BACKGROUND: Nanomedicine offers a number of innovative strategies to address major public health burdens, including complex respiratory illnesses. In this work, we introduce a multi-drug nanoparticle fabricated using femtosecond laser ablation for the treatment of influenza, SARS-CoV-2, and their co-infections. METHODS: The SARS-CoV-2 antiviral, remdesivir; the influenza antiviral, baloxavir marboxil; and the anti-inflammatory, dexamethasone, were co-crystalized and then ablated in aqueous media using a femtosecond pulsed laser and subsequently surface modified with the cationic polymer, chitosan, or poly-d-lysine. Physical and chemical properties were then characterized using multiple complimentary techniques. Finally, a clinically relevant in vitro primary mouse trachea epithelial cell-air-liquid interface culture model was used to analyze the antiviral effect of our nanoparticles against Influenza Virus A. RESULTS: Our final nanoparticle exhibited a positive zeta potential with a diameter of ~73 nm. Remdesivir, baloxavir marboxil, and dexamethasone were all present in the nanoparticle suspension at a 1:1:1 ratio. Notably, these particles exhibited a potent anti-influenza effect, decreasing the viral titer by ≈ 4 logs in comparison to vehicle controls. CONCLUSION: Overall, these findings demonstrate great promise both for the use of laser ablation to generate multi-drug nanoparticles and for the anti-viral effects of our nanoformulation against respiratory illness.

A World Health Organization (WHO) Defeating Meningitis Symposium took place as part of the 3rd International Symposium on Streptococcus agalactiae disease (ISSAD) conference which was held in Rio de Janeiro, Brazil, from October 16-18, 2023. The symposium highlighted WHO's Defeating meningitis by 2030 global road map focusing on Group B Streptococcus (GBS) meningitis and provided an overview of the meningitis burden and main challenges faced to tackle the disease across the Americas, Africa, and Asia.

OBJECTIVE: West Nile virus (WNV) is the most common cause of arboviral disease in the United States. Approximately 1% of infections involve the nervous system, most commonly resulting in West Nile encephalitis (WNE), West Nile meningitis (WNM), or acute flaccid paralysis (AFP). METHODS: In this systematic review, we characterized comprehensively the diagnostic and clinical features of WNV neuroinvasive disease (WNND) in the United States, as well as the evidence regarding prognostic factors and long-term outcomes of WNND. RESULTS: We identified 47 relevant studies reporting data on acute or longitudinal features of WNND. Across studies, the most common presenting symptoms were fever (88%), nausea/vomiting (58%), and fatigue (50%) coupled neurologically with headache (50%), altered mental status (39%), and focal weakness (32%). Pooled mortality was 9.2%, and 42.1% of reported cases required intensive care unit (ICU) admission. In meta-analyses, chronic kidney disease (odds ratio [OR] = 5.99, 95% confidence interval [CI] = 2.71-13.23), diabetes mellitus (OR = 2.43, 95% CI = 1.54-3.84), and hypertension (OR = 4.01, 95% CI = 2.39-6.72) were associated with an increased risk of mortality. Multidomain neurocognitive impairment was reported in several studies at post-hospitalization follow-up, although with marked heterogeneity between study methodology. Subjective neurocognitive impairment, most notably fatigue (37-75%), memory concerns (11-57%), concentration deficits (17-48%), and depression (17-38%), were also common at post-hospitalization follow-up. INTERPRETATION: These findings underscore the significant mortality and morbidity of WNND in the acute and long-term setting. Our findings may additionally provide utility for risk stratification of hospitalized patients with WNND and suggest the need for further evaluation of novel therapeutics to prevent substantial disease-associated acute and long-term disability. ANN NEUROL 2025.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

