BACKGROUND: Reports from China describe an increase in the frequency of fetal situs inversus in 2023 after the country's "zero-Covid" policy was lifted, suggesting an association with maternal SARS-CoV-2 infection. However, a report of birth defects surveillance data from Scandinavia observed no sustained increase during the SARS-CoV-2 pandemic (2020-2022 vs. 2018-2019). We examined birth defects surveillance data to assess any increase in situs inversus in the U.S. during the SARS-CoV-2 pandemic. METHODS: We combined data from four population-based birth defects programs in Massachusetts, Minnesota, North Carolina, and Atlanta, Georgia, to compare the prevalence of situs inversus among infants and fetuses delivered before (2017-2019) and during (2021-2022) the SARS-CoV-2 pandemic. We defined situs inversus as mirror-image transposition of the heart and/or other organs, or primary ciliary dyskinesis with situs inversus, excluding isolated dextrocardia. The programs varied in the pregnancy outcomes included (live births ± non-live births); all included both prenatal and postnatal diagnoses. RESULTS: We identified 294 infants and fetuses with situs inversus (6.8% non-live births). We estimated the combined prevalence per 10,000 live births as 1.72 during the pandemic versus 1.71 before the pandemic (OR = 1.005; 95% CI: 0.778-1.297). The estimated annual prevalence ranged from 1.41 in 2017 to 2.21 in 2019 with no significant trend across the study period (p = 0.39). CONCLUSIONS: We did not observe an increase in situs inversus during the SARS-CoV-2 pandemic. Because information about SARS-CoV-2 infection among individual pregnancies was not available from all programs, we could not assess a specific association with maternal infection.

BACKGROUND: In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either 20-valent pneumococcal conjugate vaccine (PCV20) alone or 15-valent pneumococcal conjugate vaccine (PCV15) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all PCV-unvaccinated adults aged ≥65 years (age-based) and for adults aged 19-64 years with conditions that increase the risk for pneumococcal disease (risk-based). This recommendation replaced a previous recommendation for PPSV23 with or without 13-valent pneumococcal conjugate vaccine (PCV13) for these groups. OBJECTIVE: We conducted a cost-effectiveness analysis of age-based and risk-based use of either PCV15 in series with PPSV23 or PCV20 alone when compared to previous recommendations. METHODS: We utilized probabilistic cohort models of all 65-year-olds (age-based) and 19-year-olds (risk-based through age 64 years and age-based at age 65 years). A spreadsheet-based Monte Carlo simulation software was used to estimate immunization costs, medical costs, non-medical costs, and overall disease burden under different vaccine strategies. The model tracked inpatient invasive pneumococcal disease (IPD) and non-bacteremic pneumonia (NBP) in inpatient and outpatient settings. One-way sensitivity analyses incorporated indirect effects of prospective pediatric vaccination with PCV15 and PCV20 on adult IPD and NBP incidence. Costs were reported in 2021 US dollars. All future costs and outcomes were discounted at 3 % per year. RESULTS: Age-based use of either PCV20 alone or PCV15 in series with PPSV23 at age 65 years were both shown to be cost-saving (improved health outcomes and saved costs). Combined cost-effectiveness of risk-based (19-64 years) plus age-based (65 years) (risk-and-age-based) use of PCV20 alone was cost-saving, whereas use of PCV15 in series with PPSV23 increased quality-adjusted life years (QALYs) but cost $412,111 (95 % CI: 270,295, 694,869) per QALY gained. CONCLUSION: In U.S. adults, replacing the previous recommendations with PCV20 alone or PCV15 in series with PPSV23 improved health outcomes. Except for risk-and-age-based use of PCV15 in series with PPSV23 that resulted in increased cost per QALY gained, the interventions also reduced costs.

IMPORTANCE: Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. OBJECTIVE: To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. EXPOSURE: History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. MAIN OUTCOMES AND MEASURES: The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. RESULTS: Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

