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Introduction: Wastewater surveillance is an important technique to monitor public health and is being studied extensively for pandemic prevention, force health protection and readiness, and as a potential early warning system for chem-bio defense. Wastewater surveillance has traditionally relied on techniques such as quantitative PCR or targeted sequencing, both of which are microbe- or disease-specific tools. Newer pan-viral metagenomics strategies may provide higher specificity for pathogens of interest, resulting in a lower false negative rate and reduced sequencing of undesired background nucleic acids. One such system, VirCapSeq-VERT, has been developed to target all vertebrate virus pathogens; until recently, its application has been limited to clinical samples. The objective of this study was to use VirCapSeq-VERT to interrogate wastewater samples from the U.S. Air Force Academy (USAFA), Colorado Springs, Colorado, to determine its utility in assessing complex samples and its potential application in public health surveillance., Materials and Methods: Biweekly samples were analyzed from February 2022 through May 2023. Samples were collected from the wastewater treatment facility at USAFA before treatment and stored at -20 °C until total nucleic acid (tNA: DNA and RNA) extraction. tNA was then subject to the probe-based capture system, VirCapSeq, and run through a collection of public bioinformatics pipelines to identify captured viral pathogens and perform phylogenetic analysis. It was determined by the USAFA IRB that the study was non-human subject research and was deemed exempt., Results: In total, 68 families of viruses were identified, comprising thousands of individual strains. This study focused on viruses responsible for gastrointestinal dysfunction as a test of the use of the VirCapSeq-VERT to identify human pathogenic viruses within a complex and highly enriched biological sample. Four enteric viruses dominated the wastewater samples, with Adenoviridae most prevalent before the cadet winter recess (December 17, 2022-January 4, 2023) and Astroviridae most abundant thereafter., Conclusion: Although gastroenteritis outbreaks at USAFA are commonly attributed to norovirus because of clinical presentation and the acute nature of the illness-often diagnosed and treated without confirmatory stool testing-this virus was not found in high prevalence in these wastewater samples. Among adenoviruses, F serotype 41 predominated, suggesting a role in gastrointestinal infections among the cadet population. Phylogenetic investigation of adenovirus and norovirus exposed common variants with seasonal distributions. These findings may prompt correlational studies to assess the clinical predictive capability of VirCapSeq-VERT and to determine the utility of wastewater monitoring as an outbreak early warning system., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We utilized a pan-viral capture sequencing assay, VirCapSeq-VERT, to assess viral diversity in rodents from the Eastern Province of Zambia as a model for pre-pandemic viral reservoir surveillance. We report rodent adeno-, parvo-, paramyxo-, and picornaviruses that represent novel species or isolates, including murine adenovirus 4, two additional species in the genus Chaphamaparvovirus , two paramyxoviruses distantly related to unclassified viruses in the genus Jeilongvirus , and the first Aichivirus A sequence identified from rodents in Africa. Our results emphasize the importance of rodents as a reservoir for potential zoonotic viruses.

Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed by any authors.

In May 2023, the Detroit Health Department was notified of four cases of invasive nontypeable Haemophilus influenzae (Hi) disease among students attending the same elementary school and grade, all with illness onsets within 7 days. Three patients were hospitalized, and one died. Most U.S. cases of invasive Hi disease are caused by nontypeable strains. No vaccines against nontypeable or non-type b Hi strains are currently available. Chemoprophylaxis is not typically recommended in response to nontypeable Hi cases; however, because of the high attack rate (four cases among 46 students; 8.7%), rifampin prophylaxis was recommended for household contacts of patients with confirmed cases and for all students and staff members in the school wing where confirmed cases occurred. Only 10.8% of students for whom chemoprophylaxis was recommended took it, highlighting gaps in understanding among caregivers and health care providers about persons for whom chemoprophylaxis was recommended. Public health authorities subsequently enhanced communication and education to the school community, improved coordination with health care partners, and established mass prophylaxis clinics at the school. This outbreak highlights the potential for nontypeable Hi to cause serious illness and outbreaks and the need for chemoprophylaxis guidance for nontypeable Hi disease. Achieving high chemoprophylaxis coverage requires education, communication, and coordination with community and health care partners., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jamie Loehr reports receipt of payment for presentations on general ACIP recommendations at the National Family Medicine Conference and the Virginia State Vaccine Group Conference. Katherine A. Poehling reports receipt of grant support from North Carolina Baptist Foundation, Optum Social Responsibility, Atrium Health, Wake Forest Baptist Clinical and Translational Science Institute, and the Kate B. Reynolds Foundation. No other potential conflicts of interest were disclosed.

