Reliable, validated diagnostic tests are critical for rabies control in animals and prevention in people. We present a performance assessment and updates to the LN34 real-time RT-PCR assay for rabies diagnosis in postmortem animal brain samples. In two U.S. laboratories during 2017 to 2022, routine used of the LN34 assay produced excellent diagnostic sensitivity (99.72% to 100%) and specificity (99.99% to 100%) compared to the direct fluorescence antibody test (DFA). Almost all (>90%) DFA indeterminate results caused by non-specific or atypical fluorescence were negative by LN34 testing, representing up to 111 cases where unnecessary post-exposure prophylaxis could be avoided. LN34 assay original primer sequences showed low sensitivity for some rare lyssaviruses. Increased primer concentration combined with new primer formulation showed improved performance for impacted lyssaviruses with no loss in performance across diverse rabies virus variants from clinical samples. The updated LN34 and internal control assays were combined into a single-well LN34 multiplexed (LN34M) format, run at half reagent volumes. The LN34M assay showed similar detection of rabies virus to the singleplexed assay with simplified assay set-up, lower cost, and improved quality controls.

Beyond its physical health impact, the COVID-19 pandemic also resulted in grief from loss of loved ones, isolation due to social distancing, stress, fear, and economic distress-all of which impacted mental health. How Right Now/Qué Hacer Ahora (HRN) is an award-winning, national campaign that provides emotional support to people disproportionately affected by COVID-19. We conducted a theory-based, culturally responsive evaluation to assess the campaign's effect on coping behaviors and resiliency between summer 2020 and spring 2021. We surveyed HRN's priority audiences (older adults/caregivers and those with preexisting health conditions, experiencing violence, or economic distress) in English and Spanish using NORC's national probability panel, AmeriSpeak, over three waves. We also analyzed social media data and monitored HRN website traffic and triangulated these data to understand the campaign's full impact. Campaign exposure was associated with people who were experiencing higher levels of stress and were more likely to seek information to support their emotional well-being. Campaign exposure was also positively associated with increased feelings of resilience and confidence in using coping strategies, especially for people experiencing violence or economic distress and people from racial and ethnic groups. Findings demonstrate the campaign's success in reaching its intended audiences with the mental health support they needed. Additionally, the HRN evaluation's design illustrates how the use of multiple data sources can elucidate a deeper understanding of campaign impact. Findings underscore that culturally responsive health communication interventions-like HRN-can provide needed mental health support and resources to disproportionately affected communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Peribunyavirids produce enveloped virions with three negative-sense RNA segments comprising 10.7-12.5 kb in total. The family includes globally distributed viruses in multiple genera. While most peribunyavirids are maintained in geographically restricted vertebrate-arthropod transmission cycles, others are arthropod-specific or do not have a known vector. Arthropods can be persistently infected. Human and other vertebrate animal infections occur through blood feeding by an infected vector arthropod, resulting in diverse human and veterinary clinical outcomes in a strain-specific manner. Reassortment can occur between members of the same genus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Peribunyaviridae, which is available at ictv.global/report/peribunyaviridae.

Wildlife translocation and cross-species transmission can impede control and elimination of emerging zoonotic diseases. Tracking the geographic origin of both host and virus (i.e., translocation versus local infection) may help determine the most effective response when high-risk cases of emerging pathogens are identified in wildlife. In May 2022, a coyote (Canis latrans) infected with the raccoon (Procyon lotor) rabies virus variant (RRV) was collected in Lewis County, West Virginia, USA, an area free from RRV. We applied host population genomics and RRV phylogenetic analyses to determine the most likely geographic origin of the rabid coyote. Coyote genomic analyses included animals from multiple eastern states bordering West Virginia, with the probable origin of the rabid coyote being the county of collection. The RRV phylogenetic analyses included cases detected from West Virginia and neighboring states, with most similar RRV sequences collected in a county 80 km to the northeast, within the oral rabies vaccination zone. The combined results suggest that the coyote was infected in an RRV management area and carried the RRV to Lewis County, a pattern consistent with coyote local movement ecology. Distant cross-species transmission and subsequent host movement presents a low risk for onward transmission in raccoon populations. This information helped with emergency response decision-making, thereby saving time and resources.