OBJECTIVE: To update state-specific estimates of diabetes-attributable costs in the U.S. and assess changes in spending from 2013 to 2021. RESEARCH DESIGN AND METHODS: We used an attributable fraction approach to estimate direct medical costs of diagnosed diabetes using the 2021 State Health Expenditure Accounts, the 2021 Behavioral Risk Factor Surveillance System, and the Centers for Medicare and Medicaid Services 2018-2019 Minimum Data Set. We estimated diabetes-attributable productivity losses from morbidity and mortality using the 2016-2021 National Health Interview Survey and the 2021 mortality data from the Centers for Disease Control and Prevention. Costs were adjusted to 2021 U.S. dollars. RESULTS: Total diabetes-attributable cost in 2021 was $640 billion ($335 billion in direct medical costs and $305 billion in indirect costs). The median state-level total diabetes-attributable cost was $8.2 billion (range $842 million to $81 billion). The median state-level per-person cost was $21,082, ranging from $17,452 to $37,090. Total diabetes-attributable cost increased by a median of 33% between 2013 and 2021, ranging from 16 to 68% across states. Medical costs increased by 50% overall (range 33-79%) and by 27% (range 15-41%) for per person with diabetes. Costs paid by Medicaid experienced the highest increase between 2013 and 2021 (median 153%; range 41-483%). CONCLUSIONS: State economic costs of diagnosed diabetes are substantial and increased over the last decade. These costs and their growth vary considerably across states. These findings may help state policy makers in developing evidenced-based public health interventions in their respective states to prevent and control the prevalence of diabetes.

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥ 90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and they resembled T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

INTRODUCTION: In 2019 among US adults, 1 in 9 had diagnosed diabetes and 1 in 5 had diagnosed depression. Since these conditions frequently coexist, compounding their health and economic burden, we examined state-specific trends in depression prevalence among US adults with and without diagnosed diabetes. METHODS: We used data from the 2011 through 2019 Behavioral Risk Factor Surveillance System to evaluate self-reported diabetes and depression prevalence. Joinpoint regression estimated state-level trends in depression prevalence by diabetes status. RESULTS: In 2019, the overall prevalence of depression in US adults with and without diabetes was 29.2% (95% CI, 27.8%-30.6%) and 17.9% (95% CI, 17.6%-18.1%), respectively. From 2011 to 2019, the depression prevalence was relatively stable for adults with diabetes (28.6% versus 29.2%) but increased for those without diabetes from 15.5% to 17.9% (average annual percent change [APC] over the 9-year period = 1.6%, P = .015). The prevalence of depression was consistently more than 10 percentage points higher among adults with diabetes than those without diabetes. The APC showed a significant increase in some states (Illinois: 5.9%, Kansas: 3.5%) and a significant decrease in others (Arizona: -5.1%, Florida: -4.0%, Colorado: -3.4%, Washington: -0.9%). In 2019, although it varied by state, the depression prevalence among adults with diabetes was highest in states with a higher diabetes burden such as Kentucky (47.9%), West Virginia (47.0%), and Maine (41.5%). CONCLUSION: US adults with diabetes are more likely to report prevalent depression compared with adults without diabetes. These findings highlight the importance of screening and monitoring for depression as a potential complication among adults with diabetes.

RATIONALE & OBJECTIVE: While some evidence exists of increased dementia risk from anemia, it is unclear if this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD. We therefore evaluated if anemia is associated with an increased risk of dementia among adults with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study included 620,095 veterans aged ≥45 years with incident stage 3 CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) between January 2005 and December 2016 in the US Veterans Health Administration system and followed through December 31, 2018 for incident dementia, kidney failure or death. EXPOSURES: Anemia was assessed based on the average of hemoglobin levels (g/L) during the two years prior to the date of incident CKD and categorized as normal, mild and moderate/severe anemia (≥12.0, 11.0-11.9, <11.0 g/dL, respectively for women and ≥13.0, 11.0-12.9, <11.0 g/dL for men). OUTCOMES: Dementia and the composite outcome of kidney failure or death. ANALYTICAL APPROACH: Adjusted cause-specific hazard ratios were estimated for each outcome. RESULTS: At the time of incident CKD, mean age was 72 years, 97% were male, and mean eGFR was 51 mL/min per 1.73 m(2). Over a median 4.1 years of follow-up, 92,306 (15%) veterans developed dementia before kidney failure or death. Compared to veterans with CKD without anemia, multivariable-adjusted models showed a 16% (95% confidence interval [CI] 14% to 17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI 23% to 31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI 37% to 40%) and 115% (95% CI 112% to 119%) for mild and moderate/severe anemia, respectively, compared to no anemia. LIMITATIONS: Residual confounding from the observational study design. Findings may not be generalizable to the broader U.S. CONCLUSIONS: Anemia was significantly associated with increased risk of dementia among veterans with incident CKD, underscoring the role of anemia as a predictor of dementia risk.

Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&amp;L), K1 and C7, can bind human and mouse SAMD9&amp;L, but neither can bind chSAMD9L. CRISPR-Cas9 knockout of chSAMD9L from CHO cells removed the restriction for VACV, while ectopic expression of chSAMD9L imposed the restriction for VACV in a human cell line, demonstrating that chSAMD9L is a potent restriction factor for VACV. Contrary to K1 and C7, cowpox virus CP77 can bind chSAMD9L and rescue VACV replication in cells expressing chSAMD9L, indicating that CP77 is yet another SAMD9L inhibitor but has a unique specificity for chSAMD9L. Binding studies showed that the N-terminal 382 amino acids of CP77 were sufficient for binding chSAMD9L and that both K1 and CP77 target a common internal region of SAMD9L. Growth studies with nearly all OPXV species showed that the ability of OPXVs in antagonizing chSAMD9L correlates with CP77 gene status and that a functional CP77 ortholog was maintained in many OPXVs, including monkeypox virus. Our data suggest that species-specific difference in rodent SAMD9L poses a barrier for cross-species OPXV infection and that OPXVs have evolved three SAMD9L inhibitors with different specificities to overcome this barrier.IMPORTANCE Several OPXV species, including monkeypox virus and cowpox virus, cause zoonotic infection in humans. They are believed to use wild rodents as the reservoir or intermediate hosts, but the host or viral factors that are important for OPXV host range in rodents are unknown. Here, we showed that the abortive replication of several OPXV species in a Chinese hamster cell line was caused by a species-specific difference in the host antiviral factor SAMD9L, indicating that SAMD9L divergence in different rodent species poses a barrier for cross-species OPXV infection. While the Chinese hamster SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human and mouse SAMD9L, it can be inhibited by cowpox virus CP77, indicating that OPXVs encode three SAMD9L inhibitors with different specificity. Our data suggest that OPXV host range in broad rodent species depends on three SAMD9L inhibitors with different specificities.

Introduction: As most public health decisions are made at the local level, public health interventions implemented at the local level may vary by their own unique circumstances, such as demographic composition or the availability of resources. Our objective is to estimate and characterize county-level flu vaccine uptakes among Medicare-covered adults aged ≥65 years. Methods: The flu vaccine uptake was estimated from Medicare Fee-for-Service claims for those who continuously enrolled during the 2018–2019 flu season. County-level characteristics were obtained from Centers for Disease Control and Prevention (CDC)’s Minority Health Social Vulnerability Index and Behavioral Risk Factor Surveillance System data as well as Health Resources and Services Administration's Area Health Resources File. A generalized linear regression was used to assess the relationship between selected characteristics and uptake. Results: A total of 30,265,047 beneficiaries from 3,125 counties were identified, of which 53% received a flu vaccination during the 2018–2019 flu season. For 3,006 counties with more than 500 Medicare beneficiaries, the mean county-level uptake was estimated to be 47.7%. The mean uptakes in counties designated as a health professional shortage area (HPSA) (42.6% and 48.4%, respectively), were lower than the uptakes for the non-HPSA counties (53.8%). Metro counties (53.2%) showed higher uptakes than non-metro counties (44.2%). Regression analysis results showed that the percent of working adults aged 18–64 years and female were positively associated, while the percent of Black and Hispanic adults were negatively associated. Proportions of persons with limited proficiency of English, college education or above, single parent families, multi-unit housing, and living in group quarters were positively associated and significant. Conclusions: The results confirmed that county-level flu vaccine uptakes are low, reflect persistent racial disparities in vaccine uptake, and that Medicare populations in medically underserved communities with lower socioeconomic status need more attention in improving flu vaccine uptake. © 2023

