Exploring parental perspectives: Maternal RSV vaccination versus infant RSV monoclonal antibody.

Respiratory Syncytial Virus poses a significant global public health threat, particularly affecting infants aged less than one year of age. Recently, two forms of passive immunization against infant RSV have been developed and brought to market; nirsevimab a long-acting monoclonal antibody (mAb) and RSV-PreF, a maternal RSV vaccine. The acceptability and uptake of these products will play a pivotal role in determining the success of any national immunization strategy aimed at safeguarding infants from RSV. It is crucial at this time to reflect on the factors that influence parental decisions surrounding immunization to facilitate more informed discussions, enhance healthcare communication, and contribute to the design of effective RSV prevention strategies that resonate with the concerns and aspirations of parents worldwide.

Near-term pregnant women in the Dominican Republic experience high rates of Group B Streptococcus rectovaginal colonization with virulent strains.

Maternal colonization with Group B Streptococcus (GBS) is an important cause of stillbirth, prematurity, and serious infection and death in infants worldwide. Resource constraints limit prevention strategies in many regions. Maternal GBS vaccines in development could be a more accessible prevention strategy, but data on geographic variations in GBS clones are needed to guide development of a broadly effective vaccine. In the Dominican Republic (DR), limited data suggest that pregnant women experience GBS colonization at rates among the highest globally. We aimed to determine the prevalence of maternal rectovaginal GBS colonization and describe clonal characteristics of colonizing strains in the DR. A cross-sectional study assessed rectovaginal GBS colonization in 350 near-term pregnant women presenting for routine prenatal care at an urban tertiary center in the DR. Rectovaginal samples were tested with chromogenic Strep B Carrot Broth and cultured for confirmatory whole-genome sequencing. In a secondary analysis, participants' demographics and histories were assessed for association with GBS colonization. Rectovaginal GBS colonization occurred in 26.6% of women. Serotypes Ia, Ib, II, III, IV, and V were detected, with no one serotype predominating; serotype III was identified most frequently (21.5%). Virulent and emerging strains were common, including CC17 (15.1%) and ST1010 (17.2%). In this first characterization of maternal GBS serotypes in the DR, we found high rates of rectovaginal colonization including with virulent and emerging GBS strains. The serotypes observed here are all targeted by candidate hexavalent GBS vaccines, suggesting effective protection in the DR.

Enterovirus Central Nervous System Infection in Infancy, the Value of Routine Testing.

BACKGROUND: Human nonpolio enterovirus (EV) is a major cause of infection in neonates and infants; however, the clinical presentation and cerebrospinal fluid findings vary significantly. Infection caused by EV in patients under 1 year of age can present with a broad clinical spectrum, from fever to severe systemic and/or neurological disease. METHODS: Retrospective cohort analysis of infants with EV central nervous system (CNS) infection presenting to a tertiary center between January 2017 and December 2022. We recorded patient demographics, parent-reported symptoms at presentation, and blood and cerebrospinal fluid (CSF) testing at presentation. RESULTS: Seventy-eight patients were included in the final study. Forty-one percent of infants with an EV CNS infection had a normal CSF white blood cell count. Clinical presentation was similar in infants with and without CSF pleocytosis. Median C-reactive protein was higher in cases of EV CNS infection without pleocytosis. CONCLUSION: EV CNS infection commonly presents without CSF pleocytosis. Testing for EV should be considered in febrile infants with no source regardless of CSF parameters.

Preparing for Group B Streptococcus vaccine. Attitudes of pregnant women in two countries.

Group B Streptococcus (GBS) vaccines, designed to be given to pregnant women, are in clinical trials. There is an opportunity to conduct preparatory research now to understand the drivers of and barriers to GBS vaccine acceptance. This will enable targeted interventions so that delays in vaccine uptake might be avoided. A multicenter, mixed-methodology, cross-sectional study evaluated the acceptability of a hypothetical GBS vaccine among pregnant women in two countries with differing health systems. Pregnant women in Philadelphia, US, and Dublin, Ireland, completed an electronic survey and a Discrete Choice Experiment. Five hundred and two women were included in the final analysis. Fifty-three percent of US and 30% of Irish participants reported both awareness and understanding of GBS. The median likelihood score for vaccine receipt (measured on a 10-point scale) was 9 (US: 9 (IQR 7-10), IRL: 9 (IQR 6-10)). Among the US participants, identifying as Black or African American was associated with a lower likelihood of vaccine receipt. Possession of a college degree was associated with increased likelihood of vaccine receipt. Perceived infant benefit was the most important driver of GBS vaccine acceptance. Safety concerns about a novel vaccine was the most prominent barrier identified. Good GBS vaccine uptake is achievable through strong messaging that highlights vaccine safety and the potential infant benefits. Preparation for vaccine implementation should include efforts to increase awareness among pregnant women about GBS infection and a continued focus on improving acceptability of currently recommended maternal vaccines, particularly in population subgroups with low uptake of maternal immunizations.

