INTRODUCTION: The Inflation Reduction Act (IRA) eliminated cost sharing for Medicare Part D-covered vaccines but did not address the cost burden faced by Medicare beneficiaries who did not have prescription drug coverage. This study aimed to determine the characteristics of beneficiaries without prescription drug coverage and to assess the association between the receipt of a herpes zoster vaccine and prescription drug coverage status. METHODS: We used the 2019-2023 National Health Interview Survey and included Medicare beneficiaries aged 65 years and older who enrolled in both Parts A and B or a Medicare Advantage plan. Descriptive statistics were used to examine beneficiaries' characteristics. Logistic regressions were used to examine the associations between the receipt of a herpes zoster vaccine and Medicare prescription drug coverage. RESULTS: The study included 33,578 beneficiaries and 93.5 % of beneficiaries had prescription drug coverage. The prevalence of lacking prescription drug coverage was higher among beneficiaries who did not have a college degree, had family income below the poverty level, had no flu shot and well visit within the past year, and had no usual place for care. The probability of receiving a herpes zoster vaccine was higher among beneficiaries with prescription drug coverage than those without prescription coverage (45.2 % versus 25.3 %). CONCLUSIONS: Herpes zoster vaccination disparities between beneficiaries with and without prescription drug coverage existed before the IRA. Because the IRA only addresses the cost barrier facing by beneficiaries with prescription drug coverage, vaccination disparities was greater after the IRA implementation.

BACKGROUND: Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. METHODS: We included U.S. measles cases reported from 2001-2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. RESULTS: Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5-19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5-19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. DISCUSSION: Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.

The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

Background: The opioid overdose epidemic has resulted in hundreds of thousands of overdose deaths in the United States (US). One indication for opioids is herpes zoster (HZ)—a common painful condition with an estimated 1 million cases occurring annually in the US. Objective: We aimed to characterize prescription opioid claims and trends among patients with HZ who were previously opioid naive. Design: We used a cohort study involving three insurance claims databases in the US. We included all beneficiaries 18-64 years (commercial and Medicaid) and beneficiaries 65 years and older (Medicare) who were diagnosed with incident HZ during 2007-2021. We determined the proportion of opioid-naive patients with HZ who filled an opioid prescription within 30 days and 180 days following HZ diagnosis. We also examined trends over the study period, proportion receiving moderate, high dosages (50-89 morphine milligram equivalent [MME], and ≥90 MME per day), and long-term receipt. Results: Among all three insurance databases, 2,595,837 patients had an incident episode of HZ and were opioid naive during the prior 6 months. Within 30 days following HZ, 623,515 (24 percent) filled a prescription for an opioid. The percentage with an opioid claim declined during 2007-2021 for all groups; 65 percent for commercially insured patients, 51 percent for Medicaid-insured patients, and 60 percent for Medicare-insured patients. Approximately 8-15 percent of all beneficiaries received moderate and 2-6 percent received high dosage opioids. Long-term prescription opioid use of at least 6 months was found in 7-12 percent of the patients. Conclusions: Continuing trends in judicious opioid prescribing as well as use of recommended HZ vaccines may decrease opioid prescriptions for HZ. © 2024 Journal of Opioid Management, All Rights Reserved.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

OBJECTIVE: To describe maternal demographics and compare clinical characteristics of infants with congenital cytomegalovirus (cCMV) identified through diagnostic codes and laboratory data in the United States during 2018-2023. METHODS: We used a CDC-licensed subset of HealthVerity data, which contained linked pregnant people-infant claims data from publicly and privately insured individuals during 2018-2023 (2023 Quarter 3 HealthVerity Maternal Outcomes Masterset data). We identified infants with cCMV using diagnostic codes or positive laboratory test results within 45 days of birth. RESULTS: Among 744 (4.6 per 10,000 live births) infants with cCMV during 2018-2023, 599 (81%) were identified by a diagnostic code only. Among 732 linked pregnant people, 91 (12%) had a diagnosis of CMV infection during pregnancy, with a similar distribution by age group and insurance type, but a lower proportion were Black as compared to those without CMV infection during pregnancy (14% vs. 29%, respectively). Overall, 452 (61%) infants had ≥1 cCMV-related clinical sign at birth and 185 (25%) had valganciclovir prescriptions. Eighty-eight (68%) infants identified by a positive laboratory test only had no cCMV-related signs and none had valganciclovir prescriptions. CONCLUSIONS: Using healthcare claims data, we found a minimal overlap of cCMV identified by diagnostic codes and laboratory test results. A minority of linked pregnant people with infants with cCMV had a CMV diagnosis during pregnancy. cCMV surveillance will help better understand the validity of ICD codes to identify infants with cCMV, describe the spectrum of disease, and monitor use of antivirals.

