here, we measured RNA and protein expression in several clinical trials of oral administration in HIV-uninfected individuals (using microarrays, RNAseq, droplet digital PCR, mass spectrometry, and microscopy). We found tens to hundreds of differentially expressed genes in the gastrointestinal tract, but none in the blood or female reproductive tract. In rectal samples from one trial, most of the 13 upregulated genes were related to type I/III interferon signaling. Similar changes were seen at the protein level in the same trial and in the duodenum and rectum in another trial. We conclude that tenofovir disoproxil fumarate and emtricitabine have little effect on gene expression in the blood or female reproductive tract but increase type I/III interferon signaling in the gut. This effect may enhance their anti-viral efficacy when used as pre-exposure prophylaxis, in particular to prevent rectal HIV transmission. However, it may also contribute to chronic immune activation and HIV reservoir maintenance in chronically treated people living with HIV.

Recent and sustained increases in sexually transmitted infections (STI)(1) and the SARS-CoV-2 pandemic,(2) have accelerated technological advances for disease intervention and brought new attention to communicable disease.(3 ) These events provide an opportunity for public health to reflect on the role of disease intervention in curbing infectious disease transmission and focus on methods to enhance and expand existing disease intervention functions. Additionally, substantial federal investment in disease intervention activities make this an opportune time to develop a more robust and nimble disease intervention workforce.(4) Disease intervention includes traditional functions, such as case investigation and contract tracing (CICT, also referred to as partner services), and has been in practice for numerous decades for the control and prevention of infectious diseases such as STI(5). In most instances, the primary focus of disease intervention is to reduce or halt transmission of infections. Within STI prevention, the disease intervention role is often conducted by disease intervention specialists (DIS) or communicable disease investigators (CDI) (referred to as DIS hereafter).(6 ) We propose a model that describes activities conducted by DIS and how these activities can be impacted by public health priorities and the context surrounding their work (Figure). We will discuss how DIS activities and the various contextual factors we highlight can influence or impact each othe

National trends in gonorrhea rates may obscure informative local variations in morbidity. We used group-based trajectory models to identify groups of counties with similar gonorrhea rate trajectories among non-Hispanic White (NHW) and non-Hispanic Black (NHB) females using county-level data on gonorrhea cases in US females from 2003 to 2018. We assessed models with 1-15 groups and selected final models based on fit statistics and identification of divergent trajectory groups with distinct intercepts and/or slopes. We mapped counties by assigned trajectory group and examined the association of county characteristics with group membership. We identified 7 distinct gonorrhea trajectory groups for NHW females and 9 distinct trajectory groups for NHB females. All identified groups for NHW female morbidity experienced increasing gonorrhea rates with a limited range (11.6-183.3/100,000 NHW females in 2018); trajectories of NHB female morbidity varied widely in rates (146.6-966.0/1000 NHB females in 2018) and included 3 groups of counties that experienced a net decline in gonorrhea rates. Counties with higher NHW female morbidity had lower adult sex ratios, lower health insurance coverage, and lower marital rates among NHW adults. Counties with higher NHB female morbidity were more urban, experienced higher rates of poverty, and had lower rates of marriage among NHB adults. Morbidity patterns did not always follow geographic proximity, which could be explained by variation in social determinants of health. Our results demonstrated a highly heterogenous gonorrhea epidemic among NHW and NHB US females, which should prompt further analysis into the differential drivers of gonorrhea morbidity.

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.

Spatial analyses of gonorrhea morbidity among women often highlight the Southeastern United States but may not provide information on geographic variation in the magnitude of racial disparities; such maps also focus on geographic space, obscuring underlying population characteristics. We created a series of visualizations depicting both county-level racial disparities in female gonorrhea diagnoses and variations in population size. We calculated county- and region-level race-specific relative rates (RelR) and between-race rate differences (RDs) and rate ratios (RRs) comparing gonorrhea case rates in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) women. We then created proportional symbol maps with color representing counties' RelR/RD/RR category and symbol size representing counties' female population. Gonorrhea rates among NHB women were highest in the Midwest (718.7/100,000) and West (504.8), rates among NHW women were highest in the West (74.1) and Southeast (72.1). The RDs were highest in the Midwest (654.6 excess cases/100,000) and West (430.7), whereas the RRs were highest in the Northeast (12.4) and Midwest (11.2). Nearly all US counties had NHB female rates ≥3× those in NHW women, with NHB women in most highly populated counties experiencing ≥9-fold difference in gonorrhea rates. Racial disparities in gonorrhea were not confined to the Southeast; both relative and absolute disparities were equivalent or larger in magnitude in areas of the Northeast, Midwest, and West. Our findings help counter damaging regional stereotypes, provide evidence to refocus prevention efforts to areas of highest disparities, and suggest a useful template for monitoring racial disparities as an actionable public health metric. | eng