BACKGROUND: People experiencing homelessness (PEH) are underrepresented in public health and clinical research. Study methods that can improve participation by this group are needed. METHODS: In late 2022, the Centers for Disease Control and Prevention conducted an mpox serological survey using venipuncture among PEH in San Francisco, California. Blood collection by a minimally invasive device was offered if venipuncture was not possible or preferred. Participants who had a successful blood draw using the device were asked about device acceptability. RESULTS: Of the 209 successful blood collections, 137 (66%) were among participants who underwent venipuncture and 72 (34%) were among participants who used the device. Use of the device increased overall blood collection participation by 53%. Participants reported high acceptability and preference for the device over venipuncture. CONCLUSIONS: Minimally invasive blood collection devices may increase participation and representation of PEH in serosurveys.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Although current policies discourage the use of corporal punishment (CP), its use is still widespread in the US. The objective of this study was to assess the proportion of parents who used CP during the pandemic and identify related risk and protective factors. We analyzed results of a nationwide cross-sectional internet panel survey of 9000 US caregivers who responded in three waves from November 2020 to July 2021. One in six respondents reported having spanked their child in the past week. Spanking was associated with intimate partner violence and the use of multiple discipline strategies and not significantly associated with region or racial self-identification. Parents who spanked sought out more kinds of support, suggesting an opportunity to reduce spanking through more effective parenting resources. Additionally, these results suggest that parents who report using CP may be at risk for concurrent domestic violence.

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.

The sharing of genome sequences in online data repositories allows for large scale analyses of specific genes or gene families. This can result in the detection of novel gene subtypes as well as the development of improved detection methods. Here, we used publicly available WGS data to detect a novel Stx subtype, Stx2n in two clinical E. coli strains isolated in the USA. During this process, additional Stx2 subtypes were detected; six Stx2j, one Stx2m strain, and one Stx2o, were all analyzed for variability from the originally described subtypes. Complete genome sequences were assembled from short- or long-read sequencing and analyzed for serotype, and ST types. The WGS data from Stx2n- and Stx2o-producing STEC strains were further analyzed for virulence genes pro-phage analysis and phage insertion sites. Nucleotide and amino acid maximum parsimony trees showed expected clustering of the previously described subtypes and a clear separation of the novel Stx2n subtype. WGS data were used to design OMNI PCR primers for the detection of all known stx1 (283 bp amplicon), stx2 (400 bp amplicon), intimin encoded by eae (221 bp amplicon), and stx2f (438 bp amplicon) subtypes. These primers were tested in three different laboratories, using standard reference strains. An analysis of the complete genome sequence showed variability in serogroup, virulence genes, and ST type, and Stx2 pro-phages showed variability in size, gene composition, and phage insertion sites. The strains with Stx2j, Stx2m, Stx2n, and Stx2o showed toxicity to Vero cells. Stx2j carrying strain, 2012C-4221, was induced when grown with sub-inhibitory concentrations of ciprofloxacin, and toxicity was detected. Taken together, these data highlight the need to reinforce genomic surveillance to identify the emergence of potential new Stx2 or Stx1 variants. The importance of this surveillance has a paramount impact on public health. Per our description in this study, we suggest that 2017C-4317 be designated as the Stx2n type-strain.

Hand hygiene is a cost-effective preventive measure to reduce transmission of infectious diseases. Yet, a quarter of the global population lack access to even a basic handwashing facility. | Forthcoming WHO and UNICEF guidelines on hand hygiene in community settings will provide evidence-based recommendations to guide action. | According to consulted future guideline end-users, sustainable implementation of such recommendations to improve hand hygiene requires government-led system-strengthening approaches that build sustainable and resilient national systems. | System-strengthening plans should be underpinned by a comprehensive situational analysis and needs assessment, and monitored on an ongoing basis for course correction where necessary. | Execution of system-strengthening plans should be integrated with existing programmes. | Health sector leadership is required to drive this agenda.

This report compiles and summarizes all published recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) for use of pneumococcal vaccines in adults aged ≥19 years in the United States. This report also includes updated and new clinical guidance for implementation from CDC. | | Before 2021, ACIP recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone (up to 2 doses), or both a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) in combination with 1–3 doses of PPSV23 in series (PCV13 followed by PPSV23), for use in U.S. adults depending on age and underlying risk for pneumococcal disease. In 2021, two new pneumococcal conjugate vaccines (PCVs), a 15-valent and a 20-valent PCV (PCV15 and PCV20), were licensed for use in U.S. adults aged ≥18 years by the Food and Drug Administration. | | ACIP recommendations specify the use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years and for adults aged 19–64 years with certain underlying medical conditions or other risk factors who have not received a PCV or whose vaccination history is unknown. In addition, ACIP recommends use of either a single dose of PCV20 or ≥1 dose of PPSV23 for adults who have started their pneumococcal vaccine series with PCV13 but have not received all recommended PPSV23 doses. Shared clinical decision-making is recommended regarding use of a supplemental PCV20 dose for adults aged ≥65 years who have completed their recommended vaccine series with both PCV13 and PPSV23. | | Updated and new clinical guidance for implementation from CDC includes the recommendation for use of PCV15 or PCV20 for adults who have received PPSV23 but have not received any PCV dose. The report also includes clinical guidance for adults who have received 7-valent PCV (PCV7) only and adults who are hematopoietic stem cell transplant recipients.

