CONTEXT: In fiscal year 2019, the Department of Health and Human Services (DHHS) received an appropriation from Congress specifically to update guidelines for investigating community cancer concerns. This resulted in the DHHS directing the Centers for Disease Control and Prevention (CDC) to fulfill this responsibility. PROGRAM: The CDC and the Agency for Toxic Substances and Disease Registry (ATSDR) provide guidance to state, tribal, local, and territorial (STLT) health departments and play important roles in supporting STLT programs in addressing community cancer concerns. IMPLEMENTATION: The updated guidelines offer enhancements addressing limitations and challenges regarding the process for investigating cancer clusters as expressed by STLT programs responsible for responding to inquiries and by communities impacted by unusual patterns of cancer. Additionally, the updated guidelines offer new tools and approaches associated with scientific advancements. Issues associated with improving communications and community engagement were a priority. Details in the updated guidelines provide suggestions for building and maintaining trust; provide resources via additional tools, templates, and methodology to facilitate sharing of information; provide suggestions for identifying agency and community points of contacts; and provide suggestions for establishing a community advisory committee. CONCLUSION: Enhancements to the previous guidelines were included to address advancements in statistical approaches and methods for understanding exposure pathways and also to respond to limitations described in the previous guidelines. Furthermore, these enhancements ensure communities have a voice in the process and offer methods to enhance transparency throughout the investigative process. Ultimately, the 2022 Guidelines are designed to ensure that community engagement, community input, and communication remains paramount to the process of assessing unusual patterns of cancer and environmental concerns.

BACKGROUND: Alzheimer's disease is the most common type of dementia and is responsible for up to 80% of dementia diagnoses and is the sixth leading cause of death in the United States. An estimated 38,000 American Indian/Alaska Native (AI/AN) people aged ≥65 years were living with Alzheimer's disease and related dementias (ADRD) in 2020, a number expected to double by 2030 and quadruple by 2050. Administrative healthcare data from the Indian Health Service (IHS) were used to estimate ADRD among AI/AN populations. METHODS: Administrative IHS healthcare data from federal fiscal years 2016 to 2020 from the IHS National Data Warehouse were used to calculate the count and rate per 100,000 AI/AN adults aged ≥45 years with at least one ADRD diagnosis code on their medical record. RESULTS: This study identified 12,877 AI/AN adults aged ≥45 years with an ADRD diagnosis code, with an overall rate of 514 per 100,000. Of those, 1856 people were aged 45-64. Females were 1.2 times (95% confidence interval: 1.1-1.2) more likely than males to have a medical visit with an ADRD diagnosis code. CONCLUSIONS: Many AI/AN people with ADRD rely on IHS, tribal, and urban Indian health programs. The high burden of ADRD in AI/AN populations aged 45-64 utilizing IHS health services highlights the need for implementation of ADRD risk reduction strategies and assessment and diagnosis of ADRD in younger AI/AN populations. This study provides a baseline to assess future progress for efforts addressing ADRD in AI/AN communities.

As dozens of new National Immunization Technical Advisory Groups (NITAGs) were established worldwide in the past decade, and as existing NITAGs continued to play an important role in vaccine policy, global NITAG partners recognized a need for a standardized assessment tool to evaluate and strengthen their functions. This article describes the development of the NITAG Maturity Assessment Tool (NMAT), a stepwise evaluation tool that assesses NITAGs on seven key indicators of structure and process. A draft tool was developed through an iterative, consensus-based process with an expert working group before it was piloted with an economically and geographically diverse convenience sample of NITAGs. The final NMAT is a flexible tool that can be used by in-country or external evaluators to understand NITAG maturity, identify priorities for optimization, and measure the impact of strengthening efforts.

BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. METHODS: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%. FINDINGS: Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0). INTERPRETATION: For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture. FUNDING: US National Institute of Allergy and Infectious Diseases.

Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola.

INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

Increasing opportunities for prevention of infectious diseases by new, effective vaccines and the expansion of global immunization programs across the life course highlight the importance and value of evidence-informed decision-making (EIDM) by National Immunization Technical Advisory Groups (NITAGs). The U.S. Centers for Disease Control and Prevention (CDC) and Task Force for Global Health (TFGH) have developed and made available new tools to support NITAGs in EIDM. These include a toolkit for conducting facilitated training of NITAGs, Secretariats, or work groups on the use of the Evidence to Recommendations (EtR) approach to advise Ministries of Health (MoH) on specific vaccine policies, and an eLearning module on the EtR approach for NITAG members, Secretariat and others. The CDC and TFGH have also supported final development and implementation of the NITAG Maturity Assessment Tool (NMAT) for assessing maturity of NITAG capabilities in seven functional domains. The EtR toolkit and eLearning have been widely promoted in collaboration with the World Health Organization (WHO) Headquarters and Regional Offices through workshops engaging over 30 countries to date, and the NMAT assessment tool used in most countries in 3 WHO regions (Americas, Eastern Mediterranean, African). Important lessons have been learned regarding planning and conducting trainings for multiple countries and additional ways to support countries in applying the EtR approach to complete vaccine recommendations. Priorities for future work include the need to evaluate the impact of EtR training and NMAT assessments, working with partners to expand and adapt these tools for wider use, synergizing with other approaches for NITAG strengthening, and developing the best approaches to empower NITAGs to use the EtR approach.

Brucellosis is a zoonotic disease, caused by some species within the Brucella genus. The primary and secondary objectives of this cross-sectional study were to determine the seroprevalence of Brucella antibodies in humans and cows and identify risk factors for exposure to Brucella spp. among people in Shahjadpur sub-district, Bangladesh. Twenty-five villages were randomly selected from the 303 milk-producing villages in the sub-district. We randomly selected 5% of the total households from each village. At each household, we collected demographic information and history of potential exposure to Brucella spp. in humans. In addition, we collected serum from household participants and serum and milk from cattle and tested to detect antibodies to Brucella sp. Univariate analysis was performed to detect associations between seropositivity and demographics, risk factors, and behaviors in households. We enrolled 647 households, 1313 humans, and 698 cows. Brucella antibodies were detected in sera from 27 household participants (2.1%, 95% confidence interval [95%CI]: 1.2-2.9%). Eleven (1.6%, 95%CI 0.6-2.4%) cows had detectable Brucella antibodies in either milk or serum. About half (53%) of the 698 cows exhibited more than one reproductive problem within the past year; of these, seven (2%) had Brucella antibodies. Households with seropositive individuals more frequently reported owning cattle (78% vs. 32%, P < 0.001). Despite a low prevalence of Brucella seropositivity in the study, the public health importance of brucellosis cannot be ruled out. Further studies would help define Brucella prevalence and risk factors in this region and nationally.

THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Local media narratives play an important role in how people interpret and propose solutions for health issues in their community. This research characterized narratives about adverse childhood experiences (ACEs), and/or social determinants of health (SDOH) in media coverage of substance use. Scans covered articles published in the Detroit Free Press and the Cincinnati Enquirer from March 1, 2019 to June 1, 2019 and March 1, 2021 to June 1, 2021. Scans used search terms for opioids and substance use. Included articles were coded and analyzed for narratives about why people use substances, how to prevent substance use, and how ACEs or SDOH relate to substance use. While half of the included articles reported on the overdose epidemic, the most common type of media coverage reported on criminal justice milestones. Other common narratives identified addiction as an illness that should be treated; and over-prescription of painkillers or the strength of the drugs as causes of substance use disorders. Narratives about SDOH and the primary prevention of ACEs and substance use were limited. Transformational narrative change work can increase support for addressing the root causes of ACEs and substance use. Results suggest this strategy remains largely untapped in the formal media.

This article discusses critical issues and opportunities going forward in nanotechnology environmental, health, and safety (nanoEHS) research from the perspective of Federal Government Agency participants in the United States (U.S.) National Nanotechnology Initiative (NNI) interagency Nanotechnology Environmental and Health Implications Working Group (NEHI). NEHI is responsible for coordination of Federal Science Agency nanoEHS research. As participants in NEHI, we examine these critical issues from an integrated, transdisciplinary perspective, noting examples of impactful research efforts that are advancing knowledge in these areas. Major themes identified include detection, measurement, and characterization of real-world nanomaterial exposures, understanding the biological transformation of nanomaterials and their potential (eco) toxicological implications, understanding the landscape of nanotechnology-enabled products in commerce, and advancing the EHS knowledge infrastructure related to nanomaterials and nanotechnology. Significant investments in nanoEHS research over two decades have led to establishment of a unique and diverse multidisciplinary, multisector community of practice. These investments must be leveraged and adapted not only to future nanotechnology, but also to use as a model for accelerating acquisition of safe and reliable risk information for tomorrow's emerging technologies for a more sustainable and competitive world. © 2023 The Royal Society of Chemistry.

