Randomized, Open-Label Phase 3 Study Evaluating Immunogenicity, Safety, and Reactogenicity of RSVPreF3 OA Coadministered with FLU-QIV-HD in Adults Aged ≥ 65.

INTRODUCTION: Respiratory syncytial virus (RSV) and influenza pose major disease burdens in older adults due to an aging immune system and comorbidities; seasonal overlap exists between these infections. In 2023, the RSV prefusion protein F3 older adult (RSVPreF3 OA) vaccine was first approved in the USA as a single dose for prevention of lower respiratory tract disease due to RSV in adults aged ≥ 60 years. The vaccine has since been approved in the European Union and elsewhere. RSVPreF3 OA and FLU-QIV-HD could be coadministered if immunogenicity, safety, and reactogenicity are not affected. METHODS: This open-label, randomized (1:1), controlled, phase 3 study in 1029 adults aged ≥ 65 years in the USA evaluated the immunogenicity (up to 1 month after last vaccine dose) and safety (up to 6 months after last vaccine dose) of RSVPreF3 OA coadministered with FLU-QIV-HD (co-ad group) versus FLU-QIV-HD alone followed by RSVPreF3 OA at a separate visit 1 month later (control group). Non-inferiority criterion was defined as an upper limit of the two-sided 95% confidence interval of the geometric mean titer (GMT) group ratio (control/co-ad) ≤ 1.5. Secondary endpoints included safety and reactogenicity. RESULTS: Proportions of participants across age categories between groups and proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Group GMT ratios for RSV-A neutralizing titers, hemagglutination inhibition titers for four influenza vaccine strains, and RSV-B neutralizing titers were non-inferior in the co-ad group versus the control group. No clinically meaningful differences in local or systemic solicited and unsolicited adverse events (AEs), serious AEs, and potential immune-mediated diseases were identified. The most common solicited AEs in both groups were injection-site pain and myalgia. CONCLUSION: In adults aged ≥ 65 years, coadministration of RSVPreF3 OA and FLU-QIV-HD was immunogenically non-inferior to the sequential administration of both vaccines 1 month apart, and had clinically acceptable safety and reactogenicity profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05559476.

Adults aged 65 years or older are vulnerable to infections caused by influenza and respiratory syncytial viruses, due to an aging immune system and other underlying conditions. Infections with both viruses increase during autumn and winter seasons in temperate climates. In 2023, a vaccine against respiratory syncytial virus, called RSVPreF3 OA, was first approved for use in adults aged 60 years or older in the USA; the vaccine has since also been approved in the European Union and elsewhere. Giving RSVPreF3 OA in the same vaccination visit (coadministration) with a high-dose influenza vaccine, called FLU-QIV-HD, which is given to adults aged 65 years or older, could help protect against both respiratory syncytial virus and influenza. This article reports the results of a phase 3 trial comparing coadministration of the RSVPreF3 OA and FLU-QIV-HD vaccines with sequential administration (FLU-QIV-HD followed by RSVPreF3 OA 1 month later) in 1029 adults aged 65 years or older in the USA. Proportions of participants across age categories between groups, and the proportions of male (50.4%) and female (49.6%) participants were well balanced; most participants were white (68.7%). Immune response to both the vaccines among participants in the coadministration arm was non-inferior to that in the sequential arm. Coadministration was well tolerated, with no meaningful differences in adverse reactions to the vaccines compared with sequential administration. The most common adverse reactions were pain at the injection site and muscle aches. This study supports the coadministration of RSVPreF3 OA and FLU-QIV-HD in adults aged 65 years or older.

A Dialogue about Vaccine Side Effects: Understanding Difficult Pandemic Experiences.

This paper investigates the relationship between the experiences of mass vaccinations against two pandemic viruses: the swine flu in 2009-2010 and COVID-19 in the early 2020s. We show how distressing memories from the swine flu vaccination, which led to the rare but severe adverse effect of narcolepsy in approximately 500 children in Sweden, were triggered by the COVID-19 pandemic. The narcolepsy illness story has rarely been told in academic contexts; therefore, we will provide space for this story. It is presented through a dialogue with the aim of shedding light on the interrelationship between pandemics-and between mass vaccinations-to investigate what could be termed cultural wounds that influence societies because they are characterized by the difficulty of talking about them. The paper explores the multiple shocks of illness in life and what can be learned from them by sharing them.

