BACKGROUND: The Federal Retail Pharmacy Program (FRPP) integrated pharmacies as partners in the national effort to maximize vaccination during the COVID-19 public health emergency. OBJECTIVES: The objective of this study was to quantify the contribution of pharmacies participating in FRPP to COVID-19 vaccination efforts during December 2020-September 2023 across sociodemographic groups in the United States. METHODS: Data on COVID-19 vaccine doses administered reported to CDC by FRPP and jurisdictional immunization information systems (IIS) of all 50 states, the District of Columbia, and U.S. territories were analyzed to estimate FRPP contributions. RESULTS: Approximately 314.9 million COVID-19 vaccine doses were administered by FRPP throughout this period, constituting 48.9% of all COVID-19 vaccine doses administered. FRPP contributions to COVID-19 vaccination ranged from 12.9% to 56.8% for persons aged 6 months-4 years and 12-17 years, respectively. FRPP made the highest contribution to administering COVID-19 doses to Non-Hispanic Asian (48.7%) and Hispanic/Latino (49.8%) persons. The proportion of COVID-19 doses given by FRPP pharmacies was found to be higher in urban areas (57%) compared with rural areas (45%). CONCLUSION: FRPP administered a substantial proportion of COVID-19 vaccine doses in the United States and provided vaccine access for persons across a wide range of groups. Pharmacies can complement vaccination efforts during public health emergency situations and in routine vaccination programs.

PURPOSE: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown. METHODS: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model. RESULTS: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.3 SEM1-DLX5-DLX6 locus, and their combination conferred over 7-fold increased risk of cNCS. The top variants were replicated in an independent cohort and showed pleiotropic effects on brain and facial morphology and bone mineral density. Fine mapping of 7q21.3 identified a craniofacial transcriptional enhancer (eDlx36) within the linkage region of the top variant (rs4727341; odds ratio [95% confidence interval], 0.48[0.39-0.59]; P = 1.2E-12) that was located in SEM1 intron and enriched in 4 rare risk variants. In zebrafish, the activity of the transfected human eDlx36 enhancer was observed in the frontonasal prominence and calvaria during skull development and was reduced when the 4 rare risk variants were introduced into the sequence. CONCLUSION: Our findings support a polygenic nature of cNCS risk and functional role of craniofacial enhancers in cNCS susceptibility with potential broader implications for bone health.

In 2021, the U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDC), and state partners investigated a multi-state sample-initiated retrospective outbreak investigation (SIROI) consisting of a cluster of nine Salmonella Weltevreden illnesses associated with frozen, pre-cooked shrimp imported from India. Import surveillance testing identified Salmonella Weltevreden recovered from a cooked shrimp sample from Supplier B. In total, nine patients with clinical isolates highly related via whole genome sequencing were reported in four states with illness onset dates between February 26 and July 17, 2021. Epidemiologic data was gathered by state partners for seven patients, whom all reported exposure to shrimp. Five patients reported consuming shrimp cocktail from the same retailer. A traceback investigation for five of the six patients converged on Supplier B. This evidence demonstrated that the outbreak of Salmonella Weltevreden illnesses was caused by the consumption of cooked, ready-to-eat shrimp manufactured by Supplier B. At the time of the investigation, outbreak and recall information was shared with Indian competent authorities. In March 2022, a follow up inspection of Supplier B's facility in India was conducted, and insanitary conditions and practices were observed. This outbreak investigation highlighted the importance of multidisciplinary national and international public health partnerships. The lessons learned from this investigation should continue to inform investigational activities and food safety guidance for industry.

Invasive candidiasis (IC) is an increasingly prevalent, costly, and potentially fatal infection brought on by the opportunistic yeast, Candida. Previously, IC has predominantly been caused by C. albicans which is often drug susceptible. There has been a global trend towards decreasing rates of infection secondary to C. albicans and a rise in non-albicans species with a corresponding increase in drug resistance creating treatment challenges. With advances in management of malignancies, there has also been an increase in the population at risk from IC along with a corresponding increase in incidence of breakthrough IC infections. Additionally, the emergence of C. auris creates many challenges in management and prevention due to drug resistance and the organism's ability to transmit rapidly in the healthcare setting. While the development of novel antifungals is encouraging for future management, understanding the changing epidemiology of IC is a vital step in future management and prevention.