INTRODUCTION: Testing for immunity to measles, mumps, and rubella should include only IgG; IgM testing is appropriate only if acute illness is suspected. The appropriateness of measles, mumps, and rubella IgM testing was evaluated in a national administrative dataset. METHODS: Laboratory testing for measles, mumps, and rubella during 2019-2022 was analyzed in 2024 using HealthVerity administrative claims and laboratory data. IgG, IgM, and reverse-transcriptase polymerase chain reaction (RT-PCR) testing are described by year, demographics, and region. IgM testing was examined for appropriateness, defined as an IgM test combined with diagnostic codes indicative of acute illness. RESULTS: During 2019-2022, IgM testing represented a small proportion of serologic testing (measles: 3.3%, mumps: 2.4%, rubella: 2.1%) but appeared to be appropriately performed in only 15.4% of cases for measles, 32.8% of cases for mumps, and 10.2% of cases for rubella. IgM testing was more commonly performed for female patients, with the largest discrepancy seen for rubella (90.5% female vs 9.5% male). IgM for measles and mumps was more often performed appropriately for persons aged 0-19 years (37.6% and 60.1%) compared with persons aged 20-49 years (11.8% and 22.0%) and 50+ years (16.5% and 33.8%). CONCLUSIONS: The majority of IgM testing for measles, mumps, and rubella during this period appeared inappropriate. Clinicians and health systems could ensure that IgG testing alone is performed when evaluating for immunity through modifications to electronic medical records and commercial laboratories could ensure that providers are able to test for IgG alone when evaluating immunity.

BACKGROUND: This paper highlights recent clinical complications of mumps reported in the United States and summarizes appropriate confirmatory testing for mumps, encouraging vigilance for mumps disease, an endemic vaccine-preventable illness. METHODS: Surveillance data from jurisdictions reporting confirmed and probable cases of mumps in the United States were descriptively analyzed to assess epidemiologic trends from January 1, 2018 - December 31, 2023. Data were reported to the National Notifiable Disease Surveillance System and the Epidemiology and Laboratory Capacity Project O. Cases were classified according to the Council of State and Territorial Epidemiologists 2011 mumps case definition. RESULTS: From 2018-2023, United States health departments reported 8,006 confirmed and probable mumps cases to the National Notifiable Disease Surveillance System, of which 85.4% occurred during January 1, 2018-April 4, 2020 and 14.6% during April 5, 2020-December 31, 2023. The incidence of mumps was highest among those aged 18-24 years during 2018-2020 (maximum of 4.54 cases per 100,000 persons in 2019), and highest among those aged 1-4 years during 2021-2023 (maximum 0.67 per 100,000 persons in 2023). Incidence among all age groups during 2021-2023 remained below levels during 2018-2020. Fewer than 12% of mumps cases were confirmed during 2021-2023, compared to >50% during 2018-2019. CONCLUSIONS: Although incidence has declined since the COVID-19 pandemic, these surveillance data highlight that mumps remains endemic in the United States. Therefore, maintaining high MMR vaccination coverage is essential to prevent future vaccine-preventable outbreaks and minimize severe complications from infection.

Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

BACKGROUND: Exposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations. METHOD: This study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways. RESULTS: Among the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta. CONCLUSION: Among the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43682-024-00027-7.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

OBJECTIVE: To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS: Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS: Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS: Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.