Epidemiological studies of occupational, medical, and environmental exposures have provided important information on lung cancer risk and how those risks might depend on the type of exposure, dose rate, and other potential modifying factors such as sex and age of the exposed. Analyses of data from underground miner cohorts and residential case-control studies provide convincing evidence that radon is a leading cause of lung cancer. For low-LET radiation, risk models derived from results from the Lifespan Study of Japanese atomic bomb survivors suggest that for acute exposures, lifetime attributable risks for lung cancer are greater than for other specific cancer sites and are substantially larger for females than males. However, for protracted and fractionated exposures other than from radon, results from epidemiological studies are seemingly often contradictory.

In the past few decades, reported human cases of Colorado tick fever in the western United States have decreased dramatically. The goal of this study was to conduct surveillance for Colorado tick fever virus (CTFV) in Dermacentor ticks in recreational sites in Colorado, Wyoming, and California to determine whether the virus is still present in Dermacentor ticks from these states. Surveillance focused on regions where surveys had been conducted in the 1950s, 1960s, and 1970s. Adult Rocky Mountain wood ticks (Dermacentor andersoni), Pacific Coast ticks (Dermacentor occidentalis), and winter ticks (Dermacentor albipictus) were tested by PCR. A subset of PCR-positive D. andersoni ticks (n=7) were cultured in Vero cells. CTFV-positive Rocky Mountain wood ticks were found in all states: Colorado (58% prevalence), Wyoming (21%), and California (4%). Although no winter ticks tested positive, Pacific Coast ticks tested positive in one county (Siskiyou County, 15% prevalence) and were positive only in a location that also maintained Rocky Mountain wood ticks and golden mantled ground squirrels, a known CTFV host. In summary, CTFV is prevalent in D. andersoni and D. occidentalis in regions where they are sympatric in California and in D. andersoni in Colorado and Wyoming. Although the number of human CTFV cases has declined dramatically, this decrease in reported disease does not appear to be due to the disappearance or even the decline in prevalence of this virus in ticks in historically endemic regions of the country.

BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

BACKGROUND: In 2016, CDC initiated Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) in multiple jurisdictions to enhance antibiotic resistant gonorrhea rapid detection and response infrastructure and evaluate the impact of key strategies. METHODS: Eight jurisdictions were funded to establish or enhance local gonococcal culture specimen collection in STD and community clinics, conduct rapid antimicrobial susceptibility testing (AST) in local laboratories, modify systems for enhanced data collection and rapid communication of results, and initiate enhanced partner services among patients with gonorrhea demonstrating elevated minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime or azithromycin. RESULTS: Grantees incorporated genital, pharyngeal, and rectal gonococcal culture collection from all genders at participating clinics. During 2018-2019, grantees collected 58,441 culture specimens from 46,822 patients and performed AST on 10,814 isolates (representing 6.8% (3,412) and 8.9% (4,883) of local reported cases in 2018 and 2019 respectively). Of isolates that underwent AST, 11% demonstrated elevated azithromycin MICs; fewer than 0.5% demonstrated elevated ceftriaxone or cefixime MICs. Among patients whose infections demonstrated elevated MICs, 81.7% were interviewed for partner elicitation; however, limited new cases were identified among partners and contacts. CONCLUSIONS: As a public health model to build capacity to slow the spread of emerging resistance, SURRG successfully expanded culture collection, implemented rapid AST, and implemented an enhanced partner services investigation approach in participating jurisdictions. Findings from SURRG may enhance preparedness efforts and inform a longer-term, comprehensive, and evidence-based public health response to emerging gonococcal resistance. Continued development of innovative approaches to address emerging resistance is needed.

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.

INTRODUCTION: During the E-cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) outbreak, patient data on tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (EVP) use was collected, but data on non-affected adult product use after the onset of the EVALI outbreak is limited. This study describes adult THC-EVP use after EVALI began. METHODS: THC-EVP use data came from an 18-state web-based panel survey of adult THC- and nicotine-containing EVP users conducted February 2020. Unweighted descriptive statistics were calculated; logistic regression assessed correlates of use. RESULTS: Among 3,980 THC-EVP users, 23.5% used THC-EVPs daily. Common brands of THC-EVPs used were Dank Vapes (47.7%) and Golden Gorilla (38.7%). Reported substances used included THC oils (69.6%), marijuana herb (63.6%) and THC concentrate (46.4%). Access sources included: recreational dispensaries (41.1%), friend/family member (38.6%) and illicit dealers (15.1%). Respondents aged 45-64 years had lower odds for daily use compared with those aged 25-34 years (aOR = 0.73; 95% CI = 0.60, 0.90). Compared with White respondents, Asian respondents had lower odds (aOR = 0.55; 95% CI = 0.36, 0.84) and Black respondents higher odds (aOR = 1.48; 95% CI = 1.17, 1.86) of daily use. Respondents odds of daily use and accessing THC-EVPs through commercial sources were higher among states with legalized nonmedical adult marijuana use compared to states without. CONCLUSIONS: Almost half of respondents reported daily or weekly THC-EVP use, and accessed products through both informal and formal sources, even after EVALI began. Given the potential for future EVALI-like conditions to occur, it is important to monitor the use of THC-EVPs and ensure effective education activities about associated risk.