BACKGROUND: Tuberculosis (TB) infection prevention and control (IPC) in healthcare facilities is key to reducing transmission risk. A framework for systematically improving TB IPC through training and mentorship was implemented in 9 healthcare facilities in China from 2017 to 2019. METHODS: Facilities conducted standardized TB IPC assessments at baseline and quarterly thereafter for 18 months. Facility-based performance was assessed using quantifiable indicators for IPC core components and administrative, environmental, and respiratory protection controls, and as a composite of all control types We calculated the percentage changes in scores over time and differences by IPC control type and facility characteristics. RESULTS: Scores for IPC core components increased by 72% during follow-up when averaged across facilities. The percentage changes for administrative, environmental, and respiratory protection controls were 39%, 46%, and 30%, respectively. Composite scores were 45% higher after the intervention. Overall, scores increased most during the first 6 months. There was no association between IPC implementation and provincial economic development or volume of TB services. CONCLUSIONS: TB IPC policies and practices showed most improvement early during implementation and did not differ consistently by facility characteristics. The training component of the project helped increase the capacity of healthcare professionals to manage TB transmission risks. Lessons learned here will inform national TB IPC guidance.

Machine-learning methods in the form of Bayesian networks (BN), linear projection (LP) and self-organizing tree (SOT) models were used to explore association among polymorphic sites within the HVR1 and NS5a regions of the HCV genome, host demographic factors (ethnicity, gender and age) and response to the combined interferon (IFN) and ribavirin (RBV) therapy. The BN models predicted therapy outcomes, gender and ethnicity with accuracy of 90%, 90% and 88.9%, respectively. The LP and SOT models strongly confirmed associations of the HVR1 and NS5A structures with response to therapy and demographic host factors identified by BN. The data indicate host specificity of HCV evolution and suggest the application of these models to predict outcomes of IFN/RBV therapy.

Hepatitis C Virus sequence studies mainly focus on the viral amplicon containing the Hypervariable region 1 (HVR1) to obtain a sample of sequences from which several population genetics parameters can be calculated. Recent advances in sequencing methods allow for analyzing an unprecedented number of viral variants from infected patients and present a novel opportunity for understanding viral evolution, drug resistance and immune escape. In the present paper, we compared three recent technologies for amplicon analysis: (i) Next-Generation Sequencing; (ii) Clonal sequencing using End-point Limiting-dilution for isolation of individual sequence variants followed by Real-Time PCR and sequencing; and (iii) Mass spectrometry of base-specific cleavage reactions of a target sequence. These three technologies were used to assess intra-host diversity and inter-host genetic relatedness in HVR1 amplicons obtained from 38 patients (subgenotypes 1a and 1b). Assessments of intra-host diversity varied greatly between sequence-based and mass-spectrometry-based data. However, assessments of inter-host variability by all three technologies were equally accurate in identification of genetic relatedness among viral strains. These results support the application of all three technologies for molecular epidemiology and population genetics studies. Mass spectrometry is especially promising given its high throughput, low cost and comparable results with sequence-based methods.

BACKGROUND: Studying carcinogens in tobacco and non-tobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: Golestan Cohort Study (GCS) has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma (ESCC). For this nested study, the cases comprised of all incident cases by Jan 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and tobacco-specific nitrosamines (TSNAs). We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for associations between the 90th versus the 10th percentiles of the biomarker concentrations and incident ESCC. RESULTS: Among individuals who did not currently use tobacco (148 cases/163 controls), two acrolein metabolites, two acrylonitrile metabolites, one propylene oxide metabolite and one 1,3-butadiene metabolite were significantly associated with incident ESCC (adjusted ORs between 1.8 and 4.3). Among tobacco users (57 cases/63 controls), metabolites of two other VOCs (styrene and xylene) were associated with ESCC (ORs= 6.2 and 9.0). In tobacco users, two TSNAs (NNN and N'-Nitrosoanatabine) were also associated with ESCC. Suggestive associations were seen with some PAHs (especially 2-hydroxynaphthalene) in non-users of tobacco products and other TSNAs in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

