Prophylaxis Of Influenza Research Articles

Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates.

Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model. Rhesus macaques (Macaca mulatta) (n = 3 per group) were immunized intranasally with 7.5 lg EID50 of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 105 PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection. There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate. The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials.

Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis

Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. World Health Organization.

Cold-adapted influenza-vectored RSV vaccine protects BALB/c mice and cotton rats from RSV challenge.

Respiratory syncytial virus (RSV) remains the primary cause of lower respiratory tract infections, particularly in infants and the elderly. In this study, we employed reverse genetics to generate a chimeric influenza virus expressing neuraminidase-3F protein conjugate with three repeats of the RSV F protein protective epitope inserted into the NA gene of A/California/7/2009 ca (CA/AA ca), resulting in rFlu/RSV/NA-3F (hereafter, rFRN3). The expression of NA-3F protein was confirmed by Western blotting. The morphology and temperature-sensitive phenotype of rFRN3 were similar to CA/AA ca. Its immunogenicity and protective efficiency were evaluated in BALB/c mice and cotton rats. Intranasal administration of rFRN3 elicited robust humoral, cellular, and to some extent, mucosal immune responses. Compared to controls, rFRN3 protected animals from RSV infection, attenuated lung injury, and reduced viral titers in the nose and lungs post-RSV challenge. These results demonstrate that rFRN3 can trigger RSV-specific immune responses and thus exhibits potent protective efficacy. The "dual vaccine" approach of a cold-adapted influenza vector RSV vaccine will improve the prophylaxis of influenza and RSV infection. rFRN3 thus warrants further clinical investigations as a candidate RSV vaccine.

Clinical trial of tolerability, safety and immunogenicity of influenza inactivated split-vaccine Flu-M in children aged 6 to 17 years

Purpose. To evaluate the tolerability, safety and immunogenicity of influenza inactivated split flu vaccine Flu-M during single immunization of children aged 6 to 17 years.Materials and methods. A multicentre double-blind comparative randomised clinical trial of influenza inactivated split vaccine Flu-M for immunisation of children aged 6 to 17 years (the reference agent – Ultrix vaccine) was conducted. Children aged 12 to 17 years inclusive (300 children) were studied at stage I, and children aged 6 to 12 years (300 children) at stage II. Volunteers of each age category were randomised 1:1 into 2 groups comparable in sex and age, one was vaccinated with Flu-M vaccine and the other with Ultrix vaccine. The follow-up, including various laboratory and clinical tests, lasted for 28 days from the time of vaccination.Results. Both vaccines were well tolerated by children aged 12 to 17 years and by children aged 6 to 12 years. There were no severe or serious adverse events. By all criteria of immunogenicity evaluation, vaccine Flu-M was not inferior to the comparison vaccine Ultrix.Conclusion. Influenza inactivated split Flu-M vaccine produced by SPbNIIVS is approved for use for specific prophylaxis of influenza in children aged 6 to 17 years in the Russian Federation, the Republic of Belarus, Latin America and the Caribbean.The trial is registered at ClinicalTrials. gov (NCT 05317767).

Modeling the Impacts of Antiviral Prophylaxis Strategies in Mitigating Seasonal Influenza Outbreaks in Nursing Homes.

Antiviral chemoprophylaxis is recommended for use during influenza outbreaks in nursing homes to prevent transmission and severe disease among non-ill residents. Centers for Disease Control and Prevention (CDC) guidance recommends prophylaxis be initiated for all non-ill residents once an influenza outbreak is detected and be continued for at least 14 days and until 7 days after the last laboratory-confirmed influenza case is identified. However, not all facilities strictly adhere to this guidance and the impact of such partial adherence is not fully understood. We developed a stochastic compartmental framework to model influenza transmission within an average-sized US nursing home. We compared the number of symptomatic illnesses and hospitalizations under varying prophylaxis implementation strategies, in addition to different levels of prophylaxis uptake and adherence by residents and healthcare personnel (HCP). Prophylaxis implemented according to current guidance reduced total symptomatic illnesses and hospitalizations among residents by a median of 12% and 36%, respectively, compared with no prophylaxis. We did not find evidence that alternative implementations of prophylaxis were more effective: compared to full adoption of current guidance, partial adoption resulted in increased symptomatic illnesses and/or hospitalizations, and longer or earlier adoption offered no additional improvements. In addition, increasing uptake and adherence among nursing home residents was effective in reducing resident illnesses and hospitalizations, but increasing HCP uptake had minimal indirect impacts for residents. The greatest benefits of influenza prophylaxis during nursing home outbreaks will likely be achieved through increasing uptake and adherence among residents and following current CDC guidance.