Background: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy., Methods: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011)., Findings: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient., Interpretation: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy., Funding: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In late December 1973, the United States enacted what some would come to call "the pitbull of environmental laws." In the 50 years since, the formidable regulatory teeth of the Endangered Species Act (ESA) have been credited with considerable successes, obliging agencies to draw upon the best available science to protect species and habitats. Yet human pressures continue to push the planet toward extinctions on a massive scale. With that prospect looming, and with scientific understanding ever changing, Science invited experts to discuss how the ESA has evolved and what its future might hold. -Brad Wible .

Fully online degree programs are an increasingly important part of the higher education ecosystem. Among the many challenges raised by the growth of fully online courses and degree programs is the question: Are institutions providing online students with disabilities accommodations that are comparable to those provided to students in traditional in-person degree programs? To explore this question, we compared students in a fully online biology degree program to students in the equivalent in-person degree program at a large research university. For each group, we assessed the frequency with which students register with the disability resource center, the range of specific accommodations provided, and course grades. Results show that students in the in-person program were nearly 30% more likely to be enrolled with the disability resource center, and that students in the online program were offered a narrower range of accommodations. However, in relative terms (i.e., compared to students without disabilities in their degree program), online students with disabilities perform better than in-person students with disabilities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mead et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Defending against novel, repeated, or unpredictable attacks, while avoiding attacks on the 'self', are the central problems of both mammalian immune systems and computer systems. Both systems have been studied in great detail, but with little exchange of information across the different disciplines. Here, we present a conceptual framework for structured comparisons across the fields of biological immunity and cybersecurity, by framing the context of defense, considering different (combinations of) defensive strategies, and evaluating defensive performance. Throughout this paper, we pose open questions for further exploration. We hope to spark the interdisciplinary discovery of general principles of optimal defense, which can be understood and applied in biological immunity, cybersecurity, and other defensive realms., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Naegleria fowleri is a thermophilic ameba found in freshwater that causes primary amebic meningoencephalitis (PAM) when it enters the nose and migrates to the brain. In September 2018, a 29-year-old man died of PAM after traveling to Texas. We conducted an epidemiologic and environmental investigation to identify the water exposure associated with this PAM case. The patient's most probable water exposure occurred while surfing in an artificial surf venue. The surf venue water was not filtered or recirculated; water disinfection and water quality testing were not documented. N. fowleri and thermophilic amebae were detected in recreational water and sediment samples throughout the facility. Codes and standards for treated recreational water venues open to the public could be developed to address these novel venues. Clinicians and public health officials should also consider novel recreational water venues as a potential exposure for this rare amebic infection.