In 2022, the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state health and regulatory partners investigated an outbreak of Salmonella enterica serovar Typhimurium infections linked to cantaloupes from southwest Indiana, resulting in 87 ill persons and 32 hospitalizations reported in 11 states. Epidemiologic and traceback evidence confirmed cantaloupe as the vehicle for these infections. Based on records collected by FDA, traceback of cantaloupe exposures for 14 ill people converged on a packing house in southwest Indiana, which supplied cantaloupe to eight of the 11 points of service where ill people purchased cantaloupe. Salmonella isolates were recovered from environmental samples collected by FDA from three growers and a packing house in southwest Indiana. Whole genome sequencing analyses of these isolates found that isolates collected from one grower matched the Salmonella Typhimurium outbreak strain, and samples collected from the other two growers and the packing house matched a 2020 Salmonella Newport outbreak strain. State and federal public health and agricultural partners identified potential conditions and practices that could have possibly resulted in the contamination of cantaloupe, including the presence of Salmonella spp. in on-farm, post-harvest, and off-farm environments. This is the third outbreak of salmonellosis confirmed to be linked to melons, sourced from southwest Indiana in the last decade. The 2012, 2020, and 2022 outbreaks of reoccurring and persisting strains of Salmonella illustrate the need for additional efforts to determine the source and extent of environmental contamination in the melon growing region of southwest Indiana and for outreach and education to help promote practices to reduce contamination of melons. © 2024

BACKGROUND: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants. METHODS: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI. RESULTS: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2). CONCLUSION: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.

INTRODUCTION: Blood source is a known preanalytical factor affecting hemoglobin (Hb) concentrations, and there is evidence that capillary and venous blood may yield disparate Hb levels and anemia prevalence. However, data from adolescents are scarce. OBJECTIVE: To compare Hb and anemia prevalence measured by venous and individual pooled capillary blood among a sample of girls aged 10-19 years from 232 schools in four regions of Ghana in 2022. METHODS: Among girls who had venous blood draws, a random subsample was selected for capillary blood. Hb was measured using HemoCue® Hb-301. We used Lin's concordance correlation coefficient (CCC) to quantify the strength of the bivariate relationship between venous and capillary Hb and a paired t-test for difference in means. We used McNemar's test for discordance in anemia cases by blood source and weighted Kappa to quantify agreement by anemia severity. A multivariate generalized estimating equation was used to quantify adjusted population anemia prevalence and assess the association between blood source and predicted anemia risk. RESULTS: We found strong concordance between Hb measures (CCC = 0.86). The difference between mean venous Hb (12.8 g/dL, ± 1.1) and capillary Hb (12.9 g/dL, ± 1.2) was not significant (p = 0.26). Crude anemia prevalence by venous and capillary blood was 20.6% and 19.5%, respectively. Adjusted population anemia prevalence was 23.5% for venous blood and 22.5% for capillary (p = 0.45). Blood source was not associated with predicted anemia risk (risk ratio: 0.99, 95% CI: 0.96, 1.02). Discordance in anemia cases by blood source was not significant (McNemar p = 0.46). Weighted Kappa demonstrated moderate agreement by severity (ĸ = 0.67). Among those with anemia by either blood source (n = 111), 59% were identified by both sources. CONCLUSION: In Ghanaian adolescent girls, there was no difference in mean Hb, anemia prevalence, or predicted anemia risk by blood source. However, only 59% of girls with anemia by either blood source were identified as having anemia by both sources. These findings suggest that pooled capillary blood may be useful for estimating Hb and anemia at the population level, but that caution is needed when interpreting individual-level data.