The impact of adjuvanted and non-adjuvanted influenza vaccines on <i>in vitro</i> lymphocyte immunophenotype

Vaccination is the most effective method of influenza prophylaxis resulting in reduced frequency and severity of complications. Currently, for the prevention of influenza, inactivated split and subunit vaccines as the safest and promoting formation of protective level of strain-specific virus neutralizing antibodies are used. It is known that not all inactivated vaccines are effective enough for select human groups. While nowadays the level of public health is low, there is a need to improve the effectiveness of vaccines that should activate all chains of the immune system. In order to enhance intensity of influenza virus strain-specific antibody production, adjuvant vaccines exerting other mechanisms to activate humoral and cellular immunity compared to non-adjuvant vaccines have been used. The aim of the study was to examine lymphocyte immunophenotype in 27 healthy donors treated with polymer-subunit (immunoadjuvant) and non-adjuvanted split and subunit influenza vaccines.
 Materials and methods. Peripheral blood lymphocyte subpopulations were studied in vitro by flow cytometer FC-500 Cytomics (Beckman Coulter, USA) using FITC- and PE-labeled monoclonal antibodies (mAbs).
 Results. All examined influenza vaccines activate the effectors of cellular immunity, increasing the number of NK-cells (CD16/56), NKT-lymphocytes (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, as well as cells bearing early activation marker (CD45/CD25). Among them the immunoadjuvant vaccine showed the greatest potential to induce cellular response eliciting regulatory mechanisms that prevent hyperactivation, stimulating growth of NK (CD16/56), NKT-cells (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, T-regulatory cells (Tregs, CD4/CD25/Foxp3).
 Conclusion. Vaccination against influenza besides the formation of specific antibodies render a transient, immunomodulating effect that is more noticeable after immunoadjuvant vaccine. It can be assumed that vaccination of people with dysfunctions of the immune system an additional prophylactic effect will be observed.

Baloxavir marboxil as a new specific anti-influenza drug

Baloxavir marboxil is the first antiviral drug with a unique single dose, registered in Russia in September 2020 under the trade name Xoflusa, for treating infection caused by influenza A and B viruses.
 This article presents an overview of studies on the anti-influenza activity of baloxavir marboxil by foreign colleagues. Data from scientific articles by different authors were analyzed and in vitro results and clinical data were considered, which can help in making recommendations for the use of the drug for the treatment and postexposure prophylaxis of influenza.
 Baloxavir marboxil acts as a selective low-molecular-weight inhibitor of an enzyme specific to the influenza virus in the viral RNA polymerase complex and is effective against strains resistant to oseltamivir. In the combined phenotypic analysis and analysis based on the sequence in the polymerase acidic (PA) protein, the frequency of viruses showing reduced susceptibility to the drug remains low.
 Numerous studies have demonstrated the safety profile and productivity of influenza treatment in various groups (without risk factors and high-risk patients). Baloxavir marboxil stops the replication of the influenza virus in the early stages, which terminates its release during the first day and significantly relieves the patients condition on the second day. Monitoring of the antiviral activity of the drug, especially in children aged 12 years and people with weakened immunity, should be closely monitored to develop clinical recommendations and prevent the formation of substitutions I38(T/F/M/S/L/V) in the PA of influenza A and B viruses that reduce their sensitivity to the drug.

Cross-Reactive Fc-Fused Single-Domain Antibodies to Hemagglutinin Stem Region Protect Mice from Group 1 Influenza a Virus Infection.

The continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which bind to the stem domain of hemagglutinin and efficiently neutralize H1N1 and H5N2 influenza viruses in vivo. In this study, we modified these VHHs with Fc-fragment to enhance their antiviral activity. Reformatting of G2.3 into bivalent Fc-fusion molecule increased its in vitro neutralizing activity against H1N1 and H2N3 viruses up to 80-fold and, moreover, resulted in obtaining the ability to neutralize H5N2 and H9N2 subtypes. We demonstrated that a dose as low as 0.6 mg/kg of G2.3-Fc or H1.2-Fc administered systemically or locally before infection could protect mice from lethal challenges with both H1N1 and H5N2 viruses. Furthermore, G2.3-Fc reduced the lung viral load to an undetectable level. Both VHH-Fc antibodies showed in vivo therapeutic efficacy when delivered via systemic or local route. The findings support G2.3-Fc as a potential therapeutic agent for both prophylaxis and therapy of Group 1 influenza A infection.