The emergence and rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of varying lengths and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multi-coronavirus arrays to identify specific antibody reactivity. High level IgG, IgM and IgA reactivity to structural proteins S, M and N, as well as accessory proteins, of SARS-CoV-2 were observed that was specific to COVID-19 patients. Overlapping 100, 50 and 30 amino acid fragments of SARS-CoV-2 proteins identified antigenic regions. Numerous proteins of SARS-CoV, MERS-CoV and the endemic human coronaviruses, HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients.Competing Interest StatementDavid Camerini, Arlo Z. Randall, Amit Oberai, Christopher Hung, Joshua Edgar, Adam Shandling, Vu Huynh, Andy A. Teng, Gary Hermanson, Jozelyn V. Pablo, Xiaowu Liang, Angela Yee and Joseph J. Campo are employees of Antigen Discovery Inc. In addition, Xiaowu Liang and Angela Yee have an equity interest in Antigen Discovery Inc. The other authors declare non competing interests.Funding StatementNo external funding was used in this study.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by the Mayo Clinic Human Subjects Institutional Review Board and the Centers for Disease Control and Prevention Human Subjects Office.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data are freely available.

Modern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to assure analytic and clinical validity. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention’s Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease associated genes, including common pathogenic and difficult to detect variants. Variant types nominated included 346 SNVs, 104 deletions, 37 CNVs, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 in difficult to sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.Competing Interest StatementThe authors have declared no competing interest.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study did not involve human subjects and therefore no IRB was required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data is included in the figures, tables and supplement included in the manuscript.

Polygenic risk scores (PRS), often aggregating the results from genome-wide association studies, can bridge the gap between the initial discovery efforts and clinical applications for disease risk estimation. However, there is remarkable heterogeneity in the reporting of these risk scores. This lack of adherence to reporting standards hinders the translation of PRS into clinical care. The ClinGen Complex Disease Working Group, in a collaboration with the Polygenic Score (PGS) Catalog, have updated the Genetic Risk Prediction (GRIPS) Reporting Statement to the current state of the field and to enable downstream utility. Drawing upon experts in epidemiology, statistics, disease-specific applications, implementation, and policy, this 22-item reporting framework defines the minimal information needed to interpret and evaluate a PRS, especially with respect to any downstream clinical applications. Items span detailed descriptions of the study population (recruitment method, key demographic and clinical characteristics, inclusion/exclusion criteria, and outcome definition), statistical methods for both PRS development and validation, and considerations for potential limitations of the published risk score and downstream clinical utility. Additionally, emphasis has been placed on data availability and transparency to facilitate reproducibility and benchmarking against other PRS, such as deposition in the publicly available PGS Catalog. By providing these criteria in a structured format that builds upon existing standards and ontologies, the use of this framework in publishing PRS will facilitate translation of PRS into clinical care and progress towards defining best practices.Summary In recent years, polygenic risk scores (PRS) have increasingly been used to capture the genome-wide liability underlying many human traits and diseases, hoping to better inform an individual’s genetic risk. However, a lack of adherence to existing reporting standards has hindered the translation of this important tool into clinical and public health practice; in particular, details necessary for benchmarking and reproducibility are underreported. To address this gap, the ClinGen Complex Disease Working Group and Polygenic Score (PGS) Catalog have updated the Genetic Risk Prediction (GRIPS) Reporting Statement into the 22-item Polygenic Risk Score Reporting Statement (PRS-RS). This framework provides the minimal information expected of authors to promote the validity, transparency, and reproducibility of PRS by encouraging authors to detail the study population, statistical methods, and potential clinical utility of a published score. The widespread adoption of this framework will encourage rigorous methodological consideration and facilitate benchmarking to ensure high quality scores are translated into the clinic.Competing Interest StatementMIM is on the advisory panels Pfizer, Novo Nordisk, and Zoe Global; Honoraria: Merck, Pfizer, Novo Nordisk, and Eli Lilly; Research funding: Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, Roche, Sanofi Aventis, Servier &amp; Takeda. As of June 2019, he is an employee of Genentech with stock and stock options in Roche. No other authors have competing interests to declare.Funding StatementClinGen is primarily funded by the National Human Genome Research Institute (NHGRI), through the following three grants: U41HG006834, U41HG009649, U41HG009650. ClinGen also receives support for content curation from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the following three grants: U24HD093483, U24HD093486, U24HD093487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additionally, the views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Research reported in this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number U41HG007823 (EBI-NHGRI GWAS Catalog, PGS Catalog). In addition, we acknowledge funding from the European Molecular Biology Laboratory. Individuals were funded from the following sources: MIM was a Wellcome Investigator and an NIHR Senior Investigator with funding from NIDDK (U01-DK105535); Wellcome (090532, 098381, 106130, 203141, 212259). MI, SAL, and JD were supported by core funding from: the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). SAL is supported by a Canadian Institutes of Health Research postdoctoral fellowship (MFE-171279). JD holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award. This work was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesN/A