Maternity care provider acceptance of a future Group B Streptococcus vaccine - A qualitative study in three countries.

INTRODUCTION: There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake. METHODS: This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions. RESULTS: Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine. CONCLUSION: Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.

Understanding Barriers and Facilitators to Maternal Immunization: A Systematic Narrative Synthesis of the Published Literature.

INTRODUCTION: Vaccines are being developed against Group B Streptococcus and respiratory syncytial virus. These vaccines are designed to be given to pregnant women to protect infants; thus, their success depends on uptake in this population. Maternal immunization programs have struggled to achieve target coverage rates. This systematic narrative synthesis aims to define the most important barriers and facilitators for maternal immunization and to identify priority areas for future research. METHODS: A search strategy was developed in Medline and adapted according to the requirements of additional search engines. Two reviewers independently reviewed the studies, using pre-specified inclusion and exclusion criteria. Results sections of included studies were coded, and thematic analysis was used to identify prominent themes. RESULTS: 321 studies were included in the final review. Most studies came from North America (37%), Europe (26%) or East Asia, Australia and New Zealand (22%). Low-and middle-income countries were under-represented. Five percent of studies came from Sub-Saharan Africa, and 2% came from South Asia. The prominent factors impacting maternal immunization were provider recommendation, perceived risks and benefits of maternal vaccines for the infant, race, birthplace, and access to healthcare. Few studies explored reasons behind racial and socioeconomic disparities in maternal immunization rates. DISCUSSION: A strong provider recommendation, equitable access to prenatal care and messaging that focuses on vaccine safety and infant benefits emerged as the key components for optimising vaccine uptake among pregnant women. Research among healthcare providers, minority groups and in low- and-middle-income countries was lacking. In anticipation of the expansion of maternal immunization programmes, focused research is needed to address these gaps and inform a successful public health strategy.

"This choice does not just affect me." Attitudes of pregnant women toward COVID-19 vaccines: a mixed-methods study.

Public health experts agree that pregnant women who fall into priority groups may be offered a Coronavirus Disease 2019 (COVID-19) vaccine. However, little is known about attitudes of pregnant women toward COVID-19 vaccination. We surveyed 300 pregnant women during the roll out of the Pfizer-BioNTech vaccine in Ireland. Women rated likelihood of receipt of a vaccine during pregnancy, on a 1-10 scale (1 = very unlikely, 10 = very likely). One hundred and thirteen (38%) women responded with a score of ≥8, while a similar proportion (36%) selected a score of ≤2. Safety of their unborn infant was the primary driver of decision making among survey participants, but specific safety concerns differed according to likely acceptance of a vaccine. Communication about COVID-19 vaccines to pregnant women must explicitly address safety. Pregnant women and their health-care providers should be supported with accessible interpretations of data so that they can make the best choice for their individual risk profile.

The Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Healthcare Network in the United States.

BACKGROUND: Understanding the prevalence and clinical presentation of coronavirus disease 2019 in pediatric patients can help healthcare providers and systems prepare and respond to this emerging pandemic. METHODS: This was a retrospective case series of patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across a pediatric healthcare network, including clinical features and outcomes of those with positive test results. RESULTS: Of 7256 unique children tested for SARS-CoV-2, 424 (5.8%) tested positive. Patients aged 18-21 years had the highest test positive rate (11.2%), while those aged 1-5 years had the lowest (3.9%). By race, 10.6% (226/2132) of black children tested positive vs 3.3% (117/3592) of white children. By indication for testing, 21.1% (371/1756) of patients with reported exposures or clinical symptoms tested positive vs 3.8% (53/1410) of those undergoing preprocedural or preadmission testing. Of 424 patients who tested positive for SARS-CoV-2, 182 (42.9%) had no comorbidities, 87 (20.5%) had asthma, and 55 (13.0%) were obese. Overall, 52.1% had cough, 51.2% fever, and 14.6% shortness of breath. Seventy-seven (18.2%) SARS-CoV-2-positive patients were hospitalized, of whom 24 (31.2%) required respiratory support. SARS-CoV-2-targeted antiviral therapy was given to 9 patients, and immunomodulatory therapy to 18 patients. Twelve (2.8%) SARS-CoV-2-positive patients required mechanical ventilation, and 2 patients required extracorporeal membrane oxygenation. Two patients died. CONCLUSIONS: In this large cohort of pediatric patients tested for SARS-CoV-2, the rate of infection was low but varied by testing indication. The majority of cases were mild and few children had critical illness.