Intranasal Treatment of Ferrets with Inert Bacterial Spores Reduces Disease Caused by a Challenging H7N9 Avian Influenza Virus

Background: Influenza is a respiratory infection that continues to present a major threat to human health, with ~500,000 deaths/year. Continued circulation of epidemic subtypes in humans and animals potentially increases the risk of future pandemics. Vaccination has failed to halt the evolution of this virus and next-generation prophylactic approaches are under development. Naked, “heat inactivated”, or inert bacterial spores have been shown to protect against influenza in murine models. Methods: Ferrets were administered intranasal doses of inert bacterial spores (DSM 32444K) every 7 days for 4 weeks. Seven days after the last dose, the animals were challenged with avian H7N9 influenza A virus. Clinical signs of infection and viral shedding were monitored. Results: Clinical symptoms of infection were significantly reduced in animals dosed with DSM 32444K. The temporal kinetics of viral shedding was reduced but not prevented. Conclusion: Taken together, nasal dosing using heat-stable spores could provide a useful approach for influenza prophylaxis in both humans and animals.

Assessment of influenza A (H1N1, H3N2) oseltamivir resistance during 2017-2019 in Iran.

Neuraminidase inhibitors (NAIs) as an imperative antiviral for influenza prophylaxis and treatment are being consumed worldwide. Increasing use of these antivirals might be associated with drug resistance. Regarding the significance of these variations, this study aimed to investigate the mutations occurring in the NA gene of influenza A viruses leading to oseltamivir resistance during 2017-2019 in Iran. In this cross-sectional study, 40 influenza A (H1N1, H3N2) strains, isolated in National Influenza Center (NIC) from patients with Severe Acute Respiratory Infection (SARI) during 2017-2019 were subjected to RT-PCR and sequencing of NA complete gene. The frequency of oseltamivir resistance and variation of NA amino acids in these strains were investigated. No significant mutation conferring oseltamivir resistance was detected. However, NA antigenic sites in these strains depicted minor changes compared to the vaccine strains. Among H3N2 isolates, mutations at 329, 344, 346 and 385 and among H1N1 isolates mutations at 143 and 188 residues occurred in NA antigenic regions. Evaluation of NA gene sequences, showed no resistant viruses to oseltamivir. Given that the viruses in the present study were the last viruses circulating in Iran before COVID-19 pandemic, the results will be beneficial to have a worthy comparison with the strains circulating after the pandemic. Constant monitoring for the emergence of drug-resistant variants and antigenic changes are crucial for all countries.

Peculiarities clinical course of influenza in children and modern opportunities for specific prophylactics

Annotation. Timely detection of influenza cases and modern opportunities for prevention of the disease are becoming important in the season of increasing the incidence of respiratory diseases in a pandemic COVID-19.The aim was to study the clinical and laboratory features of influenza in children in the season 2021/2022, who were hospitalized in the departments of Vinnytsia City Hospital “Mother and Child Center” since December 2021 till February 2022, as well as to analyze the current possibilities of specific prevention of the disease. 30 children were examined to clarify the clinical course of influenza. To diagnose influenza A and B, children underwent a smear of the nasal mucosa. Immunochromatographic method was used, namely cito-test of LLC "Pharmaco - Ukraine". To rule out coronavirus infection, a rapid antigen test for the coronavirus "SARS-CoV-2 Rapid Antigen Test" was performed. An analysis of prophylactic vaccination cards №063/o was performed to study the coverage of influenza vaccination. It was found that preschool children predominated (17 people – 56.7%), while school-age children accounted for 43.3%. A quarter of children (26.6%) sought medical help on the first day of illness, half (56.6%) - on the second day and the rest (16.6%) – on the third day. The children with flu mostly complained of chills, headache, loss of appetite, aches in the joints and muscles, most children suffered from high body temperature, which lasted up to 3±0.8 days. The average temperature figures were 39.52±0.58ºC. Catarrhal phenomena were present in the biggest part of children (86.7%). It was revealed a clear lung sound and vesicular breath sound in a physical examination. There were no significant changes in the blood count in 70% of children. Children were prescribed special and symptomatic therapy. No one of the hospitalized children received specific influenza prophylaxis according to the prophylactic vaccination cards №063/o, although vaccination remains the best way to protect against influenza and is of great importance, especially in a pandemic COVID-19. Inactivated tetravalent vaccines present in Ukraine provide reliable protection against influenza and are completely safe.

