BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

We describe substantial variant diversity among 23 detected SARS-CoV-2 Omicron lineage viruses cocirculating among healthcare workers and inpatients (272 sequenced samples) from Porto Alegre, Brazil, during November 2022-January 2023. BQ.1 and related lineages (61.4%) were most common, followed by BE.9 (19.1%), first described in November 2022 in the Amazon region.

Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. Nirsevimab (Bevfortus, Sanofi and AstraZeneca) is recommended to prevent RSV-associated lower respiratory tract infection (LRTI) in infants. In August 2023, the Food and Drug Administration (FDA) approved RSVpreF vaccine (Abrysvo, Pfizer Inc.) for pregnant persons as a single dose during 32-36 completed gestational weeks (i.e., 32 weeks and zero days' through 36 weeks and 6 days' gestation) to prevent RSV-associated lower respiratory tract disease in infants aged <6 months. Since October 2021, CDC's Advisory Committee on Immunization Practices (ACIP) RSV Vaccines Pediatric/Maternal Work Group has reviewed RSV epidemiology and evidence regarding safety, efficacy, and potential economic impact of pediatric and maternal RSV prevention products, including RSVpreF vaccine. On September 22, 2023, ACIP and CDC recommended RSVpreF vaccine using seasonal administration (i.e., during September through end of January in most of the continental United States) for pregnant persons as a one-time dose at 32-36 weeks' gestation for prevention of RSV-associated LRTI in infants aged <6 months. Either maternal RSVpreF vaccination during pregnancy or nirsevimab administration to the infant is recommended to prevent RSV-associated LRTI among infants, but both are not needed for most infants. All infants should be protected against RSV-associated LRTI through use of one of these products.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Since October 2021, the Advisory Committee on Immunization Practices (ACIP) Maternal and Pediatric RSV Work Group has reviewed evidence on the safety and efficacy of nirsevimab among infants and young children. On August 3, 2023, ACIP recommended nirsevimab for all infants aged <8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March. Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.

The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence Summary An interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks.

BACKGROUND: High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. METHODS: We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018-February 2020 (prepandemic) and March 2020-February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. RESULTS: Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%-35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4-268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. CONCLUSIONS: Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

BACKGROUND: Universal masking, with additional layered prevention strategies, was an essential tool for limiting the transmission of SARS-CoV-2 and ensuring a safe return to in-person learning for kindergarten through 12th grade (K-12) students and staff. Few studies have examined mask adherence in this setting and none have described types of masks worn or locations of mask adherence. This project sought to assess mask adherence, types worn, and location of mask adherence in K-12 settings. METHODS: This study used direct in-person observations to measure the proportion of persons wearing masks correctly; type of masks worn; and location of mask adherence in 19 K-12 schools in Georgia. RESULTS: A total of 16,222 observations were conducted. Among those observed, 85.2% wore masks, with 80.3% wearing the mask correctly. Persons in high school were less likely to wear masks correctly. Correct mask use was most often observed among persons wearing N95-type masks. The prevalence of persons wearing masks correctly in transitional spaces was 5% higher than in congregate spaces. CONCLUSION: In K-12 schools with a universal masking policy, correct mask adherence was high among individuals. Examining adherence to recommended prevention measures can provide K-12 schools feedback to inform targeted messaging and policies during future disease outbreaks.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).

BACKGROUND: ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by Merck & Co., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries. METHODS: We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013-2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18-50 yrs & >50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (<200 & ≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination. RESULTS: In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups. CONCLUSION: These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines. Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018.