Post-orgasmic Illness Syndrome: A Case Report.

Post-orgasmic illness syndrome (POIS) is a rare condition characterized by debilitating symptoms following ejaculation. We present a case of a 25-year-old male with flu-like symptoms post-ejaculation since age 17. Despite minimal relief from conventional treatments, a comprehensive evaluation led to the diagnosis of POIS and successful management with niacinamide therapy. The presentation of flu-like symptoms following ejaculation in this case raises several questions regarding the underlying pathophysiology. While the exact cause of his symptoms remains elusive, the resolution achieved with niacinamide therapy underscores the importance of considering alternative treatment modalities in complex cases. The role of varicocele in symptom manifestation, if any, also warrants consideration, as varicocele has been associated with male infertility and testicular dysfunction.

Design, synthesis and biological evaluation of sulfamethazine derivatives as potent neuraminidase inhibitors.

Aim: The purpose of this study is to design and synthesize a new series of sulfamethazine derivatives as potent neuraminidase inhibitors. Materials & methods: A sulfamethazine lead compound, ZINC670537, was first identified by structure-based virtual screening technique, then some novel inhibitors X1-X10 based on ZINC670537 were designed and synthesized. Results: Compound X3 exerts the most good potency in inhibiting the wild-type H5N1 NA (IC50 = 6.74 µM) and the H274Y mutant NA (IC50 = 21.09 µM). 150-cavity occupation is very important in determining activities of these inhibitors. The sulfamethazine moiety also plays an important role. Conclusion: Compound X3 maybe regard as a good anti-influenza candidate to preform further study.

[Box: see text].

A simple modification to the classical SIR model to estimate the proportion of under-reported infections using case studies in flu and COVID-19.

Background: Under-reporting and, thus, uncertainty around the true incidence of health events is common in all public health reporting systems. While the problem of under-reporting is acknowledged in epidemiology, the guidance and methods available for assessing and correcting the resulting bias are obscure. Objective: We aim to design a simple modification to the Susceptible - Infected - Removed (SIR) model for estimating the fraction or proportion of reported infection cases. Methods: The suggested modification involves rescaling of the classical SIR model producing its mathematically equivalent version with explicit dependence on the reporting parameter (true proportion of cases reported). We justify the rescaling using the phase plane analysis of the SIR model system and show how this rescaling parameter can be estimated from the data along with the other model parameters. Results: We demonstrate how the proposed method is cross-validated using simulated data with known disease cases and then apply it to two empirical reported data sets to estimate the fraction of reported cases in Missoula County, Montana, USA, using: (1) flu data for 2016-2017 and (2) COVID-19 data for fall of 2020. Conclusions: We establish with the simulated and COVID-19 data that when most of the disease cases are presumed reported, the value of the additional reporting parameter in the modified SIR model is close or equal to one, so that the original SIR model is appropriate for data analysis. Conversely, the flu example shows that when the reporting parameter is close to zero, the original SIR model is not accurately estimating the usual rate parameters, and the re-scaled SIR model should be used. This research demonstrates the role of under-reporting of disease data and the importance of accounting for under-reporting when modeling simulated, endemic, and pandemic disease data. Correctly reporting the "true" number of disease cases will have downstream impacts on predictions of disease dynamics. A simple parameter adjustment to the SIR modeling framework can help alleviate bias and uncertainty around crucial epidemiological metrics (e.g.: basic disease reproduction number) and public health decision making.

Influenza A, Influenza B, human respiratory syncytial virus and SARSCoV-2 molecular diagnostics and epidemiology in the post COVID-19 era.