BACKGROUND: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses. METHODS: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017-2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016-2017) standard-dose vaccination. RESULTS: Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017-2018 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) versus without (range, 4.3-14.3) prior 2016-2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range, .21-.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay. CONCLUSIONS: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

BACKGROUND: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. OBJECTIVE: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. DESIGN: Cohort studies using surveys and medical chart abstraction. SETTING: Two large retirement facilities in Cook County, Illinois. PATIENTS: Residents and employees at both facilities and community residents with rotavirus disease. MEASUREMENTS: Attack rates, hospitalization rates, and rotavirus genotype. RESULTS: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. LIMITATION: Medical or cognitive impairment among residents limited the success of some interviews. CONCLUSION: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. PRIMARY FUNDING SOURCE: None.

OBJECTIVE: Alcohol minimum unit pricing (MUP) policies establish a floor price beneath which alcohol cannot be sold. The potential effectiveness of MUP policies for reducing alcohol-attributable deaths in the United States has not been quantitatively assessed. Therefore, this study estimated the effects of two hypothetical distilled spirits MUP policies on alcohol sales, consumption, and alcohol-attributable deaths in one state. METHOD: The International Model of Alcohol Harms and Policies tool was used to estimate the effects of two hypothetical MUP per standard drink policies (40-cent and 45-cent) pertaining to distilled spirits products at off-premises alcohol outlets in Michigan during 2020. Prevalence estimates on drinking patterns among Michigan adults were calculated by sex and age group. Prices per standard drink and sales of 9,747 spirits products were analyzed using National Alcohol Beverage Control Association data. Analyses accounted for other alcoholic beverage type sales using cross-price elasticities. RESULTS: Increasing the MUP of the 3.5% of spirits with the lowest prices per standard drink to 40 cents could reduce total alcohol per capita consumption in Michigan by 2.6% and prevent 232 (5.3%) alcohol-attributable deaths annually. A 45-cent MUP would affect 8.0% of the spirits and reduce total alcohol per capita consumption by 3.9%, preventing 354 (8.1%) deaths. CONCLUSIONS: Modestly increasing the prices of the lowest-priced spirits with an MUP policy in a single state could save hundreds of lives annually. This suggests that alcohol MUP policies could be an effective strategy for improving public health in the United States, consistent with the World Health Organization's recommendation.

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65-3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum β-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10(-10)) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10(-11)) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

BACKGROUND: On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures. METHODS: We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions. FINDINGS: 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission. INTERPRETATION: Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting. FUNDING: US Centers for Disease Control and Prevention.

Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within the same birth cohort. With the HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA and anti-NA antibody responses since childhood influenza infections have not been evaluated in parallel at the individual level. This is partly due to the limited knowledge of changes in NA antigenicity, as seasonal influenza vaccines have focused on generating neutralising anti-HA antibodies against HA antigenic variants. Here we systematically characterised the NA antigenic variants of seasonal A(H1N1) viruses from 1977 to 1991 and completed the antigenic profile of N1 NAs from 1977 to 2015. We identified that NA proteins of A/USSR/90/77, A/Singapore/06/86, and A/Texas/36/91 were antigenically distinct and mapped N386K as a key determinant of the NA antigenic change from A/USSR/90/77 to A/Singapore/06/86. With comprehensive panels of HA and NA antigenic variants of A(H1N1) and A(H1N1)pdm09 viruses, we determined hemagglutinin inhibition (HI) and neuraminidase inhibition (NI) antibodies from 130 subjects born between 1950-2015. Age-dependent imprinting was observed for both anti-HA and anti-NA antibodies, with the peak HI and NI titers predominantly detected from subjects at 4-12 years old during the year of initial virus isolation, except the age-independent anti-HA antibody response against A(H1N1)pdm09 viruses. More participants possessed antibodies that reacted to multiple antigenically distinct NA proteins than those with antibodies that reacted to multiple antigenically distinct HA proteins. Our results support the need to include NA proteins in seasonal influenza vaccine preparations.IMPORTANCE Seasonal influenza vaccines have aimed to generate neutralizing anti-HA antibodies for protection since licensure. More recently, anti-NA antibodies have been established as an additional correlate of protection. While HA and NA antigenic changes occurred discordantly, the anti-HA and anti-NA antibody profiles have rarely been analysed in parallel at the individual level, due to the limited knowledge on NA antigenic changes. By characterizing NA antigenic changes of A(H1N1) viruses, we determined the anti-HA and anti-NA antibody landscape against antigenically distinct A(H1N1) and A(H1N1)pdm09 viruses using sera of 130 subjects born between 1950-2015. We observed age-dependent imprinting of both anti-HA and anti-NA antibodies against strains circulated during the first decade of life. 67.7% (88/130) and 90% (117/130) of participants developed cross-reactive antibodies to multiple HA and NA antigens at titers ≥1:40. With slower NA antigenic changes and cross-reactive anti-NA antibody responses, including NA protein in influenza vaccine preparation may enhance vaccine efficacy. (150 words)