BACKGROUND: Biomarkers of exposure are tools for understanding the impact of tobacco use on health outcomes if confounders like demographics, use behavior, biological half-life and other sources of exposure are accounted for in the analysis. METHODS: We performed multiple regression analysis of longitudinal measures of urinary biomarkers of alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds (VOC), and metals to examine the sample-to-sample consistency in Waves 1 and 2 of the Population Assessment of Tobacco and Health Study including demographic characteristics and use behavior variables of persons who smoked exclusively. Regression coefficients, within- and between-person variance, and intra-class correlation coefficients were compared to biomarker smoking-nonsmoking population mean ratios and biological half-lives. RESULTS: Most biomarkers were similarly associated with sex, age, race/ethnicity, and product use behavior. The biomarkers with larger smoking-nonsmoking population mean ratios had greater regression coefficients related to recency of exposure. For VOC and alkaloid metabolites, longer biological half-life was associated with lower within-person variance. For each chemical class studied, there were biomarkers that demonstrated good intra-class correlation coefficients. CONCLUSIONS: For most of the biomarkers of exposure reported in the PATH Study, for people who smoke cigarettes exclusively, associations are similar between urinary biomarkers of exposure and demographic and use behavior covariates. Biomarkers of exposure within-subject consistency is likely associated with non-tobacco sources of exposure and biological half-life. IMPACT: Biomarkers measured in the PATH Study provide consistent sample-to-sample measures from which to investigate the association of adverse health outcomes with the characteristics of cigarettes and their use.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Orthobunyaviruses have been reported to cause severe diseases in humans or animals, posing a threat to human health and social economy. Ebinur lake virus (EBIV) is a newly classified orthobunyavirus, which needs further intensive study and therapies to cope with its potential infection risk to human and animals. Here, through the reverse genetics system, the recombinant EBIV of wild type (rEBIV/WT) and NP-conjugated-eGFP (rEBIV/eGFP/S) were rescued for the application of the rapid antiviral drug screening. The eGFP fluorescence signal of the rEBIV/eGFP/S was stable in the process of successive passage in BHK-21 cells (over 10 passages) and this recombinant virus could replicate in various cell lines. Compared to the wild type EBIV, the rEBIV/eGFP/S caused the smaller plaques and its peak titers were lower, suggesting attenuation due to the eGFP insertion. Through the high-content screening (HCS) system, ribavirin showed an inhibitory effect on the rEBIV/eGFP/S with an EC50 of 21.91 μM, while favipiravir did not inhibit, even at high concentrations. In addition, five of ninety-six natural compounds had antiviral against EBIV. The robust reverse genetics system for EBIV will facilitate investigation into replication and assembly mechanisms and assist drug and vaccine development.Competing Interest StatementThe authors have declared no competing interest.

Elizabethkingia anophelis is an emerging global multidrug-resistant opportunistic pathogen. We assessed the diversity among 13 complete genomes and 23 draft genomes of E. anophelis derived from various environmental settings and human infections from different geographic regions around the world over past decades from 1950s. Thirty-one of these 36 strains harbor integrative and conjugative elements (ICEs). A total of 52 ICEs were identified, and categorized into three ICE types based on the architecture of signature genes in the conjugation module. The type II and III ICEs were found to integrate into regions adjacent to tRNA genes, while type I ICEs used a variety of integration sites, inserting into intergenic regions or even directly into a gene, sometimes disrupting gene function. Integrases such as tyrosine recombinases, serine recombinases and DDE transposases were found in most ICEs. The ICEs carry various cargo genes including transcription regulators and those involved in antibiotic resistance. The CRISPR-Cas system was found in nine strains, including four strains in which CRISPR-Cas machinery and ICEs co-exist. ICE distribution in the strains showed no geographic or temporal patterns. The ICEs in E. anophelis differ in gene structure and sequence from CTnDOT, a well-studied ICE prevalent in Bacteroides spp. This is the first set of ICEs identified in the family Flavobacteriaceae. As a prevalent type of mobile genetic elements in various strains of E. anophelis around the world, the categorization of ICEs will facilitate further investigations such as virulence, genome epidemiology and adaptation genomics of E. anophelis.Importance Elizabethkingia anophelis is an opportunistic human pathogen, and the genetic diversity between strains from around the world becomes apparent as more genomes are sequenced. The Integrative Conjugative Element (ICE), found in many bacterial species, contains genes for transfer via conjugation and integration into the chromosome, along with various cargo genes. ICEs are identified in 31 of 36 strains and categorized into three types based on architecture of modular genes, integrases, and integration sites. ICE distribution in different strains displays no spatial and temporal patterns. Several ICE-containing strains also possessed CRISPR-Cas units, considered to be the bacterial adaptive immune system providing protection against phage and predatory mobile genetic elements. This co-existence suggests that ICEs are beneficial or at least not harmful to the bacterial cells they inhabit. ICEs as a component of the mobile genetic repertoire enable recipients to resist antibiotics, survive disinfecting agents, and adapt to various ecological niches.