BACKGROUND: Diversity is a key component of diet quality and health, but no indicator exists for adolescents under the age of 15 years. OBJECTIVE: To establish a dichotomous indicator for population-level assessment of adolescent dietary diversity as a proxy for micronutrient adequacy. METHODS: We used the probability approach to construct mean probability of adequacy (MPA) of 11 micronutrients from 2 days of 24-hour dietary recall data from NHANES, 2007-2018. For each micronutrient, probability of adequacy was calculated using the best linear unbiased predictor of usual intake. Adolescent dietary diversity score (ADDS) was derived with a maximum score of 10 food groups. Generalized linear mixed models were used to examine associations between ADDS and MPA. Receiver operating characteristic analysis was used to establish a cutoff for minimum dietary diversity for adolescents (MDD-A), using an energy-adjusted logistic model with ADDS predicting MPA > 0.6. RESULTS: Probability of adequacy was greater than 80% for all nutrients except vitamin C (42.1%), folate (65.7%), and calcium (23.8%). Population MPA was 79.4%, and nearly 92% of adolescents had an MPA > 0.6. ADDS was positively associated with MPA, and energy was a significant confounder. Area under the curve was > 0.8 on both days with sensitivity and specificity ranging from 0.71-0.80. The MDD-A cutoff was calculated as 5.12 and 5.10 food groups on day 1 and 2, respectively. CONCLUSIONS: In U.S. adolescents, the best cutoff for a dichotomous indicator of dietary diversity as a proxy for micronutrient adequacy is 6 food groups in a given day. Future research could validate MDD-A and its associated cutoff for use across country contexts.

BACKGROUND: Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention. METHODS: Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data. RESULTS: Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates. CONCLUSIONS: Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data" such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are one such outcome, where specificity of exposure timing is critical. Studies with primary data collection can be designed to query details on the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world". Because birth defects are rare, etiologic studies are typically case-control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy exposureS, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information on both prescription and over-the-counter medication use and on other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case-control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects.

BACKGROUND: Re-engaging people with HIV (PWH) who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals. METHODS: A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard-of-care (SOC) where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N=333) or SOC (N=322). HIV care continuum outcomes included re-engagement at 90 days, retention in care and viral suppression (VS) by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes. RESULTS: Participants randomized to DIS were more likely to be re-engaged at 90 days (aOR=1.42, p=0.045). Independent predictors of re-engagement at 90 days were: age>40 years (aOR=1.84, p=0.012) and peri-natal HIV risk category (aOR=3.19, p=0.030). Predictors of retention at 12 months included: re-engagement at 90 days (aOR=10.31, p<0.001), drug injection HIV risk category (aOR=1.83, p=0.032), detectable HIV-1 RNA before randomization (aOR=0.40, p=0.003) and county (Hartford aOR=1.74, p=0.049; New Haven aOR=1.80, p=0.030). Predictors of VS included: re-engagement at 90 days (aOR=2.85, p<0.001), retention in HIV care (aOR=7.07, p<0.001), and detectable HIV-1 RNA pre-randomization (aOR=0.23, p<0.001). CONCLUSIONS: A D2C strategy significantly improved re-engagement at 90 days. Early re-engagement improved downstream benefits along the HIV care continuum like retention in care and VS at 12 months. Moreover, other factors predictive of care continuum outcomes can be used to improve D2C strategies.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance.IMPORTANCEIn our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

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

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10(-5)), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2(707C>T) and CAPN2(1112C>T) variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.

CDC’s Vessel Sanitation Program (VSP) monitors cases of acute gastroenteritis (AGE) on board cruise ships traveling to a U.S. port (1). Persons who have ≥3 loose stools (or more than normal for that person) within a 24-hour period or vomiting plus one other sign or symptom (e.g., fever, diarrhea, bloody stool, myalgia, abdominal cramps, or headache) meet the case definition for reportable AGE (2). When the percentage of passengers or crew members with AGE is ≥2% and the ship is due to arrive at a U.S. port within 15 days, the Maritime Illness Disease Reporting System alerts VSP and activates an investigation (1). During the first week of January 2023, VSP was notified of cases of AGE affecting >2% of passengers on board a ship that had completed three voyages in Europe and was within 15 days of arriving at a U.S. port (voyage 4)* (Figure). Ship medical crew members submitted stool samples from ill travelers for testing. All samples tested positive for norovirus genotype II. While the ship was sailing to a U.S. port, VSP monitored AGE cases on board and reviewed case data. By mid-January, passenger AGE prevalence reached 3.4%.