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Objective: U.S. healthcare utilization declined during the COVID-19 pandemic, potentially leading to spurious drops in disease incidence recorded in administrative healthcare datasets used for public health surveillance. We used time series modeling to characterize the magnitude and duration of the COVID-19 pandemic's impact on claims-based monthly incidence of 12 symptomatic conditions among Medicare beneficiaries aged >=65 years. Method(s): Time series of observed monthly incidence of each condition were generated using Medicare claims data from January 2016-May 2021. Incidence time series were decomposed through seasonal and trend decomposition using Loess, resulting in seasonal, trend, and remainder components. We fit a non-linear mixed effects model to remainder time series components and used it to estimate underlying incidence and number of unrecorded cases of each condition during the pandemic period. Result(s): Observed incidence of all 12 conditions declined steeply in March 2020 with nadirs in April 2020, generally followed by return to pre-pandemic trends. The relative magnitude of the decrease varied by condition, but month of onset and duration did not. Estimated unrecorded cases during March 2020-May 2021 ranged from 9,543 (95% confidence interval [CI]: 854-15,703) for herpes zoster to 236,244 (95% CI: 188,583-292,369) for cataracts. Conclusion(s): Due to reduced healthcare utilization during the COVID-19 pandemic, claims-based data underestimate incidence of non-COVID-19 conditions. Time series modeling can be used to quantify this underestimation, facilitating longitudinal analyses of disease incidence pre- and post-pandemic. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Introduction The main objective of this study is to conduct an individual patient data meta-analysis with collaborators from various countries to identify SARS-CoV-2 variants of concern associated with adverse maternal and neonatal outcomes. Methods Eligible studies included registries and single- or multi-site cohort studies that recruited pregnant and recently postpartum women with confirmed COVID-19. Studies must have enrolled at least 25 women within a defined catchment area. Studies also had to have data that overlapped more than a single COVID-19 variant time period. We invited principal investigators already participating in an ongoing sequential, prospective meta-analysis of perinatal COVID-19. Investigators shared individual patient data (IPD) with the technical team for review and analysis. We examined 31 outcomes related to: i) COVID-19 severity (n=5); ii) maternal morbidities including adverse birth outcomes (n=14); iii) fetal and neonatal morbidity and mortality (n=5) and iv) adverse birth outcomes (n=8). SARS-CoV-2 strains that have been identified as variants of concern (VOC) by the WHO were analyzed using the publicly available strain frequency data by Nextstrain.org and strains were classified as dominant when they were more than half of sequences in a given geographic area. We applied a 2-stage IPD meta-analytic framework to generate pooled relative risks, with 95% CI for each dominant variant and outcome pair when there were one or more studies with available data. Results Our data show that the Delta wave, compared to Omicron, was associated with a higher risk of all adverse COVID-19 severity outcomes in pregnancy including risk of hospitalization [RR 4.02 (95% CI 1.10, 14.69), n=1 study], risk of ICU admissions [RR 2.59 (95% CI 1.26, 5.30, n=3 studies], risk of critical care admission [RR 2.52 (95% CI 1.25, 5.08, n=3 studies], risk of needing ventilation [RR 3.96 (95% CI 1.47, 10.71), n=3 studies] and risk of pneumonia [RR 6.73 (95% CI 2.17, 20.90), n=3 studies]. The majority of maternal morbidity and mortality indicators were not at increased risk during any of the COVID-19 variant waves except hemorrhage, any Cesarean section, intrapartum Cesarean section and maternal composite outcome, although data was limited. Risk of fetal and neonatal morbidity and mortality did not show significant increases in risks during any of the COVID-19 waves except stillbirth and perinatal death during the Delta wave ([RR 4.84 (95% CI 1.37, 17.05, n=3 studies], [RR 6.03 (95%CI 1.63, 22.34), n=3 studies], respectively) when compared to the Pre-alpha wave. Adverse birth outcomes including very low birthweight and very preterm birth also showed increased risks during the Delta wave compared to the Pre-alpha wave. Discussion During periods of Delta strain predominance, all COVID-19 severity outcomes were more severe among pregnant women, compared to periods when other COVID-19 strains predominated. In addition, there are limited data comparing the impact of different variants on pregnancy outcomes. This highlights the importance of ongoing genomic surveillance among special populations. 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.