CONTEXT.—: Two major categories of laboratories performing nonwaived testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) are the Certificate of Accreditation (CoA) and Certificate of Compliance (CoC) laboratories. Accreditation organizations collect more detailed laboratory personnel information than the Centers for Medicare & Medicaid Services (CMS) Quality Improvement and Evaluation System (QIES). OBJECTIVE.—: To estimate total numbers of testing personnel and testing volumes in CoA and CoC laboratories, by laboratory type and state. DESIGN.—: We developed a statistical inference method by using the respective correlations between testing personnel counts and test volume by laboratory type. RESULTS.—: QIES reported 33 033 active CoA and CoC laboratories in July 2021. We estimated testing personnel to be 328 000 (95% CI, 309 000-348 000), which is supported by the count of 318 780 reported by the US Bureau of Labor Statistics. There were twice as many testing personnel in hospital laboratories as in independent laboratories (158 778 versus 74 904, P < .001). Independent laboratories had the highest test volume per person, which was twice as high as physician office laboratories (62 228 versus 30 102, P < .001). Hospital and independent laboratories comprised 34% of all CoA and CoC laboratories but performed the largest portion of testing (81%). Physician office laboratories, accounting for 44% of all CoA and CoC laboratories, performed a comparatively low proportion of total tests (9%). CONCLUSIONS.—: Numbers of testing personnel vary considerably by laboratory type and across states. These data can provide valuable insight when assessing laboratory workforce training needs and planning for public health emergencies.

Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination.

The number of testing sites receiving their first Certificate of Waiver (CoW) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) increased significantly after the start of the COVID-19 pandemic. We compared the first-time CoWs in 2020-2021 to those in 2018-2019. The total number of first-time CoWs during 2020-2021 was more than twice what it was in 2018-2019, corresponding to population testing needs during the COVID-19 pandemic, especially in assisted living facility, pharmacy, physician office, and school/student health service settings. This study highlighted the need to strengthen clinical testing strategies to be better prepared for future public health emergencies.

The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

Orthobunyaviruses have been reported to cause severe diseases in humans or animals, posing a potential threat to human health and socio-economy. Ebinur lake virus (EBIV) is a newly classified orthobunyavirus, which can induce the histopathogenic change and even the high mortality of infected BALB/c mice. Therefore, it is needed to further study the viral replication and pathogenesis, and develop the therapies to cope with its potential infection to human or animals. Here, through the reverse genetics system, the recombinant EBIV of wild type (rEBIV/WT) and NP-conjugated-eGFP (rEBIV/eGFP/S) were rescued for the application of the high-content screening (HCS) of antiviral drug. The eGFP fluorescence signal of the rEBIV/eGFP/S was stable in the process of successive passage in BHK-21 cells (over 10 passages) and this recombinant virus could replicate in various cell lines. Compared to the wild type EBIV, the rEBIV/eGFP/S caused the smaller plaques (diameter around 1 mm on 3 dpi) and lower peak titers (10(5) PFU/mL), suggesting attenuation due to the eGFP insertion. Through the high-content screening (HCS) system, two antiviral compounds, ribavirin and favipiravir, which previously reported to have effect to some bunyavirus were tested firstly. Ribavirin showed an inhibitory effect on the rEBIV/eGFP/S (EC50 = 14.38 μM) as our expect, while favipiravir with no inhibitory effect even using high doses. Furthermore, Tyrphostin A9 (EC50 = 0.72 μM for rEBIV/eGFP/S, EC50 = 0.05 μM for EBIV-WT) and UNC0638 (EC50 = 1.26 μM for rEBIV/eGFP/S, EC50 = 1.10 μM for rEBIV/eGFP/S) were identified with strong antiviral effect against EBIV in vitro from 150 antiviral compounds. In addition, the time-of-addition assay indicated that Tyrphostin A9 worked in the stage of viral post-infection, and the UNC0638 in all pre-, co-, and post-infection stages. This robust reverse genetics system will facilitate the investigation into the studying of viral replication and assembly mechanisms, and the development of drug and vaccine for EBIV in the future.