BACKGROUND: Although the importance of adolescent nutrition has gained attention in the global nutrition community, there is a gap in research focused on adolescent dietary diversity and food group consumption. OBJECTIVES: This study aimed to characterize population-level food group consumption patterns and quantify the extent of dietary diversity among United States adolescents using a large nationally representative sample of adolescents aged 10-19 y. METHODS: We used 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 to construct the 10 food groups comprising the minimum dietary diversity for women (MDD-W) indicator and estimated the prevalence of intake of each food group. A composite metric adolescent dietary diversity score (ADDS) was derived for each adolescent where 1 point was awarded per food group. Both population scores and the distribution of individual scores were estimated. Differences in proportions of food groups consumed across sociodemographic categories were tested using the Rao-Scott χ(2) test, and pairwise comparisons were expressed as population prevalence differences and prevalence ratios. RESULTS: Food group consumption patterns were very similar across 2 d of dietary recall but varied significantly by sex, race/ethnicity, and income status. The food groups with the highest prevalence of consumption were grains, white, roots, and tubers (∼99%), milk products (∼92%), and meat, poultry, and fish (∼85%), whereas <15% of adolescents consumed key micronutrient-dense foods, such as vitamin A-rich fruits and vegetables and dark green vegetables. The mean ADDS was 4.69, with modest variation across strata. CONCLUSIONS: On average, United States youth consumed fewer than 5 food groups on a given day. The lack of dietary variety and relatively low prevalence of consumption of several micronutrient-rich plant-based foods could pose a risk for adolescents' ability to achieve micronutrient adequacy in the United States.

Background Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pet cohabitants as a sub-study of an ongoing COVID-19 household transmission investigation.Methods Mammalian pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April–May 2020. Demographic/exposure information, oropharyngeal, nasal, rectal, and fur swabs, feces, and blood were collected from enrolled pets and tested by rRT-PCR and virus neutralization assays.Findings We enrolled 37 dogs and 19 cats from 34 of 41 eligible households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog’s fur swabs (2%) tested positive by rRT-PCR at the first animal sampling. Among 47 pets with serological results from 30 households, eight (17%) pets (4 dogs, 4 cats) from 6 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40–100%) compared to households with no seropositive pet (median 37%; range: 13–100%) (p=0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 hour) with the human index patient before the person’s COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the human index patient after diagnosis and none (0%) were seropositive; of the 19 (58%) pets with continued contact, 4 (21%) were seropositive.Interpretations Seropositive pets likely acquired infection from humans, which may occur more frequently than previously recognized. People with COVID-19 should restrict contact with animals.Funding Centers for Disease Control and Prevention, U.S. Department of AgricultureCompeting Interest StatementThe authors have declared no competing interest.

We describe the first cases of natural SARS-CoV-2 infection detected in animals in the United States. In March 2020, four tigers and three lions at the Bronx Zoo developed mild respiratory signs. SARS-CoV-2 RNA was detected by rRT-PCR in respiratory secretions and/or feces from all seven affected animals; viral RNA and/or antibodies were detected in their keepers. SARS-CoV-2 was isolated from respiratory secretions or feces from three affected animals; in situ hybridization co-localized viral RNA with cellular damage. Whole genome sequence and haplotype network analyses showed tigers and lions were infected with two different SARS-CoV-2 strains, suggesting independent viral introductions. The source of SARS-CoV-2 infection in the lions is unknown. Epidemiological data and genetic similarities between keeper and tiger viruses indicate human to animal transmission.Competing Interest StatementThe authors have declared no competing interest.

The natural infections and epidemiological roles of household pets in SARS-CoV-2 transmission are not understood. We conducted a longitudinal study of dogs and cats living with at least one SARS-CoV-2 infected human in Texas and found 47.1% of 17 cats and 15.3% of 59 dogs from 25.6% of 39 households were positive for SARS-CoV-2 via RT-PCR and genome sequencing or neutralizing antibodies. Virus was isolated from one cat. The majority (82.4%) of infected pets were asymptomatic. Re-sampling of one infected cat showed persistence of viral RNA at least 32 d-post human diagnosis (25 d-post initial test). Across 15 antibody-positive animals, titers increased (33.3%), decreased (33.3%) or were stable (33.3%) over time. A One Health approach is informative for prevention and control of SARS-CoV-2 transmission.

