PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2022. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2022, a total of 16 sites (located in Arizona, Arkansas, California, Georgia, Indiana, Maryland, Minnesota, Missouri, New Jersey, Pennsylvania, Puerto Rico, Tennessee, Texas [two sites: Austin and Laredo], Utah, and Wisconsin) conducted surveillance for ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2022. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in a comprehensive developmental evaluation, 2) autism special education eligibility, or 3) an ASD International Classification of Diseases, Ninth Revision (ICD-9) code in the 299 range or International Classification of Diseases, Tenth Revision (ICD-10) code of F84.0, F84.3, F84.5, F84.8, or F84.9. Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had an evaluator's suspicion of ASD documented in a comprehensive developmental evaluation. RESULTS: Among children aged 8 years in 2022, ASD prevalence was 32.2 per 1,000 children (one in 31) across the 16 sites, ranging from 9.7 in Texas (Laredo) to 53.1 in California. The overall observed prevalence estimate was similar to estimates calculated using Bayesian hierarchical and random effects models. ASD was 3.4 times as prevalent among boys (49.2) than girls (14.3). Overall, ASD prevalence was lower among non-Hispanic White (White) children (27.7) than among Asian or Pacific Islander (A/PI) (38.2), American Indian or Alaska Native (AI/AN) (37.5), non-Hispanic Black or African American (Black) (36.6), Hispanic or Latino (Hispanic) (33.0), and multiracial children (31.9). No association was observed between ASD prevalence and neighborhood median household income (MHI) at 11 sites; higher ASD prevalence was associated with lower neighborhood MHI at five sites.Record abstraction was completed for 15 of the 16 sites for 8,613 children aged 8 years who met the ASD case definition. Of these 8,613 children, 68.4% had a documented diagnostic statement of ASD, 67.3% had a documented autism special education eligibility, and 68.9% had a documented ASD ICD-9 or ICD-10 code. All three elements of the ASD case definition were present for 34.6% of children aged 8 years with ASD.Among 5,292 (61.4% of 8,613) children aged 8 years with ASD with information on cognitive ability, 39.6% were classified as having an intellectual disability. Intellectual disability was present among 52.8% of Black, 50.0% of AI/AN, 43.9% of A/PI, 38.8% of Hispanic, 32.7% of White, and 31.2% of multiracial children with ASD. The median age of earliest known ASD diagnosis was 47 months and ranged from 36 months in California to 69.5 months in Texas (Laredo).Cumulative incidence of ASD diagnosis or eligibility by age 48 months was higher among children born in 2018 (aged 4 years in 2022) than children born in 2014 (aged 8 years in 2022) at 13 of the 15 sites that were able to abstract records. Overall cumulative incidence of ASD diagnosis or eligibility by age 48 months was 1.7 times as high among those born in 2018 compared with those born in 2014 and ranged from 1.4 times as high in Arizona and Georgia to 3.1 times as high in Puerto Rico. Among children aged 4 years, for every 10 children meeting the case definition of ASD, one child met the definition of suspected ASD.Children with ASD who were born in 2018 had more evaluations and identification during ages 0-4 years than children with ASD who were born in 2014 during the 0-4 years age window, with an interruption in the pattern in early 2020 coinciding with onset of the COVID-19 pandemic.Overall, 66.5% of children aged 8 years with ASD had a documented autism test. Use of autism tests varied widely across sites: 24.7% (New Jersey) to 93.5% (Puerto Rico) of children aged 8 years with ASD had a documented autism test in their records. The most common tests documented for children aged 8 years were the Autism Diagnostic Observation Schedule, Autism Spectrum Rating Scales, Childhood Autism Rating Scale, Gilliam Autism Rating Scale, and Social Responsiveness Scale. INTERPRETATION: Prevalence of ASD among children aged 8 years was higher in 2022 than previous years. ASD prevalence was higher among A/PI, Black, and Hispanic children aged 8 years than White children aged 8 years, continuing a pattern first observed in 2020. A/PI, Black, and Hispanic children aged 8 years with ASD were also more likely than White or multiracial children with ASD to have a co-occurring intellectual disability. Identification by age 48 months was higher among children born in 2018 compared with children born in 2014, suggesting increased early identification consistent with historical patterns. PUBLIC HEALTH ACTION: Increased identification of autism, particularly among very young children and previously underidentified groups, underscores the increased demand and ongoing need for enhanced planning to provide equitable diagnostic, treatment, and support services for all children with ASD. The substantial variability in ASD identification across sites suggests opportunities to identify and implement successful strategies and practices in communities to ensure all children with ASD reach their potential.