Mpox has affected many communities in the United States (U.S.), including people experiencing homelessness (PEH). Mpox vaccination has been an important tool to disrupt transmission and protect communities at risk of infection. To better understand mpox vaccine knowledge and attitudes, we surveyed 273 PEH and people accessing homeless service sites in San Francisco. Among 64 participants previously offered mpox vaccination, 38 (59 %) had received the vaccine. Among 209 participants not previously offered mpox vaccination, 108 (52 %) reported they would receive the vaccine. Vaccine acceptance was higher among transgender female participants and among male participants who reported male sex partner preference (MSM). Half of participants who declined vaccination identified that perception of personal risk and vaccine education may increase their likelihood of receiving an mpox vaccine. Leveraging trusted information sources to provide risk communication and vaccine education may increase vaccine uptake among PEH.

Influenza pandemics typically occur in multiple waves of infection, often associated with initial emergence of a novel virus, followed (in temperate regions) by a later resurgence accompanying the onset of the annual influenza season. Here, we examined whether data collected from an initial pandemic wave could be informative, for the need to implement non-pharmaceutical measures in any resurgent wave. Drawing from the 2009 H1N1 pandemic in 10 states in the USA, we calibrated simple mathematical models of influenza transmission dynamics to data for virologically confirmed hospitalisations during the initial ‘spring’ wave. We then projected pandemic outcomes (cumulative hospitalisations) during the fall wave, and compared these projections with data. Model results show reasonable agreement for all states that reported a substantial number of cases in the spring wave. Using this model we propose a probabilistic decision framework that can be used to determine the need for pre-emptive measures such as postponing school openings, in advance of a fall wave. This work illustrates how model-based evidence synthesis, in real-time during an early pandemic wave, could be used to inform timely decisions for pandemic response.Competing Interest StatementThe authors have declared no competing interest.Funding StatementAll work funded by the USA Centre for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:NAAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data (FluSurNet) is freely available online. https://www.cdc.gov/flu/weekly/influenza-hospitalization-surveillance.htm

We updated a published mathematical model of SARS-CoV-2 transmission with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. When used at already-observed population rates of 80% for those ≥65 years and 60% for those <65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks’ source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number ≤ 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2).Article Summary Line Adapting a published SARS-CoV-2 transmission model together with updated, laboratory-derived source control and wearer protection efficacy estimates for a variety of face coverings as well as N95 respirators, we demonstrate that community masking as currently practiced has likely reduced cases and deaths and that this benefit can be increased with wider adoption of better performing masks.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThis is an epidemiological modeling study, not a clinical trialFunding StatementNo external funding was received.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:No IRB was needed as this is an epidemiological modeling study.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data/parameters used in the models are reported in the manuscript. Code is available upon request.