Vaccine Safety: Myths and Misinformation.

The World Health Organization has named vaccine hesitancy as one of the top ten threats to global health in 2019. The reasons why people choose not to vaccinate are complex, but lack of confidence in vaccine safety, driven by concerns about adverse events, has been identified as one of the key factors. Healthcare workers, especially those in primary care, remain key influencers on vaccine decisions. It is important, therefore, that they be supported by having easy access to trusted, evidence-based information on vaccines. Although parents and patients have a number of concerns about vaccine safety, among the most common are fears that adjuvants like aluminum, preservatives like mercury, inactivating agents like formaldehyde, manufacturing residuals like human or animal DNA fragments, and simply the sheer number of vaccines might be overwhelming, weakening or perturbing the immune system. As a consequence, some fear that vaccines are causing autism, diabetes, developmental delays, hyperactivity, and attention-deficit disorders, amongst others. In this review we will address several of these topics and highlight the robust body of scientific evidence that refutes common concerns about vaccine safety.

MUC5AC Levels Associated With Respiratory Syncytial Virus Disease Severity.

To assess MUC5AC as a biomarker for respiratory syncytial virus (RSV) disease severity, we tested nasal aspirates from RSV+ children with mild, moderate, and severe disease. Levels were significantly higher in those in the severe and moderate groups compared to mild group, indicating MUC5AC may be a useful biomarker for RSV disease severity.

A sibling pair with cardiofaciocutaneous syndrome (CFC) secondary to BRAF mutation with unaffected parents-the first cases of gonadal mosaicism in CFC?

Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by intellectual disability, congenital heart defects, a characteristic facial appearance, gastro-intestinal complications, ectodermal abnormalities and growth failure. The RASopathies result from germline mutations in the Ras/Mitogen-activated-protein-kinase (MAPK) pathway. CFC is associated with mutations in BRAF, KRAS, MEK1 and MEK2. CFC has been considered a "sporadic" disorder, with minimal recurrence risk to siblings. In recent years, vertical transmission of CFC has been seen in mutations involving the MEK2 and KRAS genes, but has not previously been reported with BRAF mutations. Two brothers with clinical features of CFC and mutations in BRAF (c.770A > G, p.Gln257Arg) are described. Neither parent (both phenotypically normal) had the BRAF mutation in their leukocyte DNA. Although this mutation is one of the most common mutations in CFC, to our knowledge, this is the first molecularly confirmed BRAF mutation causing CFC in siblings. This observation also likely represents the first description of germ cell mosaicism in CFC and so it is important to provide optimal genetic counselling to families regarding the risk of reoccurrence.

Mortality due to Respiratory Syncytial Virus. Burden and Risk Factors.

RATIONALE: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear. OBJECTIVES: To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants. METHODS: This was a prospective, population-based, cross-sectional, multicenter study conducted between 2011 and 2013. Hospitalizations and deaths due to severe lower respiratory tract illness (LRTI) were recorded during the RSV season. All-cause hospital deaths and community deaths were monitored. Risk factors for respiratory failure (RF) and mortality due to RSV were assessed using a hierarchical, logistic regression model. MEASUREMENTS AND MAIN RESULTS: A total of 2,588 (65.5%) infants with severe LRTI were infected with RSV. A total of 157 infants (148 postneonatal) experienced RF or died with RSV. RSV LRTI accounted for 57% fatal LRTI tested for the virus. A diagnosis of sepsis (odds ratio [OR], 17.03; 95% confidence interval [CI], 13.14-21.16 for RF) (OR, 119.39; 95% CI, 50.98-273.34 for death) and pneumothorax (OR, 17.15; 95% CI, 13.07-21.01 for RF) (OR, 65.49; 95% CI, 28.90-139.17 for death) were the main determinants of poor outcomes. CONCLUSIONS: RSV was the most frequent cause of mortality in low-income postneonatal infants. RF and death due to RSV LRTI, almost exclusively associated with prematurity and cardiopulmonary diseases in industrialized countries, primarily affect term infants in a developing world environment. Poor outcomes at hospitals are frequent and associated with the cooccurrence of bacterial sepsis and clinically significant pneumothoraxes.

Clinical Predictors of Critical Lower Respiratory Tract Illness Due to Respiratory Syncytial Virus in Infants and Children: Data to Inform Case Definitions for Efficacy Trials.