BACKGROUND: Child survival rates have improved globally, but neonatal mortality due to infections, such as group B Streptococcus (GBS), remains a significant concern. The global burden of GBS-related morbidity and mortality is substantial. However, data from low and middle-income countries are lacking. Vaccination during pregnancy could be a feasible strategy to address GBS-related disease burden. METHODS: We assessed maternal rectovaginal GBS colonization and neonatal disease rates in a prospective cohort of 6062 women-infant pairs. Surveillance for invasive infant disease occurred in parallel at 2 Kampala hospital sites. In a nested case-control study, we identified infants <90 days of age with invasive GBS disease (iGBS) (n = 24) and healthy infants born to mothers colonized with GBS (n = 72). We measured serotype-specific anticapsular immunoglobulin G (IgG) in cord blood/infant sera using a validated multiplex Luminex assay. RESULTS: We found a high incidence of iGBS (1.0 per 1000 live births) within the first 90 days of life across the surveillance sites, associated with a high case fatality rate (18.2%). Maternal GBS colonization prevalence was consistent with other studies in the region (14.7% [95% confidence interval, 13.7%-15.6%]). IgG geometric mean concentrations were lower in cases than controls for serotypes Ia (0.005 vs 0.12 µg/mL; P = .05) and III (0.011 vs 0.036 µg/mL; P = .07) and in an aggregate analysis of all serotypes (0.014 vs 0.05 µg/mL; P = .02). CONCLUSIONS: We found that GBS is an important cause of neonatal and young infant disease in Uganda and confirmed that maternally derived antibodies were lower in early-onset GBS cases than in healthy exposed controls.

BACKGROUND: Health disparities exist across socioeconomic status levels, yet empirical evidence between financial well-being (FWB) and health are limited. METHODS: This cross-sectional study combined data from 25 370 adults aged ≥18 years in the 2019 National Health Interview Survey with estimated household FWB scores from the Consumer Financial Protection Bureau's 2016 National Financial Well-being Survey. FWB associations with health service visits, biometric screenings, smoking status, body mass index and physical and mental conditions were tested using age-adjusted, sex-adjusted and health insurance coverage-adjusted linear regression analysis. RESULTS: In 2019, the mean FWB for US adults was 56.1 (range 14 (worse) to 95 (best)). With increasing time since the last health service visit or screening, FWB was increasingly lower compared with adults with visits or screenings <1 year (≥10 years or 'never', FWB ranged from -1 (blood sugar check) to -6.5 (dental examination/cleaning) points). FWB was lower with declining general health status (excellent (reference), very good (-0.5 points), good (-3.4 points) and fair/poor (-6.6 points)). Adults with physical health conditions had FWB lower than adults without (range -0.4 (high cholesterol) to -4.6 (disability) points). FWB were lower in adults who have ever been diagnosed with anxiety disorder (-1.8 points) or depression (-2 points). Adults managing their anxiety or depression (no/minimal symptoms currently) had greater FWB (anxiety: 3 points and depression: 4.1 points) than those with symptoms. CONCLUSION: Given the observed associations between FWB and health-related measures, it is crucial to consider FWB in primary and secondary health prevention efforts, recognising the relationship between economics, health and wellness.

