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Influenza vaccination during pregnancy prevents influenza among women and their infants but remains underused among pregnant women. We aimed to quantify the risk of antenatal influenza and examine its association with perinatal outcomes. We did a prospective cohort study in pregnant women in India, Peru, and Thailand. Before the 2017 and 2018 influenza seasons, we enrolled pregnant women aged 18 years or older with expected delivery dates 8 weeks or more after the season started. We contacted women twice weekly until the end of pregnancy to identify illnesses with symptoms of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing and collected mid-turbinate nasal swabs from symptomatic women for influenza real-time RT-PCR testing. We assessed the association of antenatal influenza with preterm birth, late pregnancy loss (≥13 weeks gestation), small for gestational age (SGA), and birthweight of term singleton infants using Cox proportional hazards models or generalised linear models to adjust for potential confounders. Between March 13, 2017, and Aug 3, 2018, we enrolled 11 277 women with a median age of 26 years (IQR 23–31) and gestational age of 19 weeks (14–24). 1474 (13%) received influenza vaccines. 310 participants (3%) had influenza (270 [87%] influenza A and 40 [13%] influenza B). Influenza incidences weighted by the population of women of childbearing age in each study country were 88·7 per 10 000 pregnant woman-months (95% CI 68·6 to 114·8) during the 2017 season and 69·6 per 10 000 pregnant woman-months (53·8 to 90·2) during the 2018 season. Antenatal influenza was not associated with preterm birth (adjusted hazard ratio [aHR] 1·4, 95% CI 0·9 to 2·0; p=0·096) or having an SGA infant (adjusted relative risk 1·0, 95% CI 0·8 to 1·3, p=0·97), but was associated with late pregnancy loss (aHR 10·7, 95% CI 4·3 to 27·0; p<0·0001) and reduction in mean birthweight of term, singleton infants (−55·3 g, 95% CI −109·3 to −1·4; p=0·0445). Women had a 0·7–0·9% risk of influenza per month of pregnancy during the influenza season, and antenatal influenza was associated with increased risk for some adverse pregnancy outcomes. These findings support the added value of antenatal influenza vaccination to improve perinatal outcomes. US Centers for Disease Control and Prevention. For the Thai, Hindi, Marathi and Spanish translations of the abstract see Supplementary Materials section.

In a study involving 3975 health care personnel, first responders, and other essential workers, the effectiveness of mRNA vaccines against SARS-CoV-2 infection was 91% with full vaccination. The vaccines attenuated the viral RNA load, febrile symptoms, and illness duration among those who became infected despite vaccination.

Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6–33 days after the first dose and 5–40 days after the second dose. Mpox-convalescent samples were collected 20–102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20–102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.

JYNNEOS, a third-generation smallpox vaccine, is integral to monkeypox virus (MPXV) control efforts, but the durability of this modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine's effectiveness is undefined. We optimized and used a plaque reduction neutralization test (PRNT) with authentic clade IIa MPXV and vaccinia virus to assess antibody responses over 12 months in 8 donors vaccinated with 2 doses of JYNNEOS. One donor previously received the ACAM2000 vaccine; 7 donors were smallpox vaccine-naive. IgG responses of the donors to vaccinia virus (L1, B5, and A33) or MPXV (E8, H3, A35) antigens and PRNT titers to both viruses peaked at 8 weeks postvaccination and waned rapidly thereafter in naive donors. MPXV PRNT titers were especially low; no naive donors demonstrated 90% plaque reduction. These data indicate a need for improved correlates of MPXV immunity to enable MVA-BN durability studies, given that recent clinical data support MVA-BN vaccine efficacy against MPXV despite low antibody responses.

Background Dengue virus (DENV) is endemic in many parts of the world. Antibody dependent enhancement (ADE) in DENV infections occurs when a person with primary immunity is infected by a second, different DENV strain. Antibodies to Zika virus (ZIKV), which emerged in the Western Hemisphere in 2015, are cross reactive with DENV and theoretically could provoke ADE in a DENV naïve individual. Case presentation DENV infection was suspected in a child who had recently returned from a one-month stay in the Dominican Republic. The child presented with fever, vomiting, abdominal pain, and in hypovolemic shock. Volume and pressor resuscitation were unsuccessful, and the child died less than 24 h after hospitalization. Laboratory results suggested an early acute first DENV infection since serum, plasma, and spinal fluid had DENV1 detected by polymerase chain reaction (PCR), yet the serum lacked IgG antibodies to DENV nonstructural protein 1 (NS1) of all four DENV serotypes. This acute DENV infection occurred in the presence of a remote ZIKV infection as determined by antibodies to ZIKV NS1 envelope by multiplex microsphere immunoassay and an exceptionally high plaque reduction neutralization titer to ZIKV. ZIKV IgG avidity index was high, confirming a past infection. DENV1 RNA was detected in all ten organs and tissues examined by PCR. The severe and fatal complications reported here suggest that a remote ZIKV infection may provoke an exaggerated immune response leading to hypovolemic shock when primarily infected by DENV1. Conclusion We report the first known patient in the United States with a rapidly progressive and fatal case of travel-associated DENV in which prior exposure to ZIKV likely played a role in triggering an ADE phenomenon. This association of prior ZIKV immunity and subsequent new dengue infection is a worrisome phenomenon and an important contribution to the body of knowledge on immunity to flaviviruses.