BACKGROUND: The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology laboratories. Multiplexed molecular testing on automated platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube is a useful approach for current and future diagnosis of respiratory infections in the clinical setting. METHODS: Two time periods were included in the study: from February to April 2022, an early 2022 period, during the gradual lifting of COVID-19 prevention measures in the country, and from October 2022 to April 2023, the 2022/23 respiratory infections season. We analysed a total of 1,918 samples in the first period and 18,131 respiratory samples in the second period using a multiplex molecular assay for the simultaneous detection of Influenza A (Flu-A), Influenza B (Flu-B), Human Respiratory Syncytial Virus (HRSV) and SARS-CoV-2. RESULTS: The results from early 2022 showed a strong dominance of SARS-CoV-2 infections with 1,267/1,918 (66.1%) cases. Flu-A was detected in 30/1,918 (1.6%) samples, HRSV in 14/1,918 (0.7%) samples, and Flu-B in 2/1,918 (0.1%) samples. Flu-A/SARS-CoV-2 co-detections were observed in 11/1,267 (0.9%) samples, and HRSV/SARS-CoV-2 co-detection in 5/1,267 (0.4%) samples. During the 2022/23 winter respiratory season, SARS-CoV-2 was detected in 1,738/18,131 (9.6%), Flu-A in 628/18,131 (3.5%), Flu-B in 106/18,131 (0.6%), and HRSV in 505/18,131 (2.8%) samples. Interestingly, co-detections were present to a similar extent as in early 2022. CONCLUSION: The results show that the multiplex molecular approach is a valuable tool for the simultaneous laboratory diagnosis of SARS-CoV-2, Flu-A/B, and HRSV in hospitalized and outpatients. Infections with Flu-A/B, and HRSV occurred shortly after the COVID-19 control measures were lifted, so a strong reoccurrence of various respiratory infections and co-detections in the post COVID-19 period was to be expected.

Vaccination against seasonal flu in childhood and adolescence. Recommendations of the Advisory Committee on Vaccines and Immunizations of the Spanish Association of Pediatrics (CAV-AEP) for the 2024-2025 season.

The flu is a constant threat that can sometimes cause severe forms of disease. The highest incidence rates by age group occur in children under 15 years of age, especially in those under 5 years, in whom the rate of hospitalization is also similar to the population aged 65 years and older. In addition, children are the main transmitters of the infection. In Spain, 5 influenza vaccines are authorized for the paediatric age group: three inactivated tetravalent vaccines harvested from fertilised eggs, one tetravalent inactivated vaccine obtained from cell cultures and one attenuated tetravalent vaccine for intranasal administration, which will become trivalent in the 2024-2025 season by excluding the B Yamagata lineage as recommended by the WHO. The CAV-AEP recommends systematic vaccination in children aged 6-59 months, children and adolescents belonging to risk groups, people who can transmit the flu to groups at risk of complicated flu, and household contacts or close family of infants under 6 months. From 2 years of age, the intranasal attenuated vaccine is preferred due to its greater acceptability and thus contribution to greater vaccination coverage. The CAV-AEP also considers that vaccination against influenza of healthy children and adolescents aged 5-18 years is advisable, as it provides individual protection and promotes protection at the family and community levels. It is especially important to vaccinate all health care professionals against influenza as well as pregnant women at any time during pregnancy.