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017-2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases.

OBJECTIVES: How Right Now (HRN) is an evidence-based, culturally responsive communication campaign developed to facilitate coping and resilience among US groups disproportionately affected by the COVID-19 pandemic. To inform the development of this campaign, we examined patterns in emotional health, stress, and coping strategies among HRN's audiences, focusing on differences among racial and ethnic groups. METHODS: We used a national probability panel, AmeriSpeak, to collect survey data from HRN's priority audience members in English and Spanish at 2 time points (May 2020 and May 2021). We conducted statistical testing to examine differences between time points for each subgroup (Hispanic, non-Hispanic Black, and non-Hispanic White) and differences among subgroups at each time point. RESULTS: We found disparities in COVID-19-related mental health challenges and differences in coping strategies. Non-Hispanic Black respondents were more likely than non-Hispanic White respondents to report challenges related to the social determinants of health, such as affording food and housing (26.4% vs 9.4% in May 2020) and experiencing personal financial loss (46.6% vs 29.2% in May 2020). In May 2021, 30.6% of Hispanic respondents reported being unable to meet basic food or housing needs versus 8.2% of non-Hispanic White respondents, and 51.6% reported personal financial loss versus 26.5% of non-Hispanic White respondents. CONCLUSIONS: Our study further illuminates what is needed to build emotional well-being pathways for people who historically have been economically and socially marginalized. Our findings underscore the need for public health interventions to provide culturally responsive mental health support to populations disproportionately affected by COVID-19 during the pandemic and into the future, with a focus on racial and ethnic disparities.

Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission. Serum specimens (n = 110) collected from PWID residing in four provinces were tested for molecular markers of HCV infection. Next generation sequencing (NGS) of the hypervariable region (HVR1) of HCV and Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to determine HCV genotype, genetic heterogeneity, and construct transmission networks. Among tested specimens, 47.3% were found anti-HCV positive and 34.6% were HCV RNA-positive and belonged to four genotypes, with 3a most prevalent followed by 1a, 1b and 4a. Variants sampled from five cases formed phylogenetic cluster and a transmission network. One case harbored infection with two different genotypes. High prevalence of infections and presence of various genotypes indicate frequent introduction and transmission of HCV among PWID in Pakistan. Identification of a transmission cluster across three provinces, involving 20% of all cases, suggests the existence of a countrywide transmission network among PWIDs. Understanding the structure of this network should assist in devising effective public health strategies to eliminate HCV infection in Pakistan.

Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacn, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacn, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is the leading indication for liver transplant (LT) in women and the elderly. Granular details into factors impacting survival in this population are needed to optimize management and improve outcomes. METHODS: Patients receiving LT for NASH cirrhosis from 1997 to 2017 across 7 transplant centers (NailNASH consortium) were analyzed. The primary outcome was all-cause mortality, and causes of death were enumerated. All outcomes were cross referenced with United Network for Organ Sharing and adjudicated at each individual center. Cox regression models were constructed to elucidate clinical factors impacting mortality. RESULTS: Nine hundred thirty-eight patients with a median follow-up of 3.8 years (interquartile range, 1.60-7.05 years) were included. The 1-, 3-, 5-, 10-, and 15-year survival of the cohort was 93%, 88%, 83%, 69%, and 46%, respectively. Of 195 deaths in the cohort, the most common causes were infection (19%), cardiovascular disease (18%), cancer (17%), and liver-related (11%). Inferior survival was noted in patients >65 years. On multivariable analysis, age >65 (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.04-2.77; P = .04), end-stage renal disease (HR, 1.55; 95% CI, 1.04-2.31; P = .03), black race (HR, 5.25; 95% CI, 2.12-12.96; P = .0003), and non-calcineurin inhibitors-based regimens (HR, 2.05; 95% CI, 1.19-3.51; P = .009) were associated with increased mortality. Statin use after LT favorably impacted survival (HR, 0.38; 95% CI, 0.19-0.75; P = .005). CONCLUSIONS: Despite excellent long-term survival, patients transplanted for NASH at >65 years or with type 2 diabetes mellitus at transplant had higher mortality. Statin use after transplant attenuated risk and was associated with improved survival across all subgroups, suggesting that careful patient selection and implementation of protocol-based management of metabolic comorbidities may further improve clinical outcomes.