Introduction: As most public health decisions are made at the local level, public health interventions implemented at the local level may vary by their own unique circumstances, such as demographic composition or the availability of resources. Our objective is to estimate and characterize county-level flu vaccine uptakes among Medicare-covered adults aged 65 years. Methods: The flu vaccine uptake was estimated from Medicare Fee-for-Service claims for those who continuously enrolled during the 20182019 flu season. County-level characteristics were obtained from Centers for Disease Control and Prevention (CDC)s Minority Health Social Vulnerability Index and Behavioral Risk Factor Surveillance System data as well as Health Resources and Services Administration's Area Health Resources File. A generalized linear regression was used to assess the relationship between selected characteristics and uptake. Results: A total of 30,265,047 beneficiaries from 3,125 counties were identified, of which 53% received a flu vaccination during the 20182019 flu season. For 3,006 counties with more than 500 Medicare beneficiaries, the mean county-level uptake was estimated to be 47.7%. The mean uptakes in counties designated as a health professional shortage area (HPSA) (42.6% and 48.4%, respectively), were lower than the uptakes for the non-HPSA counties (53.8%). Metro counties (53.2%) showed higher uptakes than non-metro counties (44.2%). Regression analysis results showed that the percent of working adults aged 1864 years and female were positively associated, while the percent of Black and Hispanic adults were negatively associated. Proportions of persons with limited proficiency of English, college education or above, single parent families, multi-unit housing, and living in group quarters were positively associated and significant. Conclusions: The results confirmed that county-level flu vaccine uptakes are low, reflect persistent racial disparities in vaccine uptake, and that Medicare populations in medically underserved communities with lower socioeconomic status need more attention in improving flu vaccine uptake. 2023

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

INTRODUCTION: Public health department (PHD) led COVID-19 vaccination clinics can be a critical component of pandemic response as they facilitate high volume of vaccination. However, few patient-time analyses examining patient throughput at mass vaccination clinics with unique COVID-19 vaccination challenges have been published. METHODS: During April and May of 2021, 521 patients in 23 COVID-19 vaccination sites counties of 6 states were followed to measure the time spent from entry to vaccination. The total time was summarized and tabulated by clinic characteristics. A multivariate linear regression analysis was conducted to evaluate the association between vaccination clinic settings and patient waiting times in the clinic. RESULTS: The average time a patient spent in the clinic from entry to vaccination was 9 min 5 s (range: 02:00-23:39). Longer patient flow times were observed in clinics with higher numbers of doses administered, 6 or fewer vaccinators, walk-in patients accepted, dedicated services for people with disabilities, and drive-through clinics. The multivariate linear regression showed that longer patient waiting times were significantly associated with the number of vaccine doses administered, dedicated services for people with disabilities, the availability of more than one brand of vaccine, and rurality. CONCLUSIONS: Given the standardized procedures outlined by immunization guidelines, reducing the wait time is critical in lowering the patient flow time by relieving the bottleneck effect in the clinic. Our study suggests enhancing the efficiency of PHD-led vaccination clinics by preparing vaccinators to provide vaccines with proper and timely support such as training or delivering necessary supplies and paperwork to the vaccinators. In addition, patient wait time can be spent answering questions about vaccination or reviewing educational materials on other public health services.

OBJECTIVES: To estimate the costs to implement public health department (PHD)-run COVID-19 vaccination clinics. DESIGN: Retrospectively reported data on COVID-19 vaccination clinic characteristics and resources used during a high-demand day in March 2021. These resources were combined with national average wages, supply costs, and facility costs to estimate the operational cost and start-up cost of clinics. SETTING: Thirty-four PHD-run COVID-19 vaccination clinics across 8 states and 1 metropolitan statistical area. PARTICIPANTS: Clinic managers at 34 PHD-run COVID-19 vaccination clinics. INTERVENTION: Large-scale COVID-19 vaccination clinics were implemented by public health agencies as part of the pandemic response. MAIN OUTCOMES MEASURED: Operational cost per day, operational cost per vaccination, start-up cost per clinic. RESULTS: Median operational cost per day for a clinic was $10 314 (range, $637-$95 163) and median cost per vaccination was $38 (range, $9-$206). There was a large range of operational costs across clinics. Clinics used an average of 99 total staff hours per 100 patients vaccinated. Median start-up cost per clinic was $15 348 (range, $1 409-$165 190). CONCLUSIONS: Results show that clinics require a large range of resources to meet the high throughput needs of the COVID-19 pandemic response. Estimating the costs of PHD-run vaccination clinics for the pandemic response is essential for ensuring that resources are available for clinic success. If clinics are not adequately supported, they may stop functioning, which would slow the pandemic response if no other setting or approach is possible.