As SARS-CoV-2, the virus that causes COVID-19, continues to circulate globally, high levels of vaccine- and infection-induced immunity and the availability of effective treatments and prevention tools have substantially reduced the risk for medically significant COVID-19 illness (severe acute illness and post-COVID-19 conditions) and associated hospitalization and death (1). These circumstances now allow public health efforts to minimize the individual and societal health impacts of COVID-19 by focusing on sustainable measures to further reduce medically significant illness as well as to minimize strain on the health care system, while reducing barriers to social, educational, and economic activity (2). Individual risk for medically significant COVID-19 depends on a person's risk for exposure to SARS-CoV-2 and their risk for developing severe illness if infected (3). Exposure risk can be mitigated through nonpharmaceutical interventions, including improving ventilation, use of masks or respirators indoors, and testing (4). The risk for medically significant illness increases with age, disability status, and underlying medical conditions but is considerably reduced by immunity derived from vaccination, previous infection, or both, as well as timely access to effective biomedical prevention measures and treatments (3,5). CDC's public health recommendations change in response to evolving science, the availability of biomedical and public health tools, and changes in context, such as levels of immunity in the population and currently circulating variants. CDC recommends a strategic approach to minimizing the impact of COVID-19 on health and society that relies on vaccination and therapeutics to prevent severe illness; use of multicomponent prevention measures where feasible; and particular emphasis on protecting persons at high risk for severe illness. Efforts to expand access to vaccination and therapeutics, including the use of preexposure prophylaxis for persons who are immunocompromised, antiviral agents, and therapeutic monoclonal antibodies, should be intensified to reduce the risk for medically significant illness and death. Efforts to protect persons at high risk for severe illness must ensure that all persons have access to information to understand their individual risk, as well as efficient and equitable access to vaccination, therapeutics, testing, and other prevention measures. Current priorities for preventing medically significant illness should focus on ensuring that persons 1) understand their risk, 2) take steps to protect themselves and others through vaccines, therapeutics, and nonpharmaceutical interventions when needed, 3) receive testing and wear masks if they have been exposed, and 4) receive testing if they are symptomatic, and isolate for ≥5 days if they are infected.

The COVID-19 pandemic has highlighted and exacerbated long-standing inequities in the social determinants of health (1-3). Ensuring equitable access to effective COVID-19 therapies is essential to reducing health disparities. Molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid) are oral antiviral agents effective at preventing hospitalization and death in patients with mild to moderate COVID-19 who are at high risk* for progression to severe COVID-19 when initiated within 5 days of symptom onset. These medications received Emergency Use Authorization from the Food and Drug Administration (FDA) in December 2021() and were made available at no cost to recipients through the U.S. Department of Health and Human Services (HHS) on December 23, 2021. Beginning March 7, 2022, a series of strategies was implemented to expand COVID-19 oral antiviral access, including the launch of the Test to Treat initiative.() Data from December 23, 2021-May 21, 2022, were analyzed to describe oral antiviral prescription dispensing overall and by week, stratified by zip code social vulnerability. Zip codes represented areas classified as low, medium, or high social vulnerability; approximately 20% of U.S. residents live in low-, 31% in medium-, and 49% in high-social vulnerability zip codes.() During December 23, 2021-May 21, 2022, a total of 1,076,762 oral antiviral prescriptions were dispensed (Lagevrio = 248,838; Paxlovid = 827,924). Most (70.3%) oral antivirals were dispensed during March 7-May 21, 2022. During March 6, 2022-May 21, 2022, the number of oral antivirals dispensed per 100,000 population increased from 3.3 to 77.4 in low-, from 4.5 to 70.0 in medium-, and from 7.8 to 35.7 in high-vulnerability zip codes. The number of oral antivirals dispensed rose substantially during the overall study period, coincident with the onset of initiatives to increase access. However, by the end of the study period, dispensing rates in high-vulnerability zip codes were approximately one half the rates in medium- and low-vulnerability zip codes. Additional public health, regulatory, and policy efforts might help decrease barriers to oral antiviral access, particularly in communities with high social vulnerability.