BACKGROUND: Our objective was to characterize the education and employment history of young adults with congenital heart defects (CHD) living in the United States. METHODS: The 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG collected data from young adults (ages 19-38) with CHD identified from active birth defect in Arkansas, Arizona, and Atlanta, Georgia. Educational attainment, employment history, and special education between kindergarten and 12th grade were self-/proxy-reported. Respondent percentages were standardized to the eligible population by CHD severity, birth year, site, sex, and maternal race/ethnicity and compared by CHD severity using p values from Z-scores. Log-binomial prevalence ratios (aPRs) assessed associations between respondent characteristics and outcomes, adjusting for CHD severity, age group, sex, race/ethnicity, and site. Employment models also adjusted for education. Point estimates were compared to the 2018 American Community Survey (ACS) 5-year general population estimates. RESULTS: Among 1438 respondents, 28.3% attained ≥ bachelor's degree and 22.1% were unemployed for ≥ 12 months. Estimates were comparable by CHD severity (aPRs ~1.0) and similar to general population estimates (in ACS, 21% attained ≥ bachelor's degree and 26% were unemployed). About 25.3% of adults with CHD received special education, more commonly adults with severe (32.9%) than nonsevere CHD (23.5%, p = 0.01). CONCLUSIONS: Among young adults with CHD, educational attainment and employment did not substantially differ by CHD severity or from general population rates. One in four used special education between kindergarten and 12th grade. Clinical guidelines recommend ongoing educational and vocational support to individuals with CHD as needed so this population continues to thrive.

BACKGROUND: Almost half of individuals born with Down syndrome (DS) have congenital heart defects (CHDs). Yet, little is known about the health and healthcare needs of adults with CHDs and DS. Therefore, we examined comorbidities and healthcare utilization of this population. METHODS: Data were from the 2016-2019 Congenital Heart Survey to Recognize Outcomes, Needs, and well-beinG (CH STRONG), a survey of 19-38-year-olds with CHDs identified through birth defects registries in Arkansas, Arizona, and Atlanta. Outcome estimates were standardized to the CH STRONG eligible population. Multivariable Poisson regression generated adjusted prevalence ratios (aPRs) for associations between DS and each outcome, adjusting for covariates, including CHD severity. RESULTS: Among 1500 respondents, 9.1% had DS. Compared to those without DS, respondents with DS were more commonly male (55.5% vs. 45.0%), < 25 years old (51.8% vs. 42.7%), non-Hispanic White (72.3% vs. 69.3%), and publicly insured (77.4% vs. 22.8%; all p < 0.05). Of adults with CHDs and DS, 5.5% had cardiac comorbidities, 19.3% had emergency room (ER) visits, 6.2% had hospital admissions, and 1.2% had cost-related delays in care in the last year; 0.1 to 0.6 times lower than adults with CHDs without DS. Additionally, 26.7% had non-cardiac comorbidities (aPR = 1.25 [0.92-1.72]), most commonly sleep apnea (13.7% vs. 3.2%, aPR = 3.67 [2.02-6.67]). Receipt of cardiology care in the last 2 years was similarly low (52.7% vs. 44.7%). CONCLUSIONS: Adults with CHDs and DS comprise a substantial percentage of adults with CHDs and have unique health and healthcare needs. Half of adults with CHDs and DS are not receiving recommended routine cardiac care.

Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens.

Social determinants of health (SDOH) are the conditions in which people are born, grow, live, work, and age that influence health outcomes, and structural and systemic drivers of health (SSD) are the social, cultural, political, and economic contexts that create and shape SDOH. With the integration of constructs from previous examples, we propose an SSD model that broadens the contextual effect of these driving forces or factors rooted in the Centers for Disease Control and Prevention's SDOH framework. Our SSD model (1) presents systems and structures as multidimensional, (2) considers 10 dimensions as discrete and intersectional, and (3) acknowledges health-related effects over time at different life stages and across generations. We also present an application of this SSD model to the housing domain and describe how SSD affect SDOH through multiple mechanisms that may lead to unequal resources, opportunities, and consequences contributing to a disproportionate burden of disease, illness, and death in the US population. Our enhanced SDOH framework offers an innovative and promising model for multidimensional, collaborative public health approaches toward achieving health equity and eliminating health disparities.