Background: Shiga toxin-producing E. coli (STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition, hemolytic uremic syndrome (HUS). A major outbreak of HUS occurred in 2011, and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 were rarely associated with human infections. Method(s): From 2012 to 2020 intensified STEC surveillance was performed in Germany where subtyping of ~8,000 clinical isolates by molecular methods including whole genome sequencing was carried out. Virulence traits and phylogenetic context were investigated for a subset of strains. Result(s): A rare STEC serotype O181:H4 associated with HUS was identified, belonging to sequence type (ST) 678, like the STEC O104:H4 outbreak strain. Virulence and genomic comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens. In addition, five other serotypes belonging to ST678 from human clinical infection were identified from diverse locations worldwide. Conclusion(s): Our data suggest the high virulence ensemble of STEC O104:H4 remains a global threat, but that horizontal exchange of O-antigen gene clusters has cloaked the pathogen with new O-antigens, confounding interpretation of their potential risk. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

The United States are one of the world's leading consumers of melons. In 2020, the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state health and regulatory partners investigated an outbreak of Salmonella Newport infections linked to melons from southwest Indiana, resulting in 80 ill persons and 18 hospitalizations reported across 15 states. Epidemiologic and traceback data indicated melons as the vehicle for these infections, but the collinearity of melon varieties purchased and consumed together in combination with the traceback investigation that could not rule out either melon type, did not allow investigators to delineate whether the vehicle was cantaloupe alone or, both cantaloupe and watermelons. Analysis of traceback records for cantaloupe and/or watermelon exposures for 12 ill people indicated convergence on a grower in southwest Indiana which supplied cantaloupe to the nine of eleven points of service where ill people purchased cantaloupe; similar convergence was not observed for watermelon. While Salmonella isolates were recovered from environmental samples collected by FDA throughout the growing operation, they were not highly genetically related to the outbreak strain by whole genome sequencing analyses, i.e. greater than a 20 high quality single nucleotide polymorphisms difference. This outbreak illustrates the need for additional efforts to determine the source and extent of environmental contamination in the melon growing region of southwest Indiana and emphasizes the need for outreach and education efforts to help promote farm practices to reduce pathogen contamination of melons. 2023

Shiga toxin-producing Escherichia coli (STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition hemolytic-uremic syndrome (HUS). Although STEC O157:H7 is the serotype most frequently associated with HUS, a major outbreak of HUS occurred in 2011 in Germany and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 strains have only rarely been associated with human infections. From 2012 to 2020, intensified STEC surveillance was performed in Germany where the subtyping of ~8,000 clinical isolates by molecular methods, including whole-genome sequencing, was carried out. A rare STEC serotype, O181:H4, associated with HUS was identified, and like the STEC O104:H4 outbreak strain, this strain belongs to sequence type 678 (ST678). Genomic and virulence comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens but exhibit similar virulence phenotypes. In addition, five other serotypes belonging to ST678 from human clinical infection, such as OX13:H4, O127:H4, OgN-RKI9:H4, O131:H4, and O69:H4, were identified from diverse locations worldwide. IMPORTANCE Our data suggest that the high-virulence ensemble of the STEC O104:H4 outbreak strain remains a global threat because genomically similar strains cause disease worldwide but that the horizontal acquisition of O-antigen gene clusters has diversified the O-antigens of strains belonging to ST678. Thus, the identification of these highly pathogenic strains is masked by diverse and rare O-antigens, thereby confounding the interpretation of their potential risk.