Objectives: The largest mumps outbreak in the United States since 2006 occurred in Arkansas during the 2016-17 school year. An additional dose (third dose) of measles-mumps-rubella vaccine (MMR3) was offered to school children. We evaluated the vaccine effectiveness (VE) of MMR3 compared with two doses of MMR for preventing mumps among school-aged children during the outbreak. Study design: A generalized linear mixed effects model was used to estimate the incremental vaccine effectiveness (VE) of a third dose of MMR compared with two doses of MMR for preventing mumps. Methods: We obtained school enrollment, immunization status and mumps case status from school registries, Arkansas's immunization registry, and Arkansas's mumps surveillance system, respectively. We included students who previously received 2 doses of MMR in schools with ≥1 mumps case after the MMR3 clinic. We used a generalized linear mixed model to estimate VE of MMR3 compared with two doses of MMR. Results: Sixteen schools with 9272 students were included in the analysis. Incremental VE of MMR3 versus a two-dose MMR regimen was 52.7% (95% confidence interval [CI]: -3.6%‒78.4%) overall and in 8 schools with high mumps transmission it was 64.0% (95% CI: 1.2%‒86.9%). MMR3 VE was higher among middle compared with elementary school students (68.5% [95% CI: -30.2%‒92.4%] vs 37.6% [95% CI: -62.5%‒76.1%]); these differences were not statistically significant. Conclusion: Our findings suggest MMR3 provided additional protection from mumps compared with two MMR doses in elementary and middle school settings during a mumps outbreak. © 2023