PURPOSE: Risks of occupational radiation exposures of workers involved in uranium refining and processing ("uranium processing workers") may be different from risks of other workers from the nuclear fuel cycle. Pooling of individual-level data from published studies and analysis using similar dosimetry and statistical methods might provide valuable insights into risks from occupational uranium and external ionizing radiation exposures. METHODS: We pooled the data for workers from four uranium processing facilities (Fernald Feed Materials Production Center, Ohio; Mallinckrodt Chemical Works Uranium Division, Missouri; Middlesex Sampling Plant, New Jersey; and the Port Hope Radium and Uranium Refining and Processing Plant, Canada). Employment began as early as the 1930s in Canada and follow-up for vital status was as late as 2017. These facilities used similar methods to process Belgian Congo pitchblende ore which contained high concentrations of uranium, radium, and their decay products. In addition, workers were exposed to elevated levels of gamma radiation, fission product contaminants in recycled uranium and ambient radon decay products. Non-radiation exposures of industrial hygiene concern were silica dust inhalation, heavy metal toxicity from uranium, solvents, acid mists and chemicals associated with uranium processing. Exposure and outcome data were harmonized using similar definitions and dose reconstruction methods. Standardized mortality ratios (SMR) were estimated by comparing mortality in the pooled cohort with age-, sex- and calendar time-specific general population mortality rates for the U.S. and Canada. RESULTS: Over 12,400 workers will be evaluated for cancer and non-cancer mortality in relation to exposures to uranium byproducts and gamma radiation (including ∼1,300 females). In total, death from 560 lung cancers, 503 nonmalignant respiratory diseases, 67 renal diseases, 1,596 ischemic heart diseases, and 101 dementia and Alzheimer's diseases (AD) were detected among male workers during follow-up. Mean cumulative doses were 45 millisievert for whole-body external exposures and 172 milligray for lung dose from radon decay products. Of the 16 pooled SMRs, seven were above 1.00, none were significantly low, and only one was significantly high, i.e., dementia and AD among males (SMR =1.29; 95% confidence interval: 1.04,1.54). CONCLUSIONS: This is the largest study to date to examine health risks in uranium processing workers (excluding uranium enrichment workers). The pooling of uranium processing worker data will address issues of importance today, specifically the concerns for cleanup workers and environmental contamination from the operation of past and present nuclear reactor and radiation facilities, reactor accidents, and possible terrorist events.

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.

Foodborne illness source attribution is foundational to a risk-based food safety system. We describe a method for attributing US foodborne illnesses caused by nontyphoidal Salmonella enterica, Escherichia coli O157, Listeria monocytogenes, and Campylobacter to 17 food categories using statistical modeling of outbreak data. This method adjusts for epidemiologic factors associated with outbreak size, down-weights older outbreaks, and estimates credibility intervals. On the basis of 952 reported outbreaks and 32,802 illnesses during 1998-2012, we attribute 77% of foodborne Salmonella illnesses to 7 food categories (seeded vegetables, eggs, chicken, other produce, pork, beef, and fruits), 82% of E. coli O157 illnesses to beef and vegetable row crops, 81% of L. monocytogenes illnesses to fruits and dairy, and 74% of Campylobacter illnesses to dairy and chicken. However, because Campylobacter outbreaks probably overrepresent dairy as a source of nonoutbreak campylobacteriosis, we caution against using these Campylobacter attribution estimates without further adjustment.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion(s): A combination of EHR-based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10-fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

Coronavirus disease 2019 (COVID-19) is a complex clinical illness with potential complications that might require ongoing clinical care (1-3). Few studies have investigated discharge patterns and hospital readmissions among large groups of patients after an initial COVID-19 hospitalization (4-7). Using electronic health record and administrative data from the Premier Healthcare Database,* CDC assessed patterns of hospital discharge, readmission, and demographic and clinical characteristics associated with hospital readmission after a patient's initial COVID-19 hospitalization (index hospitalization). Among 126,137 unique patients with an index COVID-19 admission during March-July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%). The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. These results support recent analyses that found chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Understanding the frequency of, and risk factors for, readmission can inform clinical practice, discharge disposition decisions, and public health priorities such as health care planning to ensure availability of resources needed for acute and follow-up care of COVID-19 patients. With the recent increases in cases nationwide, hospital planning can account for these increasing numbers along with the potential for at least 9% of patients to be readmitted, requiring additional beds and resources.