In December 2020, an interim recommendation for the use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years was made under Food and Drug Administration's Emergency Use Authorization. In preparation for Biologics License Application approval, we conducted a systematic review and meta-analysis to inform the U.S. Centers for Disease Control and Prevention's Advisory Committee for Immunization Practice's (ACIP) decision-making for a standard recommendation. We conducted a rapid systematic review and meta-analysis of Pfizer-BioNTech vaccine effectiveness (VE) against symptomatic COVID-19, hospitalization due to COVID-19, death due to COVID-19, and asymptomatic SARS-CoV-2 infection. We identified studies through August 20, 2021 from an ongoing systematic review conducted by the International Vaccine Access Center and the World Health Organization. We evaluated each study for risk of bias using the Newcastle-Ottawa Scale. Pooled estimates were calculated using meta-analysis. The body of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We identified 80 articles, selected 35 for full-text review, and included 26. The pooled VE of Pfizer-BioNTech COVID-19 vaccine was 92.4% (95% CI: 87.5%-95.3%) against symptomatic COVID-19 with moderate evidence certainty (eight studies), 94.3% (95% CI: 87.9%-97.3%) against hospitalization due to COVID-19 with moderate certainty (eight studies), 96.1% (95% CI: 91.5%-98.2%) against death due to COVID-19 with moderate certainty (four studies), and 89.3% (88.4%-90.1%) against asymptomatic SARS-CoV-2 infection with very low certainty (two studies). The Pfizer-BioNTech COVID-19 vaccine demonstrated high effectiveness in all pre-specified outcomes and extended knowledge of the vaccine's benefits to outcomes and populations not informed by the RCTs. Use of an existing systematic review facilitated a rapid meta-analysis to inform an ACIP policy decision. This approach can be utilized as additional COVID-19 vaccines are considered for standard recommendations by ACIP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: To describe national antibiotic prescribing for acute gastroenteritis (AGE)., Setting: Ambulatory care., Methods: We included visits with diagnoses for bacterial and viral gastrointestinal infections from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS; 2006-2015) and the IBM Watson 2014 MarketScan Commercial Claims and Encounters Database. For NAMCS/NHAMCS, we calculated annual percentage estimates and 99% confidence intervals (CIs) of visits with antibiotics prescribed; sample sizes were too small to calculate estimates by pathogen. For MarketScan, we used Poisson regression to calculate the percentage of visits with antibiotics prescribed and 95% CIs, including by pathogen., Results: We included 10,210 NAMCS/NHAMCS AGE visits; an estimated 13.3% (99% CI, 11.2%-15.4%) resulted in antibiotic prescriptions, most frequently fluoroquinolones (28.7%; 99% CI, 21.1%-36.3%), nitroimidazoles (20.2%; 99% CI, 14.0%-26.4%), and penicillins (18.9%; 99% CI, 11.6%-26.2%). In NAMCS/NHAMCS, antibiotic prescribing was least frequent in emergency departments (10.8%; 99% CI, 9.5%-12.1%). Among 1,868,465 MarketScan AGE visits, antibiotics were prescribed for 13.8% (95% CI, 13.7%-13.8%), most commonly for Yersinia (46.7%; 95% CI, 21.4%-71.9%), Campylobacter (44.8%; 95% CI, 41.5%-48.1%), Shigella (39.7%; 95% CI, 35.9%-43.6%), typhoid or paratyphoid fever (32.7%; (95% CI, 27.2%-38.3%), and nontyphoidal Salmonella (31.7%; 95% CI, 29.5%-33.9%). Antibiotics were prescribed for 12.3% (95% CI, 11.7%-13.0%) of visits for viral gastroenteritis., Conclusions: Overall, ∼13% of AGE visits resulted in antibiotic prescriptions. Antibiotics were unnecessarily prescribed for viral gastroenteritis and some bacterial infections for which antibiotics are not recommended. Antibiotic stewardship assessments and interventions for AGE are needed in ambulatory settings.

To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts active population-based surveillance for laboratory-diagnosed infections caused by Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia at 10 U.S. sites. This report summarizes preliminary 2021 data and describes changes in annual incidence compared with the average annual incidence for 2016-2018, the reference period for the U.S. Department of Health and Human Services' (HHS) Healthy People 2030 goals for some pathogens (1). During 2021, the incidence of infections caused by Salmonella decreased, incidence of infections caused by Cyclospora, Yersinia, and Vibrio increased, and incidence of infections caused by other pathogens did not change. As in 2020, behavioral modifications and public health interventions implemented to control the COVID-19 pandemic might have decreased transmission of enteric infections (2). Other factors (e.g., increased use of telemedicine and continued increase in use of culture-independent diagnostic tests [CIDTs]) might have altered their detection or reporting (2). Much work remains to achieve HHS Healthy People 2030 goals, particularly for Salmonella infections, which are frequently attributed to poultry products and produce, and Campylobacter infections, which are frequently attributed to chicken products (3)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