PROBLEM/CONDITION: During 2012-2021, the volume of international travel reached record highs and lows. This period also was marked by the emergence or large outbreaks of multiple infectious diseases (e.g., Zika virus, yellow fever, and COVID-19). Over time, the growing ease and increased frequency of travel has resulted in the unprecedented global spread of infectious diseases. Detecting infectious diseases and other diagnoses among travelers can serve as sentinel surveillance for new or emerging pathogens and provide information to improve case identification, clinical management, and public health prevention and response. REPORTING PERIOD: 2012-2021. DESCRIPTION OF SYSTEM: Established in 1995, the GeoSentinel Network (GeoSentinel), a collaboration between CDC and the International Society of Travel Medicine, is a global, clinical-care-based surveillance and research network of travel and tropical medicine sites that monitors infectious diseases and other adverse health events that affect international travelers. GeoSentinel comprises 71 sites in 29 countries where clinicians diagnose illnesses and collect demographic, clinical, and travel-related information about diseases and illnesses acquired during travel using a standardized report form. Data are collected electronically via a secure CDC database, and daily reports are generated for assistance in detecting sentinel events (i.e., unusual patterns or clusters of disease). GeoSentinel sites collaborate to report disease or population-specific findings through retrospective database analyses and the collection of supplemental data to fill specific knowledge gaps. GeoSentinel also serves as a communications network by using internal notifications, ProMed alerts, and peer-reviewed publications to alert clinicians and public health professionals about global outbreaks and events that might affect travelers. This report summarizes data from 20 U.S. GeoSentinel sites and reports on the detection of three worldwide events that demonstrate GeoSentinel's notification capability. RESULTS: During 2012-2021, data were collected by all GeoSentinel sites on approximately 200,000 patients who had approximately 244,000 confirmed or probable travel-related diagnoses. Twenty GeoSentinel sites from the United States contributed records during the 10-year surveillance period, submitting data on 18,336 patients, of which 17,389 lived in the United States and were evaluated by a clinician at a U.S. site after travel. Of those patients, 7,530 (43.3%) were recent migrants to the United States, and 9,859 (56.7%) were returning nonmigrant travelers.Among the recent migrants to the United States, the median age was 28.5 years (range = <19 years to 93 years); 47.3% were female, and 6.0% were U.S. citizens. A majority (89.8%) were seen as outpatients, and among 4,672 migrants with information available, 4,148 (88.8%) did not receive pretravel health information. Of 13,986 diagnoses among migrants, the most frequent were vitamin D deficiency (20.2%), Blastocystis (10.9%), and latent tuberculosis (10.3%). Malaria was diagnosed in 54 (<1%) migrants. Of the 26 migrants diagnosed with malaria for whom pretravel information was known, 88.5% did not receive pretravel health information. Before November 16, 2018, patients' reasons for travel, exposure country, and exposure region were not linked to an individual diagnosis. Thus, results of these data from January 1, 2012, to November 15, 2018 (early period), and from November 16, 2018, to December 31, 2021 (later period), are reported separately. During the early and later periods, the most frequent regions of exposure were Sub-Saharan Africa (22.7% and 26.2%, respectively), the Caribbean (21.3% and 8.4%, respectively), Central America (13.4% and 27.6%, respectively), and South East Asia (13.1% and 16.9%, respectively). Migrants with diagnosed malaria were most frequently exposed in Sub-Saharan Africa (89.3% and 100%, respectively).Among nonmigrant travelers returning to the United States, the median age was 37 years (range = <19 years to 96 years); 55.7% were female, 75.3% were born in the United States, and 89.4% were U.S. citizens. A majority (90.6%) were seen as outpatients, and of 8,967 nonmigrant travelers with available information, 5,878 (65.6%) did not receive pretravel health information. Of 11,987 diagnoses, the most frequent were related to the gastrointestinal system (5,173; 43.2%). The most frequent diagnoses among nonmigrant travelers were acute diarrhea (16.9%), viral syndrome (4.9%), and irritable bowel syndrome (4.1%).Malaria was diagnosed in 421 (3.5%) nonmigrant travelers. During the early (January 1, 2012, to November 15, 2018) and later (November 16, 2018, to December 31, 2021) periods, the most frequent reasons for travel among nonmigrant travelers were tourism (44.8% and 53.6%, respectively), travelers visiting friends and relatives (VFRs) (22.0% and 21.4%, respectively), business (13.4% and 12.3%, respectively), and missionary or humanitarian aid (13.1% and 6.2%, respectively). The most frequent regions of exposure for any diagnosis among nonmigrant travelers during the early and later period were Central America (19.2% and 17.3%, respectively), Sub-Saharan Africa (17.7% and 25.5%, respectively), the Caribbean (13.0% and 10.9%, respectively), and South East Asia (10.4% and 11.2%, respectively).Nonmigrant travelers who had malaria diagnosed were most frequently exposed in Sub-Saharan Africa (88.6% and 95.9% during the early and later period, respectively) and VFRs (70.3% and 57.9%, respectively). Among VFRs with malaria, a majority did not receive pretravel health information (70.2% and 83.3%, respectively) or take malaria chemoprophylaxis (88.3% and 100%, respectively). INTERPRETATION: Among ill U.S. travelers evaluated at U.S. GeoSentinel sites after travel, the majority were nonmigrant travelers who most frequently received a gastrointestinal disease diagnosis, implying that persons from the United States traveling internationally might be exposed to contaminated food and water. Migrants most frequently received diagnoses of conditions such as vitamin D deficiency and latent tuberculosis, which might result from adverse circumstances before and during migration (e.g., malnutrition and food insecurity, limited access to adequate sanitation and hygiene, and crowded housing,). Malaria was diagnosed in both migrants and nonmigrant travelers, and only a limited number reported taking malaria chemoprophylaxis, which might be attributed to both barriers to acquiring pretravel health care (especially for VFRs) and lack of prevention practices (e.g., insect repellant use) during travel. The number of ill travelers evaluated by U.S. GeoSentinel sites after travel decreased in 2020 and 2021 compared with previous years because of the COVID-19 pandemic and associated travel restrictions. GeoSentinel detected limited cases of COVID-19 and did not detect any sentinel cases early in the pandemic because of the lack of global diagnostic testing capacity. PUBLIC HEALTH ACTION: The findings in this report describe the scope of health-related conditions that migrants and returning nonmigrant travelers to the United States acquired, illustrating risk for acquiring illnesses during travel. In addition, certain travelers do not seek pretravel health care, even when traveling to areas in which high-risk, preventable diseases are endemic. Health care professionals can aid international travelers by providing evaluations and destination-specific advice.Health care professionals should both foster trust and enhance pretravel prevention messaging for VFRs, a group known to have a higher incidence of serious diseases after travel (e.g., malaria and enteric fever). Health care professionals should continue to advocate for medical care in underserved populations (e.g., VFRs and migrants) to prevent disease progression, reactivation, and potential spread to and within vulnerable populations. Because both travel and infectious diseases evolve, public health professionals should explore ways to enhance the detection of emerging diseases that might not be captured by current surveillance systems that are not site based.