Introduction: Population-level data on durable HIV viral load suppression (VLS) following implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viremia among persons living with HIV in 40 Ugandan communities during UTT scale-up. Method(s): In 2015-2020, we measured VLS (defined as <200 RNA copies/mL) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/mL) or high-level (>1,000 copies/mL) viremia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e., visit-pairs; ~18 month visit intervals) and classified as durable VLS (<200 copies/mL at both visits), new/renewed VLS (<200 copies/mL at follow-up only), viral rebound (<200 copies/mL at initial visit only), or persistent viremia (<200 copies/mL at neither visit). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viremia were also assessed using multivariable Poisson regression with generalized estimating equations. Result(s): Overall, 3,080 participants contributed 4,604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with viremia at the initial visit (n=1,083), 46.9% maintained viremia through follow-up, 91.3% of which was high-level viremia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viremia self-reported antiretroviral therapy (ART) use for >12 months. Prevalence of persistent high-level viremia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (versus 40-49-year-olds; adjusted risk ratio [adjRR]=2.96; 95% confidence interval [95%CI]:2.21-3.96), men (versus women; adjRR=2.40, 95%CI:1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (versus persons with marital/permanent partners only; adjRR=1.38, 95%CI:1.10-1.74), and persons exhibiting hazardous alcohol use (adjRR=1.09, 95%CI:1.03-1.16). The prevalence of persistent high-level viremia was highest among men <30 years (32.0%). Conclusion(s): Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting viremia, nearly half maintain high-level viremia for >12 months and report higher-risk behaviors associated with onward HIV transmission. Enhanced linkage to HIV care and optimized treatment retention could accelerate momentum towards HIV epidemic control. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the UNAIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 95-95-95 VLS target in the Rakai Community Cohort Study. Population VLS fell from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1,000 to <200 and <50 copies/mL. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1,000 to <200 copies/mL. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background Despite layered mitigation measures, international travel during the COVID-19 pandemic continues to facilitate global spread of SARS-CoV-2, including novel variants of concern (VOCs). On November 26, 2021, B.1.1.529 (Omicron) was designated as a VOC by the World Health Organization [1]. On December 6, 2021, as part of measures to reduce the introduction and spread of Omicron, the requirement for a negative SARS-CoV-2 test taken before air travel to the United States was shortened from three days to one day pre-departure [1]. Although SARS-CoV-2 genomic sequencing has increased significantly during the pandemic [2], there is still a gap in early detection of emerging variants among arriving travelers. In September 2021, the Centers for Disease Control and Prevention (CDC), in collaboration with private partners, implemented a voluntary SARS-CoV-2 genomic surveillance pilot program. Initially we enrolled arriving air travelers from India. On November 28, we expanded the program to include travelers arriving from countries with high travel volumes, including those where Omicron was first detected. Methods Design, Setting, and Participants During September 29-November 27, 2021, the surveillance program included travelers arriving on seven direct flights from India at three international airports: John F. Kennedy, New York (September 29), Newark Liberty, New Jersey (October 4), and San Francisco, California (October 12). During November 28-January 23, Hartsfield-Jackson Atlanta International Airport, Georgia was added, and participation was offered to travelers from South Africa, Nigeria, the United Kingdom, France, Germany, and Brazil, arriving on approximately 50 flights per day. Participants were 18 years or older, provided informed consent, and completed demographic, clinical, and travel history questions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission.