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are used for HIV treatment and prevention. Previously, we found that topical rectal tenofovir gel caused immunological changes in the mucosa. Here, we assess the effect of oral TDF/FTC in three HIV pre-exposure prophylaxis trials, two with gastrointestinal and one with cervicovaginal biopsies. TDF/FTC induces type I/III interferon-related (IFN I/III) genes in the gastrointestinal tract, but not blood, with strong correlations between the two independent rectal biopsy groups (Spearman r = 0.91) and between the rectum and duodenum (r = 0.81). Gene set testing also indicates stimulation of the type I/III pathways in the ectocervix and of cellular proliferation in the duodenum. mRNA sequencing, digital droplet PCR, proteomics, and immunofluorescence confirm IFN I/III pathway stimulation in the gastrointestinal tract. Thus, oral TDF/FTC stimulates an IFN I/III signature throughout the gut, which could increase antiviral efficacy but also cause chronic immune activation in HIV prevention and treatment settings.

OBJECTIVE: Although some studies have reported a higher incidence of HIV infection among non-US-born people than among US-born people, national data on this topic are scarce. We compared the epidemiology of HIV infection between US-born and non-US-born residents of the United States and examined the characteristics of non-US-born people with diagnosed HIV infection by region of birth (ROB). METHODS: We used a cross-sectional study design to produce national, population-based data describing HIV infection among US-born and non-US-born people. We analyzed National HIV Surveillance System data for people with HIV infection diagnosed during 2010-2017 and reported to the Centers for Disease Control and Prevention (CDC). We compared data on demographic characteristics, transmission risk category, and stage 3 infection (AIDS) classification within 3 months of HIV diagnosis, by nativity and ROB. RESULTS: During 2010-2017, 328 317 children and adult US residents were diagnosed with HIV infection and were reported to CDC: 214 973 (65.5%) were US-born, 50 301 (15.3%) were non-US-born, and 63 043 (19.2%) were missing data on country of birth. After adjusting for missing country of birth, 266 147 (81.1%) people were US-born and 62 170 (18.9%) were non-US-born. This group accounted for 15 928 of 65 645 (24.2%) HIV diagnoses among girls and women and 46 242 of 262 672 (17.6%) HIV diagnoses among boys and men. A larger percentage of non-US-born people than US-born people had stage 3 infection (AIDS) at HIV diagnosis (31.2% vs 23.9%). Among non-US-born people with HIV diagnoses, 19 876 (39.5%) resided in the South. CONCLUSIONS: Characterizing non-US-born people with HIV infection is essential for developing effective HIV interventions, particularly in areas with large immigrant populations.

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.

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from across 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.

Geotechnical mapping, rock mass characterization, and inspections of underground excavations are critical to ensuring that excavation geometry and ground support design are appropriate for stable conditions. A lack of access, poor timing, or hazardous conditions are all factors that can prohibit engineering personnel from collecting high-quality data in the field. Advances in unmanned aerial vehicles (UAV) and portable sensor technology now allow engineering personnel to remotely capture data from underground workings that can be used for developing designs, generating inputs for analyses, and making more informed decisions. Ground falls are a source of many accidents in the underground environment, and they are the focus of many geotechnical investigations and analyses. In this study, the authors investigated how portable UAV-mounted thermal and multispectral imagers could be used to detect and quantify adverse geological discontinuities in hard rock masses that are structurally controlled. Multiple thermal, multispectral, RGB (red, green, and blue), and LiDAR (light detection and ranging) data sets were captured from 5 flights in sub-level open stopes at the Barrick Golden Sunlight Mine in the state of Montana in the western United States of America. Using off-the-shelf software, the thermal, RGB, and multispectral images were processed to create individual three-dimensional point clouds and meshes, which were georeferenced using the LiDAR data. Discontinuities identified in the three-dimensional point clouds and meshes were mapped using tools found in the freeware CloudCompare. One of the thermal models identified wedges that had developed in the crown pillar of an open stope, and 4 of the multispectral models contained enough detail for mapping individual discontinuities. The results of this investigation indicate that these portable imagers are viable tools that can be used to aid engineering personnel in identifying and mapping adverse geological discontinuities and unique rock mass composition. The techniques for capturing, processing, and interpreting thermal and multispectral imagery captured in underground excavations are described in this paper and can be used as the basis for future investigations at individual underground sites.