BACKGROUND: Nursing homes (NHs) provide care in a congregate setting for residents at high risk of severe outcomes from SARS-CoV-2 infection. In spring 2020, NHs were implementing new guidance to minimize SARS-CoV-2 spread among residents and staff. OBJECTIVE: To assess whether telephone and video-based infection control assessment and response (TeleICAR) strategies could efficiently assess NH preparedness and help resolve gaps. DESIGN: We incorporated Centers for Disease Control and Prevention COVID-19 guidance for NH into an assessment tool covering 6 domains: visitor restrictions; health care personnel COVID-19 training; resident education, monitoring, screening, and cohorting; personal protective equipment supply; core infection prevention and control (IPC); and communication to public health. We performed TeleICAR consultations on behalf of health departments. Adherence to each element was documented and recommendations provided to the facility. SETTING AND PARTICIPANTS: Health department-referred NHs that agreed to TeleICAR consultation. METHODS: We assessed overall numbers and proportions of NH that had not implemented each infection control element (gap) and proportion of NH that reported making ≥1 change in practice following the assessment. RESULTS: During April 13 to June 12, 2020, we completed TeleICAR consultations in 629 NHs across 19 states. Overall, 524 (83%) had ≥1 implementation gaps identified; the median number of gaps was 2 (interquartile range: 1-4). The domains with the greatest number of facilities with gaps were core IPC practices (428/625; 68%) and COVID-19 education, monitoring, screening, and cohorting of residents (291/620; 47%). CONCLUSIONS AND IMPLICATIONS: TeleICAR was an alternative to onsite infection control assessments that enabled public health to efficiently reach NHs across the United States early in the COVID-19 pandemic. Assessments identified widespread gaps in core IPC practices that put residents and staff at risk of infection. TeleICAR is an important strategy that leverages infection control expertise and can be useful in future efforts to improve NH IPC.

The COVID-19 pandemic has disproportionately affected people with diabetes, who are at increased risk of severe COVID-19.* Increases in the number of type 1 diabetes diagnoses (1,2) and increased frequency and severity of diabetic ketoacidosis (DKA) at the time of diabetes diagnosis (3) have been reported in European pediatric populations during the COVID-19 pandemic. In adults, diabetes might be a long-term consequence of SARS-CoV-2 infection (4-7). To evaluate the risk for any new diabetes diagnosis (type 1, type 2, or other diabetes) >30 days(†) after acute infection with SARS-CoV-2 (the virus that causes COVID-19), CDC estimated diabetes incidence among patients aged <18 years (patients) with diagnosed COVID-19 from retrospective cohorts constructed using IQVIA health care claims data from March 1, 2020, through February 26, 2021, and compared it with incidence among patients matched by age and sex 1) who did not receive a COVID-19 diagnosis during the pandemic, or 2) who received a prepandemic non-COVID-19 acute respiratory infection (ARI) diagnosis. Analyses were replicated using a second data source (HealthVerity; March 1, 2020-June 28, 2021) that included patients who had any health care encounter possibly related to COVID-19. Among these patients, diabetes incidence was significantly higher among those with COVID-19 than among those 1) without COVID-19 in both databases (IQVIA: hazard ratio [HR] = 2.66, 95% CI = 1.98-3.56; HealthVerity: HR = 1.31, 95% CI = 1.20-1.44) and 2) with non-COVID-19 ARI in the prepandemic period (IQVIA, HR = 2.16, 95% CI = 1.64-2.86). The observed increased risk for diabetes among persons aged <18 years who had COVID-19 highlights the importance of COVID-19 prevention strategies, including vaccination, for all eligible persons in this age group,(§) in addition to chronic disease prevention and management. The mechanism of how SARS-CoV-2 might lead to incident diabetes is likely complex and could differ by type 1 and type 2 diabetes. Monitoring for long-term consequences, including signs of new diabetes, following SARS-CoV-2 infection is important in this age group.

One year after the first authorized COVID-19 vaccine was administered in the US, the nation celebrates a historic achievement in vaccine development and delivery. In 12 months, more than an estimated 200 million people in the US have completed their primary vaccine series. Vaccination has prevented millions of COVID-19 cases and hospitalizations and saved hundreds of thousands of lives. A report released in December 2021 by the Office of the Assistant Secretary of Planning and Evaluation highlights the large effects of vaccine on health, and also the estimated social value of avoiding COVID-19 hospitalizations and deaths.1

BACKGROUND: Historically, United States' carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: Escherichia, Klebsiella, and Enterobacter (EsKE); however, other genera can harbour mobile carbapenemases associated with CRE spread. OBJECTIVES: From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE. METHODS: State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory. SPHLs performed species identification, phenotypic carbapenemase production testing, and molecular testing for carbapenemases to identify CP-CRE. Isolates were categorized as CP if they demonstrated phenotypic carbapenemase production and ≥1 carbapenemase gene (bla (KPC), bla (NDM), bla (VIM), bla (IMP), or bla (OXA-48-like)) was detected. RESULTS: SPHLs tested 868 CRE isolates, 127 (14.6%) were from eight LCG. Overall, 195 (26.3%) EsKE isolates were CP-CRE, compared with 24 (18.9%) LCG isolates. LCG accounted for 24 (11.0%) of 219 CP-CRE identified. Citrobacter spp. was the most common CP-LCG; the proportion of Citrobacter that were CP (11/42, 26.2%) was similar to the proportion of EsKE that were CP (195/741, 26.3%). Five of 24 (20.8%) CP-LCG had a carbapenemase gene other than bla (KPC). CONCLUSIONS: Participating sites would have missed approximately 1 in 10 CP-CRE if isolate submission had been limited to EsKE genera. Expanding mechanism testing to additional genera could improve detection and prevention efforts.

Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation.

Background: Establishment of immune correlates of protection can provide a measurable criterion for assessing protection against infection or disease. For some vaccines, such as the measles vaccine, antibodies serve as the correlate of protection, but for others, such as human papillomavirus, the correlate of protection remains unknown. Merck & Co, Kenilworth, NJ, USA, in collaboration with multiple partners, developed a live recombinant vesicular stomatitis virus vaccine (rVSVG-ZEBOV-GP [ERVEBO]) containing the Zaire ebolavirus glycoprotein (GP) in place of the recombinant vesicular stomatitis virus GP to prevent Ebola virus disease. Seroresponse, defined as post-vaccination GP-ELISA of 200 ELISA units (EU) per mL or higher and two-times or more above baseline, was proposed; however, correlates of protection have not been determined. The objective of this post-hoc analysis was to infer possible correlates of protection for rVSVG-ZEBOV-GP.

BACKGROUND: The effect of malaria infection on rVSVΔG-ZEBOV-GP (ERVEBO®) immunogenicity is unknown. METHODS: The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) vaccinated 7998 asymptomatic adults with rVSVΔG-ZEBOV-GP during the 2014-6 Ebola epidemic. In STRIVE's immunogenicity sub-study, participants provided blood samples at baseline, 1, 6, and 9-12 months. Anti-glycoprotein (GP) binding and neutralizing antibodies were measured using validated assays. Baseline samples were tested for malaria parasites by PCR. RESULTS: Overall, 506 participants enrolled in the immunogenicity sub-study and had ≥1 post-vaccination antibody titer. Of 499 participants with a result, baseline malaria parasitemia was detected in 73(14.6%). All GP-ELISA and plaque reduction neutralization test (PRNT) geometric mean titers (GMTs) at 1, 6, and 9-12 months were above baseline, and 94.1% of participants seroresponded by GP-ELISA (≥2-fold rise AND ≥200 EU/ml), while 81.5% seroresponded by PRNT (≥4-fold rise) at ≥1 post-vaccination assessment. In participants with baseline malaria parasitemia, the PRNT seroresponse proportion was lower, while PRNT GMTs and GP-ELISA seroresponse and GMTs showed a trend toward lower responses at 6 and 9-12 months. CONCLUSION: Asymptomatic adults with and without malaria parasitemia had robust immune responses to rVSVΔG-ZEBOV-GP persisting for 9-12 months. Responses in those with malaria parasitemia were somewhat lower.

The COVID-19 pandemic has exposed weaknesses in disease surveillance in nearly all countries. Early identification of COVID-19 cases and clusters for rapid containment was hampered by inadequate diagnostic capacity, insufficient contact tracing, fragmented data systems, incomplete data insights for public health responders, and suboptimal governance of all these elements. Once SARS-CoV-2 became widespread, interventions to control community transmission were undermined by weak surveillance of cases and insufficient national capacity to integrate data for timely adjustment of public health measures.1, 2 Although some countries had little or no reliable data, others did not share data consistently with their own populations and with WHO and other multilateral agencies. The emergence of SARS-CoV-2 variants has highlighted inadequate national pathogen genomic sequencing capacities in many countries and led to calls for expanded virus sequencing. However, sequencing without epidemiological and clinical surveillance data is insufficient to show whether new SARS-CoV-2 variants are more transmissible, more lethal, or more capable of evading immunity, including vaccine-induced immunity.3, 4

To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.