During the Centers for Disease Control and Prevention's Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016 to June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared with areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January-March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR = 12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3 [4.7, 18.4]), and cerebral/cortical atrophy (6.7 [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

As the cases of Salmonella enterica infections associated with contaminated water are increasing, this study was conducted to address the role of surface water as a reservoir of S. enterica serotypes. We sampled rivers and streams (n=688) over a 3-year period (2015 to 2017) in a mixed-use watershed in Georgia, USA, and 70.2% of the total stream samples tested positive for Salmonella. A total of 1,190 isolates were recovered and characterized by serotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). A wide range of serotypes was identified, including those commonly associated with humans and animals, with S. enterica serotype Muenchen being predominant (22.7%) and each serotype exhibiting a high degree of strain diversity by PFGE. About half (46.1%) of the isolates had PFGE patterns indistinguishable from those of human clinical isolates in the CDC PulseNet database. A total of 52 isolates (4.4%) were resistant to antimicrobials, out of which 43 isolates were multidrug resistant (MDR; resistance to two or more classes of antimicrobials). These 52 resistant Salmonella isolates were screened for the presence of antimicrobial resistance genes, plasmid replicons, and class 1 integrons, out of which four representative MDR isolates were selected for whole-genome sequencing analysis. The results showed that 28 MDR isolates resistant to 10 antimicrobials had bla(cmy-2) on an A/C plasmid. Persistent contamination of surface water with a high diversity of Salmonella strains, some of which are drug resistant and genetically indistinguishable from human isolates, supports a role of environmental surface water as a reservoir for and transmission route of this pathogen. IMPORTANCE Salmonella has been traditionally considered a foodborne pathogen, as it is one of the most common etiologies of foodborne illnesses worldwide; however, recent Salmonella outbreaks attributed to fresh produce and water suggest a potential environmental source of Salmonella that causes some human illnesses. Here, we investigated the prevalence, diversity, and antimicrobial resistance of Salmonella isolated from a mixed-use watershed in Georgia, USA, in order to enhance the overall understanding of waterborne Salmonella. The persistence and widespread distribution of Salmonella in surface water confirm environmental sources of the pathogen. A high proportion of waterborne Salmonella with clinically significant serotypes and genetic similarity to strains of human origin supports the role of environmental water as a significant reservoir of Salmonella and indicates a potential waterborne transmission of Salmonella to humans. The presence of antimicrobial-resistant and MDR Salmonella demonstrates additional risks associated with exposure to contaminated environmental water.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

The growing field of nanoscience has shed light on the wide diversity of natural and anthropogenic sources of nano-scale particulates, raising concern as to their impacts on human health. Inhalation is the most robust route of entry, with nanoparticles (NPs) evading mucociliary clearance and depositing deep into the alveolar region. Yet, impacts from inhaled NPs are evident far outside the lung, particularly on the cardiovascular system and highly vascularized organs like the brain. Peripheral effects are partly explained by the translocation of some NPs from the lung into the circulation; however, other NPs largely confined to the lung are still accompanied by systemic outcomes. Omic research has only just begun to inform on the complex myriad of molecules released from the lung to the blood as byproducts of pulmonary pathology. These indirect mediators are diverse in their molecular make-up and activity in the periphery. The present review examines systemic outcomes attributed to pulmonary NP exposure and what is known about indirect pathological mediators released from the lung into the circulation. Further focus was directed to outcomes in the brain, a highly vascularized region susceptible to acute and longer-term outcomes. Findings here support the need for big-data toxicological studies to understand what drives these health outcomes and better predict, circumvent, and treat the potential health impacts arising from NP exposure scenarios.

Objectives. To determine the prevalence and predictors of US home health care workers' (HHWs') self-reported general, physical, and mental health. Methods. Using the 2014-2018 Behavioral Risk Factor Surveillance System, we analyzed the characteristics and health of 2987 HHWs (weighted n = 659 000) compared with 2 similar low-wage worker groups (health care aides and health care support workers, not working in the home). We conducted multivariable logistic regression to determine which characteristics predicted HHWs' health. Results. Overall, 26.6% of HHWs had fair or poor general health, 14.1% had poor physical health, and 20.9% had poor mental health; the prevalence of each outcome was significantly higher than that of the comparison groups. Among HHWs, certain factors, such as low household income, an inability to see a doctor because of cost, and a history of depression, were associated with all 3 aspects of suboptimal health. Conclusions. HHWs had worse general, physical, and mental health compared with low-wage workers not in home health. Public Health Implications. Increased attention to the health of HHWs by public health experts and policymakers is warranted. In addition, targeted interventions appropriate to their specific health needs may be required. (Am J Public Health. 2021;111(12):2239-2250. https://doi.org/10.2105/AJPH.2021.306512).