Effect of a Structured Multilevel Telehealth Service on Hospital Admissions and Mortality During COVID-19 in a Resource-Limited Region in Brazil: Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic represented a great stimulus for the adoption of telehealth and many initiatives in this field have emerged worldwide. However, despite this massive growth, data addressing the effectiveness of telehealth with respect to clinical outcomes remain scarce. OBJECTIVE: The aim of this study was to evaluate the impact of the adoption of a structured multilevel telehealth service on hospital admissions during the acute illness course and the mortality of adult patients with flu syndrome in the context of the COVID-19 pandemic. METHODS: A retrospective cohort study was performed in two Brazilian cities where a public COVID-19 telehealth service (TeleCOVID-MG) was deployed. TeleCOVID-MG was a structured multilevel telehealth service, including (1) first response and risk stratification through a chatbot software or phone call center, (2) teleconsultations with nurses and medical doctors, and (3) a telemonitoring system. For this analysis, we included data of adult patients registered in the Flu Syndrome notification databases who were diagnosed with flu syndrome between June 1, 2020, and May 31, 2021. The exposed group comprised patients with flu syndrome who used TeleCOVID-MG at least once during the illness course and the control group comprised patients who did not use this telehealth service during the respiratory illness course. Sociodemographic characteristics, comorbidities, and clinical outcomes data were extracted from the Brazilian official databases for flu syndrome, Severe Acute Respiratory Syndrome (due to any respiratory virus), and mortality. Models for the clinical outcomes were estimated by logistic regression. RESULTS: The final study population comprised 82,182 adult patients with a valid registry in the Flu Syndrome notification system. When compared to patients who did not use the service (n=67,689, 82.4%), patients supported by TeleCOVID-MG (n=14,493, 17.6%) had a lower chance of hospitalization during the acute respiratory illness course, even after adjusting for sociodemographic characteristics and underlying medical conditions (odds ratio [OR] 0.82, 95% CI 0.71-0.94; P=.005). No difference in mortality was observed between groups (OR 0.99, 95% CI 0.86-1.12; P=.83). CONCLUSIONS: A telehealth service applied on a large scale in a limited-resource region to tackle COVID-19 was related to reduced hospitalizations without increasing the mortality rate. Quality health care using inexpensive and readily available telehealth and digital health tools may be delivered in areas with limited resources and should be considered as a potential and valuable health care strategy. The success of a telehealth initiative relies on a partnership between the involved stakeholders to define the roles and responsibilities; set an alignment between the different modalities and levels of health care; and address the usual drawbacks related to the implementation process, such as infrastructure and accessibility issues.

Spending, utilization, and coverage for chronic rhinosinusitis with nasal polyposis therapies among Medicare Advantage beneficiaries.

KEY POINTS: CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery. While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS-FLU.

Surveillance outcomes of respiratory pathogen infections during the 2021-2022 season among U.S. Military Health System beneficiaries, October 3, 2021-October 1, 2022.

The Department of Defense Global Respiratory Pathogen Surveillance Program conducts continuous surveillance for influenza, severe acute respiratory syndrome 2 (SARS-CoV-2), and other respiratory pathogens at 104 sentinel sites across the globe. These sites submitted 65,475 respiratory specimens for clinical diagnostic testing during the 2021-2022 surveillance season. The predominant influenza strain was influenza A(H3N2) (n=777), of which 99.9% of strains were in clade 3C.2a1b.2a2. A total of 21,466 SARSCoV-2-positive specimens were identified, and 12,225 of the associated viruses were successfully sequenced. The Delta variant predominated at the start of the season, until December 2021, when Omicron became dominant. Most circulating SARS-CoV-2 viruses were subsequently held by Omicron sublineages BA.1, BA.2, and BA.5 during the season. Clinical manifestation, obtained through a self-reported questionnaire, found that cough, sinus congestion, and runny nose complaints were the most common symptoms presenting among all pathogens. Sentinel surveillance can provide useful epidemiological data to supplement other disease monitoring activities, and has become increasingly useful with increasing numbers of individuals utilizing COVID-19 rapid self-test kits and reductions in outpatient visits for routine respiratory testing.

A Scoping Review of the Evidence on Prevalence of Feline Upper Respiratory Tract Infections and Associated Risk Factors.