Hispanic or Latino* (Hispanic) persons are disproportionately affected by HIV in the United States. In 2019, Hispanic persons accounted for 18% of the U.S. population, but for 29% of new diagnoses of HIV infection (1). The Ending the HIV Epidemic in the U.S. (EHE) initiative aims to reduce new HIV infections by 90% by 2030 (2). Preexposure prophylaxis (PrEP), medication taken to prevent acquisition of HIV, is an effective strategy for preventing HIV infection.(†) To examine PrEP awareness and referral to providers among Hispanic persons, CDC analyzed 2019 National HIV Prevention Program Monitoring and Evaluation HIV testing data. Approximately one quarter (27%) of Hispanic persons tested for HIV at CDC-funded sites (n = 310,954) were aware of PrEP, and 22% of those who received a negative HIV test result and were eligible for referral (111,644) were referred to PrEP providers. PrEP awareness and referrals among Hispanic persons were lower compared with those among non-Hispanic White persons. Among Hispanic persons, significant differences were found in PrEP awareness and referrals by age, gender, race, population group, geographic region, and test setting. HIV testing programs can expand PrEP services for Hispanic persons by implementing culturally and linguistically appropriate strategies that routinize PrEP education and referral, collaborating with health care and other providers, and addressing social and structural barriers.

Pandemics are stressful times, full of uncertainty and fear. During the COVID-19 pandemic, many Americans have experienced feelings of stress, grief, and loss. How Right Now (HRN) – and its Spanish-language counterpart, Qué Hacer Ahora (QHA) – is an evidence-based, culturally-relevant communication campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by the COVID-19 pandemic and beyond. Developed by the Centers for Disease Control and Prevention (CDC) with support from the CDC Foundation, the campaign aims to help all Americans but has a specific focus on some of the disproportionately affected groups, including adults over 65 and their caregivers, individuals with pre-existing physical and mental health conditions, people experiencing violence, and those experiencing economic distress. Based on rapid, but robust, formative research, HRN offers audience-centric messages representing the real, everyday experiences and emotions that these audiences are having and addresses them in actionable ways. These include messages that address the social and structural barrier that disproportionately-affected groups have been facing long before the pandemic — and which are felt more acutely now. This paper provides an overview of the rapid, mixed-method, culturally-responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN’s disproportionately-affected audiences describe and discuss their emotiona well-being during COVID-19 through the lens of Social Determinants of Health (SDOH). We introduce a secondary theory, Vital Conditions for Health and Well-Being (VCHW), which conceptualizes holistic well-being and the conditions that give rise to it and identifies levers for community change and improvement. Data collection methods included an environmental scan (n≥700 publications); social listening (n≥1 million social media posts); partner needs-assessment calls (n=16); partner-convened listening sessions with community members (n=29), online focus groups (n=10), and a national probability survey (n=731), all in English and Spanish. Findings suggest that HRN’s priority audiences’ emotional well-being and SDOH are interconnected. Disruptions in SDOH du to the COVID-19 pandemic can lead to emotional well-being challenges (e.g., anxiety) for HRN’s priority audiences. While some disruptions may lead some people to adapt, connect with others, and be more resilient, there is a disparate impact of emotional well-being amid COVID-19 for those already experiencing disparities linked to SDOH. Understanding the perspectives and experiences of disproportionately affected populations through the lens of SDOH is vital to identifying the kinds of supports and services – like How Right Now/Qué Hacer Ahora – required for these populations. © 2021 Weston Medical Publishing. All rights reserved.