THIS REPORT SUMMARIZES ALL RECOMMENDATIONS FROM CDC'S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR THE USE OF LYOPHILIZED CVD 103-HGR VACCINE (CVD 103-HGR) (VAXCHORA, EMERGENT BIOSOLUTIONS, GAITHERSBURG, MD) IN THE UNITED STATES. THE LIVE ATTENUATED ORAL CHOLERA VACCINE IS DERIVED FROM: Vibrio cholerae O1 and is administered in a single dose. Cholera is a toxin-mediated bacterial gastrointestinal illness caused by toxigenic V. cholerae serogroup O1 or, uncommonly, O139. Up to 10% of infections manifest as severe cholera (i.e., cholera gravis), profuse watery diarrhea that can cause severe dehydration and death within hours. Fluid replacement therapy can reduce the fatality rate to <1%. Risk factors for cholera gravis include high dose exposure, blood group O, increased gastric pH (e.g., from antacid therapy), and partial gastrectomy. Cholera is rare in the United States, but cases occur among travelers to countries where cholera is endemic or epidemic and associated with unsafe water and inadequate sanitation. Travelers might be at increased risk for poor outcomes from cholera if they cannot readily access medical services or if they have a medical condition that would be worsened by dehydration, such as cardiovascular or kidney disease. This report describes previously published ACIP recommendations about use of CVD 103-HgR for adults aged 18-64 years and introduces a new recommendation for use in children and adolescents aged 2-17 years. ACIP recommends CVD 103-HgR, the only cholera vaccine licensed for use in the United States, for prevention of cholera among travelers aged 2-64 years to an area with active cholera transmission. Health care providers can use these guidelines to develop the pretravel consultation for persons traveling to areas with active cholera transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Unrelated to the current work, Adam J. Ratner previously received personal compensation from Janssen Pharmaceuticals for service on a compassionate use advisory board (ending in 2020). No potential conflicts of interest were disclosed by other authors.

Background: In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin., Methods: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms., Results: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin., Conclusions: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 μg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 μg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation † for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework § and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. ¶ The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. H. Keipp Talbot reports institutional grants from the National Institutes of Health. No other potential conflicts of interest were disclosed.

Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework, † and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. § In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation ¶ for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Foodborne illnesses are a substantial and largely preventable public health problem; before 2020 the incidence of most infections transmitted commonly through food had not declined for many years. To evaluate progress toward prevention of foodborne illnesses in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging Infections Program monitors the incidence of laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food reported by 10 U.S. sites.* FoodNet is a collaboration among CDC, 10 state health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS), and the Food and Drug Administration. This report summarizes preliminary 2020 data and describes changes in incidence with those during 2017-2019. During 2020, observed incidences of infections caused by enteric pathogens decreased 26% compared with 2017-2019; infections associated with international travel decreased markedly. The extent to which these reductions reflect actual decreases in illness or decreases in case detection is unknown. On March 13, 2020, the United States declared a national emergency in response to the COVID-19 pandemic. After the declaration, state and local officials implemented stay-at-home orders, restaurant closures, school and child care center closures, and other public health interventions to slow the spread of SARS-CoV-2, the virus that causes COVID-19 (1). Federal travel restrictions were declared (1). These widespread interventions as well as other changes to daily life and hygiene behaviors, including increased handwashing, have likely changed exposures to foodborne pathogens. Other factors, such as changes in health care delivery, health care-seeking behaviors, and laboratory testing practices, might have decreased the detection of enteric infections. As the pandemic continues, surveillance of illness combined with data from other sources might help to elucidate the factors that led to the large changes in 2020; this understanding could lead to improved strategies to prevent illness. To reduce the incidence of these infections concerted efforts are needed, from farm to processing plant to restaurants and homes. Consumers can reduce their risk of foodborne illness by following safe food-handling and preparation recommendations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Online education has grown rapidly in recent years with many universities now offering fully online degree programs even in STEM disciplines. These programs have the potential to broaden access to STEM degrees for people with social identities currently underrepresented in STEM. Here, we ask to what extent is that potential realized in terms of student enrollment and grades for a fully online degree program. Our analysis of data from more than 10,000 course-enrollments compares student demographics and course grades in a fully online biology degree program to demographics and grades in an equivalent in-person biology degree program at the same university. We find that women, first-generation to college students and students eligible for federal Pell grants constitute a larger proportion of students in the online program compared to the in-person mode. However, the online mode of instruction is associated with lower course grades relative to the in-person mode. Moreover, African American/Black, Hispanic/Latinx, Native American, and Pacific Islander students as well as federal Pell grant eligible students earned lower grades than white students and non-Pell grant eligible students, respectively, but the grade disparities were similar among both in-person and online student groups. Finally, we find that grade disparities between men and women are larger online compared to in-person, but that for first-generation to college women, the online mode of instruction is associated with little to no grade gap compared to continuing generation women. Our findings indicate that although this online degree program broadens access for some student populations, inequities in the experience remain and need to be addressed in order for online education to achieve its inclusive mission., Competing Interests: The authors have declared that no competing interests exist.