Urinary tract infections (UTIs) are common and may occur in foodborne Salmonella outbreaks. Using data from PulseNet, the U.S. national molecular subtyping network for foodborne disease surveillance, we analyzed the 9781 Salmonella isolates associated with the 110 outbreaks from 2004 to 2013 that included at least one urine isolate. Within each outbreak, we calculated standardized isolation dates, using these dates in a linear mixed model to estimate the difference in incubation period for infections yielding stool versus urine isolates. We estimate that the incubation period for Salmonella UTIs is on average 10.6 (95% confidence interval 6.0-15.2) days longer than for gastrointestinal illness, suggesting that outbreak investigators should interview UTI patients about a longer time period before illness onset to identify sources of infection.

BACKGROUND: Despite large reductions from 2005-2012, hospital-onset methicillin-resistant Staphylococcus aureus bloodstream infections (HO MRSA BSIs) continue be a major source of morbidity and mortality. AIM: To describe risk factors for and underlying sources of HO MRSA BSIs. METHODS: We investigated HO MRSA BSIs at eight high-burden short-stay acute care hospitals. A case was defined as first isolation of MRSA from a blood specimen collected in 2016 on hospital day >/=4 from a patient without an MRSA-positive blood culture in the 14 days prior. We reviewed case-patient demographics and risk factors by medical record abstraction. The potential clinical source(s) of infection were determined by consensus by a clinician panel. FINDINGS: Of the 195 eligible cases, 186 were investigated. Case-patients were predominantly male (63%); median age was 57 years (range 0-92). In the two weeks prior to the BSI, 88% of case-patients had indwelling devices, 31% underwent a surgical procedure, and 18% underwent dialysis. The most common locations of attribution were intensive care units (ICUs) (46%) and step-down units (19%). The most commonly identified non-mutually exclusive clinical sources were CVCs (46%), non-surgical wounds (17%), surgical site infections (16%), non-ventilator healthcare-associated pneumonia (13%), and ventilator-associated pneumonia (11%). CONCLUSIONS: Device-and procedure-related infections were common sources of HO MRSA BSIs. Prevention strategies focused on improving adherence to existing prevention bundles for device-and procedure-associated infections and on source control for ICU patients, patients with certain indwelling devices, and patients undergoing certain high-risk surgeries are being pursued to decrease HO MRSA BSI burden at these facilities.

Little information exists regarding Ebola vaccine rVSVDeltaG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

Multidrug-resistant non-typhoidal Salmonella (NTS) infection has emerged as a prominent cause of invasive infections in Africa. We investigated the prevalence of ceftriaxone-resistant invasive NTS infections, conducted exploratory analysis of risk factors for resistance, and described antimicrobial use in western Kenya. We conducted a secondary analysis of existing laboratory, epidemiology, and clinical data from three independent projects, a malaria vaccine trial, a central nervous system (CNS) study, and the International Emerging Infections Program morbidity surveillance (surveillance program) during 2009-2014. We calculated odds ratios (OR) with 95% confidence intervals (CI) for ceftriaxone-resistant NTS infections compared with ceftriaxone-susceptible infections. We surveyed hospitals, pharmacies, and animal drug retailers about the availability and use of antimicrobials. In total, 286 invasive NTS infections were identified in the three projects; 43 NTS isolates were ceftriaxone-resistant. The absolute prevalence of ceftriaxone resistance varied among these methodologically diverse projects, with 18% (16/90) of isolates resistant to ceftriaxone in the vaccine trial, 89% (16/18) in the CNS study, and 6% (11/178) in the surveillance program. Invasive ceftriaxone-resistant infections increased over time. Most ceftriaxone-resistant isolates were co-resistant to multiple other antimicrobials. Having an HIV-positive mother (OR = 3.7; CI = 1.2-11.4) and taking trimethoprim-sulfamethoxazole for the current illness (OR = 9.6, CI = 1.2-78.9) were significantly associated with acquiring ceftriaxone-resistant invasive NTS infection. Ceftriaxone and other antibiotics were widely prescribed; multiple issues related to prescription practices and misuse were identified. In summary, ceftriaxone-resistant invasive NTS infection is increasing and limiting treatment options for serious infections. Efforts are ongoing to address the urgent need for improved microbiologic diagnostic capacity and an antimicrobial surveillance system in Kenya.

BACKGROUND: Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions. RESULTS: Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process. CONCLUSIONS: InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.

Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996-2016. We observed substantially higher serotype richness in children &lt;2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.