Racial and ethnic minority patients are disproportionately affected by healthcare-associated infections (HAIs).Reference Argamany, Delgado and Reveles1–Reference Fortin-Leung and Wiley4 Patients may be at increased risk due to the underlying influence of several factors such as demographics and comorbidities. Studies of patient-level risk factors for specific HAIs have focused on racial and ethnic inequities,Reference Argamany, Delgado and Reveles1–Reference Fortin-Leung and Wiley4 but less is known about other patient-level characteristics that may place patients at greater risk of HAIs during an outbreak or facility-level factors that may place a facility at greater risk of experiencing HAI outbreaks. Additional data are needed beyond what is currently routinely collected in outbreak investigations. Are certain patients more likely to experience harm (eg, increased exposure to pathogens, infection, morbidity, or mortality) if they are in a facility experiencing an HAI outbreak? Are certain facilities (eg, based on populations served, geography, or facility type) more likely to experience HAI outbreaks? Further research is needed to better understand which patient and facility-level factors play a role in differential risk of HAI outbreaks, and collecting these additional data can help elucidate these factors.

BACKGROUND: Protection against herpes zoster (HZ) is primarily conferred by cell-mediated immunity (CMI). However, anti-VZV-glycoprotein (anti-gp) antibody responses to Zoster Vaccine Live (ZVL) correlate with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the Recombinant Zoster Vaccine (RZV) are lacking. METHODS: We compared ELISA-measured anti-gp and anti-glycoprotein E (anti-gE) antibodies and avidity in 159 participants randomized to RZV (n = 80) or ZVL (n = 79) recipients over 5 years post-vaccination and identified predictors of antibody persistence. RESULTS: The comparison between vaccine groups showed higher anti-gE and anti-gp antibody levels after RZV than ZVL over the 5-year study duration. RZV recipients also had higher anti-gE avidity for 5 years and higher anti-gp avidity in the first year post-vaccination. Compared with pre-vaccination, RZV recipients maintained higher levels of anti-gE antibodies and avidity for 5 years, whereas ZVL recipients only maintained higher anti-gE avidity. Anti-gp antibody levels and avidity decreased to pre-vaccination levels or below after 1-year post-vaccination in both groups. Independent predictors of persistence of antibody levels and avidity were the following: vaccine type, pre-vaccination and peak antibody levels and avidity, pre-vaccination and peak CMI, and age. Sex or prior ZVL administration did not affect persistence. CONCLUSION: Antibody responses and avidity were higher and more persistent in RZV than ZVL recipients. The effect of age on antibody persistence in RZV recipients is novel.