In 2018, the Navi Mumbai Municipal Corporation implemented phase 1 of a public sector typhoid conjugate vaccine campaign in Navi Mumbai, India, targeting all children aged 9 months to 14 years within its administrative boundaries. To assess associations with receipt of vaccine in phase 1, we used generalized estimating equations to calculate estimates of vaccination by child-, household-, and community-level demographics (child education and age; household head education, income, and occupation; community informal settlement percent). Campaign vaccine receipt was most associated with children enrolled in school (odds ratio [OR] = 3.84, 95% CI: 2.18-6.77), the lowest household income tertile when divided into three equal parts (OR = 1.64, 95% CI: 1.43-1.84), and lower community-level socioeconomic status (OR = 1.06, 95% CI: 1.04-1.08 per 10% informal settlement proportion). The campaign was successful in reaching the most underserved populations of its target communities.

BACKGROUND: Track PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection). METHODS: The study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection. DISCUSSION: These data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients.

Typbar-TCV®, a typhoid conjugate vaccine (TCV), was prequalified by the World Health Organization in 2017. We evaluated its effectiveness in a mass vaccination program targeting children 9 months to 14 years in Navi Mumbai, India, from September 2018 to July 2020. We compared laboratory-confirmed typhoid cases from six clinical sites with age-matched community controls. Of 38 cases, three (8.6%) received TCV through the campaign, compared with 53 (37%) of 140 controls. The adjusted odds ratio of typhoid fever among vaccinated children was 0.16 (95% CI: 0.05-0.55), equivalent to a vaccine effectiveness of 83.7% (95% CI: 45.0-95.3). Vaccine effectiveness of Typbar-TCV in this large public sector vaccine introduction was similar to prior randomized controlled trials, providing reassurance to policymakers that TCV effectiveness is robust in a large-scale implementation.

IMPORTANCE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES: To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN: Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING: Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS: Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS: Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0-71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE: We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

Measurement of IgG antibodies against group B streptococcus (GBS) capsular polysaccharide (CPS) by use of a standardized and internationally accepted multiplex immunoassay is important for the evaluation of candidate maternal GBS vaccines in order to compare results across studies. A standardized assay is also required if serocorrelates of protection against invasive GBS disease are to be established in infant sera for the six predominant GBS serotypes since it would permit the comparison of results across the six serotypes. We undertook an interlaboratory study across five laboratories that used standardized assay reagents and protocols with a panel of 44 human sera to measure IgG antibodies against GBS CPS serotypes Ia, Ib, II, III, IV, and V. The within-laboratory intermediate precision, which included factors like the lot of coated beads, laboratory analyst, and day, was generally below 20% relative standard deviation (RSD) for all six serotypes, across all five laboratories. The cross-laboratory reproducibility was < 25% RSD for all six serotypes, which demonstrated the consistency of results across the different laboratories. Additionally, anti-CPS IgG concentrations for the 44-member human serum panel were established. The results of this study showed assay robustness and that the resultant anti-CPS IgG concentrations were reproducible across laboratories for the six GBS CPS serotypes when the standardized assay was used.

Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m(3) × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310-378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m(3) × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs.

The SARS-CoV-2 main protease (M(pro)) has been proven to be a highly effective target for therapeutic intervention, yet only one drug currently holds FDA approval status for this target. We were inspired by a series of publications emanating from the Jorgensen and Anderson groups describing the design of potent, non-peptidic, competitive SARS-CoV-2 M(pro) inhibitors, and we saw an opportunity to make several design modifications to improve the overall pharmacokinetic profile of these compounds without losing potency. To this end, we created a focused virtual library using reaction-based enumeration tools in the Schrödinger suite. These compounds were docked into the M(pro) active site and subsequently prioritized for synthesis based upon relative binding affinity values calculated by FEP+. Fourteen compounds were selected, synthesized, and evaluated both biochemically and in cell culture. Several of the synthesized compounds proved to be potent, competitive M(pro) inhibitors with improved metabolic stability profiles.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