Background: When tested in a controlled clinic environment, individuals with neuromuscular-related symptoms may complete motor tasks within normal predicted ranges. However, measuring activity at home may better reflect typical motor performance. The accuracy of accelerometry measurements in individuals with congenital muscular dystrophy (CMD) is unknown. We aimed to compare accelerometry and manual step counts and assess free-living physical activity intensity in individuals with CMD using accelerometry., Methods: Ambulatory pediatric CMD participants (n = 9) performed the 6-minute walk test in clinic while wearing ActiGraph GT3X accelerometer devices. During the test, manual step counting was conducted to assess concurrent validity of the ActiGraph step count in this population using Bland-Altman analysis. In addition, activity intensity of 6 pediatric CMD participants was monitored at home with accelerometer devices for an average of 7 days. Cut-point values previously validated for neuromuscular disorders were used for data analysis., Results: Bland-Altman and intraclass correlation analyses showed no concurrent validity between manual and ActiGraph-recorded step counts. Fewer steps were recorded by ActiGraph step counts compared with manual step counts (411 ± 74 vs 699 ± 43, respectively; P = .004). Although improved, results were in the same direction with the application of low-frequency extension filters (587 ± 40 vs 699 ± 43, P = .03). ActiGraph step-count data did not correlate with manual step count (Spearman ρ = 0.32, P = .41; with low-frequency extension: Spearman ρ = 0.45, P = .22). Seven-day physical activity monitoring showed that participants spent more than 80% of their time in the sedentary activity level., Conclusions: In a controlled clinic setting, step count was significantly lower by ActiGraph GT3X than by manual step counting, possibly because of the abnormal gait in this population. Additional studies using triaxial assessment are needed to validate accelerometry measurement of activity intensity in individuals with CMD. Accelerometry outcomes may provide valuable measures and complement the 6-minute walk test in the assessment of treatment efficacy in CMD.

Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome., Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms., Results: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%)., Conclusions: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults., Methods: We identified adults hospitalized with laboratory-confirmed influenza during 2011-2015 seasons through CDC's Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors., Results: Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P < .001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20-1.76). Intensive care was more likely among IC patients 65-79 years (aOR, 1.25; 95% CI, 1.06-1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06-1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI, .83-.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05-1.36)., Conclusions: Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In 2017, state health departments notified the Centers for Disease Control and Prevention about 4 patients with shigellosis who experienced persistent illness after treatment with oral third-generation cephalosporins. Given increasing antibiotic resistance among Shigella , these cases highlight the need to evaluate the efficacy of oral cephalosporins for shigellosis., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)