Objectives. To identify promising practices for implementing COVID-19 vaccination sites. Methods. The Centers for Disease Control and Prevention (CDC) and Federal Emergency Management Agency (FEMA) assessed high-throughput COVID-19 vaccination sites across the United States, including Puerto Rico, after COVID-19 vaccinations began. Site assessors conducted site observations and interviews with site staff. Qualitative data were compiled and thematically analyzed. Results. CDC and FEMA conducted 134 assessments of high-throughput vaccination sites in 25 states and Puerto Rico from February 12 to May 28, 2021. Promising practices were identified across facility, clinical, and cross-cutting operational areas and related to 6 main themes: addressing health equity, leveraging partnerships, optimizing site design and flow, communicating through visual cues, using quick response codes, and prioritizing risk management and quality control. Conclusions. These practices might help planning and implementation of future vaccination operations for COVID-19, influenza, and other vaccine-preventable diseases. Public Health Implications. These practices can be considered by vaccination planners and providers to strengthen their vaccination site plans and implementation of future high-throughput vaccination sites. (Am J Public Health. 2023;113(8):909-918. https://doi.org/10.2105/AJPH.2023.307331).

Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the United Nations Programme on HIV/AIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 'third 95' in the Rakai Community Cohort Study. Population VLS would fall from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1000 to <200 and <50 copies/ml. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1000 to <200 copies/ml.

OBJECTIVES: The purpose of this study was to measure sexually transmitted infection (STI) testing among Medicaid enrollees initiating preexposure prophylaxis (PrEP) to prevent human immunodeficiency virus. Secondary data are in the form of Medicaid enrollment and claims data in six states in the US South. METHODS: Research partnerships in six states in the US South developed a distributed research network to accomplish study aims. Each state identified all first-time PrEP users in fiscal year 2017-2018 (combined N = 990) and measured the presence of STI testing for chlamydia, syphilis, and gonorrhea through 2019. Each state calculated the percentage of individuals with at least one STI test during 3-, 6-, and 12-month follow-up periods. RESULTS: The proportion of first-time PrEP users that received an STI test varied by state: 37% to 67% of all of the individuals in each state who initiated PrEP received a test within the first 6 months of PrEP treatment and 50% to 77% received a test within the first 12 months. CONCLUSIONS: Although the Centers for Disease Control and Prevention recommends STI testing at least every 6 months for PrEP users, our analysis of Medicaid data suggests that STI testing occurs less frequently than recommended in populations at elevated risk of syphilis, gonorrhea, and chlamydia.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was administered in Liberia in response to an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in 2021. We conducted a serological survey of polio antibodies after two national campaigns with nOPV2. METHODS: This clustered, cross-sectional, population-based seroprevalence survey was conducted in children aged 0-59 months, more than 4 weeks after the second nOPV2 vaccination round. We used a clustered sampling method in four geographical regions of Liberia, followed by a simple random sampling of households. One eligible child was randomly selected per household. Dried blood spot specimens were taken and vaccination history was recorded. The antibody titres against all three poliovirus serotypes were assessed using standard microneutralisation assays done at the US Centers for Disease Control and Prevention in Atlanta, GA, USA. FINDINGS: Analysable data were obtained from 436 (87%) of 500 enrolled participants. Of these, 371 (85%) children were reported via parental recall to have received two nOPV2 doses, 43 (10%) received one dose, and 22 (5%) received no doses. The seroprevalence against type 2 poliovirus was 38·3% (95% CI 33·7-43·0; 167 of 436 participants). No significant difference was observed between type 2 seroprevalence in children aged 6 months or older who were reported to have received two doses of nOPV2 (42·1%, 95% CI 36·8-47·5; 144 of 342), one dose (28·0%, 12·1-49·4; seven of 25), or no doses (37·5%, 8·5-75·5; three of eight; p=0·39). The seroprevalence against type 1 was 59·6% (54·9-64·3; 260 of 436), and the seroprevalence against type 3 was 53·0% (48·2-57·7; 231 of 436). INTERPRETATION: Unexpectedly, the data showed low type 2 seroprevalence after two reported doses of nOPV2. This finding is probably affected by the lower oral poliovirus vaccine immunogenicity previously demonstrated in resource-limited settings, with high prevalence of chronic intestinal infections in children and other factors discussed herein. Our results provide the first assessment of nOPV2 performance in outbreak response in the African region. FUNDING: WHO and Rotary International.

Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD) surviving into adulthood increases, more information is needed regarding their health care transition planning, an essential process for adolescents and young adults with DMD. The objective of this study was to describe the health care transition experiences of a population of males living with Duchenne or Becker muscular dystrophy (DBMD). Methods: The eligible participants, identified through the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) surveillance project, were 16-31 years old and lived in Arizona, Colorado, Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care Transitions and Other Life Experiences Survey was conducted in 2013 and administered online or in a telephone interview. Sixty-five males (25%) completed the survey. Among non-ambulatory males, response differences were compared by age group. Statistical comparisons were conducted using Fisher's exact test, or when appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory males aged 16-18 years, 28% of non-ambulatory males aged 19-23 years, 25% of non-ambulatory males aged 24-30 years, and 18 ambulatory males had a written transition plan. Nineteen percent of non-ambulatory males aged 24-30 years had delayed or gone without needed health care in the past 12 months. Among non-ambulatory males aged 24-30 years, 75% had cardiology providers and 69% had pulmonology providers involved in their care in the past 12 months. Twentyeight percent of non-ambulatory males aged 19-23 years and 25% of non-ambulatory males aged 24-30 years reported that they did not receive health care or other services at least once because they were unable to leave their home. Non-ambulatory males aged 16-18 years (29%) were less likely to have ever discussed how to obtain or keep health insurance as they get older compared to non-ambulatory males aged 24-30 years (69%) (p <0.01). Discussion: This study identified potential barriers to the successful health care transition of males with DBMD. The results of this study may indicate a lack of targeted informational resources and education focused on supporting the transition of young men with DBMD as they age from adolescence into adulthood within the healthcare system. Future studies could determine the reasons for the potential barriers to health care and identify the optimal transition programs for males with DBMD. There are a few online resources on transition available to adolescents and young adults with special health care needs.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.

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

Bats, rodents and monkeys are reservoirs for emerging zoonotic infections. We sought to describe the frequency of human exposure to these animals and the seasonal and geographic variation of these exposures in Bangladesh. During 2013-2016, we conducted a cross-sectional survey in a nationally representative sample of 10,002 households from 1001 randomly selected communities. We interviewed household members about exposures to bats, rodents and monkeys, including a key human-bat interface-raw date palm sap consumption. Respondents reported observing rodents (90%), bats (52%) and monkeys (2%) in or around their households, although fewer reported direct contact. The presence of monkeys around the household was reported more often in Sylhet division (7%) compared to other divisions. Households in Khulna (17%) and Rajshahi (13%) were more likely to report drinking date palm sap than in other divisions (1.5-5.6%). Date palm sap was mostly consumed during winter with higher frequencies in January (16%) and February (12%) than in other months (0-5.6%). There was a decreasing trend in drinking sap over the three years. Overall, we observed substantial geographic and seasonal patterns in human exposure to animals that could be sources of zoonotic disease. These findings could facilitate targeting emerging zoonoses surveillance, research and prevention efforts to areas and seasons with the highest levels of exposure.

Six refugee screening sites collaborated to estimate the prevalence of hepatitis C virus (HCV) antibodies among newly arrived refugees in the United States from 2010 to 2017, identify demographic characteristics associated with HCV antibody positivity, and estimate missed HCV antibody-positive adults among unscreened refugees. We utilized a cross-sectional study to examine HCV prevalence among refugees (N = 144,752). A predictive logistic regression model was constructed to determine the effectiveness of current screening practices at identifying cases. The prevalence of HCV antibodies among the 64,703 refugees screened was 1.6%. Refugees from Burundi (5.4%), Moldova (3.8%), Democratic Republic of Congo (3.2%), Burma (2.8%), and Ukraine (2.0%) had the highest positivity among refugee arrivals. An estimated 498 (0.7%) cases of HCV antibody positivity were missed among 67,787 unscreened adults. The domestic medical examination represents an opportunity to screen all adult refugees for HCV to ensure timely diagnosis and treatment.