BACKGROUND: Research on the association between neighborhood social deprivation and health among adults with congenital heart defects (CHD) is sparse. METHODS: We evaluated the associations between neighborhood social deprivation and health care utilization, disability, and comorbidities using the population-based 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) of young adults. Participants were identified from active birth defect surveillance systems in three U.S. sites and born with CHD between 1980 and 1997. We linked census tract-level 2017 American Community Survey information on median household income, percent of ≥25-year-old with greater than a high school degree, percent of ≥16-year-olds who are unemployed, and percent of families with children <18 years old living in poverty to survey data and used these variables to calculate a summary neighborhood social deprivation z-score, divided into tertiles. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) derived from a log-linear regression model with a Poisson distribution estimated the association between tertile of neighborhood social deprivation and healthcare utilization in previous year (no encounters, 1 and ≥2 emergency room [ER] visits, and hospital admission), ≥1 disability, and ≥1 comorbidities. We accounted for age, place of birth, sex at birth, presence of chromosomal anomalies, and CHD severity in all models, and, additionally educational attainment and work status in all models except disability. RESULTS: Of the 1435 adults with CHD, 43.8% were 19-24 years old, 54.4% were female, 69.8% were non-Hispanic White, and 33.7% had a severe CHD. Compared to the least deprived tertile, respondents in the most deprived tertile were more likely to have no healthcare visit (aPR: 1.5 [95% CI: 1.1, 2.1]), ≥2 ER visits (1.6 [1.1, 2.3]), or hospitalization (1.6 [1.1, 2.3]) in the previous 12 months, a disability (1.2 [1.0, 1.5]), and ≥1 cardiac comorbidities (1.8 [1.2, 2.7]). CONCLUSIONS: Neighborhood social deprivation may be a useful metric to identify patients needing additional resources and referrals.

India has one of the highest estimated burdens of enteric fever globally. Prior to the implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014-May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April-June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene.

We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing bla(SHV-12), associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.