Antimicrobial resistance (AMR) is a major public health problem that requires publicly available tools for rapid analysis. To identify acquired AMR genes in whole genome sequences, the National Center for Biotechnology Information (NCBI) has produced a high-quality, curated, AMR gene reference database consisting of up-to-date protein and gene nomenclature, a set of hidden Markov models (HMMs), and a curated protein family hierarchy. Currently, the Bacterial Antimicrobial Resistance Reference Gene Database contains 4,579 antimicrobial resistance gene proteins and more than 560 HMMs.Here, we describe AMRFinder, a tool that uses this reference dataset to identify AMR genes. To assess the predictive ability of AMRFinder, we measured the consistency between predicted AMR genotypes from AMRFinder against resistance phenotypes of 6,242 isolates from the National Antimicrobial Resistance Monitoring System (NARMS). This included 5,425 Salmonella enterica, 770 Campylobacter spp., and 47 Escherichia coli phenotypically tested against various antimicrobial agents. Of 87,679 susceptibility tests performed, 98.4% were consistent with predictions.To assess the accuracy of AMRFinder, we compared its gene symbol output with that of a 2017 version of ResFinder, another publicly available resistance gene database. Most gene calls were identical, but there were 1,229 gene symbol differences between them, with differences due to both algorithmic differences and database composition. AMRFinder missed 16 loci that Resfinder found, while Resfinder missed 1,147 loci AMRFinder identified. Two missing drug classes from the 2017 version of ResFinder contributed 81% of missed loci. Based on these results, AMRFinder appears to be a highly accurate AMR gene detection system.Importance Antimicrobial resistance is a major public health problem. Traditionally, antimicrobial resistance has been identified using phenotypic assays. With the advent of genome sequencing, we now can identify resistance genes and deduce if an isolate could be resistant to antibiotics. We describe a database of 4,579 acquired antimicrobial resistance genes, the largest publicly available, and a software tool to identify genes in bacterial genomes, AMRFinder. Unlike other tools, AMRFinder uses a gene hierarchy to prevent overpredicting what the correct gene call should be, enabling more accurate assessment. To assess these resources, we determined the resistance gene content of over 6,200 bacterial isolates from the National Antimicrobial Resistance Monitoring System that have been assayed using traditional methods and that also have had their genomes sequenced. We also compared our gene assessments to those of a popularly used tool. We found that AMRFinder has a high overall consistency between genotypes and phenotypes.

We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Effective COVID-19 case investigation and contact tracing (CICT) among refugee, immigrant, and migrant (RIM) communities requires innovative approaches to address linguistic, cultural and community specific preferences. The National Resource Center for Refugees, Immigrants, and Migrants (NRC-RIM) is a CDC-funded initiative to support state and local health departments with COVID-19 response among RIM communities, including CICT. This note from the field will describe NRC-RIM and initial outcomes and lessons learned, including the use of human-centered design to develop health messaging around COVID-19 CICT; training developed for case investigators, contact tracers, and other public health professionals working with RIM community members; and promising practices and other resources related to COVID-19 CICT among RIM communities that have been implemented by health departments, health systems, or community-based organizations.