We analyzed data from 524 Argentinean infants hospitalized with lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) to inform selection of clinical end points for RSV vaccine efficacy trials. Cases of LRTI due to RSV that required a mask, continuous or bilevel positive airway pressure, or mechanical ventilation were classified as critical. Oxygen saturation of ≤90%, tachypnea, and tachycardia were each associated with an increased odds of critical LRTI due to RSV (adjusted odds ratios [ORs], 2.30 [95% confidence interval {CI}, 1.26-4.24; P = .007], 2.22 [95% CI, 1.19-4.16; P = .012], and 2.35 [95% CI, 1.22-4.50; P = .010], respectively). The odds of critical LRTI due to RSV increased substantially (OR, 8.57; 95% CI, 2.19-73.5; P = .001) among individuals with ≥2 indicators. Lower chest wall indrawing was not associated with critical disease.

Anti-N-Methyl-D-Aspartate Receptor Antibody Mediated Neurologic Relapse Post Herpes Simplex Encephalitis: A Case Series.

Despite the advent of antiviral therapy, herpes simplex encephalitis (HSE) remains a devastating condition with significant morbidity and mortality. Neurologic relapse after initial improvement is generally attributed to herpes simplex virus reactivation. In 2013, inflammation caused by anti-N-methyl-D-aspartate receptor antibodies was reported in association with cases of neurologic relapse after herpes simplex encephalitis. We present 3 such cases and discuss diagnostic and management dilemmas.

Easily missed, potentially fatal complication in an extremely preterm infant.

A baby girl was delivered by emergency caesarean section at 23+6 weeks gestation weighing 440 g. Apgar scores were 1, 3 and 4 at 1, 5 and 10 min, respectively. She was intubated and transferred to the neonatal intensive care unit. Umbilical arterial and venous lines and an orogastric tube (OGT) were inserted. On day 4 of life the OGT appeared to be outside of the gastrointestinal tract on X-ray. Feeds were held and contrast oesophagography confirmed suspicion of an oesophageal perforation. She was treated with intravenous metronidazole, gentamycin and amoxicillin and placed nil by mouth for 10 days. Resolution of the perforation was confirmed on repeat contrast study (day 10) and feeds were restarted with no further complications.

1.6 W continuous-wave Raman laser using low-loss synthetic diamond.

Low-birefringence (Δn<2x10(-6)), low-loss (absorption coefficient <0.006 cm(-1) at 1064 nm), single-crystal, synthetic diamond has been exploited in a CW Raman laser. The diamond Raman laser was intracavity pumped within a Nd:YVO4 laser. At the Raman laser wavelength of 1240 nm, CW output powers of 1.6 W and a slope efficiency with respect to the absorbed diode-laser pump power (at 808 nm) of ~18% were measured. In quasi-CW operation, maximum on-time output powers of 2.8 W (slope efficiency ~24%) were observed, resulting in an absorbed diode-laser pump power to the Raman laser output power conversion efficiency of 13%.

Medication errors in the outpatient setting: classification and root cause analysis.

OBJECTIVES: To understand and classify causal factors linked to medication errors and to define opportunities for systematic changes to improve the safety of prescription medication use. DESIGN, SETTING, AND PARTICIPANTS: All recipients of liver, kidney, and/or pancreas allografts followed up by an academic medical center and encountered in the acute care facility, outpatient clinic, or by telephone during 12 months (April 1, 2004, through March 31, 2005). Errors were sought by specific review of the expected and actual medication lists. Main Outcome Measure Proportion of medication errors in each of 5 classifications developed through iterative revision. Definitions included failure to provide a correct prescription (prescription error); deliver a prescribed medication to the patient (delivery error); possess enough medication for a 24-hour or greater supply (availability error); accurately use an available, prescribed medication (patient error); and identify the type, dosage, or frequency of a medication (reporting error). RESULTS: We identified 149 errors in 93 patients who were prescribed a mean of 10.9 medications each. Adverse events were associated with 48 errors (32%), including hospitalization (17 patients) or outpatient invasive procedure (3 patients) in 13%. Nine episodes of rejection and 6 failed allografts were identified. The most common error type was patient error in 83 errors (56%) with prescription errors in 20 errors (13%), delivery errors in 20 errors (13%), availability errors in 15 errors (10%), and reporting errors in 12 errors (8%). Root cause analysis identified the patient as the cause in 101 errors (68%) while pharmacies and other sectors of the health care team caused 41 errors (27%). Finances were linked to 7 errors (5%). Error frequency was estimated during 4 weeks of outpatient visits at 15 of 219 visits. CONCLUSIONS: Outpatient medication errors are abundant, often occult, and associated with significant adverse events in a complex transplant population. The health care system is associated with nearly one third of errors.