With advancements in clinical care, it is unquestionable that survival for both children and adults with congenital heart defects has improved significantly (1). In the United States in 2010, there were an estimated 1.4 million adults and 1 million children living with congenital heart defects (2). Some stakeholders have suggested that survival is no longer a concern, based on improving results in surgical registries. However, in this issue of the Journal, the new study by Spector et al. (3) links one of the highest-quality U.S. registries collected for quality improvement to the National Death Index, and demonstrates that despite tremendous advances, people with congenital heart defects are still dying too soon. Even for the most recent time period, the 15-year mortality for those who survived surgery for their congenital heart defects (6.5% had already died before leaving the hospital) was about 10 times higher than for those of the same age and sex in the general population. Surprisingly, the continued excess mortality even among survivors of initial congenital heart surgery was observed not only among those with the most severe defects, like tricuspid atresia or hypoplastic left heart syndrome, but also for those with simple defects, like atrial septal defects, which are frequently viewed as “cured” by surgery (3). To address this early risk for death and improve the health of individuals and families affected by congenital heart defects, a public health approach is essential.

OBJECTIVE: The impact of the COVID-19 pandemic goes beyond morbidity and mortality from that disease. Increases in maternal mortality have also been described but have not been extensively studied to date. This study aimed to examine changes in maternal mortality and identify correlates and predictors of excess maternal mortality in Colombia during the pandemic. SETTING: Analysis of data from the national epidemiological surveillance databases of Colombia (Sivigila). PARTICIPANTS: Deaths among 6342 Colombian pregnant women who experienced complications associated with pregnancy, childbirth or the perperium during 2008-2020 were included in this study. For inequalities analysis, a subsample of 1055 women from this group who died in 2019 or 2020 years were analysed. METHODS: We collected data from the national surveillance system (Sivigila) on maternal mortality. Analysis was carried out in two stages, starting with a time series modelling using the Box-Jenkins approach. Data from Sivigila for 2008-2019 were used to establish a baseline of expected mortality levels. Both simple and complex inequality metrics, with the maternal mortality ratios (MMRs), were then calculated using the Multidimensional Poverty Index as a socioeconomic proxy. RESULTS: Maternal deaths in 2020 were 12.6% (95% CI -21.4% to 95.7%) higher than expected. These excess deaths were statistically significant in elevation for the months of July (97.4%, 95% CI 35.1% to 250.0%) and August (87.8%, 95% CI 30.5% to 220.8%). The MMR was nearly three times higher in the poorest municipalities compared with the most affluent communities in 2020. CONCLUSIONS: The COVID-19 pandemic had considerable impact on maternal health, not only by leading to increased deaths, but also by increasing social health inequity. Barriers to access and usage of essential health services are a challenge to achieving health-related Sustainable Development Goals.

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.

BACKGROUND: A collaborative, data-to-care strategy to identify persons with HIV (PWH) newly out-of-care, combined with an active public health intervention, significantly increases the proportion of PWH re-engaged in HIV care. We assessed this strategy's impact on durable viral suppression (DVS). METHODS: A multi-site, prospective randomized controlled trial for out-of-care individuals using a data-to-care strategy and comparing public health field services to locate, contact, and facilitate access to care versus the standard of care (SOC). DVS was defined as the last viral load (VL), the VL at least three months prior, and any VL between the two were all <200 copies/mL during the 18 months post-randomization. Alternative definitions of DVS were also analyzed. RESULTS: Between August 1, 2016 - July 31, 2018, 1,893 participants were randomized from Connecticut (CT) (n=654), Massachusetts (MA) (n=630), and Philadelphia (PHL) (n=609). Rates of achieving DVS were similar in the intervention and SOC arms in all jurisdictions (All sites: 43.4% vs 42.4%, p=0.67; CT: 46.7% vs 45.0%, p=0.67; MA: 40.7 vs 44.4%, p=0.35; PHL: 42.4% vs 37.3%, p=0.20). There was no association between DVS and the intervention (RR:1.01, CI: 0.91-1.12; p=0.85) adjusting for site, age categories, race/ethnicity, birth sex, CD4 categories, and exposure categories. CONCLUSION: A collaborative, data-to-care strategy, and active public health intervention did not increase the proportion of PWH achieving DVS suggesting additional support to promote retention in care and antiretroviral adherence may be needed. Initial linkage and engagement services, through data-to-care or other means, are likely necessary but insufficient for achieving DVS for all PWH.

INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.