Acute encephalopathy syndrome (AES) is characterized by sudden onset of seizures and altered sensorium of infectious or non-infectious origin. Seasonal outbreaks of fatal hypoglycaemic AES in children, associated with eating fruit from the Sapindaceae family (e.g., ackee, litchi), have been reported globally [1,2]. Since 1995, AES outbreaks have been reported during the litchi-harvesting season from May–July in Muzaffarpur, the largest commercial litchi-producing district of Bihar, India [3]. An AES outbreak investigation in Muzaffarpur in 2014 linked known toxins hypoglycin A and α-methylene cyclopropyl glycine (MCPG) in litchi fruit to hypoglycaemic AES in children [3]. Following the 2014 outbreak, the Government of Bihar implemented community-based interventions to prevent hypoglycemia in children. They also strengthened the clinical management of hypoglycaemic seizures in public health facilities [4]. The number of AES cases and deaths declined from 2015–18, suggesting that the interventions were effective. However, in May–June 2019, AES cases increased. We conducted a descriptive epidemiological analysis of the AES cases. | | Methods | | We identified AES cases from established hospital-based surveillance in the two tertiary referral hospitals in Muzaffarpur. We defined a suspected AES case as seizures or altered sensorium in a child aged ≤15 years admitted from 1 May to 2nd July 2019. We excluded patients aged six months to 6 years who were admitted for fever and a single generalized convulsion of <15 minutes in duration and recovered consciousness within 60 minutes of seizure. We conducted a review of medical records and abstracted data using a structured tool for socio-demographics, clinical history, duration of hospitalization, treatment, and laboratory profile. We also assembled a prospective cohort of probable cases admitted to the hospital during the investigation. We defined a probable AES case as new-onset seizures or altered sensorium of <7 days duration in a child aged ≤15 years admitted t from 1 May to 2 July 2019. For the cohort of probable cases, we interviewed the caregivers using a structured clinical-epidemiological questionnaire for socio-demographics, anthropometry, illness characteristics, treatment-seeking behavior, meal assessment, exposure to litchi fruit, and exposure to health messages. For anthropometry, we calculated Z-scores using the World Health Organization 2006 standardized growth tables [5]. | | Results | | Of the 655 suspected and probable AES cases identified, the case fatality rate (CFR) was 21% (139 deaths). The median age was four years (interquartile range: 3 months–14 years), and 58% (378) were females. The first case was reported on 5 May 2019, cases peaked on 15 June, and the last case on 2 July (Figure 1). Among cases with available data, 75% (389/518) had blood glucose levels of <70 mg/dL upon hospital admission, and 75% (476/638) were residents of Muzaffarpur district. We identified cases from 15 (94%) of 16 blocks in the Muzaffarpur district and calculated a district incidence of 22 per 100,000 children ≤15 years old. | | The prospective cohort comprised 94 probable AES cases; CFR was 26%. Among probable cases, 63% (49/78) of caregivers were wage workers, and 34% (31/91) were of low socioeconomic status. Symptoms were reported in the early morning (3 am to 8 am) for 67% (62/93) of cases, and 97% (90/93) presented with seizures. Among probable cases with anthropometry data, 62% (43/69) were underweight (i.e., weight-for-age Z score <-2), 44% (25/57) stunted (i.e., height-for-age Z score <-2), and 43% (10/23) wasted (i.e., weight-for-height Z score <-2). Primary health facilities referred 46% (43/93) of probable cases to the two tertiary hospitals for admission. Among cases referred, only 30% (13/43) received hypoglycemia and seizure management at the primary health facility. | | Eating litchis in the 24 hours and seven days before illness onset was reported by 57% (54/94) and 87% (59/68) of caregivers, respectively. Skipping any meal and skipping the evening meal in the 24 hours before illness onset was reported by 55% (48/88) and 44% (28/63) of caregivers, respectively. Among probable cases, 45% (27/60) of caregivers reported Government Supplementary Nutrition (GSN) programme enrollment. Sixty percent (50/83) of caregivers said a visit by health workers in the week before illness. Still, only 8% (7/83) reported receiving messages on AES prevention and early treatment by health workers in the past month. | | Conclusions | | The 2019 AES outbreak in Muzaffarpur district, Bihar, occurred among young children with hypoglycemia upon hospital admission and had high associated mortality. Although the Government of Bihar implemented community and clinical measures to prevent AES cases after the 2014 outbreak, a large proportion of the AES cases did not benefit from the prevention measures based on our investigation [4]. New state and district health leadership, turnover of community and facility-level healthcare workers, lack of ongoing training and focused community outreach, and competing health priorities might have been factors responsible for the resurgence. To prevent future AES cases, we recommended prompt emergency management of hypoglycemia and seizures at primary health facilities before referral. We recommend enrollment of all eligible children to GSN and enhanced community health communications to reinforce the importance of an evening meal for children and limiting the eating of litchi fruit during the harvesting season from May to July

BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

Monkeypox (mpox) is a disease caused by an Orthopoxvirus. The 2022 multinational outbreak, which began in May 2022, has spread primarily by close skin-to-skin contact, including through sexual contact. Persons experiencing homelessness have been disproportionately affected by severe mpox (1). However, mpox prevalence and transmission pathways among persons experiencing homelessness are not known, and persons experiencing homelessness have not been specifically recommended to receive mpox vaccine during the 2022 outbreak (2,3). During October 25-November 3, 2022, a CDC field team conducted an orthopoxvirus seroprevalence survey among persons accessing homeless services or staying in encampments, shelters, or permanent supportive housing in San Francisco, California that had noted at least one case of mpox or served populations at risk. During field team visits to 16 unique sites, 209 participants completed a 15-minute survey and provided a blood specimen. Among 80 participants aged <50 years who did not report smallpox or mpox vaccination or previous mpox infection, two (2.5%) had detectable antiorthopoxvirus immunoglobulin (Ig) G antibody. Among 73 participants who did not report mpox vaccination or previous mpox infection and who were tested for IgM, one (1.4%) had detectable antiorthopoxvirus IgM. Together, these results suggest that three possible undetected mpox infections occurred among a sample of persons experiencing homelessness, highlighting the need to ensure that community outreach and prevention interventions, such as vaccination, are accessible to this population.