The How Right Now communication initiative (HRN) was developed to facilitate resilience amid the COVID-19 pandemic in the United States. HRN was designed as a conduit for promoting mental health and addressing feelings of grief, worry, and stress experienced during this time. This article provides an overview of the rapid, mixed-method, culturally responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN's disproportionately affected audiences (adults aged 65 and older and their caregivers, adults with preexisting physical and mental health conditions, adults experiencing violence, and adults experiencing economic distress) describe and discuss emotional resilience, what they need to be resilient, and what factors contribute to the perceptions of their ability to "bounce back" from the conditions caused by the COVID-19 pandemic. Data collection methods included an environmental scan (n >= 700 publications), social listening (n >= 1 million social media posts), partner needs-assessment calls (n = 16), partner-convened listening sessions with community members (n = 29), online focus groups (n = 58), and a national probability survey (n = 731), all in English and Spanish. Results revealed that HRN's audiences have diverse perceptions of what constitutes resilience. However, common factors were identified across populations to support resilience amid the COVID-19 pandemic, including informal and formal social support and access to services to meet basic needs, including food and housing resources. Stress, anxiety, depression, and experience with stigma and discrimination were also linked to resilience. Understanding the perspectives and experiences of disproportionately affected populations is vital to identifying supports and services, including the engagement of community stakeholders. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The How Right Now communication initiative (HRN) was developed to facilitate resilience amid the COVID-19 pandemic in the United States. HRN was designed as a conduit for promoting mental health and addressing feelings of grief, worry, and stress experienced during this time. This article provides an overview of the rapid, mixed-method, culturally responsive formative research process undertaken to inform the development of HRN. Specifically, it describes how HRN's disproportionately affected audiences (adults aged 65 and older and their caregivers, adults with preexisting physical and mental health conditions, adults experiencing violence, and adults experiencing economic distress) describe and discuss emotional resilience, what they need to be resilient, and what factors contribute to the perceptions of their ability to "bounce back" from the conditions caused by the COVID-19 pandemic. Data collection methods included an environmental scan (n >= 700 publications), social listening (n >= 1 million social media posts), partner needs-assessment calls (n = 16), partner-convened listening sessions with community members (n = 29), online focus groups (n = 58), and a national probability survey (n = 731), all in English and Spanish. Results revealed that HRN's audiences have diverse perceptions of what constitutes resilience. However, common factors were identified across populations to support resilience amid the COVID-19 pandemic, including informal and formal social support and access to services to meet basic needs, including food and housing resources. Stress, anxiety, depression, and experience with stigma and discrimination were also linked to resilience. Understanding the perspectives and experiences of disproportionately affected populations is vital to identifying supports and services, including the engagement of community stakeholders. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p(trend)=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p(trend)<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p(trend)=0·0076); the prevalence plateaued thereafter (p(trend)=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case–control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds’ ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The United States experienced an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in August 2019. Patient diagnosis and treatment sometimes involved bronchoscopy and collection of the bronchoalveolar lavage (BAL) fluid. Although this matrix has been useful for understanding some chemical exposures in the lungs, no methods existed for measuring the nicotine content. Therefore, we developed a simple and sensitive method for measuring nicotine in the BAL fluid. Nicotine was extracted from the BAL fluid using acetone precipitation in a 96-well plate format to increase the sample throughput (200 samples/day). We optimized liquid chromatography column conditions (e.g., mobile phase, column temperature) and mass spectrometry parameters to improve the signal-to-noise ratio and lower limits of detection (LOD) for measuring nicotine in the BAL fluid. The LOD for nicotine in the BAL fluid was 0.050 ng/mL at a sample volume of 40 μL of the BAL fluid. The within-day and between-day imprecision and bias were less than 10%. This method detected nicotine in 15 of 43 BAL fluids from EVALI case patients. This method is useful for understanding recent inhalational exposure to nicotine as part of characterizing EVALI or similar illnesses.