BACKGROUND: Seasonal influenza causes substantial morbidity and mortality among older U.S. adults and those with comorbid health conditions. OBJECTIVE: To describe seasonal influenza vaccine uptake and identify factors associated with missed opportunities for influenza vaccination. DESIGN: Retrospective cohort study. SETTING: Medicare fee-for-service claims. PARTICIPANTS: 31.6 million U.S. adults continuously enrolled under Medicare Parts A and B during the 2018 to 2019 influenza season. MEASUREMENTS: Influenza vaccine uptake and missed opportunities by patient demographic characteristics, high-risk status (that is, ≥1 condition increasing influenza complication risk), Medicare-Medicaid dual-eligibility status, and health care provider visits (that is, vaccination opportunities). RESULTS: Overall, 50.5% of beneficiaries aged 19 years or older had Medicare claims for influenza vaccination: 31.6% among people aged 19 to 64 years and 54% among people aged 65 years or older. More White beneficiaries were vaccinated (52.9%) than Black (34.9%) or Hispanic (30.4%) beneficiaries. Uptake was higher (56.1%) for beneficiaries with high-risk conditions than for those without (27.6%). Among unvaccinated beneficiaries overall, 77.4% visited a provider during influenza season; among unvaccinated beneficiaries with and without high-risk conditions, 91% and 43%, respectively, had seen a provider at least once. The proportion of beneficiaries with missed opportunities for influenza vaccination was 44.2% and was higher for beneficiaries in the non-high-risk group (59.1%) than those in the high-risk group (42.2%). Uptake was lower and proportions of missed opportunities were higher among beneficiaries in younger age groups, of Black and Hispanic race/ethnicity, without high-risk conditions, or with Medicare-Medicaid dual eligibility. LIMITATIONS: Influenza vaccinations without claims could not be captured. Data on reasons for nonvaccination were unavailable. CONCLUSION: Influenza vaccination coverage for Medicare beneficiaries continues to be suboptimal, with missed opportunities despite availability of influenza vaccination with no copayment. Disparities persist in vaccination uptake by race/ethnicity. PRIMARY FUNDING SOURCE: None.

BACKGROUND: Early onset colorectal cancer (CRC) incidence is rising under age 50, with a birth cohort effect for increasing incidence among individuals born 1950 and later. It is unclear whether increasing incidence trends will confer increased risk beyond age 50, the previously most commonly recommended age to initiate screening, when screening availability might modify incidence trends. AIM: Evaluate US trends in colorectal cancer (CRC) for ages 40-59 years. METHODS: We analyzed counts and incidence rates for CRC, including by anatomic subsite, using the US Cancer Statistics dataset covering 100% of the population 2003-2017. Joinpoint regression was used to quantify Average Annual Percent Change (AAPC) in cancer incidence by age subgroup. RESULTS: 470,458 CRC cases were observed age 40-59, with absolute numbers of rectal (n = 4173) and distal cases (n = 3327) per year for age 50-54 approaching age 55-59 cases for rectal (n = 4566) and distal (n = 3682) cancer by 2017. Increasing early onset rectal cancer incidence per 100,000 occuring under age 50 was observed to extend to age 50-54, from 4.9 to 6.3 for age 40-44 (AAPC 2.1; 95% CI 1.5-2.7), 9.3 to 12.0 for age 45-49 (AAPC 1.5; 95% CI 1.1-1.4), and from 16.7 to 19.5 for age 50-54 (AAPC 1.0; 95% CI 0.7-1.3). CONCLUSIONS: CRC trends suggest observed increased risks under age 50 are also present after age 50, despite prior availability of screening for this group. Recent CRC trends support initiation of screening earlier than age 50, and promotion of "on-time" screening initiation.