Influenza pandemics typically occur in multiple waves of infection, often associated with initial emergence of a novel virus, followed (in temperate regions) by a resurgence accompanying the onset of the annual influenza season. Here, we examined whether data collected from an initial pandemic wave could be informative, for the need to implement non-pharmaceutical measures in any resurgent wave. Drawing from the 2009 H1N1 pandemic in 10 states in the USA, we calibrated simple mathematical models of influenza transmission dynamics to data for laboratory confirmed hospitalisations during the initial 'spring' wave. We then projected pandemic outcomes (cumulative hospitalisations) during the fall wave, and compared these projections with data. Model results showed reasonable agreement for all states that reported a substantial number of cases in the spring wave. Using this model we propose a probabilistic decision framework that can be used to determine the need for preemptive measures such as postponing school openings, in advance of a fall wave. This work illustrates how model-based evidence synthesis, in real-time during an early pandemic wave, could be used to inform timely decisions for pandemic response.

BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. METHODS: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. RESULTS: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. CONCLUSIONS: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing.

BACKGROUND: Muzaffarpur district in Bihar State of India recorded a resurgence of acute encephalopathy syndrome (AES) cases in the summer of 2019 after no reported outbreak in 3 y. Earlier studies generated evidence that litchi consumption and missing the previous evening's meal were associated with AES. We investigated the recent outbreak to understand the risk factors associated with AES. METHODS: We conducted a matched case-control study by comparing AES cases with healthy controls from case-households and the neighborhood community for risk factors like missing evening meal and litchi consumption before onset of AES. RESULTS: We recruited 61 cases and 239 controls. Compared with the community controls, case-patients were five times more likely to have reported eating litchi in the 7 d preceding the onset of illness (adjusted OR [AOR]=5.1; 95% CI 1.3 to 19) and skipping the previous evening's meal (AOR=5.2; 95% CI 1.4 to 20). Compared with household controls, case-patients were five times more likely to be children aged <5 y (AOR=5.3; 95% CI 1.3 to 22) and seven times more likely to have skipped the previous evening's meal (AOR=7.4; 95% CI 1.7 to 34). CONCLUSIONS: Skipping the previous evening's meal and litchi consumption were significantly associated with AES among children in Muzaffarpur and adjoining districts of Bihar.

We expanded a published mathematical model of SARS-CoV-2 transmission with complex, age-structured transmission and with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. The model was also improved to allow realistic age-structured transmission with a pre-specified R0 of transmission, and to include more compartments and parameters, e.g. for groups such as detected and undetected asymptomatic infectious cases who mask up at different rates. When masks are used at typically-observed population rates of 80% for those ≥ 65 years and 60% for those < 65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks' source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number ≤ 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2). For variants of concern similar to omicron (B.1.1.529) or the sub-lineage BA.2, modeled reductions in effective reproduction number due to similar high quality, high prevalence mask wearing is more modest (to 3.9 and 5.0 from an R(0) = 10.0 and 13.0, respectively). None-the-less, the ratio of incident risk for masked vs. non-masked populations still shows a benefit of wearing masks even with the higher R0 variants.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m(2)), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

Nursing home residents have experienced disproportionally high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1). Following reported declines in vaccine-induced immunity after primary series vaccination, defined as receipt of 2 primary doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or 1 primary dose of Ad26.COV2 (Johnson & Johnson [Janssen]) vaccine (2), CDC recommended that all persons aged ≥12 years receive a COVID-19 booster vaccine dose.* Moderately to severely immunocompromised persons, a group that includes many nursing home residents, are also recommended to receive an additional primary COVID-19 vaccine dose.(†) Data on vaccine effectiveness (VE) of an additional primary or booster dose against infection with SARS-CoV-2 (the virus that causes COVID-19) among nursing home residents are limited, especially against the highly transmissible B.1.1.529 and BA.2 (Omicron) variants. Weekly COVID-19 surveillance and vaccination coverage data among nursing home residents, reported by skilled nursing facilities (SNFs) to CDC's National Healthcare Safety Network (NHSN)(§) during February 14-March 27, 2022, when the Omicron variant accounted for >99% of sequenced isolates, were analyzed to estimate relative VE against infection for any COVID-19 additional primary or booster dose compared with primary series vaccination. After adjusting for calendar week and variability across SNFs, relative VE of a COVID-19 additional primary or booster dose was 46.9% (95% CI = 44.8%-48.9%). These findings indicate that among nursing home residents, COVID-19 additional primary or booster doses provide greater protection against Omicron variant infection than does primary series vaccination alone. All immunocompromised nursing home residents should receive an additional primary dose, and all nursing home residents should receive a booster dose, when eligible, to protect against COVID-19. Efforts to keep nursing home residents up to date with vaccination should be implemented in conjunction with other COVID-19 prevention strategies, including testing and vaccination of nursing home staff members and visitors.