Generation and in vitro characterization of engineered cold-adapted influenza A strains with modified NS gene

BACKGROUND: The high variability of influenza strains and the emergence of new variants of viruses lead to the need for constant updating of the composition of influenza vaccines. One of the options for solving this problem is the development of vaccines with enhanced cross-protection against a wide range of influenza strains. Genetically engineered preparations based on live influenza vaccine can be used for targeted stimulation of the cellular immune response. It has been experimentally established that CTL epitopes inserted into the NS gene of the live influenza vaccine strain cause the activation of lymphocytes and the formation of a pool of resident memory T-cells in the lungs of model animals. It is optimal to use experimentally confirmed immunogenic regions for insertion.
 AIM: The aim of this study was to rescue a panel of experimental cold-adapted live attenuated influenza vaccine strains with a modified NS gene using A/Leningrad/134/17/57 backbone and recent influenza strains of H1N1, H3N2 and H7N9 subtypes, and evaluate their properties in vitro.
 MATERIALS AND METHODS: A cassette encoding immunogenic, conserved among a wide range of influenza strains T-cell epitopes of the influenza virus PB1 protein restricted by common HLA-allotypes was inserted into the gene encoding the NS1 protein. The modified NS gene was cloned into the pCIPolISapIT influenza virus reverse genetics vector. Chimeric influenza viruses were rescued by transfection of Vero cells by electroporation using a standard 8-plasmid system. The growth characteristics of viruses were assessed in developing chicken embryos.
 Results: Three strains were successfully obtained based on the live influenza vaccine master donor virus A/Leningrad/ 134/17/57 with a modified NS gene and influenza viruses of the H1N1, H3N2, H7N9 subtypes. Thus, modification of NS gene by insertion of immunogenic PB1 epitopes did not affect the viability and replicative activity of the rescued chimeric live influenza vaccine strains, regardless of the composition of the surface proteins. The strains replicated well at an optimal temperature, had temperature-sensitive phenotype and were able to grow at low temperature.
 CONCLUSIONS: The strains will be further studied as candidates for influenza prophylaxis as an experimental universal influenza vaccine.

Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.