Feline upper respiratory tract infections (URI) are of concern, especially in animal shelters. This scoping review identifies epidemiological literature on URI as caused by feline herpesvirus (FHV), feline calicivirus (FCV), Chlamydia felis, Mycoplasma felis and Bordetella bronchiseptica. Four databases were searched, studies were screened, and data were extracted on a standardised template. We described patterns in spatial locations of the studies, the range of pathogens and diagnostic tests, cohort characteristics and the findings of risk factor analyses. A total of 90 articles were selected for final data extraction. There was diversity in sampling methods, precluding quantitative meta-analysis of prevalence reports. FHV was most frequently studied (n = 57/90). The most popular sampling site was conjunctival swabbing (n = 43). Most studies (n = 57) used polymerase chain reaction (PCR) to confirm diagnosis. Approximately one-third (n = 32/90) of the studies included sheltered felines. This review explores the current state of knowledge on the epidemiology and risk factors of feline URI. Assessing the impact of risk factors has the potential to alleviate the severity of disease, especially in shelters; however, the results were not easily pooled as the studies used inconsistent approaches. We present recommendations for ongoing epidemiological research on feline URI to provide a more structured framework and define research questions for future systematic reviews.

Centenarians, semi and supercentenarians, COVID-19 and Spanish flu: a serological assessment to gain insight into the resilience of older centenarians to COVID-19.

BACKGROUND: Although it is well known that the older people have been the most susceptible to COVID-19, there are conflicting data on the susceptibility of centenarians. Two epidemiological study have shown that older centenarians (> 101 years old at the time of the 2020 pandemic peak) are more resilient than the remaining centenarians, suggesting that this resilience might be linked to the 1918 Spanish Flu pandemic. To gain insight into this matter, specifically whether the resilience of older centenarians to SARS-CoV-2 infection is linked to the Spanish Flu they had been affected by, we conducted a retrospective serological study. This study examined serum samples from 33 centenarians, encompassing semi- (aged > 104 < 110 years, N = 7) and supercentenarians (aged > 109 years, N = 4), born between 1905 and 1922, against both SARS-CoV-2 and 1918 H1N1 pseudotype virus. RESULTS: Anamnestic and laboratory data suggest that SARS-CoV-2 infection occurred in 8 centenarians. The infection appeared to have been asymptomatic or mild, and hospitalization was not required, despite 3 out of 8 being between 109 and 110 years old. The levels of anti-spike antibodies in centenarians infected and/or vaccinated were higher, although not significantly, than those produced by a random sample of seventy-year-old individuals used as controls. All centenarians had antibody levels against the 1918 H1N1 virus significantly higher (almost 50 times) than those observed in the quoted group of seventy-year-old subjects, confirming the key role in maintaining immunological memory from a priming that occurred over 100 years ago. Centenarians whose blood was collected prior to the pandemic outbreak demonstrated neutralising antibodies against the 1918 H1N1 virus, but all these subjects tested negative for SARS-CoV-2. CONCLUSION: This retrospective study shows that older centenarians are quite resilient to COVID-19, as they are capable of producing good levels of neutralising antibodies and experiencing mild or asymptomatic disease. This could be attributed to the 1918 Spanish flu pandemic through mechanisms other than the presence of cross-reactive antibodies between the 1918 H1N1 virus and SARS-CoV-2. Another possibility is that the association is purely temporal, solely correlated with the advanced age of resilient centenarians compared to those born after 1918, since older centenarians are known to have better control of immune-inflammatory responses.

Predicting COVID-19 and respiratory illness: results of the 2022-2023 Armed Forces Health Surveillance Division forecasting challenge.

Since 2019, the Integrated Biosurveillance Branch of the Armed Forces Health Surveillance Division has conducted an annual forecasting challenge during influenza season to predict short-term respiratory disease activity among Military Health System beneficiaries. Weekly case and encounter observed data were used to generate 1- through 4-week advanced forecasts of disease activity. To create unified combinations of model inputs for evaluation across multiple spatial resolutions, 8 individual models were used to calculate 3 ensemble models. Forecast accuracy compared to the observed activity for each model was evaluated by calculating a weighted interval score. Weekly 1- through 4-week ahead forecasts for each ensemble model were generally higher than observed data, especially during periods of peak activity, with peaks in forecasted activity occurring later than observed peaks. The larger the forecasting horizon, the more pronounced the gap between forecasted peak and observed peak. The results showed that several models accurately predicted COVID-19 cases and respiratory encounters with enough lead time for public health response by senior leaders.

Performance evaluation of the Panbio COVID-19/Flu A&B Panel for detection of SARS-CoV-2, influenza A, and influenza B antigens using mid-turbinate nasal swabs.