INTRODUCTION: To address high levels of maternal mortality in Kigoma, Tanzania, stakeholders increased women's access to high-quality comprehensive emergency obstetric and newborn care (EmONC) by decentralizing services from hospitals to health centers where EmONC was delivered mostly by associate clinicians and nurses. To ensure that women used services, implementers worked to continuously improve and sustain quality of care while creating demand. METHODS: Program evaluation included periodic health facility assessments, pregnancy outcome monitoring, and enhanced maternal mortality detection region-wide in program- and nonprogram-supported health facilities. RESULTS: Between 2013 and 2018, the average number of lifesaving interventions performed per facility increased from 2.8 to 4.7. The increase was higher in program-supported than nonprogram-supported health centers and dispensaries. The institutional delivery rate increased from 49% to 85%; the greatest increase occurred through using health centers (15% to 25%) and dispensaries (21% to 46%). The number of cesarean deliveries almost doubled, and the population cesarean delivery rate increased from 2.6% to 4.5%. Met need for emergency obstetric care increased from 44% to 61% while the direct obstetric case fatality rate declined from 1.8% to 1.4%. The institutional maternal mortality ratio across all health facilities declined from 303 to 174 deaths per 100,000 live births. The total stillbirth rate declined from 26.7 to 12.8 per 1,000 births. The predischarge neonatal mortality rate declined from 10.7 to 7.6 per 1,000 live births. Changes in case fatality rate and maternal mortality were driven by project-supported facilities. Changes in neonatal mortality varied depending on facility type and program support status. CONCLUSION: Decentralizing high-quality comprehensive EmONC delivered mostly by associate clinicians and nurses led to significant improvements in the availability and utilization of lifesaving care at birth in Kigoma. Dedicated efforts to sustain high-quality EmONC along with supplemental programmatic components contributed to the reduction of maternal and perinatal mortality.

The Program to Reduce Maternal Deaths in Tanzania was a 13-year (2006-2019) effort in the Kigoma region that evolved over 3 phases to improve and sustain the availability of, access to, and demand for high-quality maternal and reproductive health care services. The Program intended to bring high-quality care closer to more communities. Cutting across the Program was the routine collection of monitoring and evaluation data. The Program achieved significant reductions in maternal and perinatal mortality, a significant increase in the modern contraceptive prevalence rate, and a significant decline in the unmet need for contraception. By 2017, it was apparent that the Program was on track to meet or surpass many of the targets established by the Government of Tanzania. Over the following 2-plus years, efforts to sustain Program interventions intensified. In April 2019, the Program fully transitioned to Government of Tanzania oversight. Four key lessons were learned during implementation that are relevant to governments, donors, and implementing organizations working to reduce maternal mortality: (1) multistakeholder partnerships are critical; (2) demand creation for services, while critical, must rest on a foundation of well-functioning and high-quality clinical services; (3) it is imperative to not only collect robust monitoring and evaluation data, but to be responsive in real time to what the data reveal; and, (4) it is necessary to develop a deliberate sustainability strategy from the start. The Program in Kigoma demonstrates that decentralizing high-quality maternal and reproductive health services in remote, low-resource settings is both feasible and effective and should be considered in places with similar contexts. By embedding the Program in the existing health system, and through efforts to build local capacity, the improvements seen in Kigoma are likely to be sustained. Follow-up evaluations are planned, providing an opportunity to more directly assess sustainability.