Background The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae, is largely unknown in regions lacking blood culture surveillance. New serologic markers have proven accurate in diagnosing enteric fever, but whether they could be used to reliably estimate population-level incidence is unknown.Methods We collected longitudinal blood samples from blood culture-confirmed enteric fever cases enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to Hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS). We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titers and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.Findings The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children &lt;5 years ranged between 58.5 per 100 person-years (95% CI: 42.1 - 81.4) in Dhaka, Bangladesh to 6.6 (95% CI: 4.3-9.9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.Interpretation The approach described here has the potential to expand the geographic scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographic regions and time.Funding This work was supported by the Bill and Melinda Gates Foundation (INV-000572).Evidence before this study Previous studies have identified serologic responses to two antigens (Hemolysin E [HlyE] and Salmonella lipopolysaccharide [LPS]) as promising diagnostic markers of acute typhoidal Salmonella infection. We reviewed the evidence for seroepidemiology tools for enteric fever available as of November 01, 2021, by searching the National Library of Medicine article database and medRxiv for preprint publications, published in English, using the terms “enteric fever”, “typhoid fever”, “Salmonella Typhi”, “Salmonella Paratyphi”, “typhoidal Salmonella”, “Hemolysin E”, “Salmonella lipopolysaccharide”, “seroconversion”, “serosurveillance”, “seroepidemiology”, “seroprevalence” and “seropositivity.” We found no studies using HlyE or LPS as markers to measure the incidence or prevalence of enteric fever in a population. Anti-Vi IgG responses were used as a marker of population seroprevalence in cross-sectional studies conducted in South Africa, Fiji, and Nepal, but were not used to calculate population-based incidence estimates.Added value of this study We developed and validated a method to estimate typhoidal Salmonella incidence in cross-sectional population samples using antibody responses measured from dried blood spots. First, using longitudinal dried blood spots collected from over 1400 blood culture-confirmed cases in four countries, we modeled the longitudinal dynamics of antibody responses for up to two years following infection, accounting for heterogeneity in antibody responses and age-dependence. We found that longitudinal antibody responses were highly consistent across four countries on two continents and did not differ by clinical severity. We then used these antibody kinetic parameters to estimate incidence in population-based samples in six communities across the four countries, where concomitant population-based incidence was measured using blood cultures. Seroincidence estimates were much higher than blood-culture-based case estimates across all six sites, suggestive of a high incidence of asymptomatic or unrecognized infections. Still, the rank order of seroincidence and culture-based incidence rates were the same, with the highest rates in Bangladesh and lowest in Ghana.Implications of all the available evidence Many a -risk low- and middle-income countries lack data on typhoid incidence needed to inform and evaluate vaccine introduction. Even in countries where incidence estimates are available, data are typically geographically and temporally sparse due to the resources necessary to initiate and sustain blood culture surveillance. We found that typhoidal Salmonella infection incidence can be estimated from community-based serosurveys using dried blood spots, representing an efficient and scalable approach for generating the typhoid burden data needed to inform typhoid control programs in resource-constrained settings.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by th eBill and Melinda Gates Foundation (grant INV-000572)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:Institutional Review Boards in the United States (Centers for Disease Control and Prevention; Stanford University Institutional Review Board), Bangladesh (Bangladesh Institute of Child Health Ethical Review Committee), Nepal (Nepal Health Research Council Ethical Review Board), Pakistan (AKU Ethic Review Committee and Pakistan National Bioethics Committee), Korea (International Vaccine Institute IRB), Belgium (Institute of Tropical Medicine Antwerp Institutional Review Board) and Ghana (Komfo Anokye Teaching Hospital, Committee on Human Research, Publication and Ethics) approved the study forms and protocols.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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 produced in the present study are available upon reasonable request to the authors

BACKGROUND: Prisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons. FINDINGS: Among 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58-80%] and 96% [95% CI, 67-99%]). CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population. FUNDING: Horowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.

BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p &lt; 1.12×10−7. Seven CpGs showed differences at p &lt; 1×10−5 and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

India has one of the highest estimated burdens of enteric fever globally. Prior to implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014-May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April-June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene. 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.

We performed whole genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective and retrospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. Additionally, we evaluated the relationship between the spatial distance between households and genetic clustering of isolates using hierarchical Bayesian models. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing >=3 mutations in the quinolone resistance determining region, conferring high-level resistance. Two H58 isolates carried an IncX3 resistance plasmid containing bla<inf>SHV-12</inf>, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant S. Typhi isolates from India have evolved independently on multiple occasions. Among S. Typhi isolates, we identified two main clades circulating in Navi Mumbai (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (OR 0.72 per km; 95% CrI: 0.66-0.79). This effect was seen for distances up to 5 km (OR 0.65 per km; 95% CrI: 0.59-0.73) but was not seen for distances beyond 5 km (OR 1.02 per km; 95% CrI: 0.83-1.26). Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. 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.

Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with 12 variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on its ability to detect Salmonella Typhi and its feasibility. Salmonella Typhi strains Ty21a and Ty2 were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via quantitative polymerase chain reaction (qPCR). Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses, including the Salmonella Typhi concentration it is best suited for, with a range of positive detections observed as low as 0.1-0.001 colony-forming units (CFU) Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned.