The Panbio COVID-19/Flu A&B Panel (Abbott) is an in vitro diagnostic rapid test designed for the qualitative detection of nucleocapsid proteins SARS-CoV-2 and nucleoprotein influenza A and B antigens in nasal mid-turbinate (NMT) swab specimens from symptomatic individuals meeting COVID-19 and influenza clinical and/or epidemiological criteria. This study, the largest global one to date using fresh samples, aimed to assess the diagnostic sensitivity and specificity of the Panbio COVID-19/Flu A&B Panel in freshly collected NMT swab specimens from individuals suspected of respiratory viral infection consistent with COVID-19 and/or influenza within the first 5 days of symptom onset compared with results obtained with the cobas SARS-CoV-2 and influenza A/B qualitative assay (cobas 6800/8800 systems), which were tested using nasopharyngeal swab samples. A total of 512 evaluable subjects were enrolled in the COVID-19 cohort across 18 sites, and 1,148 evaluable subjects were enrolled in the influenza cohort across 22 sites in the Asia-Pacific, Europe, and the USA. The Panbio COVID-19/Flu A&B Panel demonstrated a sensitivity of 80.4% and a specificity of 99.7% for COVID-19. For influenza A, the sensitivity and specificity rates were 80.6% and 99.3%, respectively. Likewise, for influenza B, the sensitivity and specificity rates were 80.8% and 99.4%, respectively. In conclusion, the Panbio COVID-19/Flu A&B Panel emerges as a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.4% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B. IMPORTANCE: The Panbio COVID-19/Flu A&B Panel is a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.0% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.

H1N1 nanobody development and therapeutic efficacy verification in H1N1-challenged mice.

Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.

Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorder.

People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV-OP+, (3) HIV+OP-, and (4) HIV-OP-. The differential expression of the top eight molecules ranked by median values in individual Groups 1-3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP- exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD.

Very Broadly Effective Hemagglutinin-Directed Influenza Vaccines with Anti-Herpetic Activity.

A universal vaccine that generally prevents influenza virus infection and/or illness remains elusive. We have been exploring a novel approach to vaccination involving replication-competent controlled herpesviruses (RCCVs) that can be deliberately activated to replicate efficiently but only transiently in an administration site in the skin of a subject. The RCCVs are derived from a virulent wild-type herpesvirus strain that has been engineered to contain a heat shock promoter-based gene switch that controls the expression of, typically, two replication-essential viral genes. Additional safety against inadvertent replication is provided by an appropriate secondary mechanism. Our first-generation RCCVs can be activated at the administration site by a mild local heat treatment in the presence of an antiprogestin. Here, we report that epidermal vaccination with such RCCVs expressing a hemagglutinin or neuraminidase of an H1N1 influenza virus strain protected mice against lethal challenges by H1N1 virus strains representing 75 years of evolution. Moreover, immunization with an RCCV expressing a subtype H1 hemagglutinin afforded full protection against a lethal challenge by an H3N2 influenza strain, and an RCCV expressing a subtype H3 hemagglutinin protected against a lethal challenge by an H1N1 strain. Vaccinated animals continued to gain weight normally after the challenge. Protective effects were even observed in a lethal influenza B virus challenge. The RCCV-based vaccines induced robust titers of in-group, cross-group and even cross-type neutralizing antibodies. Passive immunization suggested that observed vaccine effects were at least partially antibody-mediated. In summary, RCCVs expressing a hemagglutinin induce robust and very broad cross-protective immunity against influenza.

Spatio-temporal dynamics and drivers of highly pathogenic avian influenza H5N1 in Chile.