BACKGROUND: Diabetes mellitus (DM) is a leading contributor to morbidity and mortality in the United States (US). Prior DM prevalence estimates in Asian Americans are predominantly from Asians aggregated into a single group, but the Asian American population is heterogenous. OBJECTIVE: To evaluate self-reported DM prevalence in disaggregated Asian American subgroups to inform targeted management and prevention. DESIGN: Serial cross-sectional analysis. PARTICIPANTS: Respondents to the US Behavioral Risk Factor Surveillance System surveys who self-identify as non-Hispanic Asian American (NHA, N=57,001), comprising Asian Indian (N=11,089), Chinese (N=9458), Filipino (N=9339), Japanese (N=10,387), and Korean Americans (N=2843), compared to non-Hispanic White (NHW, N=2,143,729) and non-Hispanic Black (NHB, N=215,957) Americans. MAIN MEASURES: Prevalence of self-reported DM. Univariate Satterthwaite-adjusted chi-square tests compared the differences in weighted DM prevalence by sociodemographic and health status. KEY RESULTS: Self-reported fully adjusted DM prevalence was 8.7% (95% confidence interval 8.2-9.3) in NHA, compared to 14.3% (14.0-14.6) in NHB and 10.0% (10.0-10.1) in NHW (p<0.01 for difference). In NHA subgroups overall, DM prevalence was 14.4% (12.6-16.3) in Filipino, 13.4% (10.9-16.2) in Japanese, 10.7% (9.6-11.8) in Asian Indian, 5.1% (4.2-6.2) in Chinese, and 4.7% (3.4-6.3) in Korean Americans (p<0.01). Among those aged ≥65 years, DM prevalence was highest in Filipino (35.0% (29.4-41.2)) and Asian Indian (31.5% (25.9-37.8)) Americans. Adjusted for sex, education, and race/ethnicity-specific obesity category, NHA overall had a 21% higher DM prevalence compared to NHW (prevalence ratio 1.21 [1.14-1.27]), while prevalence ratios were 1.42 (1.24-1.63) in Filipinos and 1.29 (1.14-1.46) in Asian Indians. CONCLUSIONS: Adjusted self-reported DM prevalence is higher in NHA compared with NHW. Disaggregating NHA reveals heterogeneity in self-reported DM prevalence, highest in Filipino and Asian Indian Americans.

BACKGROUND: The Community Preventive Services Task Force (CPSTF) has recommended several interventions that have been demonstrated to be effective at increasing vaccination coverage. OBJECTIVE: Conduct a systematic review to examine the costs of interventions designed to increase vaccination coverage among children and adolescents in the United States. DATA SOURCES: PubMed, EconLit, Embase, and Cochrane. STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS: Peer-reviewed articles from January 1, 2009 to August 31, 2019. APPRAISAL AND SYNTHESIS METHODS: Studies were identified with systematic searches of the literature, reviewed for inclusion criteria, abstracted for data on intervention, target population, costs, and risk of bias. Cost measures were reported as costs per child in the target population, costs per vaccinated child, incremental costs per vaccinated child, and costs per vaccine dose administered. Results were stratified by intervention type, vaccine, and age group. RESULTS: Thirty-seven studies were identified for full-text review. Across all interventions and age groups, the cost per child ranged from $0.10 to $537.38, and the incremental cost per vaccinated child ranged from $6.52 to $5,098.57. Provider assessment and feedback interventions had the lowest (median) cost per child ($0.17) and a healthcare system-based combined intervention with multiple components had the lowest (median) incremental cost per vaccinated child ($26.65). A community-based combined intervention with multiple components had the highest median cost per child ($537.38) and the highest median incremental cost per vaccinated child ($5,098.57). LIMITATIONS: A small number of included intervention types and inconsistent cost definition. CONCLUSIONS: There is substantial variability in the costs of CPSTF-recommended interventions.

In June 2019, the Advisory Committee on Immunization Practices (ACIP) changed the recommendation for routine 13-valent pneumococcal conjugate vaccine (PCV13) use in immunocompetent adults aged ≥65 years, including those with select chronic medical conditions (CMC). ACIP now recommends PCV13 for this group of adults based on shared clinical decision-making. Because adults with CMC continue to be at increased risk for pneumococcal disease, we assessed the cost-effectiveness of administering PCV13 in series with the recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥19 years with CMC. We used a probabilistic model following a cohort of 19-year-old adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$], societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. We used PCV13 efficacy and post-licensure vaccine effectiveness (VE) data to estimate VE against PCV13 type disease (separately for disease by serotype 3 [ST3], the most common PCV13 type, and all other PCV13 serotypes). We considered a range of estimates for sensitivity analyses. Analyses were performed in 2019. In the base case, assuming no PCV13 effectiveness against ST3 disease, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY gained. This declined to $79,416 per QALY if VE against ST3 was estimated to be equivalent to other PCV13-types. Administering PCV13 in series with the recommended PPSV23 for adults with CMC was not cost saving. Results were sensitive to estimated PCV13 VE against ST3 disease.

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.