Recommendations for Prevention and Control of Influenza in Children, 2021-2022.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021–2022 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report.1 The American Academy of Pediatrics recommends annual influenza immunization of all children without medical contraindications, starting at 6 months of age. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during the 2021–2022 influenza season. Any licensed, recommended, age-appropriate vaccine available can be administered, without preference for one product or formulation over another. Antiviral treatment of influenza with any licensed, recommended, age-appropriate influenza antiviral medication is recommended for children with suspected or confirmed influenza who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza. Antiviral treatment may be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications, in whom an influenza diagnosis is confirmed or suspected, if treatment can be initiated within 48 hours of illness onset and for children whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza.Children consistently have the highest attack rates of influenza in the community during seasonal influenza epidemics. Children play a pivotal role in the transmission of influenza virus infection to household and other close contacts and can experience substantial morbidity, including severe or fatal complications from influenza infection.2 Children younger than 5 years, especially those younger than 2 years, and children with certain underlying medical conditions are at increased risk of hospitalization and complications attributable to influenza (Table 1).2 School-aged children bear a large influenza disease burden and are more likely to seek influenza-related medical care compared with healthy adults.2,3 Reducing influenza virus transmission among children decreases the burden of childhood influenza and transmission of influenza virus to household contacts and community members of all ages.2,3 Influenza vaccination is particularly important during the severe acute respiratory syndrome coronavirus 2 pandemic to reduce the burden of respiratory illnesses and hospitalizations and preserve the capacity of the health care infrastructure. The American Academy of Pediatrics (AAP) recommends routine influenza vaccination and antiviral agents for the prevention and treatment of influenza in children, respectively. This policy statement summarizes updates and recommendations for the 2021–2022 influenza season. An accompanying technical report provides further detail regarding recent influenza seasons, influenza vaccine effectiveness (VE), detailed updates of inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs), influenza vaccination coverage, vaccine implementation, and timing of vaccination and duration of protection.1Children and adolescents with certain underlying medical conditions have a high risk of complications from influenza (Table 1). Although universal influenza vaccination is recommended for everyone starting at 6 months of age, emphasis should be placed in ensuring that high-risk and vulnerable children and their household contacts and caregivers receive annual influenza vaccine.The seasonal influenza vaccines licensed for children and adults for the 2021–2022 season are shown in Table 2. More than one product may be appropriate for a given patient, and vaccination should not be delayed to obtain a specific product.All 2021–2022 seasonal influenza vaccines will be quadrivalent and contain the same influenza strains as recommended by the World Health Organization and the US Food and Drug Administration Vaccines and Related Biological Products Advisory Committee for the Northern Hemisphere.4,5 Both influenza A(H1N1) and A(H3N2) components are different in this season’s vaccine. The B components are unchanged. The influenza A strains may be different for egg-based versus cell- or recombinant-based vaccines on the basis of their optimal characteristics for each platform, but all are matched to the strains expected to circulate in the 2021–2022 season.The contraindications and precautions for the use of IIV and LAIV are described in Table 3, and further details are provided in the technical report.1 Anaphylactic and severe allergic reactions to any influenza vaccine are contraindications to vaccination. The AAP recommends that children who have had an allergic reaction after a previous dose of any influenza vaccine should be evaluated by an allergist to determine if future receipt of the vaccine is appropriate.Antivirals available for the treatment and prophylaxis of influenza in children are described in Table 4.Antiviral chemoprophylaxis is recommended after known or suspected influenza exposure in the following situations: Jennifer M. Frantz, MPH

Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial

BackgroundIn a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial.MethodsThis study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP.DiscussionA 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects.Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881. Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015

Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus.

An escalating pandemic of the novel SARS-CoV-2 virus is impacting global health, and effective antivirals are needed. Umifenovir (Arbidol) is an indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It has been shown that umifenovir has broad spectrum activity against different viruses. We evaluated the sensitivity of different coronaviruses, including the novel SARS-CoV-2 virus, to umifenovir using in vitro assays. Using a plaque assay, we revealed an antiviral effect of umifenovir against seasonal HCoV-229E and HCoV-OC43 coronaviruses in Vero E6 cells, with estimated 50% effective concentrations (EC50) of 10.0 ± 0.5 µM and 9.0 ± 0.4 µM, respectively. Umifenovir at 90 µM significantly suppressed plaque formation in CMK-AH-1 cells infected with SARS-CoV. Umifenovir also inhibited the replication of SARS-CoV-2 virus, with EC50 values ranging from 15.37 ± 3.6 to 28.0 ± 1.0 µM. In addition, 21–36 µM of umifenovir significantly suppressed SARS-CoV-2 virus titers (≥2 log TCID50/mL) in the first 24 h after infection. Repurposing of antiviral drugs is very helpful in fighting COVID-19. A safe, pan-antiviral drug such as umifenovir could be extremely beneficial in combating the early stages of a viral pandemic.

Influenza Management During the COVID-19 Pandemic: A Review of Recent Innovations in Antiviral Therapy and Relevance to Primary Care Practice.

Seasonal influenza requires appropriate management to protect public health and resources. Decreasing the burden of influenza will depend primarily on increasing vaccination rates as well as prompt initiation of antiviral therapy within 48 hours of symptom onset, especially in the context of the current coronavirus disease 2019 pandemic. A careful approach is required to prevent health services from being overwhelmed by a surge in demand that could exceed capacity. This review highlights the societal burden of influenza and discusses the prevention, diagnosis, and treatment of influenza as a complicating addition to the challenges of the coronavirus disease 2019 pandemic. The importance of vaccination for seasonal influenza and the role of antiviral therapy in the treatment and prophylaxis of seasonal influenza, including the most up-to-date recommendations from the Centers for Disease Control and Prevention for influenza management, will also be reviewed.

#5: Trends in Seasonal Prevalence of Respiratory Pathogens Among Children in the United Arab Emirates: A Multi-Center Study.