Introduction: Highly pathogenic avian influenza A H5N1 clade 2.3.4.4b (hereafter H5N1) is causing vast impacts on biodiversity and poultry around the globe. In Chile, lethal H5N1 cases have been reported in a wide range of wild bird species, marine mammals, backyard and industrial poultry, and humans. This study describes the spatio-temporal patterns of the current epizootic of H5N1 in Chile and test drivers that could be associated with outbreak occurrence. Methods: We used H5N1 cases reported by the Chilean National Animal Health Authority from 5 December 2022 to 5 April 2023. These included wild bird cases confirmed through an avian influenza-specific real-time reverse transcription PCR assay (RT-qPCR), obtained from passive and active surveillance. Data were analyzed to detect the presence of H5N1 clusters under space-time permutation probability modeling, the association of H5N1 with distance and days since the first outbreak through linear regression, and the correlation of H5N1 presence with a number of ecological and anthropogenic variables using general linear modeling. Results: From 445 H5N1 identified outbreaks involving 613 individual cases in wild birds, a consistent wave-like spread of H5N1 from north to south was identified, which may help predict hotspots of outbreak risk. For instance, seven statistically significant clusters were identified in central and northern Chile, where poultry production and wildlife mortality are concentrated. The presence of outbreaks was correlated with landscape-scale variables, notably temperature range, bird richness, and human footprint. Discussion: In less than a year, H5N1 has been associated with the unusual mortality of >100,000 individuals of wild animals in Chile, mainly coastal birds and marine mammals. It is urgent that scientists, the poultry sector, local communities, and national health authorities co-design and implement science-based measures from a One Health perspective to avoid further H5N1 spillover from wildlife to domestic animals and humans, including rapid removal and proper disposal of wild dead animals and the closure of public areas (e.g., beaches) reporting high wildlife mortalities.

Quadrivalent Live-Attenuated Influenza Vaccine in Milan preschools: an Italian experience of school-located flu vaccination within the 2022-2023 season.

BACKGROUND: In Italy, since the 2020-2021 flu season, the flu vaccine recommendation was extended to all children aged 6 months to 6 years and quadrivalent Live-Attenuated Influenza Vaccine (qLAIV) was introduced. Since school-aged children are important carriers of annual influenza epidemics, a school-based influenza vaccination program may potentially increase vaccine uptake. Recent studies, conducted in the UK and the US, show that school-based vaccination can reach higher percentage of paediatric vaccination coverage compared to children vaccinated in other settings. METHODS: During 2022-2023 flu season in 9 preschools located in Milan healthcare personnel vaccinated children with qLAIV at the end of a school day. A Google Form questionnaire was administered to preschoolers' parents of all preschools within the Municipality of Milan. RESULTS: In the preschools engaged in the vaccination program, 233 out of 1939 children were vaccinated (12%). Among these, 61 (26.2%) had never been vaccinated for influenza before. Vaccination coverage was 11.5% for Italian children and 14.3% for children coming from an immigrant background. We collected 3659 questionnaire responses, divided according to study participation status (371 from preschools that participated in the vaccination program and 3288 from other preschools in Milan). 57% of the families who answered to the questionnaire vaccinated their children for flu. qLAIV accounted for 85.6% of vaccinations. We observed a statistically significant difference in the percentage of vaccinated children between those attending a school participating in the project (67.9%) and children attending other schools (56%) (p < 0.001). Vaccination was administered by family pediatricians (48.9%), in vaccination centers (34.8%), in vaccine hubs (11.3%), in schools (2.6%), by private pediatricians (1.6%) and in other settings (0.7%). Focusing on the responses from families whose children attend schools participating in the vaccination program, 21.8% stated that the vaccination was provided in school. CONCLUSION: According to our experience, in Italy, at the moment, only the cooperation between health providers and alternative settings, including schools, may expand flu vaccination coverage. In particular, schools are to be considered a place to inform and reach out to families, useful to increase vaccination coverage.

Over-the-Counter Medications Encountered in the Postmortem Pediatric Population from 2010-2020.

In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days - 18 years), particularly those given to individuals less than five years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from eleven years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine, and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen, and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine, and pseudoephedrine), gastrointestinal (GI) aids (dicyclomine and loperamide), and/or sleep aids (melatonin). Antihistamines, cold/flu medications, and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g., antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse, and suicidal overdoses can occur in the vulnerable, pediatric population.