OBJECTIVE: To assess the prevalence of diagnosed diabetes among employed U.S. adults from 36 states by occupation group using data from 2014-2018 Behavioral Risk Factor Surveillance System. METHODS: Prevalence of diabetes was calculated by 22 broad and 93 detailed occupation groups among a sample of 366,633 employed respondents. Wald chi-square values were used to determine the significance of associations between diabetes and occupation groups after adjusting for sex, age, and race/ethnicity. RESULTS: The prevalence of diabetes was 6.4% among employed U.S. adults. The three broad occupation groups with the highest adjusted prevalence of diabetes were protective services (8.9%), farming, fishing, and forestry (8.8%), and community and social services (8.4%). CONCLUSIONS: Prevalence of diabetes differed by occupation. Work-related factors (e.g. shift work, job stress) should be further examined in relation to risk of developing diabetes.

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread globally. Genome sequencing of SARS-CoV-2 allows reconstruction of its transmission history, although this is contingent on sampling. We have analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020 which subsequently spread locally before active community surveillance was implemented.

BACKGROUND: Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother-infant pairs has not previously been evaluated in the AN population. METHODS: Serum samples collected during pregnancy and at birth from AN mother-infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000-2011; n = 75) and predominantly white pairs in Seattle, Washington (2014-2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites. RESULTS: Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother-infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD. CONCLUSIONS: Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother-infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US.

Currently, the Advisory Committee on Immunization Practices recommends one-time tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination for all adults 19 years and older. This study is designed to evaluate the cost-effectiveness of Tdap vaccination for Tdap-eligible adults aged 19 through 85 in the United States. A cost-effectiveness model was developed to compute costs and health outcomes associated with pertussis among 100,000 Tdap-eligible persons of each age cohort. From the societal perspective, the cost per quality-adjusted life-year (QALY) saved was evaluated under the vaccination scenarios. Sensitivity analyses were also conducted to evaluate the impacts of changes in key variables. All costs were adjusted to 2018 US$ with an annual discount rate of 3% applied to costs and outcomes. The incremental cost-effectiveness ratios (ICERs) for vaccinating US adults aged 19 to 85 with Tdap ranged from $248,000/QALY to $900,000/QALY. The lowest cost per QALY was found to be $248,000 for the age 65 cohort, followed by $332,000 for the cohort of age 19, and followed by $477,000 for the age 50 cohort. Sensitivity analysis showed the most dramatic changes in ICER occurred when changing the underreporting factor, vaccine effectiveness and vaccination costs. While Tdap vaccination may not be as cost effective as predicted earlier, it remains the best available preventive measure against pertussis. Further investigation of the true burden of pertussis disease among adults and the effectiveness of Tdap vaccination in this population is needed to better estimate the impact of Tdap vaccination.

Zika virus infection during pregnancy can cause congenital brain and eye abnormalities and is associated with neurodevelopmental abnormalities (1-3). In areas of the United States that experienced local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy increased in the second half of 2016 compared with the first half (4). To update the previous report, CDC analyzed population-based surveillance data from 22 states and territories to estimate the prevalence of birth defects potentially related to Zika virus infection, regardless of laboratory evidence of or exposure to Zika virus, among pregnancies completed during January 1, 2016-June 30, 2017. Jurisdictions were categorized as those 1) with widespread local transmission of Zika virus; 2) with limited local transmission of Zika virus; and 3) without local transmission of Zika virus. Among 2,004,630 live births, 3,359 infants and fetuses with birth defects potentially related to Zika virus infection during pregnancy were identified (1.7 per 1,000 live births, 95% confidence interval [CI] = 1.6-1.7). In areas with widespread local Zika virus transmission, the prevalence of birth defects potentially related to Zika virus infection during pregnancy was significantly higher during the quarters comprising July 2016-March 2017 (July-September 2016 = 3.0; October-December 2016 = 4.0; and January-March 2017 = 5.6 per 1,000 live births) compared with the reference period (January-March 2016) (1.3 per 1,000). These findings suggest a fourfold increase (prevalence ratio [PR] = 4.1, 95% CI = 2.1-8.4) in birth defects potentially related to Zika virus in widespread local transmission areas during January-March 2017 compared with that during January-March 2016, with the highest prevalence (7.0 per 1,000 live births) in February 2017. Population-based birth defects surveillance is critical for identifying infants and fetuses with birth defects potentially related to Zika virus regardless of whether Zika virus testing was conducted, especially given the high prevalence of asymptomatic disease. These data can be used to inform follow-up care and services as well as strengthen surveillance.