BACKGROUND: Congenital syphilis can cause severe morbidity, including miscarriage and stillbirth, and rates are increasing rapidly within the United States. However, congenital syphilis can be prevented with early detection and treatment of syphilis during pregnancy. Current screening recommendations propose that all women should be screened early in pregnancy, whereas women with elevated risks for congenital syphilis should be screened again later in pregnancy. The rapid increase in congenital syphilis rates suggests that there are still gaps in prenatal syphilis screening. OBJECTIVE: This study aimed to examine associations between the odds of prenatal syphilis screening and sexually transmitted infection history or other patient characteristics across 3 states with elevated rates of congenital syphilis. STUDY DESIGN: We used the Medicaid claims data from Kentucky, Louisiana, and South Carolina for women with deliveries between 2017 and 2021. Within each state, we examined the log-odds of prenatal syphilis screening as a function of the mother's health history, demographic factors, and Medicaid enrollment history. Patient history was established using a 4-year lookback period of the Medicaid claims data; in state A, sexually transmitted infection surveillance data were used to improve the sexually transmitted infection history. RESULTS: The prenatal syphilis screening rates varied by state, ranging from 62.8% to 85.1% of deliveries to women without a recent history of sexually transmitted infections and from 78.1% to 91.1% of deliveries to women with a previous sexually transmitted infection. For the main outcome of syphilis screening at any time during pregnancy, deliveries associated with previous sexually transmitted infections had 1.09 to 1.37 times higher adjusted odds ratios of undergoing screening. Deliveries to women with continuous Medicaid coverage throughout the first trimester also had higher odds of syphilis screening at any time (adjusted odds ratio, 2.45-3.15). Among deliveries to women with a previous sexually transmitted infection, only 53.6% to 63.6% underwent first-trimester screening and this rate was still just 55.0% to 69.5% when considering only deliveries to women with a previous sexually transmitted infection and full first-trimester Medicaid coverage. Fewer delivering women underwent third-trimester screening (20.3%-55.8% of women with previous sexually transmitted infection). Compared with deliveries to White women, deliveries to Black women had lower odds of first-trimester screening (adjusted odds ratio, 0.85 in all states) but higher odds of third-trimester screening (adjusted odds ratio, 1.23-2.03), potentially impacting maternal and birth outcomes. For state A, linkage to surveillance data doubled the rate of detection of a previous sexually transmitted infection because 53.0% of deliveries by women with a previous sexually transmitted infection would not have had sexually transmitted infection history detected using Medicaid claims alone. CONCLUSION: A previous sexually transmitted infection and continuous preconception Medicaid enrollment were associated with higher rates of syphilis screening, but Medicaid claims alone do not fully capture the sexually transmitted infection history of patients. The overall screening rates were lower than would be expected given that all women should undergo prenatal screening, but the rates in the third trimester were particularly low. Of note, there are gaps in early screening for non-Hispanic Black women who had lower odds of first-trimester screening when compared with non-Hispanic White women despite being at elevated risk for syphilis.

As SARS-CoV-2 testing declines worldwide, surveillance of international travelers for SARS-CoV-2 enables detection of emerging variants and fills gaps in global genomic surveillance (1). Because SARS-CoV-2 can be detected in feces and urine of some infected persons (2), wastewater surveillance in airports and on aircraft has been proposed by the global public health community† as a low-cost mechanism to monitor SARS-CoV-2 variants entering the United States. Sampling wastewater directly from aircraft can be used to link SARS-CoV-2 lineage data with flight origin countries without active engagement of travelers (3). | | During August 1–September 9, 2022, the biotech company Ginkgo Bioworks, in collaboration with CDC, evaluated the feasibility of SARS-CoV-2 variant detection in aircraft wastewater from incoming international flights. Aircraft wastewater samples were collected from selected flights from the United Kingdom, Netherlands, and France arriving at John F. Kennedy International Airport in New York City. Wastewater (approximately 0.25 gal [1 L]) was collected from each plane during normal maintenance using a device that attaches to the lavatory service panel port and the lavatory service truck hose.

Human norovirus (HuNoV) is an important cause of acute gastroenteritis and can be transmitted by water exposures, but its persistence in water is not well understood. Loss of HuNoV infectivity in surface water was compared with persistence of intact HuNoV capsids and genome segments. Surface water from a freshwater creek was filter-sterilized, inoculated with HuNoV (GII.4) purified from stool, and incubated at 15 or 20 °C. We measured HuNoV infectivity via the human intestinal enteroid system and HuNoV persistence via reverse transcription-quantitative polymerase chain reaction assays without (genome segment persistence) or with (intact viral capsid persistence) enzymatic pretreatment to digest naked RNA. For infectious HuNoV, results ranged from no significant decay to a decay rate constant ("k") of 2.2 day(-1). In one creek water sample, genome damage was likely a dominant inactivation mechanism. In other samples from the same creek, loss of HuNoV infectivity could not be attributed to genome damage or capsid cleavage. The range in k and the difference in the inactivation mechanism observed in water from the same site could not be explained, but variable constituents in the environmental matrix could have contributed. Thus, a single k may be insufficient for modeling virus inactivation in surface waters.