Background: The WHO recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018 the Navi Mumbai Municipal Corporation (NMMC), implemented a TCV campaign. The campaign targeted all children aged 9-months through 14-years within NMMC boundaries (~320,000 children) over 2 vaccination phases. The phase 1 campaign occurred from July 14-August 25, 2018 (71% coverage, ~113,420 children). We evaluated the campaign's programmatic effectiveness in reducing typhoid cases at the community level. Method(s): We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai, offering blood cultures to children presenting with fever for at least 3 days. We employed a cluster-randomized test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched culture-confirmed typhoid cases with up to 3 culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. Result(s): Between September 1, 2018-March 31, 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (campaign effectiveness, 56%, 95%CI: 25%-74%, p=0.002). Cases >= 5-years-old were 0.37 times as likely (95% CI: 0.19-0.70; p-value = 0.002) and cases during the first year of surveillance were 0.30 times as likely (95% CI: 0.14-0.64; p-value = 0.002) to live in vaccine campaign communities. Conclusion(s): Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever. 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.

Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of Typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens, and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with twelve variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on their ability to detect Salmonella Typhi and feasibility. Salmonella Typhi strains, Ty21a and Ty2, were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via qPCR. Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses including the Salmonella Typhi concentrations they are best suited for with a range of positive detections observed as low as 0.1-0.001 CFU Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned. 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: Limited population-based information is available on long-term survival of US individuals with congenital heart defects (CHDs). Therefore, we assessed patterns in survival from birth until young adulthood (ie, 35 years of age) and associated factors among a population-based sample of US individuals with CHDs. METHODS: Individuals born between 1980 and 1997 with CHDs identified in 3 US birth defect surveillance systems were linked to death records through 2015 to identify those deceased and the year of their death. Kaplan-Meier survival curves, adjusted risk ratios (aRRs) for infant mortality (ie, death during the first year of life), and Cox proportional hazard ratios for survival after the first year of life (aHRs) were used to estimate the probability of survival and associated factors. Standardized mortality ratios compared infant mortality, >1-year mortality, >10-year mortality, and >20-year mortality among individuals with CHDs with general population estimates. RESULTS: Among 11 695 individuals with CHDs, the probability of survival to 35 years of age was 81.4% overall, 86.5% among those without co-occurring noncardiac anomalies, and 92.8% among those who survived the first year of life. Characteristics associated with both infant mortality and reduced survival after the first year of life, respectively, included severe CHDs (aRR=4.08; aHR=3.18), genetic syndromes (aRR=1.83; aHR=3.06) or other noncardiac anomalies (aRR=1.54; aHR=2.53), low birth weight (aRR=1.70; aHR=1.29), and Hispanic (aRR=1.27; aHR=1.42) or non-Hispanic Black (aRR=1.43; aHR=1.80) maternal race and ethnicity. Individuals with CHDs had higher infant mortality (standardized mortality ratio=10.17), >1-year mortality (standardized mortality ratio=3.29), and >10-year and >20-year mortality (both standardized mortality ratios ≈1.5) than the general population; however, after excluding those with noncardiac anomalies, >1-year mortality for those with nonsevere CHDs and >10-year and >20-year mortality for those with any CHD were similar to the general population. CONCLUSIONS: Eight in 10 individuals with CHDs born between1980 and 1997 survived to 35 years of age, with disparities by CHD severity, noncardiac anomalies, birth weight, and maternal race and ethnicity. Among individuals without noncardiac anomalies, those with nonsevere CHDs experienced mortality between 1 and 35 years of age, similar to the general population, and those with any CHD experienced mortality between 10 and 35 years of age, similar to the general population.

Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations.

During the COVID-19 pandemic, the Mashpee Wampanoag Tribe of southeastern Massachusetts requested US federal government assistance. The tribe collaborated successfully with many partners in response to the COVID-19 pandemic. In this case study, the authors describe the tribe's collaboration with a team from the Centers for Disease Control and Prevention who assisted with epidemiology, case investigation and contact tracing, infection prevention and control, community prevention measures, and vaccination. Collaborative efforts resulted in over 200 public service announcements and videos produced, 55 tribal staff trained, 222 people followed up for contact tracing, 80% of tribal members vaccinated, and 5 COVID-19 response plans written. Deployment response teams learned elements essential to partnering with a Native American tribe. This successful partnership during a rapidly evolving pandemic suggests the US federal government and tribal nations can work together effectively to build response capacity for future infectious disease threats.