Abstract Background Pediatric respiratory infections cause a high disease burden globally. Their seasonality and molecular epidemiology in the United Arab Emirates (UAE) are not well understood. This data is important for clinical practice, to monitor disease outbreaks and optimize vaccination for influenza and RSV prophylaxis in high risk infants and children. Our objective was to describe the seasonality and molecular epidemiology of respiratory pathogens during a full calendar year among children in Dubai, UAE. Methods Children 0–18 years of age who presented to multiple hospitals and clinics within a large private healthcare group in Dubai between January 1st and December 31st, 2019, and had upper respiratory samples positive for any pathogen on multiplex polymerase chain reaction (mPCR) were included in this retrospective analysis. Sociodemographic, clinical, and molecular data were collected. Results Two thousand four hundred and twenty-seven children had mPCR sample positive for at least one pathogen. The median age of our population was 39 months, and 56.8% were male. Emergency room was the most common site (32.3%) of sample collection and the vast majority presented with fever (85.7%). Rhinovirus/enterovirus was the most common infection (45%) and peaked in September; followed by respiratory syncytial virus (RSV) (17.1%) which peaked in October; and adenovirus (15.6%) which peaked in June. The latter accounted for 43% of hospitalizations in our study (p<0.05). Viral co-infections, most commonly human rhinovirus/enterovirus and RSV, were seen in 22.1% of children. Other infections occurred in 34.1% of children comprising mainly of streptococcal pharyngitis. Conclusions RSV is a common viral pathogen in the UAE, and the RSV season begins earlier than reported in other countries regionally. RSV prophylaxis in high risk infants should be considered in August to provide maximal protection. Adeno – Adenovirus; Corona – Coronavirus; hMPV – Human Metapneumovirus; Influ A – Influenza A; Influ B – Influenza B; Rhino/Entero – Human rhinovirus/Enterovirus; Para – Parainfluenza virus; RSV – Respiratory Syncytial Virus; Mycoplasma – Mycoplasma pneumoniae; Bordatella para – Bordatella parapertussis; Bordatella Per – Bordatella pertussis; Chlamydia – Chlamydia pneumoniae.

Prophylaxis and treatment of influenza: options, antiviral susceptibility, and existing recommendations.

Influenza viruses of types A and B attack 5–10% of adults and 20–30% of children, thereby causing millions of acute respiratory infections in Germany annually. A significant number of these infections are associated with complications such as pneumonia and bacterial superinfections that need hospitalization and might lead to death. In addition to vaccines, drugs were developed that might support influenza prevention and that can be used to treat influenza patients. The timely application of anti-influenza drugs can inhibit virus replication, help reduce and shorten the symptoms, and prevent death as well as virus transmission.This review concisely describes the mechanism of action, the potential for prophylactic and therapeutic use, and the knowledge on resistance of anti-influenza drugs approved today. However, the main aim is to give an overview on the recommendations available in Germany for the proper use of these drugs. In doing so, the recommendations published in statements and guidelines of medical societies as well as the German influenza pandemic preparedness plan are summarized with the consideration of specific circumstances and groups of patients.

Antiviral activity and mechanism of ESC-1GN from skin secretion of Hylarana guentheri against influenza A virus

Development of new and effective antiinfluenza drugs is critical for prophylaxis and treatment of influenza A virus (IAV) infection. A wide range of amphibian skin secretions have been identified to show antiviral activity. Our previously reported ESC-1GN, a peptide from the skin secretion of Hylarana guentheri, displayed good antimicrobial and antiinflammatory effects. Here, we found that ESC-1GN possessed significant antiviral effects against IAVs. Moreover, ESC-1GN could inhibit the entry of divergent H5N1 and H1N1 virus strains with the IC50 values from 1.29 to 4.59 μM. Mechanism studies demonstrated that ESC-1GN disrupted membrane fusion activity of IAVs by interaction with HA2 subunit. The results of site-directed mutant assay and molecular docking revealed that E105, N50 and the residues around them on HA2 subunit could form hydrogen bonds with amino acid on ESC-1GN, which were critical for ESC-1GN binding to HA2 and inhibiting the entry of IAVs. Altogether, these not only suggest that ESC-1GN maybe represent a new type of excellent template designing drugs against IAVs, but also it may shed light on the immune mechanism and survival strategy of H.guentheri against viral pathogens.