Macrophages (MØs) are sentinels of the immune system that use pattern recognition receptors such as Toll-like receptors (TLR) to detect invading pathogens and immune receptors such as FcγR to sense the host's immune state. Crosstalk between these two signaling pathways allows the MØ to tailor the cell's overall response to prevailing conditions. However, the molecular mechanisms underlying TLR-FcγR crosstalk are only partially understood. Therefore, we employed an immunologically-relevant MØ stimulus, an inactivated gram-negative bacterium that bears TLR2 agonists but no TLR4 agonist (iBTLR2) opsonized with a monoclonal antibody (mAb-iBTLR2), as a tool to study FcγR regulation of TLR2-driven production of IL-6, a key inflammatory cytokine. We chose this particular agonist as an investigational tool because MØ production of any detectable IL-6 in response to mAb-iBTLR2 requires both TLR2 and FcγR signaling, making it an excellent system for the study of receptor synergy. Using genetic, pharmacological and immunological approaches, we demonstrate that the murine MØ IL-6 response to mAb-iBTLR2 requires activation of both the TLR/NF-κB and FcγR/ITAM signaling pathways. mAb-iBTLR2 engagement of TLR2 drives NF-κB activation and up-regulation of IL-6 mRNA but fails to result in IL-6 cytokine production/release. Here, Src family kinase-driven FcγR ITAM signaling is necessary to enable IL-6 mRNA incorporation into polysomes and translation. These results reveal a novel mechanism by which FcγR ITAM signaling synergizes with TLR signaling, by \"licensing\" cytokine mRNA ribosome binding/translation to drive a strong murine MØ cytokine response.

Given the widespread presence of non-native vegetation in urban and Mediterranean watersheds, it is important to evaluate how these sensitive ecosystems will respond to activities to manage and restore native vegetation conditions. This research focuses on Del Cerro, a tributary of the San Diego River in California, where non-native vegetation dominates the riparian zone, creating flooding and fire hazards. Field data were collected in 2018 to 2021 and consisted of water depth, streamflow, and stream temperature. Our data set also captured baseline conditions in the floodplain before and after the removal of burned non-native vegetation in November 2020. Observed changes in hydrologic and geomorphic conditions were used to parameterize and calibrate a two-dimensional hydraulic model to simulate urban floodplain hydraulics after vegetation removal. We utilized the U.S. Army Corps of Engineers’ Hydrologic Engineering Center River Assessment System (HEC-RAS) model to simulate the influence of canopy loss and vegetation disturbance and to assess the impacts of vegetation removal on stream restoration. We simulated streamflow, water depth, and flood extent for two scenarios: (1) 2019; pre-restoration where non-native vegetation dominated the riparian area, and (2) 2021; post-restoration following the removal of non-native vegetation and canopy. Flooding after restoration in 2021 was more frequent compared to 2019. We also observed similar flood extents and peak streamflow for storm events that accumulated half the amount of precipitation as pre-restoration conditions. Our results provide insight into the responses of small urban stream reaches to the removal of invasive vegetation and canopy cover.

ObjectivesTo investigate the association of reported legal performance enhancing substance (PES) use and consideration of banned PES use among sport-specialised and non-sport-specialised young athletes.Methods and designCross-sectional study of 1049 young athletes enrolled in an injury prevention programme from 2013 to 2020. We used logistic regression modelling to determine the independent association between sports specialisation. We reported (1) legal PES use and (2) consideration of banned PES use after adjusting for the effects of gender, age, having a relative as a coach, unrestricted internet access, use of a weight training regimen, and weeknight hours of sleep.ResultsThe final cohort consisted of 946 athletes with a mean age of 14. 56% were female, and 80% were sport-specialised athletes. 14% reported legal PES use, and 3% reported consideration of banned PES use. No difference was found between sport-specialised athletes who reported legal PES use (OR=1.4; 95% CI 0.81 to 2.43; p=0.23) or consideration of banned PES use (OR=3.2; 95% CI 0.78 to 14.92; p=0.1) compared with non-sport-specialised athletes. Reported legal PES use was more common among athletes who were male, older, used weight training, and slept less. Reported consideration of banned PES use was more common among male and older athletes.ConclusionsPES use is not independently associated with sport specialisation in young athletes. Athlete sex, age, training, and sleep patterns are important factors for young athletes to consider in PES use.

•Mothers in Albania, Nicaragua, Philippines, and Jordan completed a survey.•Influenza vaccine is not routinely given in these countries.•Many mothers were unaware of the disease or vaccine.•Perceived safety was an important predictor of vaccine intentions. Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers’ knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers’ intent to vaccinate their child. From 2015 to 2017, infants 0–11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6–11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis. In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample. Intent to vaccinate infants aged 6–11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants.

Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials (1,2); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020-March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19-associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) per 1,000 person-days. In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.